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Hassaam S Choudhry,1 Usman Toor,1 Alexandra J Sanchez,1 Shahzad I Mian2 1Rutgers New Jersey Medical School, Newark, NJ, USA; 2University of Michigan Medical School, Ann Arbor, MI, USACorrespondence: Shahzad I Mian, University of Michigan Medical School, 1000 Wall Street, University of Michigan Medical School, Ann Arbor, MI, 48105, USA, Email smian@umich.eduPurpose: In the past few years, there has been remarkable progress in accessibility of open-source artificial intelligence (AI) image generators, developed to help humans understand how AI sees our world. Here, we characterize perception of racial and sex diversity in ophthalmology by AI.Methods: OpenAI’s open-source DALL E-2 AI was used for image generation of ophthalmologists with queries that all included “American” and “portrait photo”. Factors used for queries contained categories of following: “Positive Characteristic”, “Negative Characteristic”, “Finances”, “Region”, “Experience”, “Academic Rank”, and “Subspecialty”. The first 40 faces for each search were categorized on the basis of race and sex by two independent reviewers. If race or sex was not agreed upon, a third reviewer independently provided a classification, or if still indeterminate, the image was labeled as such. Images that did not adequately show facial features were excluded from categorization.Results: A total of 1560 images were included in the analysis. Control search queries specifying solely ophthalmologist sex and/or race outputted (100%) accurate images validating the tool. The query “American ophthalmologist, portrait photo” portrayed the majority of ophthalmologists as White (75%) and male (77.5%). Young/inexperienced/amateur ophthalmologists were perceived to have greater non-White racial diversity (27.5%) and female representation (28.3%) relative to old/experienced/mature ophthalmologists (23.3% non-White and 18.3% female). Ophthalmology department chairs (25%) had slightly more racial diversity compared to residents (22.5%), but residents had greater female representation (30%) compared to chairs (15%).Conclusion: Our results suggest the DALL E-2 AI may perceive a trend of increasing racial and sex diversity in younger, newer ophthalmologists compared to more senior ophthalmologists. Future investigations should attempt to validate how AI may be used as a tool to evaluate ophthalmology’s progress towards becoming more inclusive of increasingly diverse ophthalmologists.Keywords: artificial intelligence, race, sex

Promoting endogenous neurogenesis for brain repair is emerging as a promising strategy to mitigate the functional impairments associated with various neurological disorders characterized by neuronal death. Diterpenes featuring tigliane, ingenane, jatrophane and lathyrane skeletons, frequently found in Euphorbia plant species, are known protein kinase C (PKC) activators and exhibit a wide variety of pharmacological properties, including the stimulation of neurogenesis. Microbial transformation of these diterpenes represents a green and sustainable methodology that offers a hitherto little explored approach to obtaining novel derivatives and exploring structure-activity relationships. In the present study, we report the biotransformation of euphoboetirane A (4) and epoxyboetirane A (5), two lathyrane diterpenoids isolated from Euphorbia boetica, by Mucor circinelloides MC NRRL3631. Our findings revealed the production of nine biotransformation products (6-14), including jatrophane derivatives originated through an unprecedented rearrangement from the parent lathyranes. The chemical structures and absolute configurations of the new compounds were elucidated through comprehensive analysis using NMR and ECD spectroscopy, as well as MS. The study evaluated how principal metabolites and their derivatives affect TGFα and NRG1 release, as well as their potential to promote proliferation or differentiation in cultures of NSC isolated from the SVZ of adult mice. In order to shed some light on the mechanisms underlying the ability of 12 as a neurogenic compound, the interactions of selected compounds with PKC δ-C1B were analyzed through molecular docking and molecular dynamics. Based on these, it clearly appears that the ability of compound 12 to form both acceptor and donor hydrogen bonds with certain amino acid residues in the enzyme pocket leads to a higher affinity compound-PKC complex, which correlates with the observed biological activity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Premyrsinane-type diterpenoids have been considered to originate from the cyclization of a suitable 5,6- or 6,17-epoxylathyrane precursor. Their biological activities have not been sufficiently explored to date, so the development of synthetic or microbial approaches for the preparation of new derivatives would be desirable. Epoxyboetirane A ( 4 ) is an 6,17-epoxylathyrane isolated from Euphorbia boetica in a large enough amount to be used in semi-synthesis. Transannular cyclization of 4 mediated by Cp 2 Ti III Cl afforded premyrsinane 5 in good yield as an only diasteroisomer. To enhance the structural diversity of premyrsinanes so their potential use in neurodegenerative disorders could be explored, compound 5 was biotransformed by Mucor circinelloides NRRL3631 to give rise to hydroxylated derivatives at non-activated carbons ( 6 - 7 ), all of which were reported here for the first time. The structures and absolute configurations of all compounds were determined through extensive NMR and HRESIMS spectroscopic studies.

