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In this paper we study some geometrical properties of the polytope of 3-tolerant fuzzy measures. To achieve this task, we profit that this polytope is an order polytope and hence many properties can be extracted from the subjacent poset. The main result in the paper is a straightforward procedure for obtaining a random 3-tolerant fuzzy measure. We also compute the volume and obtain some other properties of this polytope. These results can be also applied by duality to the polytope of 3-intolerant measures and they can also be easily extended to other subfamilies of fuzzy measures.

OBJECTIVE Avoiding intracranial hypertension after traumatic brain injury (TBI) is a foundation of neurocritical care, to minimize secondary brain injury related to elevated intracranial pressure (ICP). However, this approach at best is reactive to episodes of intracranial hypertension, allowing for periods of elevated ICP before therapies can be initiated. Accurate prediction of ICP crises before they occur would permit clinicians to implement preventive strategies, minimize total time with ICP above threshold, and potentially avoid secondary injury. The objective of this study was to develop an algorithm capable of predicting the onset of ICP crises with sufficient lead time to enable application of preventative therapies. METHODS Thirty-six patients admitted to a level I trauma center with severe TBI (Glasgow Coma Scale score < 8) between April 2015 and January 2019 who underwent continuous intraparenchymal ICP monitor placement were retrospectively identified. Continuous ICP data were extracted from each monitoring period (range 4–96 hours of monitoring). An ICP crisis was treated as a binary outcome, defined as ICP > 22 mm Hg for at least 75% of the data within a 5-minute interval. ICP data preceding each ICP crisis were grouped into four total data sets of 1- and 2-hour epochs, each with 10- to 20-minute lead-time intervals before an ICP crisis. Crisis and noncrisis events were identified from continuous time-series data and randomly split into 70% for training and 30% for testing, from a subset of 30 patients. Machine learning algorithms were trained to predict ICP crises, including light gradient boosting, extreme gradient boosting, and random forest. Accuracy and area under the receiver operating characteristic curve (AUC) were measured to compare performance. The most predictive algorithm was optimized using feature selection and hyperparameter tuning to avoid overfitting, and then tested on a validation subset of 5 patients. Precision, recall, F1 score, and accuracy were measured. RESULTS The random forest model demonstrated the highest accuracy (range 0.82–0.88) and AUC (range 0.86–0.88) across all four data sets. Further validation testing revealed high precision (0.76), relatively low recall (0.46), and overall strong predictive performance (F1 score 0.57, accuracy 0.86) for ICP crises. Decision curve analysis showed that the model provided net benefit at probability thresholds above 0.1 and below 0.9. CONCLUSIONS The presented model can provide accurate and timely forecasts of ICP crises in patients with severe TBI 10–20 minutes prior to their occurrence. If validated and implemented in clinical workflows, this algorithm can enable earlier intervention for ICP crises, more effective treatment of intracranial hypertension, and potentially improved outcomes following severe TBI.

In this paper we study some geometrical questions about the polytope of bi-capacities. For this, we introduce the concept of pointed order polytope, a natural generalization of order polytopes. Basically, a pointed order polytope is a polytope that takes advantage of the order relation of a partially ordered set and such that there is a relevant element in the structure. We study which are the set of vertices of pointed order polytopes and sort out a simple way to determine whether two vertices are adjacent. We also study the general form of its faces. Next, we show that the set of bi-capacities is a special case of pointed order polytope. Then, we apply the results obtained for general pointed order polytopes for bi-capacities, allowing to characterize vertices and adjacency, and obtaining a bound for the diameter of this important polytope arising in Multicriteria Decision Making.

Introduction The evaluation of penile deformity in PD is a critical step in therapeutic decision making and is generally the main outcome in PD clinical trials. 3D reconstruction is becoming increasingly common in the medical field, with highly accurate and long term accessible images. To date, there is no widely accepted 3D documentation protocol for penile deformity. Objective To evaluate the feasibility of 3D imaging and its accuracy in quantifying penile deformity. Methods Video images captured intraoperatively during saline-induced rigid erection were acquired from 4 PD patients undergoing penile surgery. Penile curvature measurements were obtained by the surgeon with a goniometer. Video images were obtained with an iPhone 11 (Apple Inc, Cupertino, CA) camera in full HD or 4k resolution, traveling in a circular 360o motion around the penile shaft. Video images were analysed by a team with 3D expertise using the open source software Blender (Blender Foundation, Amsterdan, NE) and its addon OrtogonBlender, and 3D reconstructed images were created. The 3D team performed curvature measurements using the software tools. A non-concordance magnitude was defined as a measurement difference (between physician measurement and 3D image) of 20% or 10o, whichever was smaller. Results The 3D reconstruction was possible in all cases and all videos used took Conclusions In this pilot study, deformity analysis and measurement with tolerable error was performed using video images acquired quickly intraoperatively, with a smartphone. With further development, this strategy may contribute to a more objective follow up of complex PD cases, as those with biplanar curvature or volume loss deformities. Disclosure No

