A series of novel inflammation-related indexes has been confirmed to be efficient indicators of human immune and inflammatory status, with great potential as predictors for a variety of diseases. However, the association between inflammation-related indexes and sex hormones in the general population remained uncertain.We incorporated data from the NHANES 2013-2016 survey of American adults. On the basis of distribution and comparison analysis, we chose to undertake separate analyses of men and women . Multivariable weighted linear regression models, eXtreme Gradient Boosting (XGBoost) models, generalized linear analysis, stratified models, logistic regression models and sensitivity analysis were utilized to assess the relationships between inflammation-related indexes and sex hormones.2).Total 9372 participants out of 20146 were fitted into our research. We conducted separate gender analysis due to different distribution. Multivariable weighted linear regression indicated every component of the inflammation-related index was negatively correlated with at least one component of the male hormone indexes. However, SII, NLR, PPN, and NC were associated positively with female estradiol. XGBoost identify SII, PLR and NLR were the critical indexes on sex hormones. Inflammation-related indexes was associated with Testosterone deficiency in male and postmenstrual group and associated with Excessive Estradiol in premenstrual group. Finally, the subgroup analysis revealed that the association between sex hormones and inflammatory indicators was prominent in American adults over the age of 60 or those with BMI (>28 kg/mIn all, inflammation-related indexes act as independent risks associated with sex hormone alterations and metabolic disorder in both genders. Using multiple models, we revealed the relative importance of inflammation-related indexes. Subgroup analysis also identified the high-risk population. More prospective and experimental research should be conducted to validate the results. These indicators, for example, are elevated in patients with inflammatory diseases and are associated with disease activity , 2. AddiA few prior epidemiological studies have investigated the association between the inflammation-related indexes and reproductive health. For instance, leukocytosis was recognized to bridge low-grade chronic inflammation and polycystic ovary syndrome (PCOS) which presented with hyperandrogenism, and NLR level seemed to be a potential effective predictor among several parameters , 14. Mor2) are the two primary sex hormones in humans. SHBGs are a kind of transporter protein found in plasma that binds and transports testosterone and estradiol, hence controlling the amount of biologically active non-protein-bound sex hormones  and estradiol , SHBG, FAI and TT/E2 using data of two cycles (2013–2016) from the U.S. National Health and Nutrition Examination Survey (NHANES). We hypothesized that inflammation-related indexes might contribute to changes in sex hormone concentrations and further constructed multiple statistical models to systemically evaluate the association between inflammation-related indexes and sex hormones in American general adult population.However, due to the limited studies, the relationship between inflammation-related indexes and sex hormones remains unclear and requires further investigation. In this study, we aimed to explore the association by adjusting covariates between inflammation-related index and sex hormones, including total testosterone (TT), estradiol (E22.1https://www.cdc.gov/nchs/nhanes/index.htm) which is updated biennially. Institutional Review Board (IRB) and NCHS Research Ethics Review Board (ERB) granted research authorization, thus no more permission was required.The National Health and Nutrition Examination Survey (NHANES) was conducted by National Center for Health Statistics (NCHS) and the Centers for Disease Control/Prevention (CDC) aiming for evaluating general American health and nutritional status through 2-years cycle examinations and interviews . It has 2.2Since 1999, NHANES published their data biennially . Complet2.3We identified menopausal status based on the self-reported of the reproductive health questionnaire. We identified the postmenopausal status were female who answered “no” to the question “Have you had at least one menstrual period in the past 12 months?” and then answered “hysterectomy” or “menopause/change of life” to the question “What is the reason that you have not had a period in the past 12 months?”. The details of the self-reported reproductive health questionnaire are available on the NHANES website. Among them, there are 2221 postmenopausal females and 2618 premenopausal females.2.4CDC-developed routine chapter analyzes the isotope dilution liquid chromatography tandem mass spectrometry (ID-LC-MS/MS) technology for simultaneous detection of total testosterone and estradiol in blood, following dissociation from binding proteins and elimination of possibly interfering substances. The technique was designed for a high sample throughput and exhibits great exactness over a number of years. Measuring the chemiluminescence of the reaction product of SHBG with an immune antibody that happens after two incubation periods and subjected to a magnetic field are used to quantify SHBG. A photomultiplier tube can detect the chemiluminescent reaction that takes place when the microparticles are captured on an electrode. The results are compared to a calibration curve that is specific to the device and lot. Free testosterone can be calculated by detecting the concentration of total testosterone, SHBG and albumin. The ratio of Testosterone to Estradiol was used to measure the percentage of sexual hormones. Calculate free androgen index% (FAI)=(TT/SHBG) × 100. Measuring testosterone level on the basis of correcting SHBG abnormality is a good indicator for evaluating hyperandrogenism. The specifics of measurement may be found on the NHANES website in the laboratory protocol handbook. The detection limits were constant for all of the analytes in the data set. The value of results below the lower limit of detection (LLOD) is the lower limit of detection divided by the square root of 2 [LLOD/sqrt  discusses in depth specimen collecting and processing. As a fundamental Inflammation-related index, we used the platelet count (PLT), neutrophil count (NC), and lymphocyte count (LC). For a more complete examination of the connection between inflammation-related indexes and sex hormones, we computed systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and the product of platelet count and neutrophil count (PPN). PLT, NC, and LC were measured at a concentration of 1000 cells/uL. SII was computed by multiplying PLT by (NC/LC). PLR was determined by dividing PLT by LC. NC/LC was used to compute NLR. PPN was determined by multiplying PLT by NC. The detection limits were constant for all of the analytes in the data set. None of the results were below the limits of detection.2.62) as a piece of information from a medical exam and a person’s life history into our research. On the NHANES website, you can find variables that are more complicated.Based on what we already knew from other studies , 33, we 2.7https://www.cdc.gov/nchs/nhanes/index.htm). For statistical analysis, the NHANES analytic guidelines were used . We utilized the mobile examination center (MEC) exam weight (WTMEC2YR) for weighted analysis since some of the variables in this research were gathered at the MEC. In addition, the sample weight utilized in the final analysis was equivalent to double the value of “WTMEC2YR” since two NHANES survey cycles were merged. The weighted mean and standard error (SE) (continuous variables) as well as the weighted percentage  represented the characteristics of the sample at participant baseline. If it is a continuous variable, the Kruskal-Wallis rank sum test was used. If the number of theoretical counting variables is fewer than 10, Fisher’s exact probability test was employed. In the case of categorical data, the p-value was calculated using weighted chi-square (2), smoking and drinking. We aimed to explore independent relationships between inflammation-related indexes and sex hormones by adjusting covariates. Smooth curve fitting and generalized additive models were used to describe the nonlinear link between the inflammation-related indexes and sex hormones. Then, we developed the machine learning XGBoost algorithm model to investigate the relative impact of inflammation-related index on sex hormone concentrations  were used to perform all types of statistical studies . In our research, statistical significance is determined when the p-value is less than 0.05.We employed a Systematic statistical analysis between inflammation-related indexes and sex hormone levels according to CDC standards (i-square Table 1.trations . Using s studies . Our stu33.12. Platelet count (PLT), neutrophil count (NC), lymphocyte count (LC), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and the product of platelet count and neutrophil count (PPN) comprised the immune-inflammation indexes. All indicators of sex hormones and the inflammation-related indexes revealed statistically significant between the two gender groups differences with p values less than 0.05. Intriguingly, the distribution of the ratio of poverty to income, race, education level, marital status, body mass index, drinking status, and smoking status differed statistically between the two gender groups.3.22, while females had higher levels of estradiol and SHBG. The potential relationship between inflammation-related indexes and sex hormones must be analyzed separately.To have a clearer understanding of the data distribution, we have represented the data using histograms Figure 23.32. This relationship varies among American women . For the postmenstrual group, we found inflammation-related indexes including SII, PPN, LC, NC, PLT were negatively associated with serum SHBG in the fully adjusted model, while SII and NLR were negatively associated with Testosterone. For the premenstrual group, SII, NLR, PPN and NC were positively associated with Estradiol. Thus, inflammation-related indexes represent different relationship with sex hormone levels in premenstrual and postmenstrual groups.In order to exclude the influence of premenstrual and postmenstrual status, we constructed the multivariable weighted linear regression models in both groups S10. Fo3.42 that were U-shaped. Inflammation-related indexes demonstrated a negative linear connection with testosterone in American women . The results of the sensitivity analysis matched those studies of weighted linear regression models. Specifically, we discovered that when hormone levels rose, the influence of the inflammation-related indexes became increasingly substantial. The findings of the sensitivity analysis indicated that the quarter of the American population with higher inflammation-related indexes ere more significantly affected by inflammatory disturbance and exhibited a more pronounced variation compared to in sex hormones than the quarter with a lower inflammation-related indexes. More information on the sensitivity analysis is included in 42 in the male population, while NLR predicted the highest gain value for estradiol. Populations with BMI>25 and age>60 demonstrated a greater degree of relevance. Inflammation-related indexes were associated with Testosterone deficiency in male and postmenstrual group. In the premenopausal group, the inflammation-related indexes were associated with Excessive Estradiol.The relationship between inflammation-related indexes and sex hormones in the American population was exhaustively examined by our research. We chose to provide the log2 value inflammation-related indexes for normalization. SII and other inflammation-related indexes were found to be inversely correlated with male testosterone and estradiol levels. These negative correlations were depicted as linear, although PLR was positively correlated with testosterone. In contrast, an elevated inflammation-related index was associated with a reduction in serum testosterone and an increase in estradiol concentrations in females. Both genders exhibited a decreasing trend in SHBG levels as the inflammation-related index increased. SII was the most useful indicator for female sex hormones other than SHBG. PLR was the most valuable SHBG index for both men and women. SII predicted the highest gain value for testosterone and TT/ESeveral previous studies have investigated the relationship between inflammatory indicators and sex hormones. Li et al. found that high SII levels in men were related with an increased prevalence of testosterone deficiency (TD), defined as a serum testosterone level ≤ 300ng/dl . M. InfaIn comparison to earlier research, our paper has numerous advantages. Firstly, just one study observed the link between the SII and low testosterone deficiency in men. Our study presented new information about the quantitative relationships between the inflammation-related indexes and a wide variety of sex hormone indicators in the American general population. We identified additional inflammatory indicators and assessed their relative significance using XGBoost models. Secondly, in contrast to prior investigations, we evaluated the connection between sex hormones and inflammatory markers obtained from Complete blood count (CBC) including PLT, NC, and LC, one of the most common examinations in clinical work. Thirdly, we evaluated various types of other sex hormone