In-contest body acceleration profiles for the judo male and female weight divisions.

Introduction: This study aimed to determine the body accelerations (BA) profile of the judo contest of the male and female weight divisions and to ascertain the involvement of the vertical, mediolateral and anteroposterior axes in it. Methods: Forty-eight male and forty-eight female national and international level athletes (some of them medalists in World, European and national championships) participated in a 5-min simulated contest (official fight time plus breaks) against an opponent of the same sex and weight division, wearing an accelerometer. Heart rate, blood lactate and ratings of perceived exertion were recorded to certify that the athletes performed the fullest. Results: The t2way test expressed differences in the athletes' BA (p = 0.001) and three profiles were identified: the light/middle weight male divisions, the light/middle weight female divisions and the heavy male and female ones. Athletes of all weight divisions performed their BA during the contest in all three directions (the one-sample Person's chi-square did not detect any significantly predominant one: p = 0.400, p = 0.631, p = 0.844, p = 0.749, p = 0.644 and p = 0.895, for male light, moderate and heavy, female light, moderate and heavyweight athletes, respectively). Monte Carlo method simulations suggested as the most likely scenarios those with BA involving all axes, with a slight preference of the anteroposterior and mediolateral ones. Discussion: These results suggest that the demands on judo athletes in a contest differ between weight classes and sexes.

Intention to use physical restraint in paediatric intensive care units and correlated variables: A multicentre and cross-sectional study.

OBJECTIVES: To determine the intention to use physical restraint (PR) and the relationship with sociodemographic and professional variables of the Paediatric Intensive Care Unit (PICU) nurses. RESEARCH METHODOLOGY/DESIGN AND SETTING: A multicentre and correlational study was carried out from October 2021 to December 2023 in five paediatric intensive care units from five maternal and child hospitals in Spain. The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire was provided. Moreover, sociodemographic and employment variables were registered. RESULTS: A total of 230 paediatric nurses participated in the study. A total of 87.7 % were females with an average age of 35.5 ± 9.7 years and working experience of 10.5 ± 8.4 years. The mean scores obtained were 21.1 ± 3.8 for attitude, 13.1 ± 5.0 for subjective norms, 14.4 ± 4.3 for perceived behavioural control and 28.0 ± 6.0 for intention. The nurses apply more physical restraint to anxious patients, with scarce analgesics and sedation, those affected with pharmacological withdrawal symptoms and those with a high risk of accidental removal of vital support devices or fall from bed. The sex (p = 0.007) and type of employment contract (p = 0.01) are the variables that are significantly correlated with the intention to use of PR. CONCLUSION: The paediatric nurses analysed had a moderate attitude, social pressure and perceived behavioural control towards the use of PR. IMPLICATIONS FOR CLINICAL PRACTICE: It is important to know the factors that influence the intention to use physical restraint in order to standardise safe practice for critically ill paediatric and to ensure that patients' rights are respected by obtaining informed consent and assessing the prescription, continuation and removal of physical restraint.

Climate change impacts on temperate fruit and nut production: a systematic review.

Temperate fruit and nut crops require distinctive cold and warm seasons to meet their physiological requirements and progress through their phenological stages. Consequently, they have been traditionally cultivated in warm temperate climate regions characterized by dry-summer and wet-winter seasons. However, fruit and nut production in these areas faces new challenging conditions due to increasingly severe and erratic weather patterns caused by climate change. This review represents an effort towards identifying the current state of knowledge, key challenges, and gaps that emerge from studies of climate change effects on fruit and nut crops produced in warm temperate climates. Following the PRISMA methodology for systematic reviews, we analyzed 403 articles published between 2000 and 2023 that met the defined eligibility criteria. A 44-fold increase in the number of publications during the last two decades reflects a growing interest in research related to both a better understanding of the effects of climate anomalies on temperate fruit and nut production and the need to find strategies that allow this industry to adapt to current and future weather conditions while reducing its environmental impacts. In an extended analysis beyond the scope of the systematic review methodology, we classified the literature into six main areas of research, including responses to environmental conditions, water management, sustainable agriculture, breeding and genetics, prediction models, and production systems. Given the rapid expansion of climate change-related literature, our analysis provides valuable information for researchers, as it can help them identify aspects that are well understood, topics that remain unexplored, and urgent questions that need to be addressed in the future.