Lathyrane-type diterpenes have a wide range of biological activities. Among them, euphoboetirane A ( 1 ) exerts neurogenesis-promoting activity. In order to increase the structural diversity of this type of lathyrane and explore its potential use in neurodegenerative disorders, the biotransformation of 1 by Streptomyces puniceus BC-5GB.11 has been investigated. The strain BC-5GB.11, isolated from surface sediments collected from the intertidal zone of the inner Bay of Cadiz, was identified as Streptomyces puniceus , as determined by phylogenetic analysis using 16S rRNA gene sequence. Biotransformation of 1 by BC-5GB.11 afforded five products ( 3 - 7 ), all of which were reported here for the first time. The main biotransformation pathways involved regioselective oxidation at non-activated carbons ( 3 - 5 ) and isomerization of the ∆ 12,13 double bond ( 6 ). In addition, a cyclopropane-rearranged compound was found ( 7 ). The structures of all compounds were elucidated on the basis of extensive NMR and HRESIMS spectroscopic studies.

Codification of DNA Encoded Libraries (DELs) is critical for successful ligand identification of molecules that bind a protein of interest (POI). There are different encoding strategies that permit, for instance, the customization of a DEL for testing single or dual pharmacophores (single strand DNA) or for producing and screening large diversity libraries of small molecules (double strand DNA). Both approaches challenges, either from the synthetic and encoding point of view, or from the selection methodology to be utilized for the screening. The Head-Piece contains the DNA sequence that is attached to a chemical compound, allowing the encoding of each molecule with a unique DNA tag. Designing the Head-Piece for a DNA-encoded library involves careful consideration of several key aspects including DNA barcode identity, sequence length and attachment chemistry. Here we describe a double stranded DNA versatile Head-Piece that can be used for the generation of single or dual pharmacophore libraries, but also shows other advanced DEL functionalities, stability and enlarged encoding capacity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Ferric hexacyanoferrate, Fe 4 [Fe(CN) 6 ] 3 · xH 2 O, known as Prussian blue (PB), has proven its effectiveness as an antidote in cases of accidental poisoning or poisoning caused by radioactive materials such as cesium (Cs) and thallium (Tl); which due to their solubility in water, when absorbed by the human body, cause serious damage to vital organs. The local development of a drug with PB as an active ingredient arises as a response to the civil and military needs established within the Ministry's pharmacy request for national defense. This fact contemplates the circumstances related to public health protection in the nuclear, radiological, biological and chemical (NRBQ) of the emergency institutions in health and national security. In this paper and by using various analytical techniques, the characterization of the locally synthesized PB with pharmaceutical quality has been described, as a first step to predict its behavior in the preparation of a drug that contains it as an active ingredient. The research findings demonstrate that locally synthesized PB is suitable for use in oral dosage forms, enabling the local development of drug formulations incorporating PB, thus being able to potentially become a main resource in the treatment of Cs and Tl poisoning in any accidental or intended of the population. This development opens up the possibility of creating drug formulations that incorporate PB at a local level, making it a potentially significant resource in the treatment of Cs and Tl poisoning. The ability to locally produce and utilize PB in oral dosage forms could be crucial in addressing cases of accidental or intentional exposure within the population. This advancement not only contributes to the scientific understanding of PB but also holds promising implications for practical applications in public health and emergency situations., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This research received financial support from Government of Spain Ministry of Defense., (© 2024 The Authors. Published by Elsevier Ltd.)

Diterpenes from the Euphorbia genus are known for their ability to regulate the protein kinase C (PKC) family, which mediates their ability to promote the proliferation of neural precursor cells (NPCs) or neuroblast differentiation into neurons. In this work, we describe the isolation from E. resinifera Berg latex of fifteen 12-deoxyphorbol esters ( 1 - 15 ). A triester of 12-deoxy-16-hydroxyphorbol ( 4 ) and a 12-deoxyphorbol 13,20-diester ( 13 ) are described here for the first time. Additionally, detailed structural elucidation is provided for compounds 3 , 5 , 6 , 14 and 15 . The absolute configuration for compounds 3 , 4 , 6 , 13 , 14 and 15 was established by the comparison of their theoretical and experimental electronic circular dichroism (ECD) spectra. Access to the above-described collection of 12-deoxyphorbol derivatives, with several substitution patterns and attached acyl moieties, allowed for the study of their fragmentation patterns in the collision-induced dissociation of multiple ions, without precursor ion isolation mass spectra experiments (HRMS E ), which, in turn, revealed a correlation between specific substitution patterns and the fragmentation pathways in their HRMS E spectra. In turn, this allowed for a targeted UHPLC-HRMS E analysis and a biased non-targeted UHPLC-HRMS E analysis of 12-deoxyphorbols in E. resinifera latex which yielded the detection and identification of four additional 12-deoxyphorbols not previously isolated in the initial column fractionation work. One of them, identified as 12-deoxy-16-hydroxyphorbol 20-acetate 13-phenylacetate 16-propionate ( 20 ), has not been described before.