indexes in both genders to evaluate the inflammation effect completely. Finally, our research undertook a stratified analysis to access the potential impact of other factors on the association between the inflammation-related indexes and the sex hormone concentrations, which was a fundamental distinction between our study and those of the previous researchers.The current study examined the connection between Inflammatory status and sex hormone endocrine disorder. It is critical to highlight that due to the study’s cross-sectional design, causality could not be determined. Higher inflammation-related parameters, which might indicate an inflammatory state, may have led to sex hormone imbalances. In contrast, abnormal sex hormone levels may cause alterations in inflammatory state and immune response. Although the exact mechanism behind the association between inflammation-related markers and sex hormone concentrations remains undetermined, there are several possible explanations that might involve the interaction between the immune and reproductive systems. When inflammation occurs, pro-inflammatory cytokines would typically stimulate the hypothalamic-pituitary-adrenal axis (HPA) in order to prevent the overreaction of inflammation through the anti-inflammatory effects of glucocorticoids (GC) , 38. DurOur discovery has significant implications for clinical use and future research. Firstly, the results indicated that population with high levels of inflammation-related indexes had higher potential risk of sex hormone changes and endocrine disorder, although the causality of two factor haven’t been figure out. Second, a traditional blood count test can be administered in primary health care facilities and big hospitals. SII and other inflammation-related indexes can be utilized as a novel predictive index to evaluate the likelihood of sex hormone changes and endocrine problem. Finally, a comprehensive comparison was conducted between the sex hormone indexes and inflammatory markers generated from PLT, NC, and LC, including SII, NLR, PLR, and PPN. Fourthly, we discovered that PLR was positively correlated with male testosterone, which separated PPN from other inflammation-related indexes. Fifthly, the subgroup analysis revealed that the correlation between sex hormones and inflammation-related indexes were stronger in populations with BMI>25 and age>60, indicating greater significance. Hence, specific populations in inflammatory status, such as those aged 60 and those who are overweight, should be mindful of the possibility of endocrine problem.However, our study existed some limitations. First of all, we could not establish the causality between inflammation status and sex hormones due to the cross-sectional design of NHANES. Then we only included two-cycles population due to lack of data. Although we performed a weighted analysis, the sample size is relatively small. Thus, more prospective studies are required with larger sample sizes because the level of inflammation may have a long-term effect on sex hormones. Moreover, our analyzed based on NHANES dataset collecting from American population which may cause region bias. Finally, residual confounding of unmeasured factors may bias our results to some extent, such as medical conditions, diet, occupational status, timing of the sample collection, and medication use.5Overall, GLM models suggested that inflammation-related index as an independent risk factor may be responsible for sex hormone alterations in both gender. Using XGBoost models, the relative importance of sex hormones index among US adults was determined. A stratified study indicated the sex hormones at high risk for inflammation based on its status. Our study used a cross-sectional design. To validate our results and elucidate the underlying molecular pathways, more prospective and experimental research should be conducted.The original contributions presented in the study are included in the article/CW: Conceptualization, Data curation, Formal analysis, Methodology, Software, Visualization, Writing – original draft, Writing – review & editing. WZ, JC and QH: Conceptualization, Methodology, Writing – review & editing. LC and PZ: Validation, Writing – review & editing. CD and MX: Writing – review & editing. YH: Writing – review & editing. HG, MW and ZC: Conceptualization, Data curation, Formal analysis, Methodology, Software, Visualization, Writing – original draft, Writing – review & editing.


National data suggest that non-Hispanic, White youth engage in electronic cigarette (e-cigarette) use at the highest rates. These results are not likely to be mirrored across regional contexts. State-representative data from Utah in 2019  were used to estimate the odds of lifetime and past 30-day vaping across seven racial/ethnic categories. Youth in grades 8, 10, and 12  self-reported race/ethnicity and vaping product use history, including e-cigarettes, vape pens, or mods. A Cox proportional hazards model estimated the cumulative probabilities for initiating vaping product use. The results indicated that American Indian or Alaskan Native, Black or African American, Hispanic/Latino, Multiracial, and Native Hawaiian or other Pacific Islander youth had significantly higher odds of both lifetime and past 30-day vaping compared to non-Hispanic White youth. The results showed significant variation in the cumulative probability of initiation by race/ethnicity, with Hispanic/Latino youth reporting the highest odds of initiation at each age. The regional patterns of vaping across racial/ethnic groups may not mirror national trends. State- and community-level data should be used to inform efforts to reduce e-cigarette use and promote health equity among youth. As of 2019, more than 35% of high school students in the United States (U.S.) had reported using an electronic cigarette (e-cigarette) at some point in their lifetime, and more than 20% reported use within the past month . As expected, the pattern of statistical significance for the results of the Cox model was substantively identical to the results of the logistic regression model examining lifetime e-cigarette use and, therefore, were not described in full. The proportional hazard assumption evaluated via the Wald F statistic did not indicate a violation ) [The data were analyzed with SPSS v27. Descriptive statistics and all the models were estimated using complex sample procedures to apply stratification by district, clustering by grade, and weighting to approximate population characteristics. Logistic regression models for lifetime and past 30-day e-cigarette use, including age and gender as covariates, were estimated with the CSLOGISTIC command. Odds ratios (OR) and 95% confidence intervals (CIs) were computed. Sensitivity tests examining racial/ethnic differences in lifetime and past 30-day e-cigarette use, while controlling for youth perceived risk of harm for e-cigarette use, produced substantively identical results to those presented below. A Cox proportional hazard model estimated the cumulative probability of e-cigarette initiation by race/ethnicity using the CSCOXREG command. The participants who never initiated e-cigarette use were right-censored at their current age. The Efron approximation was used to break ties and estimate the baseline survival function. The overall differences by race/ethnicity were evaluated via the Wald F statistic and showed significant variation [F = 64.75, Unweighted and weighted sample characteristics are provided in The epidemic of e-cigarette use and potential harms to youth health continue to be a source of substantial concern among healthcare and public health professionals. The results of the current study indicate some local divergence from national e-cigarette use trends and suggest that regional variation may play an important role in understanding e-cigarette use across racial/ethnic groups. In Utah, Hispanic/Latino youth make up approximately 19% of the population of youth emphasizing the broad potential for harm from e-cigarette use. The already well-established health disparities among Hispanic/Latino and other minority youth in the United States  in conjuThe patterns of e-cigarette use by grade among Utah youth agree with emerging trends on e-cigarette use among younger Hispanic/Latinos. A recent review by Unger and Falcon stated “Hispanic adolescents are at risk for experimenting with e-cigarettes at early ages, potentially leading to nicotine dependence. However, for the older generations who were not exposed to e-cigarettes during adolescence, uptake of e-cigarettes is less prevalent among Hispanics than among some other groups” . Recent Limitations of the current study should be noted. Importantly, the results of the current study are largely descriptive and did not hypothesize about risk or protective factors that may help explain observed racial/ethnic differences in e-cigarette use. Recent research has noted that e-cigarette use among youth is linked to a range of individual, peer, parental, and socioeconomic factors ,30,31. IThe results of the current study highlight the importance of examining regional or state-level differences in e-cigarette use among youth for both researchers and community practitioners . Further


SnRK1 (sucrose non-fermenting-related kinase protein), two main components of the sugar-signaling pathways [SnRK1, these authors proposed that NSC remobilization in the stem may follow a “feast-or-famine”-like model, which fits perfectly well with the fluctuating source–sink relationship during the grain filling stage. In addition, this remobilization could be mainly driven by the sink strength of the panicle. These two works lay a solid foundation for further exploring the relationship between the stem sugar signaling network, the stem carbon metabolism and sink strength, and open up promising research prospects on the molecular regulatory network and the way sink organs remotely control carbon remobilization in the stem.Sucrose and its derivative hexoses are key metabolites of the plant metabolism, structural units of cell walls and stored reserves , and also crucial metabolic signals that interplay with other metabolic, hormonal and environmental cues to fine-tune plant growth and development ,2,3. TheDimocarpus longan), a subtropic fruit tree with high economic value and sensitivity to cold, ref. [cis-acting elements and tissue-expression patterns. They found that this transporter family is divided into four clades with conserved motifs and similar exon–intron organization. More notably, and based on the genetic approach, they found evidence that only DiSWEET1 was greatly induced by cold, supporting its contribution to the adaptive response of longan to low temperature. Similarly, ref. [CsSWEET2 in the cold tolerance of cucumber (Cucumis sativus). CsSWEET2 encodes an energy-independent hexose/H+ uniporter and is localized on the plasma membrane and endoplasmic reticulum. Interestingly, its overexpression in Arabidopsis plants resulted in the accumulation of soluble sugars (glucose and fructose) and resistance to cold stress. All these results point out the functional diversity of SWEET sugar transporters in plant physiology and open new avenues of research on the molecular network orchestrating SWEET upregulation by environmental factors.Sugar transport across the plant involves a variety of transporters gathered into three main families: monosaccharide transporter-like (MST) genes, sucrose transporters (SUTs/SUCs) and sugar-will-eventually-be-exported transporters (SWEETS) . In addild, ref.  carried ly, ref.  highlighVitis vinifira maturation, stress, abscisic-acid induced; VvMSA) transcriptionally regulates the hexose transporter gene Vitis vinifera Hexose Transporter 1 (VvHT1), and its expression is at the crosstalk of glucose and ABA signaling [VvMSA in glucose signaling, ref. [VvMSA gain- and loss-of-function embryogenic and non-embryogenic grapevine cells. The choice of these two models is crucial for discriminating between glucose-sensitive signaling and glucose-metabolism-dependent processes. These authors clearly highlighted that VvMSA acts as a transcriptional regulator of the glucose transporter gene VvHT1 in glycolysis-dependent glucose signaling and regulates the interplay between glucose metabolism, transport and signaling. These results shed new light on the regulatory network of the ASR family and fill a gap in our understanding of the regulation of this complex protein family.Sugar-signaling pathways interact with hormonal pathways in several biological contexts and throughout the life cycle of the plant ,9,10,11.ignaling . To gainng, ref.  used a cRosa sp. roots [Among the sugar-related signaling pathways, the oxidative pentose phosphate pathway (OPPP) remains the least investigated, even though it is involved in sugar-mediated nitrate and sulfate transporters in p. roots  and bud p. roots ,19. In tp. roots  focused Concluding remarks. This Special Issue “Sugar Transport, Metabolism and Signaling in Plants” is an excellent opportunity to gather a variety of scientific research works involving in-depth investigations. Each of them sheds new and interesting light on sugar-related topics, including the sink–source relationship, focusing on the role of the stem node, the role of SWEET in plant stress responses and the hitherto neglected sugar-signaling pathway within the OPPP. They open up promising avenues for uncovering the molecular regulatory network behind this physiological function and integrating this knowledge within the overall functioning of the plant.