Introduction Androgen deprivation therapy (ADT) has been the cornerstone of prostate cancer treatment. ADT delays cancer progression, alleviates cancer-related symptoms, and is associated with survival gains. Despite these established benefits, the therapy comes with known side effects, such as increased cardiovascular adverse events and metabolic changes. Despite the well-established association between the level of circulating testosterone and endothelial integrity, the direct effects of ADT on endothelial function remain controversial. Objective The aim of the present study was to investigate the impact of ADT on endothelial function, through the analysis of vascular parameters of the brachial artery, and the measurement of serum inflammatory markers. It was also our goal to evaluate early impact of ADT on anthropometric and metabolic parameters Methods We prospectively evaluated men with moderate to high-risk prostate cancer treated with ADT from January to July 2022 at our institution. Patients with decompensated diabetes mellitus (HbA1c >9%), active smokers or smokers who have ceased for less than 5 years and those with confirmed diagnosis of peripheral artery disease, coronary artery disease, angina, congestive heart failure, myocardial infarction, coronary revascularization or stroke, were excluded. Brachial artery assessment included vascular diameter and flow-mediated (endothelium-dependent) vasodilation (FMD) using high-resolution B-mode ultrasound. Our metabolic and inflammatory profile included serum measurement of total cholesterol and fractions, triglycerides, fasting glucose, glycated hemoglobin, basal insulin, C-reactive protein, and bioimpedance assessment of body fat distribution. All measurements were performed at baseline and after 3 months of ADT initiation with goserelin acetate 10.80mg. Results A total of 14 men with mean age of 67.9 ± 6.9 years were included. The prevalence of diabetes in the present cohort was 21.4%. FMD demonstrated a slight increase following ADT, which did not reach statistical significance after 3 months (median 2.2% vs. 5.0%; p = 0.8224 – Figure 1). Baseline brachial artery diameter significantly decreased with ADT compared to baseline (median diameter 0.43cm vs 0.40cm; p = 0.006). With regard to the metabolic profile, ADT significantly increased insulin resistance: fasting insulin levels (mean 9.67 ± 6.09 vs 13.19 ± 7.47; p = 0.002), glycated hemoglobin (mean 5.79% ± 0.47 vs 6.22% ± 0.75; p = 0.009) and homeostatic model assessment insulin resistance increased significantly after 3 months (p = 0.006). Low-density lipoprotein cholesterol (mean 112.00 ± 27.35 vs 128.90 ± 29.00; p = 0.01) and triglycerides (mean 145.40 ± 78.52 vs 168.20 ± 105.80; p = 0.03) concentrations were higher after 3 months of ADT. No significant differences were found in body fat distribution. Conclusions Although the present study has not demonstrated a significant change in brachial artery FMD, we verified an important and surprisingly early worsening of the metabolic profile with ADT, especially increased insulin resistance and dyslipidemia, which represent well-established risk factors for cardiovascular events. Disclosure No

An integrative approach is presented which combines genomics, transcriptomics, and cell biology to address leaf scald disease. The results presented here disclose that the disease is not associated with a single shared characteristic between the most pathogenic strains or a unique genomic pattern.

The use of information and communications technology (ICT) has revolutionized the way people communicate and interact with one another. While there is an extensive ICT utilization in a plethora of disciplines, an exploration of the specific field of health education poses significant implications. This chapter used bibliometric analysis to describe how ICT is applied in health education. Specifically, it followed a five-step workflow to achieve this goal. Among the key findings of this chapter is that ICT research on health education has been roughly stagnant in recent years. Most of the published health technology research is trending toward nursing, e-learning, social media, graduate and higher education, communication, and distance education. Western countries dominated the number of publications, and the USA remains the most productive country in this research area. Overall, this chapter provides an overview of the research landscape when it comes to the application of ICT in health education. Future research undertakings were offered to propel the health technology literature.

The advent of recombinant protein-based therapeutic agents in the 1980s and subsequent waves of innovation in molecular biology and engineering of biologics has permitted the production of an increasingly broad array of complex, high molecular weight constructs. While this has opened a powerful new toolbox of molecular scaffolds with which to probe and interdict biological processes, it also makes deciphering the architectural nuances between individual constructs intuitively difficult. Key to downstream data processes for the detection of data trends is the ability to unambiguously identify, compare, and communicate the nature of molecular compositions. Existing small molecule orientated software tools are not intended for structures such as peptides, proteins, antibodies, and RNA, and do not contain adequate atomistic or domain-level detail to appropriately convey their higher structural complexity. Similarly, there is a paucity of large molecule-focused data analysis and visualization tools. This article will describe four new approaches we developed for the graphical representation and analysis of complex large molecules and experimental data. These tools help fulfill key needs in scientific communication and structure-property analysis of complex biologics and modified oligonucleotide-based drug candidates.

This work was intended to evaluate the effects of the homeopathic medicine Nux vomica 12CH in stressed mice submitted to a sleep deprivation protocol. The remedy was chosen according to the homeopathic similarity law. Male mice were divided in 4 groups: sleep deprived (SD); animals allowed to sleep (control) and treated with water; SD treated with Nux vomica 12 CH (SD-NV); and control mice treated with Nux vomica (NV). The animals were exposed to sleep deprivation for 3 days. The animals were weighed and submitted to open field (OF) and elevated plus maze (PM) tests before and after the SD. At the end of the experiment, the animals were sacrificed.During the experiment, 10 µl of water or medicine were given orally to the mice, daily, between 9 and 10 a.m. The experiment was blindly conducted. All sleep deprived animals had decrease of weight gain, independent of the treatment employed. The group of animals treated with NV produced more excrement on second OF exposition, but the results, taken together, suggest that Nux vomica 12CH had no anxiolytic effects on sleep deprived animals.