Adaptation and validation of the Physical Restraint-Theory of Planned Behaviour Questionnaire to the paediatric context.

OBJECTIVE: To create and test psychometrically a paediatric version of the Physical Restraint-Theory of Planned Behaviour Questionnaire to assess paediatric critical care nurses' intention to use physical restraint. DESIGN: A psychometric study. SETTING: Five medical-surgical Paeditric Intensive care Units from five hospitals in Spain. METHODS: The study took place in three phases. In phase 1, the questionnaire was adapted. In phase 2, the content validity of each item was determined, and a pilot test was conducted. In phase 3, we administered the questionnaire and determined its psychometric properties. RESULTS: The assessment of the intention to use physical restraint was extended to all critical paediatric patients, two items were eliminated from the initial questionnaire, four new items were included, and the clinical scenarios of the intention subscale were expanded from three to six. Overall content validity index for the full instrument of 0.96 out of 1. The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire is made up of four subscales (attitude, subjective norms (SN), perceived behavioural control (PBC), and intention) subdivided into 7 factors and 51 items. The internal consistency for the attitude subscale obtained a Cronbach's Alpha of 0.80 to 0.73, for the SN it was 0.72 to 0.89, for the PBC it was from 0.80 to 0.73 and for the intention subscale it was 0.75. CONCLUSIONS: The Paediatric Physical Restraint-Theory of Planned Behaviour Questionnaire is an instrument composed of seven factors and 51 items that validly and reliably assesses the intention of paediatric nurses to apply PR in PICUs. RELEVANCE FOR CLINICAL PRACTICE: Having this instrument will help health centres move towards restraint-free care by allowing managers to assess professionals' attitudes, beliefs, and intentions around the use of PR in PICUs.

Comprehensive conservation assessments reveal high extinction risks across Atlantic Forest trees.

Biodiversity is declining globally, yet many biodiversity hotspots still lack comprehensive species conservation assessments. Using multiple International Union for Conservation of Nature (IUCN) Red List criteria to evaluate extinction risks and millions of herbarium and forest inventory records, we present automated conservation assessments for all tree species of the Atlantic Forest biodiversity hotspot, including ~1100 heretofore unassessed species. About 65% of all species and 82% of endemic species are classified as threatened. We rediscovered five species classified as Extinct on the IUCN Red List and identified 13 endemics as possibly extinct. Uncertainties in species information had little influence on the assessments, but using fewer Red List criteria severely underestimated threat levels. We suggest that the conservation status of tropical forests worldwide is worse than previously reported.

Implementation feasibility of animal-assisted therapy in a pediatric intensive care unit: effectiveness on reduction of pain, fear, and anxiety.