Background or Purpose: His bundle pacing (HBP) is the most physiological form of ventricular pacing. Few prospective studies have analyzed lead localization using imaging techniques and its relationship with electrical parameters and capture patterns. The objective of this study is to examine the correlation between electrical parameters and lead localization using three-dimensional transthoracic echocardiography (3D TTE)., Methods: This single-center, prospective, nonrandomized clinical research study (January 2018 to June 2020) included patients with an indication of permanent pacing, in whom 3D TTE was performed to define lead localization as supravalvular or subvalvular., Results: A total of 92 patients were included: 56.5% of leads were supravalvular, and 43.5% were subvalvular, which resembles previous anatomic descriptions of autopsied hearts of His bundle localization within the triangle of Koch (ToK). R-wave sensing was higher when the His lead was localized subvalvular instead of supravalvular. His lead localization was not associated with HBP threshold or impedance differences, nor with the two different HBP patterns of capture, or with the ability of HBP to correct baseline BBB. The thresholds remained stable during follow-up visits, regardless of His lead localization. Higher R-wave sensing was observed during follow-up than at baseline, mainly in the subvalvular His leads. However, lead impedances in both positions decreased during follow-up., Conclusions: Lead localization in relation to the tricuspid valve did not influence the electrical performance of HBPs. Wide anatomical variations of the His bundle within the ToK explain our findings, reinforcing the idea that the technique for HBP should be fundamentally guided by electrophysiological and not anatomical parameters., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancer is a disease with the highest mortality and morbidity rate worldwide. First-line drugs induce several side effects that drastically reduce the quality of life of people with this disease. Finding molecules to prevent it or generate less aggressiveness or no side effects is significant to counteract this problem. Therefore, this work searched for bioactive compounds of marine macroalgae as an alternative treatment. An 80% ethanol extract of dried Caulerpa sertularioides (CSE) was analyzed by HPLS-MS to identify the chemical components. CSE was utilized through a comparative 2D versus 3D culture model. Cisplatin (Cis) was used as a standard drug. The effects on cell viability, apoptosis, cell cycle, and tumor invasion were evaluated. The IC 50 of CSE for the 2D model was 80.28 μg/mL versus 530 μg/mL for the 3D model after 24 h of treatment exposure. These results confirmed that the 3D model is more resistant to treatments and complex than the 2D model. CSE generated a loss of mitochondrial membrane potential, induced apoptosis by extrinsic and intrinsic pathways, upregulated caspases-3 and -7, and significantly decreased tumor invasion of a 3D SKLU-1 lung adenocarcinoma cell line. CSE generates biochemical and morphological changes in the plasma membrane and causes cell cycle arrest at the S and G2/M phases. These findings conclude that C. sertularioides is a potential candidate for alternative treatment against lung cancer. This work reinforced the use of complex models for drug screening and suggested using CSE's primary component, caulerpin, to determine its effect and mechanism of action on SKLU-1 in the future. A multi-approach with molecular and histological analysis and combination with first-line drugs must be included.

The Neotropical region hosts 4225 freshwater fish species, ranking first among the world's most diverse regions for freshwater fishes. Our NEOTROPICAL FRESHWATER FISHES data set is the first to produce a large-scale Neotropical freshwater fish inventory, covering the entire Neotropical region from Mexico and the Caribbean in the north to the southern limits in Argentina, Paraguay, Chile, and Uruguay. We compiled 185,787 distribution records, with unique georeferenced coordinates, for the 4225 species, represented by occurrence and abundance data. The number of species for the most numerous orders are as follows: Characiformes (1289), Siluriformes (1384), Cichliformes (354), Cyprinodontiformes (245), and Gymnotiformes (135). The most recorded species was the characid Astyanax fasciatus (4696 records). We registered 116,802 distribution records for native species, compared to 1802 distribution records for nonnative species. The main aim of the NEOTROPICAL FRESHWATER FISHES data set was to make these occurrence and abundance data accessible for international researchers to develop ecological and macroecological studies, from local to regional scales, with focal fish species, families, or orders. We anticipate that the NEOTROPICAL FRESHWATER FISHES data set will be valuable for studies on a wide range of ecological processes, such as trophic cascades, fishery pressure, the effects of habitat loss and fragmentation, and the impacts of species invasion and climate change. There are no copyright restrictions on the data, and please cite this data paper when using the data in publications., (© 2022 The Ecological Society of America.)