Objective: To determine in-hospital costs associated with performing an EEA to anterior skull base pathology and to identify drivers of cost variability for patients undergoing endoscopic anterior skull base surgery. Methods: All endoscopic anterior skull base surgeries performed over a period from January 1st, 2015 to October 24th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using Stata software. Results: An EEA was associated with an average total in-hospital cost of $44 545. Compared to patients undergoing a transsphenoidal approach to pituitary tumor resection, EEA patients incurred higher in-hospital costs across all variables including a total cost increase of $15 921 (95% confidence interval $5720-26 122, P = .002). Univariate analysis of all endoscopic anterior skull base surgery patients showed a cost increase of $30 616 associated with post-operative cerebrospinal fluid (CSF) leak ($10 420-50 811, P = .004), $14 610 with post-operative diabetes insipidus (DI) ($4610-24 609, P = .004), and $11 522 with African-American patients relative to Caucasian patients ($3049-19 995, P = .008). Conclusions: Patients who undergo endoscopic EEA for resection of anterior skull base tumors typically incur greater in-hospital costs than patients undergoing a standard TSA. Post-operative complications such as CSF leak and DI, as well as ethnicity, are significant drivers of cost-variability.

We report TeV gamma-ray observations of the ultra-high-energy source MGRO J1908+06 using data from the High Altitude Water Cherenkov (HAWC) Observatory. This source is one of the highest-energy known gamma-ray sources, with emission extending past 200 TeV. Modeling suggests that the bulk of the TeV gamma-ray emission is leptonic in nature, driven by the energetic radio-faint pulsar PSR J1907+0602. Depending on what assumptions are included in the model, a hadronic component may also be allowed. Using the results of the modeling, we discuss implications for detection prospects by multi-messenger campaigns., Comment: accepted by ApJ, in press

This study aimed to characterize papaya lines via microsatellite markers, and select genotypes based on the fixation index in order to promote the genetic purification of important commercial hybrids parent lines. Overall, 400 genotypes from three parental lines (JS-12, SS-72/12, and Sekati) were genotyped. Expected (HE), observed (HO) heterozygosity, and fixation index (F), were estimated. Genetic distances were estimated using an unweighted index, which was graphically presented via cluster analysis using the UPGMA and PCoA. Intra-genotypic variability was detected in both JS-12 and Sekati lines, while an absence of it was observed in SS-72/12. Such variability may positively contribute to the fitting of ‘UENF/Caliman 01’ and ‘UC-10’ hybrids into the traits of commercial interest how size and weight fruit. Regarding the fixation index, 293 genotypes showed maximum values (F=1) facilitating the genotypes selection process. Concerning population analysis, a close proximity between heterotic group ‘Formosa’ lines was observed, while a greater distance among ‘Solo’ group ones, and this enables systematic exploitation of such material. The fixation index maximum enabled the 80 genotypes selection thereby contributing to the parents genetic purification, since, the selected genotypes will be used in future hybridization steps to generate hybrids fitted into the traits of commercial interest.

Magnetic skyrmions are prime candidates for the nextgenerationof spintronic devices. Skyrmions and other topological magnetic structuresare known to be stabilized by the Dzyaloshinskii-Moriya interaction(DMI) that occurs when the inversion symmetry is broken in thin films.Here, we show by first-principles calculations and atomistic spindynamics simulations that metastable skyrmionic states can also befound in nominally symmetric multilayered systems. We demonstratethat this is correlated with the large enhancement of the DMI strengthdue to the presence of local defects. In particular, we find thatmetastable skyrmions can occur in Pd/Co/Pd multilayers without externalmagnetic fields and can be stable even near room temperature conditions.Our theoretical findings corroborate with magnetic force microscopyimages and X-ray magnetic circular dichroism measurements and highlightthe possibility of tuning the intensity of DMI by using interdiffusionat thin film interfaces.

The High-Altitude Water Cherenkov (HAWC) observatory is a second-generation continuously operated, wide field-of-view, TeV gamma-ray observatory. The HAWC observatory and its analysis techniques build on experience of the Milagro experiment in using ground-based water Cherenkov detectors for gamma-ray astronomy. HAWC is located on the Sierra Negra volcano in M\'exico at an elevation of 4100 meters above sea level. The completed HAWC observatory principal detector (HAWC) consists of 300 closely spaced water Cherenkov detectors, each equipped with four photomultiplier tubes to provide timing and charge information to reconstruct the extensive air shower energy and arrival direction. The HAWC observatory has been optimized to observe transient and steady emission from sources of gamma rays within an energy range from several hundred GeV to several hundred TeV. However, most of the air showers detected are initiated by cosmic rays, allowing studies of cosmic rays also to be performed. This paper describes the characteristics of the HAWC main array and its hardware., Comment: Accepted for publications in Nuclear Inst. and Methods in Physics Research, A (2023) 168253 ( https://www.sciencedirect.com/science/article/abs/pii/S0168900223002437 ); 39 pages, 14 Figures

Vaccines are essential for the eradication of diseases. Yet for many reasons, individuals do not embrace them completely. In the COVID-19 pandemic and with the possibility of the Brazilian population's immunization against the disease, both political and health-related dimensions might have had a role in individual COVID-19 vaccination acceptance. In two studies (n = 974), we tested the hypothesis that participants' vaccination acceptance is related to their past vote in the 2018 Brazilian presidential election (being or not being a Jair Bolsonaro voter) and their different levels of perceived vulnerability to disease (PVD). We further tested whether Bolsonaro's opposition or ambiguous messages towards vaccination (vs. control) increased vaccination rejection among those who have (vs. have not) voted for him and who are low (vs. high) in PVD. Results show that Bolsonaro (vs. non-Bolsonaro) voters accepted less vaccination, with higher rejection rates when participants expressed low (vs. high) PVD. Also, when primed either with Bolsonaro's opposed or ambiguous messages towards COVID-19 vaccination, such participants accepted less vaccines (vs. participants primed with neutral information). These findings are the first to show that the COVID-19 vaccine acceptance is related to their past vote and leadership influence but also different levels of perceived vulnerability to disease.

