Thermal escape box: A cost-benefit evaluation paradigm for investigating thermosensation and thermal pain.

Thermosensation, the ability to detect and estimate temperature, is an evolutionarily conserved process that is essential for survival. Thermosensing is impaired in various pain syndromes, resulting in thermal allodynia, the perception of an innocuous temperature as painful, or thermal hyperalgesia, an exacerbated perception of a painful thermal stimulus. Several behavioral assays exist to study thermosensation and thermal pain in rodents, however, most rely on reflexive withdrawal responses or the subjective quantification of spontaneous nocifensive behaviors. Here, we created a new apparatus, the thermal escape box, which can be attached to temperature-controlled plates and used to assess temperature-dependent effort-based decision-making. The apparatus consists of a light chamber with an opening that fits around temperature-controlled plates, and a small entryway into a dark chamber. A mouse must choose to stay in a brightly lit aversive area or traverse the plates to escape to the enclosed dark chamber. We quantified escape latencies of adult C57Bl/6 mice at different plate temperatures from video recordings and found they were significantly longer at 5 °C, 18 °C, and 52 °C, compared to 30 °C, a mouse's preferred ambient temperature. Differences in escape latencies were abolished in male Trpm8-/- mice and in male Trpv1-/- animals. Finally, we show that chronic constriction injury procedures or oxaliplatin treatement significantly increased escape latencies at cold temperatures compared to controls, the later of which was prevented by the analgesic meloxicam. This demonstrates the utility of this assay in detecting cold pain. Collectively, our study has identified a new and effective tool that uses cost-benefit valuations to study thermosensation and thermal pain.

X-ray structure and enzymatic study of a bacterial NADPH oxidase highlight the activation mechanism of eukaryotic NOX.

NADPH oxidases (NOX) are transmembrane proteins, widely spread in eukaryotes and prokaryotes, that produce reactive oxygen species (ROS). Eukaryotes use the ROS products for innate immune defense and signaling in critical (patho)physiological processes. Despite the recent structures of human NOX isoforms, the activation of electron transfer remains incompletely understood. SpNOX, a homolog from Streptococcus pneumoniae, can serves as a robust model for exploring electron transfers in the NOX family thanks to its constitutive activity. Crystal structures of SpNOX full-length and dehydrogenase (DH) domain constructs are revealed here. The isolated DH domain acts as a flavin reductase, and both constructs use either NADPH or NADH as substrate. Our findings suggest that hydride transfer from NAD(P)H to FAD is the rate-limiting step in electron transfer. We identify significance of F397 in nicotinamide access to flavin isoalloxazine and confirm flavin binding contributions from both DH and Transmembrane (TM) domains. Comparison with related enzymes suggests that distal access to heme may influence the final electron acceptor, while the relative position of DH and TM does not necessarily correlate with activity, contrary to previous suggestions. It rather suggests requirement of an internal rearrangement, within the DH domain, to switch from a resting to an active state. Thus, SpNOX appears to be a good model of active NOX2, which allows us to propose an explanation for NOX2's requirement for activation.

Methyl N-{(1R)-2-[(meth-oxy-carbon-yl)-oxy]-1-phenyleth-yl}carbamate.

The title mol-ecule, C12H15NO5, is a methyl carbamate derivative obtained by reacting (R)-2-phenyl-glycinol and methyl chloro-formate, with calcium hydroxide as heterogeneous catalyst. Supra-molecular chains are formed in the [100] direction, based on N-H⋯O hydrogen bonds between the amide and carboxyl-ate groups. These chains weakly inter-act in the crystal, and the phenyl rings do not display significant π-π inter-actions.

What factors are associated with a better restoration of pelvic version after adult spinal deformity surgery?