Animal-assisted therapies are an innovative strategy within health care humanization initiatives, and they could play a role in the reduction of pain or anxiety. The main objective of this work was to evaluate the feasibility of implementing animal-assisted therapy in a pediatric intensive care unit and its effectiveness for the reduction of pain, fear, and anxiety. A prospective, quasi-experimental study of animal-assisted therapy was designed in the pediatric intensive care unit of the Hospital Universitario 12 de Octubre of Madrid, from January 2019 to December 2019. The study sample included patients who had been admitted to the unit and were over 3 years old. Satisfaction surveys were collected from the patients, family, and health personnel involved. Physiological variables and the level of pain (visual analog scale or Wong-Baker scale), fear (Child Medical Fear Scale), and anxiety (modified Yale Preoperatory Anxiety Scale) were evaluated before and after each session. Any existence of adverse events was recorded. A total of 74 therapy sessions were performed on 61 patients. All sessions were completed without any adverse effects. A total of 164 surveys were collected, providing an overall project rating of 9.69 out of a possible 10. The survey comments were found to be positive in most cases. No differences were found in the physiological variables measured before and after each session. There was a statistically significant decrease in pain, fear, and anxiety levels (p < 0.01).   Conclusion: The implementation of an animal-assisted therapy project in a pediatric intensive care unit is feasible and safe and has a high degree of acceptance among both participants and healthcare staff. Animal-assisted therapy is effective for the reduction of pain, fear, and anxiety, and therefore, it could be considered an adjunct to non-pharmacological therapy. What is Known: • Animal assisted therapies (AAT) are an innovative strategy that could be beneficial to help pediatrics patients cope with admission difficulties and could even play a role in reducing pain, anxiety and/or delirium. • To date there are not studies to analyze the effectiveness of AAT in the field of Pediatric Intesive Care. What is New: • Our study confirms the feasibility and effectiveness of the implementation of an AAT in the field of Pediatric Intensive Care with a high degree of acceptance by participants, caregivers and healthcare personnel. • AAT demonstrated a reduction in pain, fear and anxiety in pediatrics patients admitted to Pediatric Intensive Care Unit.

A novel missense mutation in the AIRE gene underlying autoimmune polyglandular syndrome type 1.

The immune regulator gene AIRE plays an essential role in the establishment of immune tolerance and the prevention of autoimmunity. This transcription factor plays a critical role in promoting self-tolerance in the thymus by regulating the expression of a large number of self-antigens that share the common feature of being tissue-restricted in their expression pattern in the periphery. Dysfunction of AIRE in humans causes a rare disease, autoimmune polyglandular syndrome type 1 (APS1), characterized by an autoimmune response against peripheral tissues, particularly endocrine tissues. Although a few dominant mutations have been described, the inactivation of AIRE is usually caused by recessive mutations. Recent data suggests that alterations in AIRE function contribute not only to APS1 but also to more common forms of autoimmune disease. Here, we present a previously unreported missense mutation (NM_000383.2:c.260 T > C) in exon 2 of the AIRE gene, predicted to cause the substitution (p.(Leu87Pro)) in the CARD domain of the AIRE protein. When inherited in conjunction with another dysfunctional AIRE allele, this mutation was associated with immune dysregulation in a pediatric patient. The presence of hypergammaglobulinemia, malabsorption syndrome, ectodermal dysplasia, mucocutaneous candidiasis, vitiligo, and hypothyroidism as well as the presence of multiple autoantibodies allowed us to confirm an APS1 diagnosis.

Laser Ablation for Nondestructive Sampling of Microplastics in Single-Particle ICP-Mass Spectrometry.

In this work, laser ablation (LA) was characterized as a method for sampling and introducing microplastic particles (MPs) into an inductively coupled plasma (ICP) for subsequent 13C+ monitoring using an ICP-mass spectrometer operated in single-event mode. MPs of different types (PS, PMMA, and PVC) and sizes (2-20 µm) were introduced intactly. The laser energy density did not affect the particle sampling across a wide range (0.25-6.00 J cm-2). Single-shot analysis separated clustered MPs (2-7 MPs per cluster) during the LA and particle transport processes, allowing the temporally resolved analysis of the individual constituting MPs. Line scanning showed superior performance when using a small laser beam diameter combined with a high repetition rate. The 13C+ signal intensity correlated linearly (R2 >0.9945) with the absolute C mass in a 2-10 µm size range, while the use of He in the collision-reaction cell (CRC) allowed extension of the linear range to 20 µm. The LA approach generated narrower 13C+ signal distributions than the traditional solution-based approach (dry versus wet plasma conditions) and proved successful for the analysis of a mixed suspension (containing four sizes of PS MPs in a 2-5 µm size range) and for sampling MPs from PVDF and glass microfiber filters, with the latter offering a lower background.

Pathology of neurodegenerative disease for the general neurologist.