Environmental heterogeneity is an important driver of ecological communities. Here, we assessed the effects of local and landscape spatial environmental heterogeneity on ant community structure in temperate seminatural upland grasslands of Central Germany. We surveyed 33 grassland sites representing a gradient in elevation and landscape composition. Local environmental heterogeneity was measured in terms of variability of temperature and moisture within and between grasslands sites. Grassland management type (pasture vs. meadows) was additionally included as a local environmental heterogeneity measure. The complexity of habitat types in the surroundings of grassland sites was used as a measure of landscape environmental heterogeneity. As descriptors of ant community structure, we considered species composition in terms of nest density, community evenness, and functional response traits. We found that extensively grazed pastures and within-site heterogeneity in soil moisture at local scale, and a high diversity of land cover types at the landscape scale affected ant species composition by promoting higher nest densities of some species. Ant community evenness was high in wetter grasslands with low within-site variability in soil moisture and surrounded by a less diverse landscape. Fourth-corner models revealed that ant community structure response to environmental heterogeneity was mediated mainly by worker size, colony size, and life history traits related with colony reproduction and foundation. We discuss how within-site local variability in soil moisture and low-intensity grazing promote ant species densities and highlight the role of habitat temperature and humidity affecting community evenness. We hypothesize that a higher diversity of land cover types in a forest-dominated landscape buffers less favorable environmental conditions for ant species establishment and dispersal between grasslands. We conclude that spatial environmental heterogeneity at local and landscape scale plays an important role as deterministic force in filtering ant species and, along with neutral processes (e.g., stochastic colonization), in shaping ant community structure in temperate seminatural upland grasslands., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Previous research on sexual violence suggests that there is a higher likelihood of students from LGBTQ+ community experiencing sexual violence and not reporting it. This study investigates various types of sexual violence experienced by the LGBTQ+ students and the prevalence of reporting it. The study further determines why different types of sexual violence are not being reported. This study uses a LGBTQ+ scholarship survey data conducted in 2019. Using Pearson's chi square analysis, the study investigates the relationship between who experienced various kinds of sexual violence and those who do not report it. The study provides descriptive analysis of reasons for not reporting sexual violence across different types of sexual violence. The results show that there is a statistically significant relationship between those who experienced various kinds of sexual violence and those who do not report it. In addition, the study illustrates mistrust in support services and fear of embarrassment as the major reasons resulting in non-reporting behaviors. In conclusion, the study illustrates high prevalence for various types of sexual violence against LGBTQ+ students as well as high underreporting. Study results have implications for health professionals and institutions to focus efforts in making school environments safe and inclusive for LGBTQ+ students.

The aim of this study was to examine the convergent validity of self-reported diary times for commuting to and from school with device-measured positional data (Global Positioning System; GPS) in Spanish adolescents., Methods: Cross-sectional data were obtained from four Spanish public secondary schools in 2021, comprising 47 adolescents and 141 home-school and school-home trips. Participants self-reported the time they left and arrived at home and school through a commuting diary. They wore a GPS device recording the objective time during three trips (i.e., one home-school trip and two school-home trips). Agreement between commuting diary and GPS data regarding home-school trips and school-home trips was evaluated using Bland-Altman plots., Results: Total commuting time differed by 1 min (95% limits of agreement were 16.1 min and -18.1 min) between subjective and objective measures (adolescents reported 0.8 more minutes in home-school trips and 1 more minute in school-home trips compared to objective data). Passive commuters reported 0.7 more minutes and active commuters reported 1.2 more minutes in the total commuting time compared to objective data., Conclusions: Self-reported commuting diaries may be a useful tool to obtain commuting times of adolescents in epidemiological research or when tools to measure objective times are not feasible.