Taenia solium, and is a leading cause of epilepsy and chronic headaches in endemic areas including Latin America, Africa, and Asia. The epidemiology of NCC has not been well-studied in the United States to date, but small epidemiological studies suggest evidence of this disease in populations living in poverty and who have immigrated from an endemic region. There is a population living in Starr County, Texas along the Texas-Mexico border in whom the presence of other neglected tropical diseases has been demonstrated due to the intersection of poverty, climate, and high rate of immigration.Neurocysticercosis (NCC) is a parasitic infection caused by the tapeworm Our study was a serologic survey and risk factor analysis of cysticercosis in a pre-existing cohort of Mexican-Americans in Starr County, Texas. We used a triplex enzyme-linked immunoassay (ELISA) against cysticercosis-specific antigens and self-reported survey data and neighborhood-level variables to conduct a risk-factor analysis of seropositive participants.T. solium in 7.4% (45/605) of the cohort which likely represents a combination of parasite exposure, T. solium disease outside of the central nervous system, old calcified NCC, and viable or degenerating NCC. Female gender, specific occupation and indoor versus outdoor occupation were found to be significantly associated with cysticercosis seropositivity. Thirty-nine of the 45 seropositive participants were female (p 0.021), 26 were employed in healthcare, caregiving, or social service (p 0.009), and 42 were employed in an indoor occupation (p < 0.001). These occupations could pose a risk for T. solium transmission. A geospatial analysis of cases at the census tract level showed increased percentage of seropositivity centered around urban cities Rio Grande City and Roma, as well as smaller city La Grulla and census-designated place Alto Bonito.We identified an overall seropositivity to There is a critical need to investigate these cysticercosis-seropositive cases with brain imaging to evaluate for neurocysticercosis, as well as conduct an epidemiological investigation to determine disease transmission in Starr County.All Authors: No reported disclosures


This implies that the inability to dissipate metabolic heat leads to the saturation and eventual decrease in travel speed with increasing body mass as larger animals must reduce their realised travel speeds in order to avoid hyperthermia during extended locomotion bouts. As a result, the highest travel speeds are achieved by animals of intermediate body mass, suggesting that the largest species are more limited in their movement capacities than previously anticipated. Consequently, we provide a mechanistic understanding of animal travel speed that can be generalised across species, even when the details of an individual species’ biology are unknown, to facilitate more realistic predictions of biodiversity dynamics in fragmented landscapes.Movement is critical to animal survival and, thus, biodiversity in fragmented landscapes. Increasing fragmentation in the Anthropocene necessitates predictions about the movement capacities of the multitude of species that inhabit natural ecosystems. This requires mechanistic, trait-based animal locomotion models, which are sufficiently general as well as biologically realistic. While larger animals should generally be able to travel greater distances, reported trends in their maximum speeds across a range of body sizes suggest limited movement capacities among the largest species. Here, we show that this also applies to travel speeds and that this arises because of their limited heat-dissipation capacities. We derive a model considering how fundamental biophysical constraints of animal body mass associated with energy utilisation  and heat-dissipation  limit aerobic travel speeds. Using an extensive empirical dataset of animal travel speeds (532 species), we show that this  Reported trends in the maximum travel speeds of animals across a range of body sizes suggest that the largest species have limited movement capacities. By simultaneously considering body mass-dependent constraints on energy utilization and heat dissipation, this study provides a mechanistic explanation of animals’ cruising speeds. The movements of animals over land, in water, and through air are a central component of several ecological processes that together give rise to patterns of biodiversity and ecosystem functioning –3. MovemA central component of an animal’s movement capacity is its sustained  travel speed, which fundamentally depends on its locomotion mode, body mass, and the temperature that it experiences. Unlike the travel speeds of foraging animals, which can be predicted by optimal foraging theory, the travel speeds of nonforaging animals are subject to context-dependent trade-offs between energy costs, travel time, and distance ,20. AmonBased on prior models of maximum speed ,41, we aWe derive a general allometric model that considers how fundamental biophysical constraints associated with the supply, utilisation, and dissipation of energy and heat limit the travel speeds of flying, running, and swimming animals during extended locomotion bouts. Our model builds on previous biomechanical and metabolic approaches by considering the body mass dependence of (1) aerobic metabolism ,46 and (metabolic model), (2) constant across all species (constant heat-dissipation model), or (3) increases with body mass , a saturating function (constant heat-dissipation model), or a hump-shaped function , exclusively towards locomotion and, therefore, travel at speeds that minimise their absolute metabolic cost of locomotion. This yields a power-law scaling of realised travel speed with body mass (tdiss (s), towards the dissipation of metabolic heat—an inevitable by-product of muscular contractions  allometric scaling model  that, by accounting for differences in the locomotion rate constant, v0, among locomotion modes, describe the realised travel speeds of all flying, running, and swimming species as a function of their body mass  as opposed to within the terrestrial realm (air) would result in higher realised travel speeds among the largest swimming animals. Although both models had comparable prediction accuracies to that of our best-performing model  metabolic power input and locomotion efficiency . Similarly, the allometric scaling exponent that describes the body mass dependence of heat-dissipation time, and thus, larger animals’ greater thermal inertia, also fell within the range of values derived from theoretical and empirical estimates of maximal heat-dissipation capacity . Together, these results support the conclusion that these different allometric scaling processes jointly influence the realised travel speeds of animals.The aints on  metaboliaints on  metaboliallometric heat-dissipation model. This leads to 2 general insights about the fate of metabolic energy that goes towards the production of mechanical work and that which is dissipated as heat: First, despite possessing the metabolic potential to sustain higher travel speeds, the realised travel speeds of the largest animals are limited due to the risk of hyperthermia. Second, flying animals sustain a higher metabolic power input and higher travel speeds and, therefore, begin to limit their realised travel speeds at smaller body masses than running or swimming animals that travel more slowly. By jointly considering how allometric constraints shape metabolic demands as well as the dissipation of heat, we can provide generalised predictions of animal travel speeds across different locomotion modes and ecosystem types when only the body mass is known.We found a hump-shaped scaling relationship of travel speed with body mass across running, flying, and swimming animals, which we explain using fundamental biophysical constraints on the supply, utilisation, and dissipation of energy and heat, as incorporated within our metabolic model), which, by overestimating the travel speeds of the largest animals, fails to capture the empirical data’s hump-shaped trends in log-log space. To address this, existing power-law models report values of the allometric scaling exponent, which are inconsistent across taxonomic groups and different body mass ranges: One pattern that emerges across studies is the tendency for larger scaling exponents to be reported within groups of small-bodied animals such as arthropods Major commentsThis study developed a generalised biophysical model that integrates physiology in terms ofmetabolic heat dissipation with locomotor capacity to explain average speed across body size from awide range of taxa. This is an interesting paper and I really enjoyed reading the logic and reasoningbehind the model. The main conceptual critique is on the term “dispersal” used throughout the paper.While dispersal is ecologically important to understand how animals respond to a rapidly changingworld, the general allometric model is looking at average movement (Table 1 step 1) and energyexpenditure of locomotion (Table 1 step 3 and 4). I would recommend not limiting study to discussingdispersal because dispersal is a behavioural process or state of a one-way, long-distance movementto a new environment that is determined by intrinsic and extrinsic factors , which locomotor capacity  and energy expenditure  are one of thelimiting factors for the rate of dispersal. In fact, the description of the data collection section indicatesaverage speed from “maintaining sustained and directed movements within an unrestrained setting”was extracted which could indicate general activity or movement that can encompasses foraging,exploration, seeking shelter or mate, dispersal, or migration. There is no indication that the speedsextracted were specific to dispersal. Therefore, the study itself looks at how heat dissipation affectsmovement or locomotor capacity and not solely on dispersal. I would reframe the study to focus onlocomotor capacity, with part of the argument that dispersal is an important component of locomotion.Therefore, the introduction, methods, results, and discussion should reflect this.Bowler, D. E., & Benton, T. G. (2005). Causes and consequences of animal dispersal strategies: relating individualbehaviour to spatial dynamics. Biological Reviews, 80, 