Neurodegeneration refers to progressive dysfunction or loss of selectively vulnerable neurones from brain and spinal cord regions. Despite important advances in fluid and imaging biomarkers, the definitive diagnosis of most neurodegenerative diseases still relies on neuropathological examination. Not only has careful clinicopathological correlation shaped current clinical diagnostic criteria and informed our understanding of the natural history of neurodegenerative diseases, but it has also identified conditions with important public health implications, including variant Creutzfeldt-Jakob disease, iatrogenic amyloid-ß and chronic traumatic encephalopathy. Neuropathological examination may also point to previously unsuspected genetic diagnoses with potential implications for living relatives. Moreover, detailed neuropathological assessment is crucial for research studies that rely on curated postmortem tissue to investigate the molecular mechanisms responsible for neurodegeneration and for biomarker discovery and validation. This review aims to elucidate the hallmark pathological features of neurodegenerative diseases commonly seen in general neurology clinics, such as Alzheimer's disease and Parkinson's disease; rare but well-known diseases, including progressive supranuclear palsy, corticobasal degeneration and multiple system atrophy and more recently described entities such as chronic traumatic encephalopathy and age-related tau astrogliopathy.

Serum Mg Isotopic Composition Reveals That Mg Dyshomeostasis Remains in Type 1 Diabetes despite the Resolution of Hypomagnesemia.

Hypomagnesemia was historically prevalent in individuals with type 1 diabetes mellitus (T1DM), but contemporary results indicate an incidence comparable to that in the general population, likely due to improved treatment in recent decades, resulting in better glycemic control. However, a recent study found a significant difference between the serum Mg isotopic composition of T1DM individuals and controls, indicating that disruptions to Mg homeostasis persist. Significant deviations were also found in samples taken one year apart. To investigate whether the temporal variability in serum Mg isotopic composition is linked to the transient impact of administered insulin, Mg isotope ratios were determined in serum from 15 T1DM individuals before and one hour after insulin injection/meal consumption using multi-collector inductively coupled plasma-mass spectrometry. Consistent with results of the previous study, significant difference in the serum Mg isotopic composition was found between T1DM individuals and 10 sex-matched controls. However, the average difference between pre- and post-insulin injection/meal T1DM samples of 0.05 ± 0.13‱ (1SD) was not significant. No difference was observed for controls before (-0.12 ± 0.16‱) and after the meal (-0.10 ± 0.13‱) either, suggesting a lack of a postprandial Mg isotopic response within one hour of food consumption, and that the timing of the most recent meal may not require controlling for when determining serum Mg isotopic composition.

Assessment of gunshot residue detection on a large variety of surfaces by portable LIBS system for crime scene application.

The application of Laser-Induced Breakdown Spectroscopy (LIBS) in forensic science has garnered increasing attention. The ability to perform real-time, on-site analysis of Gunshot Residue (GSR) particles and potential elements originating from bullets or projectile cores on various surfaces holds the potential to assist in resolving firearms-related cases. This includes facilitating trajectory determination by locating distinct impact points and identifying the types of ammunition used. This study evaluates the utilization of a portable LIBS device for ballistic forensic purposes. Additionally, it focuses on the assessment of potential false positives and false negatives arising from the different materials where the shots have been fired. Since the system performs laser ablation of both surface particles and the substrate, it emphasizes the importance of conducting preliminary screening in an area with the same composition as the impact zone to minimize potential false positives during direct surface analysis. Furthermore, the results demonstrate the capability to detect the constituent elements of characteristic gunshot residue particles (GSR particles): lead (Pb), antimony (Sb), and barium (Ba) adhering to bullets, as well as the principal elements composing the jacket or core of the projectile: lead (Pb), copper (Cu), and zinc (Zn) through direct analysis, without the need for a sampling kit, on different surfaces such as walls, furniture, or fabrics. Analyses conducted a month after the shots were fired indicate the potential for finding residues in the vicinity of the bullet hole. Analyses conducted a month after the shots were fired indicate the possibility of finding residues in the area around the bullet hole.