INTRODUCTION: Poor restoration of pelvic version after adult spinal deformity (ASD) surgery is associated with an increased risk of mechanical complications and worse quality of life. We studied the factors linked to the improvement of postoperative pelvic version. MATERIALS AND METHODS: This is a retrospective analysis of a prospective multicenter ASD database. Selection criteria were: operated patients having preoperative severe pelvic retroversion as per GAP score (Relative Pelvic Version-RPV < - 15°); panlumbar fusions to the pelvis; 2-year follow-up. Group A comprised patients with any postoperative improvement of RPV score, and group B had no improvement. Groups were compared regarding baseline characteristics, surgical factors, and postoperative sagittal parameters. Parametric and non-parametric analyses were employed. RESULTS: 177 patients were studied, median age 67 years (61; 72.5), 83.6% female. Groups were homogeneous in baseline demographics, comorbidities, and preoperative sagittal parameters (p > 0.05). The difference in RPV improvement was 11.56º. Group A (137 patients) underwent a higher percentage of ALIF procedures (OR = 6.66; p = 0.049), and posterior osteotomies (OR = 4.96; p < 0.001) especially tricolumnar (OR = 2.31; p = 0.041). It also showed a lower percentage of TLIF procedures (OR = 0.45; p = 0.028), and posterior decompression (OR = 0.44; p = 0.024). Group A displayed better postoperative L4-S1 angle and relative lumbar lordosis (RLL), leading to improved sacral slope (and RPV), and global alignment (RSA). Group A patients had longer instrumentations (11.45 vs 10; p = 0.047) and hospitalization time (13 vs 11; p = 0.045). All postoperative sagittal parameters remained significantly better in group A through follow-up. However, differences between the groups narrowed over time. CONCLUSIONS: ALIF procedures and posterior column osteotomies improved pelvic version postoperatively, and associated better L4-S1 and lumbar lordosis restoration, indirectly improving all other sagittal parameters. However, these improvements seemed to fade during the 2-year follow-up.

H3K4 methylation regulates development, DNA repair, and virulence in Mucorales.

Mucorales are basal fungi that opportunistically cause a potentially fatal infection known as mucormycosis (black fungus disease), which poses a significant threat to human health due to its high mortality rate and its recent association with SARS-CoV-2 infections. On the other hand, histone methylation is a regulatory mechanism with pleiotropic effects, including the virulence of several pathogenic fungi. However, the role of epigenetic changes at the histone level never has been studied in Mucorales. Here, we dissected the functional role of Set1, a histone methyltransferase that catalyzes the methylation of H3K4, which is associated with the activation of gene transcription and virulence. A comparative analysis of the Mucor lusitanicus genome (previously known as Mucor circinelloides f. lusitanicus) identified only one homolog of Set1 from Candida albicans and Saccharomyces cerevisiae that contains the typical SET domain. Knockout strains in the gene set1 lacked H3K4 monomethylation, dimethylation, and trimethylation enzymatic activities. These strains also showed a significant reduction in vegetative growth and sporulation. Additionally, set1 null strains were more sensitive to SDS, EMS, and UV light, indicating severe impairment in the repair process of the cell wall and DNA lesions and a correlation between Set1 and these processes. During pathogen-host interactions, strains lacking the set1 gene exhibited shortened polar growth within the phagosome and attenuated virulence both in vitro and in vivo. Our findings suggest that the histone methyltransferase Set1 coordinates several cell processes related to the pathogenesis of M. lusitanicus and may be an important target for future therapeutic strategies against mucormycosis.

In Vitro and In Vivo Insights into a Broccoli Byproduct as a Healthy Ingredient for the Management of Alzheimer's Disease and Aging through Redox Biology.

Broccoli has gained popularity as a highly consumed vegetable due to its nutritional and health properties. This study aimed to evaluate the composition profile and the antioxidant capacity of a hydrophilic extract derived from broccoli byproducts, as well as its influence on redox biology, Alzheimer's disease markers, and aging in the Caenorhabditis elegans model. The presence of glucosinolate was observed and antioxidant capacity was demonstrated both in vitro and in vivo. The in vitro acetylcholinesterase inhibitory capacity was quantified, and the treatment ameliorated the amyloid-ß- and tau-induced proteotoxicity in transgenic strains via SOD-3 and SKN-1, respectively, and HSP-16.2 for both parameters. Furthermore, a preliminary study on aging indicated that the extract effectively reduced reactive oxygen species levels in aged worms and extended their lifespan. Utilizing broccoli byproducts for nutraceutical or functional foods could manage vegetable processing waste, enhancing productivity and sustainability while providing significant health benefits.

Do Patterns of Adolescent Participation in Arts, Culture and Entertainment Activities Predict Later Wellbeing? A Latent Class Analysis.