205-225.Stevens, V. M., Whitmee, S., Le Galliard, J. F., Clobert, J., Böhning‐Gaese, K., Bonte, D., ... & Baguette, M. (2014).A comparative analysis of dispersal syndromes in terrestrial and semi‐terrestrial animals. Ecology Letters, 17, 1039-1052.Wu, N. C., & Seebacher, F. (2022). Physiology can predict animal activity, exploration, and dispersal.Communications Biology, 5, 1-11.ResultsL244-252: I disagree with this paragraph that the model did not include the covariables because theydid not correspond to systematic deviations. This was a visual assessment and while there is largevariation between each covariates examined (in the supplementary figures), a sensitivity analysis ormodel comparison is highly recommended to statistically support the influence of these variables onthe model output. Comparing these models therefore can provide confident when reasoning whetherthe covariables are necessary in the study.MethodsTo ensure standardised practice and transparency in reporting methods and results for comparativestudies , I have included a “Transparency, openness, and reproducibility” checklistat the end of the document from the Tools for Transparency in Ecology and Evolution  website. This is to warrant appropriate methodological details reported in thestudy.Parker, T. H., Griffith, S. C., Bronstein, J. L., Fidler, F., Foster, S., Fraser, H., Forstmeier, W., Gurevitch, J.,Koricheva, J. and Seppelt, R. (2018). Empowering peer reviewers with a checklist to improve transparency. NatureEcology & Evolution 2, 929-936.The methods section was straight forward and easy to follow. There were some important informationmissing from the data synthesis and analysis stage of the main document that requires furtherclarification:- What was the total records from the Web of Science and Google Scholar search?- How many studies were retained and excluded?- What was the inclusion and exclusion criteria for keeping studies in the data.- Provide the proper references in the raw data instead of numbers.- Provide the R code for the analysis,- Provide references for the R packages used and the R software in the main document.Some additional caveats need to be acknowledged with the heat dissipation models, the modelassumes the animal is constantly moving for the heat-dissipation model to function and ignores howmany times the animal would need to rest. Under a hypothetical scenario it is fine but needs to bestated.TablesTable 1. Some missing descriptions of symbols such as �! and �!, which I assume are the interceptsof the power function?FiguresFig 1: For part C - time budget, is the fraction of heat-dissipation relative to body size or total?S1_TextLS34-36: A recent study suggest metabolic-size scaling is due to evolutionary optimisation for lifehistory , while another theory suggests the scaling relationship is due to themetabolic boundaries of cells . It would be worth considering when describingmechanistic basis for metabolic-size scaling relationships.Glazier, D. S. (2005). Beyond the ‘3/4-power law’: variation in the intra-and interspecific scaling of metabolic rate inanimals. Biological Reviews, 80, 611-662.Glazier, D. S. (2010). A unifying explanation for diverse metabolic scaling in animals and plants. Biological Reviews,85, 111-138.White, C. R., Alton, L. A., Bywater, C. L., Lombardi, E. J., & Marshall, D. J. (2022). Metabolic scaling is the productof life-history optimization. Science, 377, 834-839.Eq 7: Is T in Celsius or Kevin?Minor commentsL637: Journal missing in this paper.Transparency openness, and reproducibility checklist... [see attachment]Reviewer #2:[identifies himself as Douglas S. Glazier]General comments:This is a fascinating, thoughtful and well-written study that attempts to explain why sustained speed during dispersal events relates to body mass in a humped (concave downward) left-skewed fashion. Previous publications have reported how and why maximum speed shows a humped relationship , but this is the first study to show how and why this also occurs for sustained speed. I especially liked how the authors developed three alternative mathematical models and then compared them to the empirical data. Bravo! However, I have three major concerns that I believe that the authors should address. 1) The authors consider 'conduction' in their heat-dissipation models, but apparently ignore 'convection' resulting from air/water flow. Therefore, their heat-dissipation models do not consider that an increased rate of body movement (speed) should increase heat dissipation via increased convection resulting from increased air/water movement across body surfaces. Therefore, there could be an interaction between speed and heat dissipation [i.e. between the mass scaling exponents for potential dispersal time (c) and heat-dissipation time (d)] that, if included, would change the predictions of their heat-dissipation models (i.e. reduce their downward curvature). This should be explored. 2) I am concerned that the data presented in Fig. 2 do not show clear hump-shaped patterns. They appear to be largely indistinguishable from saturation curves because no marked negative decrease is obvious at large body sizes . Perhaps including the effects of convection in their models would help explain this. Please clarify.3) In my opinion, the authors should further explore how thermoregulatory mode (endothermy vs. ectothermy) and macrohabitat  would affect the body-mass scaling of speed . If the author's allometric heat-dissipation model is correct, then sustained speed should peak at lower body masses in endotherms vs. ectotherms, because endotherms typically have higher body temperatures at rest, thus reducing the increase in body temperature that can be tolerated. In addition, sustained speed should peak at lower body masses in terrestrial vs. aquatic species, because of greater heat dissipation in water, which has a higher heat capacity than air. However, unexpectedly no large difference in the scaling patterns exist between aquatic and terrestrial species , and the endotherm-ectotherm comparison is complicated by the inclusion of flying birds and aquatic mammals. It would be useful to tease out these various effects because they importantly bear on the validity of the authors' heat dissipation models. Please clarify. Specific comments:L 200-203: In the text the authors say that Fig. 2 depicts "a single hump-shaped relationship", but actually three relationships (three curved lines) are shown for each of the three major modes of locomotion. Please clarify.Reviewer #3:This revised manuscript seems sound. I have no substantial comments. The details of the modeling are beyond my ability to critique. I did come across one reference that should be included and checked for data:Garland, T., Jr., and R. L. Albuquerque. 2017. Locomotion, energetics, performance, and behavior: a mammalian perspective on lizards, and vice versa. Integrative and Comparative Biology 57:252-266.AttachmentPBIOLOGY-D-22-01874_R1 - Review.pdfSubmitted filename: Click here for additional data file. 27 Jan 2023AttachmentDyerA_2023_ReponseToReviewers_Rev1.docxSubmitted filename: Click here for additional data file. 20 Feb 2023Dear Dr Dyer,Thank you for your patience while we considered your revised manuscript "Heat dissipation drives the hump-shaped scaling of animal travel speed with body mass" for publication as a Short Reports at PLOS Biology. This revised version of your manuscript has been evaluated by the PLOS Biology editors, the Academic Editor and the original reviewers.Based on the reviews, we are likely to accept this manuscript for publication, provided you satisfactorily address the remaining points raised by reviewer #1 and the following data and other policy-related requests:IMPORTANT: Please address the following:a) Please change your title to something more explicit and appealing. We suggest: "The travel speeds of large animals are limited by their heat-dissipation capacities."b) Please attend to the remaining points raised by reviewer #1.https://zenodo.org/record/7554842"c) Thank you for provided all the underlying data and code in Zenodo. Please cite the location of the data clearly in all relevant main and supplementary Figure legends, e.g. “The data underlying this Figure can be found in d) I note that you mention the reviewers in the Acknowledgements. While we appreciate the sentiment, this is against PLOS policy, so please could you remove this?As you address these items, please take this last chance to review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. 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Read more information on sharing protocols at Please do not hesitate to contact me should you have any questions.Sincerely,Roli RobertsRoland Roberts, PhDSenior Editor,rroberts@plos.org,PLOS Biology------------------------------------------------------------------------DATA NOT SHOWN?- Please note that per journal policy, we do not allow the mention of "data not shown", "personal communication", "manuscript in preparation" or other references to data that is not publicly available or contained within this manuscript. Please either remove mention of these data or provide figures presenting the results and the data underlying the figure(s).------------------------------------------------------------------------REVIEWERS' COMMENTS:Reviewer #1:[identifies himself as Nicholas C Wu]The authors did an excellent job addressing the reviewer's comments. The inclusion of a detailed description of the searches and data extraction is valuable for understanding how the data was obtained and what was included. The discussion is also more intuitive in interpreting the results. I have no further comments on the paper.There are some minor comments to consider below:L50-51: The terms "allee-, rescue-, source-sink, and drainage effects" might be too jargon for none experts. I would recommend describing them or just omit these examples.L84: "scored", past tense for consistency.L422-424: Expand on the phrase "Therefore, allometric locomotion models such as our allometric heat dissipation model could provide the modular "building blocks" of dynamic meta-community or meta food web models" as it was not mentioned anywhere previously in the main text.SI_Text.docxEq. 