The Science and Social Validity of Companion Animal Welfare: Functionally Defined Parameters in a Multidisciplinary Field.

Social validity refers to the social significance and acceptability of intervention goals, procedures, and outcomes. Animal practitioners, who are often guided by the principles of ABA, lack the benefit of verbal participants (at least with respect to target animals) with which to assess a client's needs and preferences. The study of a learner's welfare is useful for determining areas where intervention is needed or how the learner feels about an intervention that is underway. Three tenets of animal welfare measurement include physiological function, naturalistic behavior, and affect, where affect refers to private events, including emotions, which are a function of the same variables and contingencies responsible for controlling public behavior. The development of new technologies allows us to look "under the skin" and account for subjective experiences that can now be observed objectively. We introduce the reader to tools available from the animal welfare sciences for the objective measurement of social validity from the learner's perspective.

Ultrasonography in rheumatology: time to learn from patient views.

OBJECTIVE: The objective of this observational, descriptive, cross-sectional, multicentre study was to assess the perceived quality and grade of satisfaction expressed by patients with chronic arthropathies regarding the use of musculoskeletal (MSK) ultrasonography by rheumatologists as an integrated clinical care tool. METHODS: All Spanish rheumatology departments with MSK ultrasonography incorporated in their healthcare services were invited to participate in the study. A Spanish-language survey was offered to fill out anonymously to all consecutive patients with chronic arthropathies under follow-up in the rheumatology outpatient clinics who attended their centre for a period of 3 months. The survey consisted of three sections. The first section contained patients' demographics, disease data, frequency of performing rheumatological ultrasound and information about who performed their ultrasound assessments. The second section consisted of 14 questions about patient's experience and opinion on different aspects of the management, performance and perceived usefulness of performing ultrasound, to be answered on a Likert scale 1-5. The third section of the survey was addressed to the rheumatologist ultrasonographers. RESULTS: Nine hundred and four patients from 16 university hospital rheumatology departments completed the survey. All questions reached an overall favourable response ≥ 80%. Patients who reported usual ultrasound examinations in their rheumatology care and those in which it was their attending rheumatologist who performed the ultrasound assessments responded more favourably. CONCLUSION: Our encouraging patient-centred results may be useful in facilitating the implementation of rheumatological ultrasound in rheumatology care worldwide. Key Points • This is the largest multicentre survey carried out in patients with chronic joint diseases designed to assess their experience and perceived benefits with the use of ultrasonography performed by rheumatologists in daily practice. • Musculoskeletal ultrasound incorporated into rheumatology care was very well accepted and valued by most patients. • The patients perceived that ultrasonography helps not only their rheumatologist but also themselves to better understand their condition. • The patients believed that ultrasonography helps them accept and comply with the proposed treatment.

Development of genomic markers associated to growth-related traits and sex determination in lumpfish (Cyclopterus lumpus).

Cleaner fish species have gained great importance in the control of sea lice, among them, lumpfish (Cyclopterus lumpus) has become one of the most popular. Lumpfish life cycle has been closed, and hatchery reproduction is now possible, however, current production is reliant on wild caught broodstock to meet the increasing demand. Selective breeding practices are called to play an important role in the successful breeding of most aquaculture species, including lumpfish. In this study we analysed a lumpfish population for the identification of genomic markers linked to production traits. Sequencing of RAD libraries allowed us to identify, 7193 informative markers within the sampled individuals. Genome wide association analysis for sex, weight, condition factor and standard length was performed. One single major QTL region was identified for sex, while nine QTL regions were detected for weight, and three QTL regions for standard length. A total of 177 SNP markers of interest (from QTL regions) and 399 high Fst SNP markers were combined in a low-density panel, useful to obtain relevant genetic information from lumpfish populations. Moreover, a robust combined subset of 29 SNP markers (10 associated to sex, 14 to weight and 18 to standard length) provided over 90% accuracy in predicting the animal's phenotype by machine learning. Overall, our findings provide significant insights into the genetic control of important traits in lumpfish and deliver important genomic resources that will facilitate the establishment of selective breeding programmes in lumpfish.