Purpose: To analyze if perioperative and oncologic outcomes with stenting as a bridge to surgery (SEMS-BS) and interval colectomy performed by acute care surgeons for left-sided occlusive colonic neoplasms (LSCON) are non-inferior to those obtained by colorectal surgeons for non-occlusive tumors of the same location in the full-elective context., Methods: From January 2011 to January 2021, patients with LSCON at University Regional Hospital in Málaga (Spain) were directed to a SEMS-BS strategy with an interval colectomy performed by acute care surgeons and included in the study group (SEMS-BS). The control group was formed with patients from the Colorectal Division elective surgical activity dataset, matching by ASA, stage, location and year of surgery on a ratio 1:2. Stages IV or palliative stenting were excluded. Software SPSS 23.0 was used to analyze perioperative and oncologic (defined by overall -OS- and disease free -DFS-survival) outcomes., Results: SEMS-BS and control group included 56 and 98 patients, respectively. In SEMS-BS group, rates of technical/clinical failure and perforation were 5.35% (3/56), 3.57% (2/56) and 3.57% (2/56). Surgery was performed with a median interval time of 11 days (9-16). No differences between groups were observed in perioperative outcomes (laparoscopic approach, primary anastomosis rate, morbidity or mortality). As well, no statistically significant differences were observed in OS and DFS between groups, both compared globally (OS:p < 0.94; DFS:p < 0.67, respectively) or by stages I-II (OS:p < 0.78; DFS:p < 0.17) and III (OS:p < 0.86; DFS:p < 0.70)., Conclusion: Perioperative and oncologic outcomes of a strategy with SEMS-BS for LSCON are non-inferior to those obtained in the elective setting for non-occlusive neoplasms in the same location. Technical and oncologic safety of interval colectomy performed on a semi-scheduled situation by acute care surgeons is absolutely warranted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Chemical epigenetic manipulation of Botrytis cinerea strain B05.10 with the histone deacetylase inhibitor SAHA led to the isolation of a new cryptic metabolite, botrycinereic acid (22a). This compound was also overproduced by inactivating the stc2 gene, which encodes an unknown sesquiterpene cyclase. Its structure and absolute configuration were determined by extensive spectroscopic NMR and HRESIMS studies, and electronic circular dichroism calculations. Its biosynthesis was studied by feeding 2 H and 13 C isotopically labeled precursors to B. cinerea Δstc2 mutant. A detailed analysis of the labeling and coupling patterns into botrycinereic acid (22a) revealed that this compound derives from l-phenylalanine and l-leucine., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The low rates of active commuting to/from school in Spain, especially by bike, and the wide range of cycling interventions in the literature show that this is a necessary research subject. The aims of this study were: (1) to assess the feasibility of a school-based cycling intervention program for adolescents, (2) to analyse the effectiveness of a school-based cycling intervention program on the rates of cycling and other forms of active commuting to/from school (ACS), and perceived barriers to active commuting in adolescents. A total of 122 adolescents from Granada, Jaén and Valencia (Spain) participated in the study. The cycling intervention group participated in a school-based intervention program to promote cycling to school during Physical Education (PE) sessions in order to analyse the changes in the dependent variables at baseline and follow up of the intervention. Wilcoxon, Signs and McNemar tests were undertaken. The association of the intervention program with commuting behaviour, and perceived barriers to commuting, were analysed by binary logistic regression. There were improvements in knowledge at follow-up and the cycling skill scores were medium-low. The rates of cycling to school and active commuting to/from school did not change, and only the "built environment (walk)" barrier increased in the cycling group at follow-up. School-based interventions may be feasibly effective tools to increase ACS behaviour, but it is necessary to implement a longer period and continue testing further school-based cycling interventions.

Lathyrane diterpenoids are one of the primary types of secondary metabolites present in the genus Euphorbia and one of the largest groups of diterpenes. They are characterized by having a highly oxygenated tricyclic system of 5, 11 and 3 members. These natural products and some synthetic derivatives have shown numerous interesting biological activities with clinical potential against various diseases, such as cytotoxic activity against cancer cell lines, multi-drug resistance reversal, antiviral properties, anti-inflammatory activity and their capability to induce proliferation or differentiation into neurons of neural progenitor cells. The structure of the lathyrane skeleton could be considered privileged because its framework is able to direct functional groups in a well-defined space. The favorable arrangement of these makes interaction possible with more than one target. This review aims to highlight the evidence of lathyranes as privileged structures in medicinal chemistry. Chemical structures of bioactive compounds, the evaluation of biological properties of natural and semisynthetic derivatives, and the exploration of the mechanisms of action as well as target identification and some aspects of their targeted delivery are discussed.