Participation in arts, culture, and entertainment (PACE) activities may promote adolescent wellbeing. However, little is known about how such activities cluster together, and previous research has used small samples, cross-sectional designs, focused on single activities, and/or has not considered the influence of socio-demographic factors on participation. Using latent class analysis, the aims of this study were to establish: (i) classes of adolescent PACE activities; (ii) associations between socio-demographic characteristics and PACE classification; and, (iii) whether PACE classification predicts later wellbeing. Longitudinal data from the #BeeWell study (N = 18,224 adolescents; mean age at T1 = 12 years 7 months (±3.56 months); 50.54% female) were analyzed. Four latent classes were established: the 'Dynamic Doers' (high, wide-ranging participation; 11.87%); the 'Mind and Body Crew' (reading, arts, videogames, sports/exercise; 39.81%); the 'Game and Gain Squad' (videogames and sports/exercise; 29.05%); and the 'Activity Free Adolescents' (uniformly low participation; 19.27%). Associations between socio-demographic characteristics and PACE classification were observed (e.g., socio-economic disadvantage increased the likelihood of Activity Free Adolescents classification, compared to Game and Gain Squad classification). Finally, PACE classification predicted later wellbeing (e.g., Dynamic Doers reported significantly higher wellbeing than Activity Free Adolescents). These findings are discussed in relation to the need to improve accessibility and appeal of arts, culture, and entertainment provision for adolescents as a means to optimize their wellbeing. PRE-REGISTRATION: The analysis plan for this study was pre-registered on the Open Science Framework and can be found here: https://osf.io/2jtpd.

Influence of incubation temperature, maternal effects, and paternity on quality of olive ridley hatchlings (Lepidochelys olivacea) from a mass-nesting beach in the Mexican Pacific.

Future climate change scenarios project that the increase in surface temperatures will affect ocean temperatures, inducing shifts in marine biodiversity. Sea turtles are species that are particularly vulnerable to the effects of climate change because temperature is a factor that influences embryonic development. We collected clutches of olive ridley turtles from a mass-nesting beach in the Mexican Pacific, which were incubated in ex situ conditions. When the hatchlings emerged, we measured the body condition index-which evaluates the weight-length relationship-and swim thrust, both were considered traits associated with fitness, termed "fitness proxies," and evaluated the effects of incubation temperature, maternal effects, and paternity on these fitness proxies. The body condition index was correlated positively and significantly with the arribada month and temperature during the last third of the incubation period but showed an inverse relationship with the maternal effect. While swim thrust was positively correlated with the maternal effect and the arribada month, there was an inverse relationship with incubation temperature during the first third of the period. Paternity, whether single or multiple, did not have a significant effect on either fitness proxies; however, it may have effects on the average fitness of a population of hatchlings. These results underscore the need to expand research on the sublethal effects of high incubation temperatures on the adaptation and survival of sea turtles, particularly in scenarios of rapid climate change.

Effect of olive leaf phytochemicals on the anti-acetylcholinesterase, anti-cyclooxygenase-2 and ferric reducing antioxidant capacity.

In this study, the phytochemical profile of fifty olive leaves (OL) extracts from Spain, Italy, Greece, Portugal, and Morocco was characterized and their anti-cholinergic, anti-inflammatory, and antioxidant activities were evaluated. Luteolin-7-O-glucoside, isoharmnentin, and apigenin were involved in the acetylcholinesterase (AChE) inhibitory activity, while oleuropein and hydroxytyrosol showed noteworthy potential. Secoiridoids contributed to the cyclooxygenase-2 inhibitory activity and antioxidant capacity. Compounds such as oleuropein, ligstroside and luteolin-7-O-glucoside, may exert an important role in the ferric reducing antioxidant capacity. It should be also highlighted the role of hydroxytyrosol, hydroxycoumarins, and verbascoside concerning the antioxidant activity. This research provides valuable insights and confirms that specific compounds within OL extracts contribute to distinct anti-cholinergic, anti-inflammatory, and anti-oxidative effects.

Total en bloc vertebrectomy and immunochemotherapy for chondrosarcoma colliding with intraosseous lymphoma.

A 59-year-old woman diagnosed with a Grade I chondrosarcoma in T7 underwent total en bloc vertebrectomy. Analysis of the surgical piece established diagnosis of a Grade 1 chondrosarcoma confined to T7. Surprisingly, an infiltration with diffuse large B-cell lymphoma was found. Systemic disease was ruled out and diagnosis was established as intracompartmental Grade 1 chondrosarcoma colliding with intraosseous extranodal diffuse large B-cell lymphoma. Resection of chondrosarcoma was considered complete and treatment with four cycles of RCHOP was indicated. Two years after surgery, the patient remains at complete metabolic response. To date, this is the first reported case of chondrosarcoma colliding with lymphoma. Although Grade 1 chondrosarcoma is typically managed with local control through complete surgical resection, the mentioned finding of the lymphoma indicated the need for systemic treatment with immunochemotherapy.