Late Presentation of Chronic Traumatic Encephalopathy in a Former Association Football Player.

Background: Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by widespread accumulation of hyperphosphorylated tau that typically occurs in people who have suffered repetitive head impacts. To date, very few cases have been reported in association football players. Objectives: To describe the clinicopathological features of a case of CTE in an 84-year-old former football player who was clinically diagnosed as having dementia with Lewy bodies (DLB). Methods: A retrospective review of the patient's primary care and hospital medical records was performed along with a comprehensive neuropathological examination. Results: This patient presented at age 84 with symmetrical parkinsonism and cognitive impairment that was exacerbated by prochlorperazine. His condition was rapidly progressive with recurrent falls within 1 year. Other features included headaches, depression, anxiety, suicidal ideation, disturbed sleep and aggression. He received a clinical diagnosis of DLB and died approximately 2 years after the onset of symptoms. A post-mortem examination revealed stage 4 CTE. Conclusions: While the contemporaneous onset of parkinsonism and cognitive symptoms in the context of possible neuroleptic sensitivity is suggestive of DLB, the additional symptoms of aggressive behavior, depression and suicidality in a former football player are consistent with the neuropathological diagnosis of CTE. This case, which is notable for the late presentation, demonstrates that CTE may masquerade as other dementias and highlights the importance of seeking a history of repetitive head impacts.

[Electroencephalographic findings in preterm neonates]. / Hallazgos electroencefalográficos en recién nacidos pretérmino.

Background: The electroencephalogram (EEG) in the newborn period is highly superior to the clinical exam in the detection and prognosis of brain dysfunctions, since it allows continuous functional documentation of the brain at the patient's bedside in a non-invasive way. However, there is still some disagreement about these findings. Objective: To describe the electroencephalographic findings in newborns with a history of prematurity. Material and methods: Cross-sectional, descriptive, retrospective study. The inclusion criteria were: newborns with a history of prematurity, regardless of gender, who underwent an EEG from June 2017 to June 2021. Patients with incomplete electroencephalographic records or clinical records without complete data were excluded; patients using sedatives (thiopental, fentanyl, midazolam, diazepam) were eliminated from the study. Results: 107 patients (37 women and 70 men) with a history of prematurity were included, with a mean gestational age at birth of 30.9 WOG ± 3.25. Electroencephalographic findings were normal in 40%, abnormal in 32%, and immature in 28%. The most frequent abnormal finding was focal paroxysmal activity in 86%. 93.4% of the participants presented comorbidities, the most frequent being neurological. Conclusion: Preterm neonates are at high risk of neurologic sequelae, and EEG is a sensitive method for assessing neuromotor and cognitive prognosis. In our study population, one-third had abnormal findings. Early postnatal screening is helpful, but additional records are usually needed to detect high-risk newborns. It would be important to continue studying this line of research in pediatrics.

Introducción: el electroencefalograma (EEG) en el periodo neonatal es muy superior al examen clínico en la detección y pronóstico de disfunciones cerebrales, pues permite hacer una documentación funcional cerebral continua y no invasiva junto a la cama del paciente. Sin embargo, todavía hay cierto desacuerdo sobre estos hallazgos. Objetivo: describir los hallazgos electroencefalográficos en recién nacidos (RN) con antecedente de prematurez. Material y métodos: estudio transversal, descriptivo, retrospectivo. Los criterios de inclusión fueron: RN con antecedente de prematurez, sin distinción de género, a quienes se les haya hecho un EEG de junio de 2017 a junio de 2021. Se excluyeron pacientes con registro electroencefalográfico incompleto o expediente clínico sin datos completos; se eliminaron del estudio pacientes que usaran sedantes (tiopental, fentanilo, midazolam, diazepam). Resultados: se incluyeron 107 pacientes (37 mujeres y 70 hombres) con antecedente de prematurez, con una edad gestacional media al nacer de 30.9 SDG ± 3.25. Los hallazgos de EEG fueron normales en 40%, anormales en 32% e inmaduros en 28%. El hallazgo anormal más frecuente fue la actividad paroxística focal en 86%. El 93.4% de los participantes presentaban comorbilidades, sobre todo neurológicas. Conclusión: los RN pretérmino tienen un alto riesgo de secuelas neurológicas y el EEG es un método sensible para evaluar el pronóstico neuromotor y cognitivo. En nuestra población un tercio tuvo hallazgos anormales. El rastreo posnatal temprano es útil, pero se necesitan registros adicionales para detectar RN de alto riesgo. Es importante continuar esta línea de investigación en pediatría.