In the quest for high-energy neutrino sources, the Astrophysical Multimessenger Observatory Network has implemented a new search by combining data from the High Altitude Water Cherenkov (HAWC) Observatory and the Astronomy with a Neutrino Telescope and Abyss environmental RESearch (ANTARES) neutrino telescope. Using the same analysis strategy as in a previous detector combination of HAWC and IceCube data, we perform a search for coincidences in HAWC and ANTARES events that are below the threshold for sending public alerts in each individual detector. Data were collected between 2015 July and 2020 February with a live time of 4.39 yr. Over this time period, three coincident events with an estimated false-alarm rate of, The National Science Foundation under grants PHY-1708146, PHY-1806854, The Institute for Gravitation and the Cosmos of the Pennsylvania State University, Centre National de la Recherche Scientifique (CNRS), Commissariat à l’énergie atomique et aux énergies alternatives (CEA), Commission Européenne (FEDER fund and Marie Curie Program), Institut Universitaire de France (IUF), LabEx UnivEarthS (ANR-10-LABX-0023 and ANR-18-IDEX-0001), Région Île-de-France (DIM-ACAV), Région Alsace (contrat CPER), Région Provence-Alpes-Côte d’Azur, Département du Var and Ville de La Seyne-sur-Mer, Bundesministerium für Bildung und Forschung (BMBF), Istituto Nazionale di Fisica Nucleare (INFN), Nederlandse organisatie voor Wetenschappelijk Onderzoek (NWO), Executive Unit for Financing Higher Education, Research, Development and Innovation (UEFISCDI), Romania; Ministerio de Ciencia, Innovación, Investigación y Universidades (MCIU), Programa Estatal de Generación de Conocimiento (refs. PGC2018- 096663-B-C41, -A-C42, B-C43, B-C44, PID2021- 124591NB-C41, C42, C43, (MCIU/FEDER), Generalitat Valenciana, Prometeo (PROMETEO/2020/019), Grisolía (refs. GRISOLIA/2018/119, /2021/192), GenT (refs. /2019/043, /2020/049, /2021/023) programs, Junta de Andalucía (ref. A-FQM-053-UGR18), La Caixa Foundation (ref. LCF/BQ/IN17/11620019), MSC program (ref. 101025085), Spain; Ministry of Higher Education, Scientific Research and Innovation, The Arab Fund for Economic and Social Development, Kuwait, US National Science Foundation (NSF), The US Department of Energy Office of High-Energy Physics, Laboratory Directed Research and Development (LDRD) program of Los Alamos National Laboratory, Consejo Nacional de Ciencia y Tecnología (CONACyT), México, grants 271051, 232656, 260378, 179588, 254964, 258865, 243290, 132197, A1-S-46288, A1- S-22784, Cátedras 873, 1563, 341, 323, Red HAWC, México, DGAPA-UNAM grants IG101320, IN111716-3, IN111419, IA102019, IN110621, IN110521, VIEP-BUAP, PIFI 2012, PROFOCIE 2014, 2015, the University of Wisconsin Alumni Research Foundation, The Institute of Geophysics, Planetary Physics, Signatures at Los Alamos National Laboratory, Polish Science Centre grant, DEC-2017/27/B/ ST9/02272, Coordinación de la Investigación Científica de la Universidad Michoacana; Royal Society—Newton Advanced Fellowship 180385, Generalitat Valenciana, grant CIDEGENT/ 2018/034, The Program Management Unit for Human Resources & Institutional Development, Research and Innovation, NXPO (grant No. B16F630069), Coordinación General Académica e Innovación (CGAI-UdeG), PRODEP-SEP UDGCA- 499; Institute of Cosmic Ray Research (ICRR), University of Tokyo, NASA under award number 80GSFC21M0002

Experimental realizations of two-dimensional materials are hardly free of structural defects such as e.g. vacancies, which, in turn, modify drastically its pristine physical defect-free properties. In this work, we explore effects due to point defect clustering on the electronic and transport properties of bilayer graphene nanoribbons, for AA and AB stacking and zigzag and armchair boundaries, by means of the tight-binding approach and scattering matrix formalism. Evident vacancy concentration signatures exhibiting a maximum amplitude and an universality regardless of the system size, stacking and boundary types, in the density of states around the zero-energy level are observed. Our results are explained via the coalescence analysis of the strong sizeable vacancy clustering effect in the system and the breaking of the inversion symmetry at high vacancy densities, demonstrating a similar density of states for two equivalent degrees of concentration disorder, below and above the maximum value.