Mental Health and Well-being Measures for Mean Comparison and Screening in Adolescents: An Assessment of Unidimensionality and Sex and Age Measurement Invariance.

Adolescence is a period of increased vulnerability for low well-being and mental health problems, particularly for girls and older adolescents. Accurate measurement via brief self-report is therefore vital to understanding prevalence, group trends, screening efforts, and response to intervention. We drew on data from the #BeeWell study (N = 37,149, aged 12-15) to consider whether sum-scoring, mean comparisons, and deployment for screening were likely to show bias for eight such measures. Evidence for unidimensionality, considering dynamic fit confirmatory factor models, exploratory graph analysis, and bifactor modeling, was found for five measures. Of these five, most showed a degree of non-invariance across sex and age likely incompatible with mean comparison. Effects on selection were minimal, except sensitivity was substantially lower in boys for the internalizing symptoms measure. Measure-specific insights are discussed, as are general issues highlighted by our analysis, such as item reversals and measurement invariance.

Variation in global network properties across risk factors for adolescent internalizing symptoms: evidence of cumulative effects on structure and connectivity.

BACKGROUND: Identifying adolescents at risk of internalizing problems is a key priority. However, studies have tended to consider such problems in simple ways using diagnoses, or item summaries. Network theory and methods instead allow for more complex interaction between symptoms. Two key hypotheses predict differences in global network properties for those at risk: altered structure and increased connectivity. METHODS: The current study evaluated these hypotheses for nine risk factors (e.g. income deprivation and low parent/carer support) individually and cumulatively in a large sample of 12-15 year-olds (N = 34 564). Recursive partitioning and bootstrapped networks were used to evaluate structural and connectivity differences. RESULTS: The pattern of network interactions was shown to be significantly different via recursive partitioning for all comparisons across risk-present/absent groups and levels of cumulative risk, except for income deprivation. However, the magnitude of differences appeared small. Most individual risk factors also showed relatively small effects for connectivity. Exceptions were noted for gender and sexual minority risk groups, as well as low parent/carer support, where larger effects were evident. A strong linear trend was observed between increasing cumulative risk exposure and connectivity. CONCLUSIONS: A robust approach to considering the effect of risk exposure on global network properties was demonstrated. Results are consistent with the ideas that pathological states are associated with higher connectivity, and that the number of risks, regardless of their nature, is important. Gender/sexual minority status and low parent/carer support had the biggest individual impacts on connectivity, suggesting these are particularly important for identification and prevention.

Structural and optical properties of the Agn-tyrosine complexes (n = 3-12): a density functional theory study.

We study the optical properties of Agn (n = 3-12) neutral clusters and their coordination with a tyrosine (Tyr) molecule. A global search strategy coupled with density functional theory (DFT) computations explored the potential energy surface. Adsorption energy calculations predicted that Tyr coordination stabilizes the metal clusters, favouring the Agn-Tyr complexes with an even number of silver atoms. For the Agn low-lying isomers, the general shape and the major transitions of the calculated time dependent-DFT (TD-DFT) absorption spectra align with those of previous reports measured in an argon environment. We use the analysis of non-covalent interactions to identify the specific interactions between each silver cluster and functional groups of Tyr. The TD-DFT absorption spectra for the Agn-Tyr complexes showed that Tyr significantly modifies the optical properties of the coordinated silver clusters and affects the smaller systems to a greater extent. The optical absorption results of the bare Agn clusters and the Agn-Tyr complexes are compared and discussed in detail.

Protective factors for resilience in adolescence: analysis of a longitudinal dataset using the residuals approach.