7: Is the Newtonian rate constant of temperature change independent to the surface area in this case? Make it clear, as Newton's law of cooling is the rate of cooling per unit surface areaReviewer #2:[identifies himself as Douglas S. Glazier]Good job! 6 Mar 2023AttachmentDyerA_2023_ReponseToReviewers_Rev2.docxSubmitted filename: Click here for additional data file. 7 Mar 2023Dear Dr Dyer,Thank you for the submission of your revised Short Report "The travel speeds of large animals are limited by their heat-dissipation capacities" for publication in PLOS Biology. On behalf of my colleagues and the Academic Editor, Anders Hedenström, I'm pleased to say that we can in principle accept your manuscript for publication, provided you address any remaining formatting and reporting issues. These will be detailed in an email you should receive within 2-3 business days from our colleagues in the journal operations team; no action is required from you until then. Please note that we will not be able to formally accept your manuscript and schedule it for publication until you have completed any requested changes.http://www.editorialmanager.com/pbiology/, click the "Update My Information" link at the top of the page, and update your user information to ensure an efficient production process.Please take a minute to log into Editorial Manager at biologypress@plos.org. If you have previously opted in to the early version process, we ask that you notify us immediately of any press plans so that we may opt out on your behalf.PRESS: We frequently collaborate with press offices. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximise its impact. If the press office is planning to promote your findings, we would be grateful if they could coordinate with http://www.plos.org/about/media-inquiries/embargo-policy/.We also ask that you take this opportunity to read our Embargo Policy regarding the discussion, promotion and media coverage of work that is yet to be published by PLOS. As your manuscript is not yet published, it is bound by the conditions of our Embargo Policy. Please be aware that this policy is in place both to ensure that any press coverage of your article is fully substantiated and to provide a direct link between such coverage and the published work. For full details of our Embargo Policy, please visit Thank you again for choosing PLOS Biology for publication and supporting Open Access publishing. We look forward to publishing your study. Sincerely, Roli RobertsRoland G Roberts, PhD, PhDSenior EditorPLOS Biologyrroberts@plos.org


The morbidity and mortality of young-onset colorectal cancer (YO-CRC) patients have been increasing in recent years. Moreover, YO-CRC patients with synchronous liver-only metastases (YO-CRCSLM) have various survival outcomes. Therefore, the purpose of this study was to construct and validate a prognostic nomogram for patients with YO-CRCSLM.The YO-CRCSLM patients were rigorously screened from the Surveillance, Epidemiology, and End Results (SEER) database in January 2010 and December 2018 and then assigned to a training and validation cohort randomly . Moreover, the 122 YO-CRCSLM patients who were enrolled in The First Affiliated Hospital of Nanchang University were served as a testing cohort. The variables were selected using the multivariable Cox model based on the training cohort and then developed a nomogram. The validation and testing cohort were used to validate the model’s predictive accuracy. The calibration plots were used to determine the Nomogram’s discriminative capabilities and precision, and the decision analysis (DCA) was performed to evaluate the Nomogram’s net benefit. Finally, the Kaplan-Meier survival analyses were performed for the stratified patients based on total nomogram scores classified by the X-tile software.P < 0.001).The Nomogram was constructed including ten variables: marital status, primary site, grade, metastatic lymph nodes ratio (LNR), T stage, N stage, carcinoembryonic antigen (CEA), Surgery, and chemotherapy. The Nomogram performed admirably in the validation and testing group according to the calibration curves. The DCA analyses showed good clinical utility values. Low-risk patients (score<234) had significantly better survival outcomes than middle-risk (234–318) and high-risk (>318) patients (A nomogram predicting the survival outcomes for patients with YO-CRCSLM was developed. In addition to facilitating personalized survival prediction, this nomogram may assist in developing clinical treatment strategies for patients with YO-CRCSLM who are undergoing treatment. Colorectal cancer (CRC) is a prevalent and aggressive malignancy of the gastrointestinal tract, ranking third in morbidity and second in mortality among malignant tumors globally . CRC patYO-CRC is characterized by the presence of microsatellite instability-high MSI-H, 10%-30%), poorly differentiated tumor cells, and an abundance of signet-ring cell components . Especia%-30%, poTherefore, this study aimed to develop and evaluate a more effective model that incorporates clinicopathological factors and blood indicators to predict survival in YO-CRCSLM. Our findings may offer clinicians a more individualized and thorough outlook for YO-CRCSLM receiving treatment.YO-CRCSLM patients between January 2010 and December 2018 were retrospectively extracted from the SEER database. The inclusion criteria include (1): CRC was the only primary tumor (2), patients aged 18 to 49 at the time of diagnosis, and (3) complete prognostic information. Patients who lacked or had insufficient clinicopathological data of interest, such as age, gender, histological differentiation, primary site, tumor size, and treatment, were excluded. According to the above inclusion and exclusion criteria, 2127 pathologically proven YO-CRCSLM patients were ultimately identified for model construction and were then randomly assigned to the training cohort  to create the prediction model and the validation cohort . Moreover, 122 YO-CRCSLM patients recruited from the First Affiliated Hospital of Nanchang University during January 2012 to December 2020 were finally selected as a testing cohort. The First Affiliated Hospital of Nanchang University Ethics Committee approved this observational retrospective investigation, and patients who participated in the study signed informed consent forms (2022)CDYFYYLK(12-003).We collected the following sixteen demographic and clinicopathologic variables: gender, age, marital status, tumor size, primary site, histological type, grade, metastatic lymph nodes ratio (LNR), perineural invasion, T stage, N stage, carcinoembryonic antigen (CEA), Surgery, radiotherapy, and chemotherapy. The patients were divided into three groups based on their primary site: the right-side colon , the left-side colon , and the rectum. The variable of Surgery included primary site surgery (Surg Prim Site), distant metastasis surgery (Surg Dis Site), primary and distant metastasis site combined surgery Surg Com Site and no surgery. Specifically, the information about R0  or R1 resection performed on primary or metastasis sites is unavailable. The LNR was defined as the ratio of the number of lymph nodes with pathologically confirmed tumor infiltration to the total number of lymph nodes cleared. The primary outcome was overall survival (OS), defined as the time from diagnosis of YO-CRCSLM to death from any cause or the last follow-up.Univariate Cox proportional hazards regression was used to identify potential risk factors, and the statistically significant variables were found as independent prognostic factors in a multivariate Cox regression analysis, and a nomogram was developed to predict the OS of patients with YO-CRCSLM.The Nomogram’s performance was evaluated using discriminative ability and calibration . The calP < 0.05 was considered statistically significant.The Chi-square test was utilized to compare categorical data represented as numbers and percentages. A COX proportional risk model was used to analyze the prognosis of YO-CRCSLM patients, and a nomogram map was drawn using the R package “rms”. Calibration curves were plotted using a bootstrap of 1000 samples to evaluate the nomogram fit. Calibration plots were assessed using the R package “rms”. The R package “DCA” was used for the net benefits analysis of the model, and time points of 1, 2, and 3 years were selected, respectively. R statistical software was used for statistical analysis of the data, X-tile software was used for risk stratification according to the Nomogram prediction score, and survival curves were drawn to compare the prognosis of patients at different risks. All tests were bilateral, and Following the inclusion criteria, the SEER database was eventually used to acquire 2127 eligible YO-CRCSLM patients, who were then assigned into a training group (n=1488) and a validation cohort (n=639) by the stratified random sampling method at a 7:3 ratio. Moreover, a cohort of 122 CRCSLM patients from the First Affiliated Hospital of Nanchang University was defined as the testing cohort, among whom 70 patients died at the follow-up. P < 0.001), higher LNR , higher N stage  and positive CEA  were related to the worse prognosis. In addition, the primary site , Surgery  and chemotherapy  were significantly associated with better survival outcome. Interestingly, married status was also a protective factor for these patients’ prognosis.Moreover, we included sixteen clinicopathological factors to explore their association with overall survival in the training cohort Table 2.Then a predictive nomogram model was established based on the factors identified above Figure 2In this study, we evaluated the discriminatory ability of the Nomogram by the ROC curve. In the training cohort, the AUC values of the Nomogram for the probability of survival at 1-  for the publication of any potentially identifiable images or data included in this article.TYL and XL conceived and designed the study, acquisition and interpretation of data. TL was involved in interpretation of data and drafting of the manuscript; YL, ZZ and HS were involved in analysis, acquisition and interpretation of data; DW, ML and HL were involved in acquisition of data; TYL and XL were involved in critical revision of the manuscript for important intellectual content. All authors contributed to the article and approved the submitted version.