SummaryTourism can be a powerful tool for wildlife conservation if well controlled and responsibly managed. Apex predators constitute particularly attractive subjects for tourism, but simultaneously they may generate conflict with local communities. Harpy Eagles Harpia harpyja are the largest eagle species and are highly sought-after by ecotourists. The last stronghold of the Harpy Eagle is the Amazon Forest, which is being deforested for cattle ranching. We tested methods for developing Harpy Eagle ecotourism as a potential tool to harmonize these issues. Using camera traps, we collected data on timing of Harpy Eagle visits to their nests, as well as on probabilities of viewing an eagle. Harpy Eagles can only be seen predictably during the first 12 of the 30–36 month nest cycle. In nests with nestlings (up to 5–7 months), adults are visible on a daily basis, and this period lasts 16.6% of the nesting cycle, demanding a minimum of 13, 17, and 26 nests to have at least one nest with a nestling on 90%, 95% and 99% of the days. After this 5–7 month window, we found that two and 4.16 days spent at nests afforded high probabilities of sighting a fledgling or adult eagle, respectively. Harpy Eagles were mainly active at the beginning and the end of the day. Activity core lasted 6.5 decimal hours for adults, peaking at 10h00, and 7.45 decimal hours for fledged eagles, peaking at 15h00. Our results demonstrate that Harpy Eagles fit several criteria for a viable wildlife attraction: predictable in activity and location, viewable, and diurnal, even though at the same time they are considered a rarity. In a broader perspective, Harpy Eagle tourism shows every indication of being a significant tool for more robust rainforest conservation.

Objective To determine the in-hospital cost implications of an endoscopic expanded endonasal approach (EEEA) for meningioma resection relative to the open transcranial approach. Methods All anterior skull base meningioma surgeries performed over a period from January 1st, 2015 to October 31th, 2017 were evaluated. The electronic medical record was reviewed for patient factors, tumor characteristics, and cost variables associated with each hospital stay and univariate analysis was performed using R software. All cost data were converted into August 2021-equivalent dollar amounts using the United States Bureau of Labor Statistics consumer price index. Results Thirty-five patients met study criteria, including 27 patients undergoing an open transcranial approach and 8 undergoing an EEEA. Average length of stay for patients undergoing an open approach was 9.3 days compared to 5.6 within the EEEA group ( P = .126). The average total in-hospital cost of patient undergoing an EEEA was $35417.1 compared to $46406.9 among patients undergoing an open transcranial approach ( P = .168). On univariate analysis, the cost of an open transcranial approach relative to the EEEA was $10989.8 ( P = .411). Conclusions The open transcranial approach remained the dominant surgical approach to anterior skull base meningiomas over our study time period. However, despite limited patient numbers the EEEA was associated with decreased total in-hospital costs.

The existence of crime-related racial stereotypes has been well documented. People tend to associate certain groups with specifc crimes, which, in turn, impacts criminal-sentencing decisions through the perceptions of crime severity. This evidence calls for regular updating of rating norms combining these variables. With this objective, and given that most of the normative studies provide norms for a small number of crimes and/or with an insufcient number of participants, a new norming study was conducted. Furthermore, norms from European countries are absent, and the existing ones (mostly with USA-based populations) do not simultaneously examine crime stereotypicality and crime severity. The Crime Stereotypicality and Severity Database (CriSSD) presents normative ratings for a set of 63 crimes on three dimensions: White stereotypicality, Black stereotypicality, and crime severity. The crimes were selected according to a comprehensive procedure. A total of 340 Portuguese participants (72.6% female; Mage=26.86, SD=7.65) answered an online survey. Each crime was evaluated by a range of 46–60 participants. Data allowed us to identify a crime typology with three clusters. We present descriptive data (means, standard deviations, and 95% confdence intervals) for each crime. Crime evaluations were associated with sociodemographic characteristics. Additionally, this study gives input regarding the understudied link between crime stereotypes and crime severity, showing that crime severity is predicted by ratings of both Black and White stereotypicality. The CriSSD (available at osf.io/gkbrm) provides a valuable resource for researchers in the feld of social psychology to conduct studies with controlled materials on potential disparities in criminal-sentencing decisions. Fundação para a Ciência e Tecnologia - FCT info:eu-repo/semantics/publishedVersion

Background Patients with irritable bowel syndrome (IBS) often report gastrointestinal symptoms after consuming wheat and gluten-containing foods. It is, however, unclear whether gluten is the main driver of symptoms, as other immunogenic peptides, such as amylase trypsin inhibitors (ATI), poorly digestible fiber (inulin, part of FODMAP) or even the nocebo effect may contribute to symptom generation. Purpose To evaluate whether whole wheat containing ATIs and/or purified gluten trigger gastrointestinal symptoms compared to nocebo in patients with IBS adopting a gluten-free diet (GFD). Method We conducted a double-blind, randomized, nocebo-controlled crossover study in adult IBS patients (Rome IV criteria) who previously perceived improvement of symptoms while on a GFD. The study was approved by the Hamilton Research Ethics Board (HiREB #4367). Participants were challenged for 7 days with whole wheat, purified gluten, and nocebo (gluten-free flour) added to low FODMAP cereal bars. Each challenge was followed by a 2-week washout. Patients remained on a GFD throughout the study, diet adherence was assessed by a dietitian and stool gluten immunogenic peptides (GIP; Biomedal). Gastrointestinal symptoms were assessed by IBS Symptom Severity Score (IBS-SSS); increases >50 points were considered a significant worsening. Blood samples were collected to assess immune markers and celiac (HLA DQ2, DQ8 and DQ7) genotype. Statistical comparisons used Friedman rank sum tests and paired Wilcoxon signed rank tests. Result(s) Twenty-nine IBS patients (27 female, mean age=42, SD=14.4 years) were enrolled in the study; 1 dropped. Similar proportions of patients reacted symptomatically to wheat (11/28, 39.3%), gluten (10/28, 35.7%) and nocebo (8/28, 28.6%). However, there was an overall significant increase in IBS symptoms after wheat (+39.5 on IBS-SSS; p=0.030) but not after gluten (+27.5; p=0.051) or nocebo (+5.5; p=0.236) challenges (Figure 1). Ten participants experienced IBS-SSS symptoms >175 during baseline and did not worsen further during the challenges. TNF-α trended from 1.35 pg/mL after nocebo, 1.47 pg/mL after gluten, to 1.57 pg/mL after wheat; however, this was not significant. Baseline adherence to a GFD was rated excellent in 19 (68%), good in 6 (21%), and fair in 3 (11%) participants. Median GIP levels were 0.584 µg/g after wheat, 0.432 µg/g after gluten, and 0.095 µg/g after nocebo; p Image Conclusion(s) IBS patients self-reporting wheat or gluten sensitivity had worse symptoms after whole wheat, but not purified gluten or nocebo challenge. However, similar proportions of IBS patients reacted to each intervention, suggesting that central mechanisms play an important role in symptom genesis. Furthermore, one third of patients had high symptoms during a GFD and did not react to wheat or gluten challenges, suggesting that other mechanisms are driving their IBS symptoms. Please acknowledge all funding agencies by checking the applicable boxes below CIHR, Other Please indicate your source of funding; Society for the Study of Celiac Disease (Nestle); Canadian Digestive Health Foundation Disclosure of Interest None Declared