INTRODUCTION: The residuals approach, in which residual scores from regression models are used as a proxy for resilient functioning, offers great potential to increase understanding of resilience processes. However, its application in child and adolescent wellbeing research is limited to date. We use this approach to examine how adversity exposure impacts later wellbeing (life satisfaction, and internalising mental health difficulties) in the early-to-middle adolescence transition; whether gender and ethnic differences in resilience exist; which internal and external factors confer protective effects for resilience; and, whether the protective effect of these factors differs by gender and level of adversity exposure. METHOD: Secondary analysis of the #BeeWell longitudinal data set (N = 12,130 adolescents, aged 12/13 at T1 and 13/14 at T2, representative of Greater Manchester, England) was undertaken, using a series of linear regressions to establish adversity indices for later wellbeing, before assessing the protective effects of internal and external factors on resilience. RESULTS: Multiple adversity factors (e.g., home material deprivation, sexuality discrimination, bullying) were found to impact later wellbeing. Girls and white adolescents presented lower levels of resilience than their peers. Internal psychological factors (self-esteem, emotional regulation, optimism) consistently conferred the strongest protective effects, but behavioural/activity factors (physical activity, sleep) also contributed to resilience. Among external factors, friendships and peer support were the most salient. Physical activity yielded stronger protective effects among boys (compared to girls). Effects of protective factors were stronger among those at lower (compared to higher) levels of adversity exposure. CONCLUSION: The residuals approach can make a considerable contribution to our understanding of the interplay between adversity exposure and access to protective factors in determining adolescent wellbeing outcomes. Moreover, its application provides clear implications for policy and practice in terms of prevention (of adversity exposure) and intervention (to facilitate resilience).

Heart Transplantation in a Patient With a Heterotopic Percutaneous Tricuspid Valve Prosthesis: A Case Report.

The bicaval transcatheter prosthesis (TricValve) allows the treatment of cava reflux in patients with severe tricuspid regurgitation and high surgical risk. It consists of the implantation of 2 self-expanding valves in both vena cava without directly approaching the native tricuspid valve. Heart transplantation in this setting may require some modifications compared with the conventional bicaval technique. We describe the clinical case of a 69-year-old woman with a background of rheumatic mitral valve disease who required a mitral valve replacement a few decades before. Ongoing clinical deterioration with biventricular dysfunction and severe tricuspid regurgitation was treated with a percutaneous bicaval heterotopic self-expanding valve system, with no clinical benefit. The patient underwent an elective heart transplantation. For the surgical approach, venous cannulation was performed percutaneously for both the right internal jugular and right femoral vein. Due to the impossibility of extracting percutaneous caval valves, the biatrial technique was selected for heart implantation. The postoperative course was difficult, but the patient was successfully discharged home 2 months postoperatively. She remains in good clinical condition with normal heart function 1 year after the transplant. To our knowledge, this is the first report describing a heart transplant in a patient with a bicaval transcatheter prosthesis.

Heart Transplantation and Thromboembolic Risk In Patients With Percutaneous Aortic Valve Prosthesis and Left Ventricular Assist Device: A Case Report.

Transcatheter aortic valve replacements have become a good option for patients with aortic valve disease and high surgical risk. Thromboembolism is reported as a relatively common complication of Transcatheter aortic valve replacement. This risk may be increased in patients who have left ventricular assist devices, as valve motion is drastically reduced. We present the case of a 65-year-old man with a history of alcoholism and valvular cardiomyopathy (severe chronic aortic insufficiency) with severe left ventricular dysfunction. Improvement in ventricular function followed the cessation of alcohol consumption, but still in poor clinical condition. Due to his high surgical risk, it was decided to implant a percutaneous aortic valve to treat the valve deficiency. Two months later, he suffered from a first episode of embolic stroke, which he successfully recovered. Despite the treatment, his clinical status did not improve (INTERMACS 3-4), and he was referred for heart transplantation. A left ventricular assist device was implanted as a bridge to the transplant. While on the waiting list, he suffered from other 3 episodes of stroke, 2 of them requiring mechanical thrombectomy. Finally, his transplant was performed with a favorable postoperative clinical course. Heart transplantation may be feasible in patients with multiple intracardiac devices in left chambers, although we must be aware of the increased thromboembolic risk, especially when used in combination.

Gender and sexual identity-based inequalities in adolescent wellbeing: findings from the #BeeWell Study.