This article was migrated. The article was marked as recommended.Objectives: The incidence of burnout in medical students and residents continues to outpace that of the general population. Self-compassion, a concept in the study of well-being, may moderate against adverse mental health outcomes. The aim of this study is to extend prior research by investigating self-compassion levels in relation to sociodemographic variables and self-reported burnout in Dutch medical students and residents.Methods: We used a cross-sectional survey design. After inclusion, 295 participants completed the online survey. Self-compassion was measured using the Self-Compassion Scale Short-Form. Self-defined burnout symptoms were measured using a single-item measure. Data were analysed using multiple linear regression.Results: Being male was associated with having higher levels of self-compassion  as well as being of higher age . Reporting burnout was negatively associated with self-compassion .Discussion: This study substantiated previous research linking low self-compassion to burnout, and showed a potential increased vulnerability of young and female students. Further investigation of causality and the processes underlying self-compassion development are needed to investigate whether self-compassion interventions can enhance the well-being of medical students and residents. Clinical wards are increasingly understood as risk environments for future doctors’ mental and emotional health. Studies suggest that medical students and residents experience higher rates of burnout than their peers  and poinThe high burnout rates among future doctors are often related to contextual factors inherent to their professional environment . Dutch met al., 2016;In clinical medical education, self-compassion may be an insightful construct in explaining differences in vulnerability in particular. Encouraged to become excellent, empathic and self-reflective professionals, medical students are inclined to perfectionism and the associated intolerance for ambiguity, mistakes and loss . Self-coSo far, a myriad of compassion interventions has been implemented and evaluated  which arTo replicate and extend this primarily preliminary research on self-compassion in medical training, this study investigated self-compassion levels of Dutch medical students and residents in relation to sociodemographic characteristics and self-defined burnout. By doing so, we aimed to contribute to a better understanding of the self-compassion construct and it’s applicability within Dutch medical education. Based on previous literature indicating gender and burnout differences with regard to self-compassion levels, we hypothesized that female gender and burnout would predict lower levels of self-compassion. Because age and ethnicity differences in self-compassion have not been systematically studied among young adults but have been identified as potential substantive factors , followed by three years of clinical rotation (master) (master) . To entemaster) . To pursRecruitment: Participants were recruited through the networks of medical student associations and through senior clinical staff involved in this study. They were invited to fill out an online survey by means of a link, to which a total of 393 responded. Two respondents were excluded because they were not part of the study population. 94 respondents (24%) were excluded because they did not complete the survey or showed missing values in the sociodemographic questionnaire  and faculty of medical studies.Participants completed a demographic survey, including gender , age, identification with ethnical background , medical study progress . The SCS-SF correlates highly with the 26-item Self-Compassion Scale (SCS-LF) when examining the total scores (r≥0.97) (“I enjoy my work. I have no symptoms of burnout” to (5) “I feel completely burned out and often wonder if I can go on. I am at the point where I may need some changes or may need to seek some sort of help”.This measure can be dichotomized as ≤ 2 (no symptoms of burnout) and ≥3 (1 or more symptoms of burnout)  . ResponsPrior to descriptive statistics, self-compassion total scores were computed. Subsequently, analyses proceeded in two phases. First, all potential associations were assessed using Pearson’s correlations to investigate covariance  and identify potential multicollinearity (r≥.8). Second, multiple linear regression was performed to quantify and test the effects of the sociodemographic variables and burnout on self-compassion. Even though Likert scale items are ordinal in nature, usage of parametric tests was justified because summative ratings of Likert scales can be treated as interval-level variables .Multiple linear regression was conducted using a standard non-sequential entry approach. Age, gender ethnicity and burnout were used as independent variables to set up a parsimonious explanatory model of self-compassion. The variable study progress was not included because of suspected collinearity with age. After excluding a severe outlier , the results of tests on normality, linearity, homoscedasticity and multicollinearity indicated that the assumptions needed for multiple linear regression were met . InteracCorrelation analyses showed a low positive correlation between self-compassion and older age  and male gender . A moderate negative correlation was found between self-compassion and reporting symptoms of burnout (range 3-5) (r=-.344), p<.001). No significant correlation was found between self-compassion and ethnicity background. The AIOS level of study progress was weakly correlated to higher levels of self-compassion  but strongly correlated to older age  and being male . These results indicated collinearity between age and study progress conforming to our expectations.2=.323, adjusted R2=.306) =19.5, p<.001), explaining 32 percent of the variance of self-compassion (R306) see. Except This study quantified self-compassion in a sample of Dutch medical students and residents. The average total score on the SCS-SF corresponded with the average score of the normative population . Self-coThese findings may be relevant to medical education in particular. Implicit and explicit criteria related to medical professionalism lead to shared understandings around who is seen as a good physician, and who is not . Self-caConfirming our hypothesis, we found that female medical students reported significantly lower levels of self-compassion. An interaction between ethnicity and gender, comparable to the findings of a meta-analysis byConsistent with previous research, younger respondents reported lower self-compassion . One expThis study furthered the field of medical student well-being research by quantifying students’ self-compassion and burnout levels during clinical medical education. We did, however, identify several limitations. First, we did not have enough power to reliably investigate the relationship between residential specialties, ethnicity and other aspects of diversity and self-compassion. This limits our ability to distinguish differences in self-compassion between majority and minority subgroups which may be at higher risk of burnout due to intentional and unintentional homogenizing influences in medical training .In addition, the cross-sectional design did not allow for investigation of causality, limiting our ability to gain deeper insight in the relationship between self-compassion and burnout-related symptoms. Furthermore, our findings might have been prone to over- or underestimation as a result of response bias, such as social desirability or self-presentational biases  and seleDespite its limitations, this study suggests self-compassion to be a valuable construct to gain insight in medical student well-being. The detected determinants of interpersonal differences, age and gender, could provide a handle for curricular integration of the concept, but further research is needed to investigate physiological and psychological processes that underlie self-compassion development. Longitudinal studies on self-compassion in medical education are needed to study causality between low self-compassion and burnout, and prove the ability of self-compassion interventions to improve the well-being of medical students and residents. Such studies could also tell more about the predictive value of self-compassion in relation to other student-level outcomes including compassion and learning outcomes. Additional clinometric evaluation of the SCS-SF questionnaire could provide insight in its usefulness as a screening or case finding tool.Moreover, we need to study the effects of present work ethics in medical education and practice on student well-being. A sole focus on resilience training would suggest that an individual’s failure to cope results from personal incapacity rather than from dysfunctional educational system. Stigma related to self-care could severely hinder efforts to provide students with individual coping capital. In-depth qualitative research is essential to gain insight in student experiences and the processes that underlie the relationship between self-compassion, burnout and contextual factors. Extra attention should be paid to potentially vulnerable subgroups, such as female students and students of non-majority backgrounds, in order to add to our understanding of ways in which these groups can be empowered and supported , is medical student and researcher, dept. Medical Humanities, Amsterdam UMC, location VUmc., MSc, PhD is researcher and lecturer in Diversity in Health and Health Professions Education, dept. Medical Humanities, Amsterdam UMC, location VUmc.Maaike Muntinga, MD, PhD, holds chair of ECG, former surgeon and former President Association Surgeons of the Netherlands.Piet LeguitTheo Niessen, MSc, PhD, Dean of Nursing Research at Canisius Wilhelmina Hospital, Nijmegen, the Netherlands., MSc, PhD is deputy head of the dept. Medical Humanities, professor Participation & Diversity, research leader in Amsterdam Public Health research institute, Amsterdam University Medical Centres. Director of Leyden Academy on Vitality and Ageing, Leiden.Tineke A. Abma This review has been migrated. The reviewer awarded 5 stars out of 5 An interesting paper dealing with self-compassion among Dutch medical students and residents. This is a useful topic, as burnout among medical students is well-documented, and the concept of self-compassion is posited as a counter to this phenomenon.The background is clearly explained, and the study has been well-conducted, using validated tools. The results are fairly presented, and the limitations acknowledged.All-round, a solid and useful piece of research, not only for researchers in the field, but also for all medical educators.I do have one query on the interpretation of the correlation. A (r=.281, pReviewer Expertise:NANo decision status is available This review has been migrated. The reviewer awarded 4 stars out of 5 This is an interesting study on self-care and self-compassion among caregivers. The authors introduce the concept of self-compassion which is an important one for medical students and doctors. The description is well structured and detailed information about the study methodology is provided. Self-care and resilience are important characteristics and have become even more important during the ongoing pandemic. The article will be of interest to a broad group of medical educators.Reviewer Expertise:NANo decision status is available


The term “waste” refers to items in our immediate environment that should be recycled, reused, decreased, or even removed if feasible. Global waste is predicted to eventually amount to 3.40 billion tons by 2050. Nevertheless, bio-waste may be seen as a source of environmental toxins or pollutants, depending on how it is handled. Large volumes of bio-waste from the agri-food sector are created these days, stressing the environment. Bio-wastes derived from agri-food are frequently produced at every stage of the food supply chain, from harvest to disposal. The phases and the food product determine the different quantities. For instance, European homes account for 53% of bio-waste, with processing accounting for 19% of all food waste. Production (11%) and wholesale and retail (5%), along with catering (12%), account for the remaining 28%. As a result, it has become clear that a shift toward a sustainable circular economy is necessary.Zero Waste Economy,” where waste is converted into valuable goods and finds practical applications by offering potential energy savings. Sustainability concerns related to industrialization and the economy are addressed by agro-food bio-waste management. The European Commission sought to advance the circular economy. Businesses predicted that when the Green Deal was unveiled, which aimed to make Europe carbon neutral by 2050, bio-waste and its harmful environmental effects would decline in the future. The “Farm to Fork” plan also aims to integrate circular economy concepts into food processing successfully.Ensuring the industry's economic, social, and environmental sustainability requires improving waste management. Agro-food by-product revalorization may be influenced by the concept of a “The agricultural food industry's biowastes are abundant in hydrophilic and lipophilic phytochemicals. Numerous phytochemicals, including vitamins, carotenoids, pigments, phenolics, and tocols, may improve the nutritional value of food. Because of their superior nutritional worth, the enriched products may also be designated as functional foods. Phytochemicals recovered from agro-food bio-wastes can potentially extend the shelf life of various products, including food, cosmetics, and pharmaceuticals. The phytochemicals' antioxidant and antibacterial traits may also enhance these benefits. These days, a global strategy aims to produce value-added products for potential uses like food additives or coloring, bio-fertilizers, biodiesel, and nutraceuticals through the sustainable utilization of agro-food bio-wastes. According to this viewpoint, choosing the best extraction method and specifying the intended applications are crucial for improving the value of agro-food bio-wastes. Meanwhile, unique environmental-friendly methods, including ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE), and supercritical fluid extraction (SFE), have been developed for the sustainable recovery of phenolics from agro-food bio-wastes. In addition, a new generation of sustainable green solvents has been used –5.This Research Topic is aimed at collecting papers suitable to improve our knowledge and understanding of the extraction, characterization, and applications of bioactive compounds from agro-food bio-wastes, considering their biological traits and use in nutraceuticals, food enrichment, preservation or packaging, or for pharmaceutical and cosmetic applications. Potential subtopics included (1) novel techniques for green extraction of bioactive compounds from agro-food waste, (2) characterizing natural compounds from by-products and evaluating biological properties in correlation with food applications and human health benefits, and (3) new systems for the administration of by-product biomolecules, in correlation with the application in food products.Psidium guajava by-products in traditional Mexican medicine . In this review, the authors concluded that the valorization of Psidium guajava bio-waste may benefit the agroindustry economically and could represent an alternative to traditional antimicrobials. The second research article reported on deep eutectic solvent-ultrasound assisted extraction (UAE-DES) for enhanced extraction of naringenin from Searsia tripartita and retained their bioactivities  In this research, the UAE-DES technique produced high-efficiency naringenin extraction while retaining bioactivity, implying broad application potential and making it a high-throughput green extraction method worthy of consideration. In the third research article , the authors studied the encapsulation of betalain-rich extract from beetroot bio-waste using a blend of gum Arabic and maltodextrin to promote a food circular economy. They highlighted that although blending gum Arabic and maltodextrin has the potential to improve the quality of beetroot waste extract powder, using these biopolymers separately showed a promise to promote a food circular economy. In the last research article , the authors studied the potential use of Indian rice flour or husk to fortify pan bread. They highlighted the possible use of rice husk fibers in baking goods and the possible health benefits while contributing to the long-term use of agricultural waste. Meanwhile, the results reported in those studies highlighted and reviewed new relevant data on the valorization of bioactive compounds from bio-wastes of the agro-food sector using green technology.Four articles covering the aspects mentioned above were published in this Research Topic. The first article reviewed the potential of NT: Writing – original draft. IM: Writing – original draft. MFR: Writing – original draft, Writing – review & editing.