Background The link between diet, disease activity and symptoms in IBD patients have recently gained attention and recommendations on dietary interventions to manage symptoms are common. Most studies have explored the correlation between dietary patterns and increased risk of IBD or symptom severity. However, there is limited understanding and no relevant systematic review of IBD patients’ perspectives and barriers to adopt the prescribed diets. We thus conducted a scoping review for this topic. Purpose Aim: We performed a scoping review of current evidence to investigate the extent of evidence on IBD adult patients’ perspectives on dietary modification to manage their symptoms and gaps for future research to explore patients' experiences. Method We followed the JBI (Joanna Briggs Institute) method for scoping reviews. A systematic search of Ovid Medline, Embase and Cochrane Library was conducted in April 2022 to retrieve published English language qualitative, quantitative and mixed methods studies that report IBD patients’ perspectives, behaviours, beliefs related to diet modification and barriers to diet adoption for managing their symptoms or disease activity. We manually reviewed reference lists of reviews on this topic. Since this is a scoping review, no statistical comparison is needed. Result(s) Out of 2822 papers screened, 42 studies met the inclusion criteria. Various methods were used in included studies with heterogenous outcomes reported. Of the 42 studies, 19 reported IBD patients' beliefs and behaviors related to diet as a primary outcome. Most patients reported changing their diet after being diagnosed with IBD, and food avoidance and restrictive diet were commonly reported to prevent relapse. Some studies reported that many patients reduced their opportunities for social life, such as eating out, practicing outdoor sports, having dinner with family in the same household and meeting friends. The dietary modification was more significant among individuals with active than inactive disease. Most studies showed that patients believe food can play a role in causing or preventing relapse, but beliefs are varied regarding the role of diet as initiating factor for IBD. Some patients believe dietary modification could be more important than medication to manage their disease symptoms. Few studies focused on patients' barriers when changing their diet, but financial barriers and limited nutritional guidance were commonly reported acknowledging searching for dietary advice on the internet. Conclusion(s) Food avoidance and social restriction for relapse prevention are standard practices by most IBD patients. The belief that nutrition is key in managing IBD is prevalent. This scoping review highlights the need to identify patients' barriers to accessing professional dietary guidance and nutritional interventions and provides direction for clinical studies and systematic reviews of focused research questions. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Context Adrenarche reflects the developmental growth of the adrenal zona reticularis, which produces increasing adrenal androgen secretion (eg, dehydroepiandrosterone [DHEA]/dehydroepiandrosterone sulfate [DHEAS]) from approximately age 5 to 15 years. Objective We hypothesized that the study of the genetic determinants associated with variations in serum DHEAS during adrenarche might detect genetic variants influencing the rate or timing of this process. Methods Genome-wide genotyping was performed in participants of the Chilean pediatric Growth and Obesity Chilean Cohort Study (GOCS) cohort (n = 788). We evaluated the genetic determinants of DHEAS levels at the genome-wide level and in targeted genes associated with steroidogenesis. To corroborate our findings, we evaluated a polygenic risk score (PRS) for age at pubarche, based on the discovered variants, in children from the same cohort. Results We identified one significant variant at the genome-wide level in the full cohort, close to the GALR1 gene (P = 3.81 × 10–8). In addition, variants suggestive of association (P Conclusion Our results disclose one variant associated with DHEAS concentrations at the level of genome-wide association study significance, and several variants with a suggestive association that may be involved in the genetic regulation of adrenarche.