Sequence-oriented sensitive analysis for PM2.5 exposure and risk assessment using interactive process mining.

The World Health Organization has estimated that air pollution will be one of the most significant challenges related to the environment in the following years, and air quality monitoring and climate change mitigation actions have been promoted due to the Paris Agreement because of their impact on mortality risk. Thus, generating a methodology that supports experts in making decisions based on exposure data, identifying exposure-related activities, and proposing mitigation scenarios is essential. In this context, the emergence of Interactive Process Mining-a discipline that has progressed in the last years in healthcare-could help to develop a methodology based on human knowledge. For this reason, we propose a new methodology for a sequence-oriented sensitive analysis to identify the best activities and parameters to offer a mitigation policy. This methodology is innovative in the following points: i) we present in this paper the first application of Interactive Process Mining pollution personal exposure mitigation; ii) our solution reduces the computation cost and time of the traditional sensitive analysis; iii) the methodology is human-oriented in the sense that the process should be done with the environmental expert; and iv) our solution has been tested with synthetic data to explore the viability before the move to physical exposure measurements, taking the city of Valencia as the use case, and overcoming the difficulty of performing exposure measurements. This dataset has been generated with a model that considers the city of Valencia's demographic and epidemiological statistics. We have demonstrated that the assessments done using sequence-oriented sensitive analysis can identify target activities. The proposed scenarios can improve the initial KPIs-in the best scenario; we reduce the population exposure by 18% and the relative risk by 12%. Consequently, our proposal could be used with real data in future steps, becoming an innovative point for air pollution mitigation and environmental improvement.

The intrinsically disordered, epigenetic factor RYBP binds to the citrullinating enzyme PADI4 in cancer cells.

RYBP (Ring1 and YY 1 binding protein) is a multifunctional, intrinsically disordered protein (IDP), best described as a transcriptional regulator. It exhibits a ubiquitin-binding functionality, binds to other transcription factors, and has a key role during embryonic development. RYBP, which folds upon binding to DNA, has a Zn-finger domain at its N-terminal region. By contrast, PADI4 is a well-folded protein and it is one the human isoforms of a family of enzymes implicated in the conversion of arginine to citrulline. As both proteins intervene in signaling pathways related to cancer development and are found in the same localizations within the cell, we hypothesized they may interact. We observed their association in the nucleus and cytosol in several cancer cell lines, by using immunofluorescence (IF) and proximity ligation assays (PLAs). Binding also occurred in vitro, as measured by isothermal titration calorimetry (ITC) and fluorescence, with a low micromolar affinity (~1 µM). AlphaFold2-multimer (AF2) results indicate that PADI4's catalytic domain interacts with the Arg53 of RYBP docking into its active site. As RYBP sensitizes cells to PARP (Poly (ADP-ribose) polymerase) inhibitors, we applied them in combination with an enzymatic inhibitor of PADI4 observing a change in cell proliferation, and the hampering of the interaction of both proteins. This study unveils for the first time the possible citrullination of an IDP, and suggests that this new interaction, whether it involves or not citrullination of RYBP, might have implications in cancer development and progression.