In the field of pediatric traumatic brain injury (TBI), relationships between pre-injury and injury-related characteristics and post-TBI outcomes  and their impact on disease-specific health-related quality of life (HRQoL) are under-investigated. Here, a multidimensional conceptual model was tested using a structural equation model (SEM). The final SEM evaluates the associations between these four latent variables. We retrospectively investigated 152 children (8–12 years) and 148 adolescents (13–17 years) after TBI at the recruiting clinics or online. The final SEM displayed a fair goodness-of-fit , explaining 39% of the variance across the four latent variables and 45% of the variance in HRQoL in particular. The relationships between pre-injury and post-injury outcomes and between post-injury outcomes and TBI-specific HRQoL were moderately strong. Especially, pre-injury characteristics  may aggravate post-injury outcomes, which in turn may influence TBI-specific HRQoL negatively. Thus, the SEM comprises potential risk factors for developing negative post-injury outcomes, impacting TBI-specific HRQoL. Our findings may assist healthcare providers and parents in the management, therapy, rehabilitation, and care of pediatric individuals after TBI. The estimated incidence of traumatic brain injuries (TBI) is more than 50 million individuals worldwide annually and around 262 per 100,000 inhabitants in Europe , post-coRegarding socio-demographics, a lower socioeconomic status (SES) is related to a higher frequency of PCS  and an iConcerning injury characteristics, higher TBI severity has a negative impact on various outcomes after pediatric TBI, including functional recovery , cognitiThe prevalence of post-injury outcomes, e.g., pediatric PCS, ranges from 29.3% to 52% depending on the diagnostic criteria, assessment tools, and patient populations . They maPrevious research has mostly assessed outcomes after pediatric TBI unidimensionally and relied on parental reporting, which may lead to rater bias , misdiagThe multidimensional assessment of HRQoL represents a step towards capturing a more comprehensive patient-centered picture of the consequences of TBI in several domains of life. It encourages collecting children’s and adolescents’ self-reports after TBI and is well suited to capture the complex nature of TBI from a subjective perspective. This multidimensional construct covers individuals’ well-being in the domains of emotional, cognitive, physical, social, and daily life functioning and can be measured using generic or disease-specific instruments . GenericThe multitude of impaired outcomes after TBI underlines the need for a comprehensive multidimensional outcome assessment ,41 to brThe aim of this pediatric TBI study is to test a multidimensional conceptual model investigating the relationship between pre-injury and injury-related characteristics and post-injury outcomes , as well as their impact on TBI-specific HRQoL. In the clinical context, a multidimensional model offers the possibility of a truly comprehensive outcome evaluation. Based on this, guidance is provided on how to treat a pediatric individual after TBI with specific pre-injury and injury-related characteristics, e.g., identifying those that should receive priority treatment compared to low-risk patients.For this retrospective multicenter study, 300 participants with a history of TBI from the German-language context were included, meeting the following criteria: (a) 8–17 years of age; (b) a diagnosis of TBI at least 3 months but no more than 10 years before study participation; (c) a formal Glasgow Coma Scale (GCS) score or TBI severity recorded; (d) outpatients (or about to resume inpatient treatment); and (e) able to understand and answer the questions. Participants were excluded if they: (a) were currently in a vegetative state ; (b) had spinal cord damage; (c) had severe mental illness before TBI ; (d) had epilepsy before TBI; (e) had a disease leading to death; or (f) had very severe poly-trauma.Further clinical details, such as loss of consciousness, amnesia, requirement for ventilation, neurosurgical intervention, presence of a lesion on imaging, resuscitation, nausea/vomiting, and post-traumatic epilepsy, were also collected. This information was used to describe the TBI in the absence of a GCS score. An open-ended text field completed for other post-TBI symptoms contained post-TBI agitation and/or delirium, reported in eight children (2.7%).Participants who met the inclusion criteria were contacted by postal mail and invited to participate in the study. Participants and their families were informed about the research aim and procedure before giving their written consent. All participants and their parents signed the informed consent and medical records release form. Participants were recruited from January 2019 until January 2022 from hospital registries in Germany.A sample size estimation for the project was performed beforehand for all planned analyses assuming equal numbers of factors in all age groups indicating the need for at least 140 subjects per age group .The study was conducted in accordance with all relevant laws of Germany including but not limited to the ICH Harmonized Tripartite Guideline for Good Clinical Practice (“ICH GCP”) and the World Medical Association Declaration of Helsinki . The study (application number 19/4/18) was approved by the Ethics Committee of the University Medical Center in Göttingen.The examinations were administered face-to-face at the recruiting clinics (74.7%) or online (25.3%). Eligible and consenting participants, their parents, and investigators provided the data. Clinical data were retrieved from medical records by clinicians and psychologists and transcribed into the patient case report forms (CRFs). Parents filled out paper and pencil CRFs at the recruiting centers or sent these back via postal mail. Age-appropriate CRF booklets were administered to two different age groups (8–12 and 13–17 years of age). The age split was based on the biopsychosocial developmental model of Havighurst  and receA comprehensive multidimensional conceptual model  inspiredThe conceptual recursive model contained the following pre-injury data: age  and sex, parental education, employment status, previous TBIs, presence of neurological disease, presence of chronic disease, treatment for mental health disorder prior to the injury, any sensory, cognitive, or physical impairment (reported by parents). Pre-injury characteristics form a latent variable that takes into account the effect of chronic diseases, as well as age, sex, etc. This allows the influence of, for example, chronic diseases to be controlled for, since pre-injury characteristics are related to the rest of the latent variables in the model, including the post-injury outcome.Clinical data retrieved from the medical notes included the severity of the injury, presence of any lesion detected by CT or MRI, presence of retrograde amnesia, LOC, and neurosurgical intervention following injury, and time since injury.Functional recovery was determined using clinical ratings using the Kings Outcome Scale for Childhood Head Injury  ; PCS wasDuring the process of the model building based on the multidimensional conceptual model , the folDescriptive statistics were calculated to summarize all variables, subscales, and total scores of the measures by age group: KIDs (8–12 years), ADOs (13–17 years), and overall. Means, standard deviations, medians, and ranges were used for continuous variables, and counts and percentages for categorical variables. Continuous data were assessed for normality. In the absence of normality, data were transformed using the appropriate transformation .Differences between the two age groups were investigated using parametric and non-parametric tests, depending on the data distribution. Differences between SES, measured in terms of parental education, and HRQoL, PCS, anxiety, and depression symptoms  were also examined using non-parametric Kruskal–Wallis tests.Missing data for self-reported measures were expected at the item or scale level. For missing data at the item level, prorating was performed for all self-reported measures if a minimum number of items had been completed. For PCSI, if the number of missing items was one or two, prorating was used to calculate a score . If up tTo fully utilize all the available information from the study data set in the presence of missing values, the full information maximum likelihood (FIML) method was used to handle missing data on demographics and clinical characteristics and in cases where the entire questionnaires were missing. All analyses were conducted using SAS software, version 9.4, using the PROC CALIS procedure.The following latent factors were integrated into the path analysis: pre-injury and injury-related characteristics, post-injury outcome, and TBI-specific HRQoL. The indicator variables defining each latent variable are listed in the multidimensional conceptual model section see .A two-step procedure was performed  in buildFirst, the measurement model for testing the strength of the relationship between the observed variables and the factors was created using a confirmatory analysis. Path analysis determined whether the model accounted for the relationships observed in the sample. It was also checked whether the direction of the relationships between the observed variables in the conceptual model was valid for the sample. The covariance was estimated to relate each latent variable to each other. Every latent variable contained at least four manifest variables. Furthermore, a composite reliability index and variance extracted estimates were calculated for each latent factor. A composite reliability index assesses the degree of reliability with which the latent factor explains the variance in indicator variables. This is an indicator of the internal consistency of indicators within a given factor . A reliaIn the second step, the measurement model was modified to create an empirical model based on the original conceptual model. The model was tested and revised until a theoretically and statistically acceptable model was obtained.