BACKGROUND: Gender and sexual minority adolescents experience greater symptoms of psychological distress than their peers, but little is known about broader aspects of their wellbeing. This study examines wellbeing inequalities relating to gender and sexual identity among adolescents from Greater Manchester in the United Kingdom. METHOD: 37,978 adolescents (aged 12-15, attending 165 secondary schools) completed surveys of life satisfaction, positive and negative affect (hedonic framework); autonomy, self-esteem, optimism, and positive relationships (eudaimonic framework); and, symptoms of distress and mental wellbeing (complete state framework). Structural correlated factors models were used to assess gender and sexual identity wellbeing inequalities. RESULTS: The magnitude of wellbeing inequalities pertaining to gender and sexual identity were routinely substantially greater than those concerning other characteristics (e.g., socio-economic disadvantage). Gender identity wellbeing inequalities followed a consistent pattern, with the largest disparities evident between gender diverse adolescents and boys. Sexual identity wellbeing inequalities also followed a consistent pattern, with the largest disparities evident between sexual minority youth (both gay/lesbian and bi/pansexual) and their heterosexual peers. Finally, variation was evident across wellbeing domains. For example, observed gender identity (boys vs. girls) and sexual identity (heterosexual vs. sexual minority) disparities were substantially greater for symptoms of distress than for mental wellbeing in the complete state model. CONCLUSIONS: LGBTQ + adolescents experience lower wellbeing than their peers, and this is evident across a range of wellbeing domains. Accordingly, there is an urgent need for the prioritisation of improved prevention and intervention efforts that can better meet the needs of gender diverse and sexual minority youth, and future research should be conducted to improve understanding of the mechanisms underpinning the wellbeing inequalities observed.

Elevated Lipoprotein A Levels and Development of Moderate or Severe Cardiac Allograft Vasculopathy in Patients with Heart Transplants.

BACKGROUND: Cardiac allograft vasculopathy (CAV) is a high-incident complication of heart transplant (HT) and is the leading cause of death beyond the first post-HT year. Traditional risk factors have been related to CAV development. Elevated lipoprotein (a) (Lp[a]) is an independent, genetic, and causal risk factor for cardiovascular disease; nonetheless, its association with the development or worsening of CAV in HT has not been firmly established. METHODS: An observational nested case-control study including HT recipients under follow-up in a tertiary center. Lipoprotein (a) levels were determined at the time of inclusion. We considered elevated Lp(a) ≥30 mg/dL. We evaluated the association between Lp(a) levels and the presence and severity of CAV (The International Society For Heart And Lung Transplantation [ISHLT] Cardiac Allograft Vasculopathy Grading Scheme), dividing the sample between No or Mild CAV (0-1) and Moderate-Severe CAV (2-3). Routine coronary angiographies were performed the first year after the transplant and were subsequently symptom-driven. RESULTS: One hundred fifty patients with HTs were included, with a mean follow-up of 110 ± 77 months. Patients with CAV 2 to 3 presented higher median Lp(a) levels (17 vs 86 mg/dL, P = 0.001). Elevated Lp(a) level was an independent risk factor for developing CAV 2 to 3 (odds ratio 8.57 [95% CI 2.82-26.04]; P < .001). Patients with Lp(a) ≥30 mg also showed an earlier onset compared with those with Lp(a) <30 mg/dL. CONCLUSIONS: Our study suggests that Lp(a) may play a role in the development of CAV. Lipoprotein (a) ≥30 mg/dL defines a subgroup of high-risk patients with HTs as portends to earlier onset and more severe CAV. Lipoprotein (a) determination should be a standard-of-care test in patients with HTs.

Quantifying online citizen science: Dynamics and demographics of public participation in science.

Citizen scientists around the world are collecting data with their smartphones, performing scientific calculations on their home computers, and analyzing images on online platforms. These online citizen science projects are frequently lauded for their potential to revolutionize the scope and scale of data collection and analysis, improve scientific literacy, and democratize science. Yet, despite the attention online citizen science has attracted, it remains unclear how widespread public participation is, how it has changed over time, and how it is geographically distributed. Importantly, the demographic profile of citizen science participants remains uncertain, and thus to what extent their contributions are helping to democratize science. Here, we present the largest quantitative study of participation in citizen science based on online accounts of more than 14 million participants over two decades. We find that the trend of broad rapid growth in online citizen science participation observed in the early 2000s has since diverged by mode of participation, with consistent growth observed in nature sensing, but a decline seen in crowdsourcing and distributed computing. Most citizen science projects, except for nature sensing, are heavily dominated by men, and the vast majority of participants, male and female, have a background in science. The analysis we present here provides, for the first time, a robust 'baseline' to describe global trends in online citizen science participation. These results highlight current challenges and the future potential of citizen science. Beyond presenting our analysis of the collated data, our work identifies multiple metrics for robust examination of public participation in science and, more generally, online crowds. It also points to the limits of quantitative studies in capturing the personal, societal, and historical significance of citizen science.