Introduction: Restless legs syndrome (RLS) is a disorder characterised by an irresistible urge to move the legs, usually accompanied by unpleasant sensations. It is more frequent in patients with multiple sclerosis (MS) than in the general population., Objectives: To evaluate the prevalence of RLS, defined according to the 4 essential requirements included in the diagnostic criteria proposed by the International Restless Leg Syndrome Study Group, in a cohort of patients with MS; and to identify potential risk factors and the clinical impact of RLS., Results: The sample included 120 patients with MS, with a mean age of symptom onset of 40 years and an average disease duration of 46 months. The prevalence rate of RLS was 23.3%. MS progression time was significantly shorter in patients with RLS (P=.001). A recent relapse, and symptoms of anxiety, depression, and neuropathic pain were significantly associated with risk of RLS (P=.001, P<.001, P<.001, and P=.001, respectively). In addition, patients with RLS had a greater risk of poor sleep quality, fatigue, daytime sleepiness, and poor quality of life than those without RLS (P=.002, P=.017, P=.013, and P=.009, respectively)., Conclusions: RLS should be considered in the neurological evaluation of patients with MS; early diagnosis and treatment would improve the quality of life of patients with MS presenting RLS., (Copyright © 2019 Sociedad Española de Neurología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: The aim of this work is to present a ready to industrialize low-cost and easy-to-install bleeding detector for use in intraoperative electron radiation therapy (IOERT). The detector works in stand-alone mode and is embedded into a translucent polymethylmethacrylate (PMMA) applicator avoiding any contact with the patient, which represent a novelty compared to previous designs. The use of this detector will prevent dose misadministration during irradiation in the event of accumulation of fluids in the applicator., Methods: The detector is based on capacitive sensor and wireless power-supply electronics. Both sensor and electronics have been embedded in the applicator, so that any contact with the patient would be avoided. Since access to the tumor can be done through different trajectories, the detector has been calibrated for different tilting angles., Results: The result of the calibration provides us with a fit curve that allows the interpolation of the results at any angle. Comparison of estimated fluid height vs real height gives an error of 1 mm for tilting angles less than 10° and 2 mm for tilting angles greater than 15°. This accuracy is better than the one required by clinic., Conclusions: The performance of the bleeding detector was evaluated in situ. No interference was observed between the detector and the beam. In addition, a user-friendly mobile application has been developed to help the surgical team making decisions before and during irradiation. The measurement provided by the mobile application was stable during the irradiation process., (Copyright © 2021 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

In vehicular communications, the increase of the channel load caused by excessive periodical messages (beacons) is an important aspect which must be controlled to ensure the appropriate operation of safety applications and driver-assistance systems. To date, the majority of congestion control solutions involve including additional information in the payload of the messages transmitted, which may jeopardize the appropriate operation of these control solutions when channel conditions are unfavorable, provoking packet losses. This study exploits the advantages of non-cooperative, distributed beaconing allocation, in which vehicles operate independently without requiring any costly road infrastructure. In particular, we formulate the beaconing rate control problem as a Markov Decision Process and solve it using approximate reinforcement learning to carry out optimal actions. Results obtained were compared with other traditional solutions, revealing that our approach, called SSFA, is able to keep a certain fraction of the channel capacity available, which guarantees the delivery of emergency-related notifications with faster convergence than other proposals. Moreover, good performance was obtained in terms of packet delivery and collision ratios., (© 2022. The Author(s).)

Botrytis cinerea has high potential for the production of specialized metabolites. The recent resequencing of the genome of the B05.10 strain using PacBio technology and the resulting update of the Ensembl Fungi (2017) database in the genome sequence have been instrumental in identifying new genes that could be involved in secondary metabolism. Thus, a new sesquiterpene cyclase (STC) coding gene (Bcstc7) has been included in the gene list from this phytopathogenic fungus. We recently constructed the null and complement transformants in STC7 which enabled us to functionally characterize this STC. Deletion of the Bcstc7 gene abolished (+)-4-epi-eremophilenol biosynthesis, and could then be re-established by complementing the null mutant with the Bcstc7 gene. Chemical analysis of the complemented transformant suggests that STC7 is the principal enzyme responsible for the key cyclization step of farnesyl diphosphate (FDP) to (+)-4-epi-eremophil-9-en-11-ols. A thorough analysis of the metabolites produced by two wild-type strains, B05.10 and UCA992, and the complemented mutant compl ΔBcstc7 niaD , revealed the isolation and structural characterization of six 11,12,13-tri-nor-eremophilene derivatives, in addition to a large number of known eremophilen-11-ol derivatives. The structural characterization was carried out by extensive spectroscopic techniques. The biosynthesis of these compounds is explained by a retroaldol reaction or by dehydration and oxidative cleavage of C11-C13 carbons. This is the first time that this interesting family of degraded eremophilenols has been isolated from the phytopathogenous fungus B. cinerea., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Clovane and isocaryolane derivatives have been proven to show several levels of activity against the phytopathogenic fungus Botrytis cinerea . Both classes of sesquiterpenes are reminiscent of biosynthetic intermediates of botrydial, a virulence factor of B. cinerea . Further development of both classes of antifungal agent requires exploration of the structure-activity relationships for the antifungal effects on B. cinerea and phytotoxic effects on a model crop. In this paper, we report on the preparation of a series of alkoxy-clovane and -isocaryolane derivatives, some of them described here for the first time ( 2b , 2d , 2f - 2h , and 4c - 4e ); the evaluation of their antifungal properties against B. cinerea , and their phytotoxic activites on the germination of seeds and the growth of radicles and shoots of Lactuca sativa (lettuce). Both classes of compound show a correlation of antifungal activity with the nature of side chains, with the best activity against B. cinerea for 2d , 2h , 4c and 4d . In general terms, while 2-alkoxyclovan-9-ols ( 2a - 2e ) exert a general phytotoxic effect, this is not the case for 2-arylalkoxyclovan-9-ols ( 2f - 2i ) and 8-alkoxyisocaryolan-9-ols ( 4a - 4d ), where stimulating effects would make them suitable candidates for application to plants.