Andes Large-area PArticle detector for Cosmic-ray physics and Astronomy (ALPACA) is an international experiment that applies southern very-high-energy (VHE) gamma-ray astronomy to determine the origin of cosmic rays around the knee energy region ($10^{15}\, {\rm eV} - 10^{16}\, {\rm eV}$). The experiment consists of an air shower (AS) array with a surface of $83, 000\, {\rm m}^2$ and an underground water Cherenkov muon detector (MD) array covering $5, 400\, {\rm m}^2$. The experimental site is at the Mt. Chacaltaya plateau in La Paz, Bolivia, with an altitude of $4, 740\, {\rm m}$ corresponding to $572\, {\rm g}/{\rm cm}^2$ atmospheric thickness. As the prototype experiment of ALPACA, the ALPAQUITA experiment aims to begin data acquisition in late 2021. The ALPAQUITA array consists of a smaller AS array ($18, 450\, {\rm m}^2$) and underground MD ($900\, {\rm m}^2$), which are now under construction. ALPAQUITA's sensitivity to gamma-ray sources is evaluated with Monte Carlo simulations. The simulation finds that five gamma-ray sources observed by H.E.S.S. and HAWC experiments will be detected by ALPAQUITA beyond 10 TeV and one out of these five - HESS J1702-420A - above 300 TeV in one calendar year observation. The latter finding means that scientific discussions can be made on the emission mechanism of gamma rays beyond 100 TeV from southern sources on the basis of the observational results of this prototype experiment., This is the manuscript accepted by Experimental Astronomy. For the published article, see https://doi.org/10.1007/s10686-021-09796-8

With the increasing numbers of immigrant and refugee students across the US K–12 system, the xenophobia of the current political climate, and the effects of COVID-19 on the immigrant community, it is critical to examine schools that serve immigrant students and their families. Drawing on case studies of two public high schools that exclusively serve immigrant students, authors Adriana Villavicencio, Chandler Patton Miranda, Jia-Lin Liu, and Hua-Yu Sebastian Cherng examine how educators frame the current political context and how this frame informs their collective approach to engaging with and supporting families. The study finds that these schools shifted norms of parental engagement by proactively forging relationships with families, cultivating alliances with community partners, and mediating within families around challenges related to work and higher education to benefit the communities they serve. In so doing, these school actors have shifted the norms of parental engagement to center the perspectives, voices, and experiences of immigrant families.

The manganese(III) porphyrin MnTnHex-2-PyP5+ (MnTnHex) is a potent superoxide dismutase mimic and modulator of redox-based transcriptional activity that has been studied in the context of different human disease models, including cancer. Nevertheless, for lung cancer, hardly any information is available. Thus, the present work aims to fill this gap and reports the effects of MnTnHex in non-small cell lung cancer (NSCLC) cells, more specifically, A549 and H1975 cells, in vitro. Both cell lines were initially characterized in terms of innate levels of catalase, glutathione peroxidase 1, and peroxiredoxins 1 and 2. To assess the effect of MnTnHex in NSCLC, alone or in combination with cisplatin, endpoints related to the cell viability, cell cycle distribution, cell motility, and characterization of the volatile carbonyl compounds (VCCs) generated in the extracellular medium (i.e., exometabolome) were addressed. The results show that MnTnHex as a single drug markedly reduced the viability of both NSCLC cell lines, with some IC50 values reaching sub-micromolar levels. This redox-active drug also altered the cell cycle distribution, induced cell death, and increased the cytotoxicity pattern of cisplatin. MnTnHex also reduced collective cell migration. Finally, the metabolomics study revealed an increase in the levels of a few VCCs associated with oxidative stress in MnTnHex-treated cells. Altogether these results suggest the therapeutic potential of MnTnHex to be further explored, either alone or in combination therapy with cisplatin, in NSCLC.

Periodontitis is a highly prevalent disease in psychiatric patients, including those undergoing symptomatic treatment with second-generation antipsychotics. Some of these drugs, such as clozapine (CLO) and olanzapine (OLA), have prominent metabolic effects such as weight gain, hyperglycemia, and dyslipidemia, which are risk factors for periodontitis. In addition to the metabolic effects, there are reports of changes in salivary flow, gingival bleeding, and caries. In this context, we aimed to evaluate if the metabolic effects of OLA and CLO alter periodontal parameters in an animal model of periodontitis without the environmental and psychosocial biases inherent to human diseases.In the first set of experiments, male and female adult Wistar rats received oral administration of CLO, OLA, or vehicle for 45 days. They were evaluated for body mass composition and weight gain, blood glucose parameters (fasting and glucose tolerance and insulin resistance tests), and lipid profile (HDL, total cholesterol, and triglycerides). In a second set of experiments, the same measurements were performed in female rats exposed to the antipsychotics for 45 days and ligature-induced periodontitis on the 30th day of treatment. Macroscopic measurements of exposed roots, microtomography in the furcation region of the first molar, and histological evaluation of the region between the first and second molars were evaluated to assess bone loss. Additionally, gingival measurements of myeloperoxidase activity and pro-inflammatory cytokine TNF-α were made.Only females exposed to OLA had more significant weight gain than controls. They also exhibited differences in glucose metabolism. Ligature-induced periodontitis produced intense bone retraction without changing the density of the remaining structures. The bone loss was even higher in rats with periodontitis treated with OLA or CLO and was accompanied by a local increase in TNF-α caused by CLO. These animals, however, did not exhibit the same metabolic impairments observed for animals without periodontitis.The use of clozapine and olanzapine may be a risk factor for periodontal disease, independent of systemic metabolic alterations.

Diante da necessidade de recrutar uma maior parcela da sociedade para agir em prol do meio ambiente, é necessário disseminar a Educação Ambiental (EA) através de diferentes meios, entre eles, o jogo digital. Este artigo mostra o resultado da análise do jogo de entretenimento “Alba: uma aventura selvagem” sob a perspectiva da EA, e tem como base o modelo conceitual Player Involvement Model. Diversos elementos de jogo são citados e associados a correntes da EA e às dimensões de envolvimento do jogador. Em conclusão, o jogo transita entre as seis dimensões de envolvimento do jogador e pode ser usado como referência no desenvolvimento de aplicações futuras que visem a EA.