χ2/df < 3) [The ratio of chi-square statistics/degrees of freedom (/df < 3) ;The root mean square error of approximation , as well as 90% confidence limits  ;Standardized root mean square residual  ;Goodness-of-fit index (GFI) and comparative fit index (CFI)  .Recommendations for reporting the results of data analyzed using structural equation modeling  were folAll indices were checked and the model was modified until it was acceptable, until the factors made theoretical or clinical sense and further modifications were not appropriate. All changes from the original conceptual model were documented. Standardized graphical model solutions were presented.A total of 300 children and their parents participated in the study, with 152 in the KID group and 148 in the ADO group; see the flow chart in In terms of injury characteristics, a large proportion of participants had experienced a mild TBI (71.7%). Lesions in the CT or MRI were reported for 28.7% of participants, 25.0% of individuals reported retrograde amnesia and 31.7% experienced LOC. Neurosurgical interventions were necessary for 17.0% of the patients. The time since injury ranged from 0 to 10 years, as per eligibility criteria, with a median of 3.7 years in the KID group and 4.5 years in the ADO group. Statistically significant differences were determined between age categories concerning retrograde amnesia and LOC following injury; a higher proportion of participants in the ADO group reported amnesia and LOC compared with those in the KID group.Summaries of the post-injury outcome measures are presented in QOLIBRI-KID/ADO self-reported scores by subscale and overall are summarized in Scores for depression, anxiety, post-concussion symptoms, and HRQOL differentiated by parental education are listed in No systematic pattern was observed in the structure of the missing data. In all but the PCSI variable, there were 5% or fewer values missing in the indicator variables. We considered data to be missing completely at random. A total of 13.7% of overall PCSI scores were missing for the participants recruited at the beginning of the study due to the PCSI questionnaire data not being collected at that time.The initial measurement model comprised all variables and latent factors as stated in the multidimensional conceptual model see .p-value < 0.01); those whose factor loadings were not significant were excluded: sex, employment, previous TBI, and time since injury.The goodness-of-fit statistics for the initial measurement model are presented in With a sample of 300 participants and 166 degrees of freedom (df), the statistical power of the model was approximately 0.99. The global fit statistics and model are shown in The absolute value of the t-statistics for each factor loading and path coefficient between pre-injury characteristics and post-injury outcome, and post-injury outcome and TBI-specific HRQoL, exceeded 1.96. The path coefficient linking the latent constructs of pre-injury characteristics and injury-related characteristics and the path coefficients from injury-related characteristics to the post-injury outcome and TBI-specific HRQoL displayed a t-value smaller than 1.96, suggesting there is evidence that these paths are not statistically significant. The standardized path coefficient for the path from pre-injury to injury-related characteristics was small, at 0.14. The standardized path coefficients from injury-related characteristics to post-injury outcome (0.09) and TBI-specific HRQoL (0.02) were also small. This indicates that the model does not account for the relationship between these latent factors. Therefore, in the revised empirical SEM, the weakest path between injury-related characteristics and TBI-specific HRQoL was removed with no change to the revised measurement model .p = 0.051), suggesting that the empirical model provides an adequate fit with the data and is not significantly worse than the fit of the revised model : pre-injury characteristics , post-injury characteristics , post-injury outcome , and TBI-specific HRQoL (QOLIBRI-KID/ADO) . The modThe present study aimed to assess a multidimensional conceptual framework of factors impacting outcomes after TBI, inspired by an illustration of the development of PCS . From thBefore examining the final model, differences in pre-injury and injury-related characteristics between the KID and the ADO groups were explored. The groups only differed concerning retrograde amnesia, where a higher proportion of ADOs reported retrograde amnesia compared to the KIDs. This may be because more adolescents have suffered LOC. Regarding recovery status, good or complete recovery was reported more frequently than moderate or severe disability. This pattern of predominantly good recovery after pediatric TBI is consistent with previous findings  and maybParental education and lower SES have been linked to emotional and behavioral outcomes, including anxious/depressive symptomatology ,60, and Significant differences between both age groups were also found regarding disease-specific HRQoL after TBI, with adolescents reporting lower scores for the subscales Cognition, Self, Daily life and autonomy, and Social relationships compared with the younger group. The literature shows that age at injury is strongly associated with HRQoL after pediatric TBI; children who are younger at the time of injury have better HRQoL than older ones . As prevSeveral steps had to be performed to reach the final SEM  based onVariables without statistically significant loadings  with respect to the assumed latent constructs were excluded from the final SEM.The need to exclude the parental employment variable contrasts with findings in the literature indicating that SES has an impact on a child’s ability to recover from injury and post-injury therapy . Lower fSex is also a controversial variable regarding outcomes after TBI. In our study, it did not display a significant factor loading on injury-related characteristics when inspecting the initial SEM. There are several preclinical studies supporting the importance of sex differences in response to pediatric TBI. However, TBI outcomes are also likely to depend on many other factors, such as age at injury, mechanisms of injury, and time post-injury .Previous TBI and time since injury were also excluded from the final SEM as they were not significant. Only a small proportion of children had reported prior TBIs.The relationship between injury-related characteristics and pediatric post-TBI outcomes remains relatively unclear . In partNevertheless, the final SEM suggests the importance of post-injury outcomes as part of the pathway between pre-injury characteristics and disease-specific HRQoL. Several pre-injury characteristics  may aggravate post-injury outcomes , which in turn may influence TBI-specific HRQoL negatively. Previous studies have consistently described significant relationships between children’s pre-injury psychiatric disorders and depressive post-injury symptomatology ,42,66 anThe literature in the field of pediatric TBI is not clear concerning the relationship between injury-related characteristics and HRQoL, e.g., TBI severity has been inconsistently associated with generic HRQoL . In our However, we observed a moderately strong negative association between post-injury characteristics and TBI-specific HRQoL. This finding confirms observations from previous studies that have systematically reported a link between depression , anxietyIn summary, according to our final SEM , the relThis study has several limitations. Firstly, pre-injury and post-injury latent variables presented relatively low composite reliability . The weak reliability of the pre-injury characteristics  may be bSecondly, prior literature has described other variables that may be involved in post-TBI outcomes, such as a family history of depression/anxiety  and biomThe integration of detailed cognitive outcomes in the current SEM would have gone beyond the scope of this study. However, these are being implemented in our ongoing re-validation of our model in a different pediatric sample after TBI. Although we tried hard to include all severity levels, most of the patients had experienced a mild TBI. Thus, our results could differ for those who faced more severe TBI.Also, the fact that the range of time since injury was broad (0–10 years) may imply that the recovery of children might already have been completed several years after the TBI. Further studies are needed, including a shorter post-TBI time period, to better determine the impact of injury-related characteristics on outcomes and investigate their longitudinal development and trajectories of multidimensional recovery.The identification of influential factors for recovery, amelioration of TBI-specific HRQoL after pediatric TBI, and their interrelationships impacting the development of evidence-based interventions is still limited. In our study, pre-injury characteristics appear to play a more important role in predicting post-injury outcomes than injury-related ones; they may influence TBI-specific HRQoL through their impact on post-injury anxiety, depression, PCS, and recovery status. The results of our final SEM offer support to clinicians and researchers by complementing their evaluation of patients and ameliorating clinical management, care, and rehabilitation after pediatric TBI. Early psychological therapy and, where indicated, medical treatment of depression, anxiety, and PCS arise as potential targets for improving HRQoL following pediatric TBI .This study investigated the impact of pre-injury and injury-related characteristics, as well as post-TBI outcomes , on the disease-specific HRQoL of individuals after pediatric TBI. To our knowledge, the current study is the first to integrate a variety of manifest and latent variables concerning TBI in a single multidimensional SEM. Injury-related characteristics were only weakly associated with post-injury outcomes and not directly with TBI-specific HRQoL. Contrary to our hypothesis, pre-injury characteristics were only very weakly related to injury-related variables. The final SEM suggests that pre-injury characteristics impact post-injury outcomes directly, in turn influencing HRQoL after pediatric TBI.Since our final SEM identifies potential key risk factors that can exacerbate negative outcomes, our findings may serve to better inform patients, caregivers, and clinicians about treatment and care options and can be used in developing preventive and therapeutic programs. Healthcare providers should consider the specific characteristics of children and adolescents  as well as the characteristics of their parents (lower education) as potential risk factors that can aggravate post-TBI depression, anxiety, PCS, and recovery. Moreover, our results suggest that, if negative post-TBI outcomes arise, targeted and adequate interventions may prevent the deterioration of children’s HRQoL.