Fish and fish products are considered a fundamental part of the human diet due to their high nutritional value. Food-borne diseases are considered a major public health challenge worldwide due to their incidence, associated mortality, and negative economic repercussions. Food safety is the guarantee that foods will not cause harm to the health of those who consume them, and it is a fundamental property of food quality. Food safety can be at risk of being lost at any stage of the food chain if the food is contaminated by pathogenic microorganisms. Many diverse bacteria are present in the environment and as part of the microbiota of food that can be transmitted to humans during the handling and consumption of food. Plesiomonas shigelloides has been mainly associated with outbreaks of gastrointestinal diseases due to the consumption of fish. This bacterium inhabits the environment and aquatic animals and is associated with the microbiota of fish such as tilapia, a fish of importance in fishing, aquaculture, commercialization, and consumption worldwide. The purpose of this document is to provide, through a bibliographic review of databases (Scopus, Web of Science, and Google Scholar, among others), a general informative perspective on food-borne diseases and, in particular, the consumption of fish and tilapia. Diseases derived from contamination by Plesiomonas shigelloides are included, and control and prevention actions and sanitary regulations for fishery products established in several countries around the world are discussed to promote the safety of foods of aquatic origin intended for human consumption and to protect public health., Competing Interests: The authors declare that they have no conflicts of interest in the development and publication of this document., (Copyright © 2021 Alejandro De Jesús Cortés-Sánchez et al.)

This work reports the first amperometric immunosensor for the simultaneous determination of four fertility-related hormones in saliva: progesterone (P4), luteinizing hormone (LH), estradiol (E2), and prolactin (PRL). The immune platform involves direct competitive (P4 and E2), and sandwich (LH and PRL) assays implemented onto functionalized magnetic microbeads (MBs). The amperometric transduction was performed upon placing the MBs-immunoconjugates onto each of the four working electrodes of the SPCE array (SP4CEs) and applying a detection potential of -0.20 V (vs. Ag pseudo-reference electrode) using the H2O2/hydroquinone (HQ) system. The achieved analytical and operational characteristics of the developed multiplexed immunoplatform showed a sensitivity that allows the determination of these hormones in saliva, and an adequate selectivity to analyse complex clinical samples. The bioplatform was employed for the determination of the set of four hormones in human saliva samples collected from individuals with different hormonal profiles. The results obtained using a conventional potentiostat were compared with those provided employing a novel low-cost custom-designed and field-portable quadruple potentiostat. Similar results were found which also agreed with those obtained by applying ELISA methods for the determination of single hormones.

Physical Education is one of the subjects that arouses the most interest in children. The aim of this study is to find out the opinion that primary school students have about the Physical Education class. Drawings from a sample of 62 students from an educational centre in the city of Jaén, aged between six and eight years old, were analysed. The results show that the larger size of the drawings corresponds to the aspects that are to be emphasised. This subject is carried out regularly in the sports pavilion of the centre, making frequent use of materials such as sticks, hoops or balls. Cheerful colours are used, reflecting their enthusiasm for the subject. The smiling facial expression represents the schoolchildren's interest in the subject. The most popular games or sports are basketball and pichi, both of them collective.

Background: The use of a functional electromechanical dynamometer (FEMD) has been proposed as a valid and effective tool to evaluate specific movement patterns. The aim of this study was to determine the reliability of FEMD on swing eccentric hamstring exercise (SEHE) measures in soccer players., Methods: Nineteen federated male soccer players (20.74 ± 4.04 years) performed the SEHE at three different isokinetic velocities (20-40-60 cm/s). These evaluations were conducted in four sessions, two for familiarization and two for registration. The average and maximum load (N) of the three isokinetic velocities was calculated from the values obtained from the FEMD (Dynasystem ® , Bangalore)., Results: The main results of this research showed that the reliability was high for the average load in the condition of 40 cm/s, presenting the highest ICC value (0.94). For maximum load, reliability was high in the condition of 20 cm/s. The manifestation of the most reliable load was the maximum load (ICC = 0.91-0.87)., Conclusions: FEMD (Dynasystem ® , Bangalore) is a reliable device to evaluate the eccentric strength of the hamstring muscles in soccer players., Competing Interests: The authors declare that they have no competing interests., (© 2021 Sánchez-Sánchez et al.)