The manganese(III) porphyrin MnTnHex-2-PyP

Apex predators are widely threatened globally and generally considered a priority on the conservation biology agenda. The harpy eagle, Harpia harpyja, is an apex predator threatened by habitat loss and persecution and a flagship species for Neotropical conservation. We investigated the roles of social, economic and environmental factors related to livestock depredation by harpy eagles, causes of reported harpy eagle persecution by local landholders and the intent of future harpy eagle killings. We explored these issues using structured interviews with 184 local livestock owners, who had admitted killing a combined total of 181 harpy eagles. We found that livestock abundance and livestock husbandry were the best positive predictors of levels of self-reported livestock predation by harpy eagles. Domestic livestock reported to be killed by harpy eagles (192) were mainly chickens (47.9%), followed by goats (22.4%), pigs (18.2%) and sheep (8.3%), with pets representing only ~3% of kills. Few harpy eagle killings were related to livestock predation, which accounted for less than 20% of all eagles killed. Instead, the main reason for killing harpy eagles was simple curiosity, and many interviewees reported later regretting their acts. Regarding intent to kill harpy eagles in the future, interviewees’ perceptions of the threat posed to livestock and humans by eagles, and the subjective norm, were unrelated to intent to kill harpy eagles further. The single most important factor in predicting intent to kill harpy eagles was whether the interviewee had suffered livestock predation by eagles in the past. Additionally, the intention to kill eagles was negatively associated with landholding size. Most of our interviewees were relatively large landowners, but they are typically outnumbered by smallholders who are more likely to persecute harpy eagles. Consequently, education, compensation and tourism activities should be directed to smallholders to mitigate unnecessary persecution and mortality of harpy eagles.

Lung cancer (LC) is the leading cause of cancer deaths worldwide, being non-small lung cancer (NSCLC) sub-types the most prevalent. Since most LC cases are only detected during the last stage of the disease the high mortality rate is strongly associated with metastases. For this reason, the migratory and invasive capacity of these cancer cells as well as the mechanisms involved have long been studied to uncover novel strategies to prevent metastases and improve the patients' prognosis. This narrative review provides an overview of the main in vitro migration and invasion assays employed in NSCLC research. While several methods have been developed, experiments using conventional cell culture models prevailed, specifically the wound-healing and the transwell migration and invasion assays. Moreover, it is provided herewith a summary of the available information concerning chemical contaminants that may promote the migratory/invasive properties of NSCLC cells in vitro, shedding some light on possible LC risk factors. Most of the reported agents with pro-migration/invasion effects derive from cigarette smoking [e.g., Benzo(a)pyrene and cadmium] and air pollution. This review further presents several studies in which different dietary/plant-derived compounds demonstrated to impair migration/invasion processes in NSCLC cells in vitro. These chemicals that have been proposed as anti-migratory consisted mainly of natural bioactive substances, including polyphenols non-flavonoids, flavonoids, bibenzyls, terpenes, alkaloids, and steroids. Some of these compounds may eventually represent novel therapeutic strategies to be considered in the future to prevent metastasis formation in LC, which highlights the need for additional in vitro methodologies that more closely resemble the in vivo tumor microenvironment and cancer cell interactions. These studies along with adequate in vivo models should be further explored as proof of concept for the most promising compounds.

Observation techniques of high-energy gamma rays using air showers have remarkably progressed via the Tibet AS$\gamma$, HAWC, and LHAASO experiments. These observations have significantly contributed to gamma-ray astronomy in the northern sky's sub-Peta electron volts (PeV) region. Moreover, in the southern sky, the ALPACA experiment is underway at 4,740\,m altitude on the Chacaltaya plateau in Bolivia. This experiment estimates the gamma-ray flux from the difference between the number of on-source and off-source events by real data, utilizing the gamma-ray detection efficiency calculated through Monte Carlo simulations, which in turn depends on the hadronic interaction models. Even though the number of cosmic-ray background events can be experimentally estimated, this model dependence affects the estimation of gamma-ray detection efficiency. However, previous reports have assumed that the model dependence is negligible and have not included it in the error of gamma-ray flux estimation. Using ALPAQUITA, the prototype experiment of ALPACA, we quantitatively evaluated the model dependence on hadronic interaction models for the first time. We evaluate the model dependence on hadronic interactions as less than 3.6\,\% in the typical gamma-ray flux estimation performed by ALPAQUITA; this is negligible compared with other uncertainties such as energy scale uncertainty in the energy range from 6 to 300 TeV, which is dominated by the Monte Carlo statistics. This upper limit of 3.6\,\% model dependence is expected to apply to ALPACA.

The radio galaxy M87 is the central dominant galaxy of the Virgo Cluster. Very high-energy (VHE, ≳0.1 TeV) emission from M87 has been detected by imaging air Cherenkov telescopes. Recently, marginal evidence for VHE long-term emission has also been observed by the High Altitude Water Cherenkov Observatory, a gamma-ray and cosmic-ray detector array located in Puebla, Mexico. The mechanism that produces VHE emission in M87 remains unclear. This emission originates in its prominent jet, which has been spatially resolved from radio to X-rays. In this paper, we construct a spectral energy distribution from radio to gamma rays that is representative of the nonflaring activity of the source, and in order to explain the observed emission, we fit it with a lepto-hadronic emission model. We found that this model is able to explain nonflaring VHE emission of M87 as well as an orphan flare reported in 2005.