A complete contextual marketing platform including an indoor positioning system (IPS) for smartphones is proposed and evaluated to later be deployed in large infrastructures, such as malls. To this end, we design and implement a novel methodology based on location-as-a-service (LAAS), comprising all the required phases of IPS generation: mall digital map creation, the tools/procedures for offline calibration fingerprint acquisition, the location algorithm, the smartphone app acquiring the fingerprint data, and a validation procedure. To select an appropriate fingerprint location algorithm, a comparison among K-nearest neighbors (KNN), support vector machine (SVM), and Freeloc is accomplished by employing a set of different smartphones in two malls and assessing different occupancy levels. We demonstrate that our solution can be quickly deployed at shop level accuracy in any new location, resulting in a robust and scalable proposal.

A small library of phorbol 12,13-diesters bearing low lipophilicity ester chains was prepared as potential neurogenic agents in the adult brain. They were also used in a targeted UHPLC-HRMS screening of the latex of Euphorbia resinifera . Two new 12-deoxy-16-hydroxyphorbol 13,16-diesters were isolated, and their structures were deduced using two-dimensional NMR spectroscopy and NOE experiments. The ability of natural and synthetic compounds to stimulate transforming growth factor alpha (TFGα) release, to increase neural progenitor cell proliferation, and to stimulate neurogenesis was evaluated. All compounds that facilitated TGFα release promoted neural progenitor cell proliferation. The presence of two acyloxy moieties on the tigliane skeleton led to higher levels of activity, which decreased when a free hydroxyl group was at C-12. Remarkably, the compound bearing isobutyryloxy groups was the most potent on the TGFα assay and at inducing neural progenitor cell proliferation in vitro , also leading to enhanced neurogenesis in vivo when administered intranasally to mice.

Hippocampal neurogenesis has widely been linked to memory and learning performance. New neurons generated from neural stem cells (NSC) within the dentate gyrus of the hippocampus (DG) integrate in hippocampal circuitry participating in memory tasks. Several neurological and neuropsychiatric disorders show cognitive impairment together with a reduction in DG neurogenesis. Growth factors secreted within the DG promote neurogenesis. Protein kinases of the protein kinase C (PKC) family facilitate the release of several of these growth factors, highlighting the role of PKC isozymes as key target molecules for the development of drugs that induce hippocampal neurogenesis. PKC activating diterpenes have been shown to facilitate NSC proliferation in neurogenic niches when injected intracerebroventricularly. We show in here that long-term administration of diterpene ER272 promotes neurogenesis in the subventricular zone and in the DG of mice, affecting neuroblasts differentiation and neuronal maturation. A concomitant improvement in learning and spatial memory tasks performance can be observed. Insights into the mechanism of action reveal that this compound facilitates classical PKCα activation and promotes transforming growth factor alpha (TGFα) and, to a lesser extent, neuregulin release. Our results highlight the role of this molecule in the development of pharmacological drugs to treat neurological and neuropsychiatric disorders associated with memory loss and a deficient neurogenesis.

This manuscript describes the rationale and protocol of a school-based randomized controlled trial called "Cycling and Walk to School" (PACO, by its Spanish acronym) that aims to promote cycling to and from school and physical activity (PA) in adolescents. This study will examine the effects of this intervention in cycling and active commuting to and from school (ACS), PA and several ACS-related factors based on self-determination theory (SDT) and a social-ecological model (SEM). A total of 360 adolescents attending six high schools (three experimental and three control) from three Spanish cities will participate in this randomized controlled trial. The intervention (four cycling sessions; 1-2 h per session, one session per week) will be conducted by the research staff; the control group will continue their usual activities. PA levels will be measured by accelerometers, whereas ACS and the other study variables will be self-reported using questionnaires at baseline and post-intervention. The primary outcomes will be: rates of cycling to school, ACS and PA levels. In addition, SDT-related variables and individual, interpersonal, community, and environment variables relevant to ACS will be based on SEM. The findings will provide a comprehensive understanding of the short-term effects of this school-based intervention on cycling to school behaviour, ACS and PA levels in Spanish adolescents.

Mountain ranges generate clouds, precipitation, and perennial streamflow for water supplies, but the role of forest cover in mountain hydrometeorology and cloud formation is not well understood. In the Luquillo Experimental Forest of Puerto Rico, mountains are immersed in clouds nightly, providing a steady precipitation source to support the tropical forest ecosystems and human uses. A severe drought in 2015 and the removal of forest canopy (defoliation) by Hurricane Maria in 2017 created natural experiments to examine interactions between the living forest and hydroclimatic processes. These unprecedented land-based observations over 4.5 y revealed that the orographic cloud system was highly responsive to local land-surface moisture and energy balances moderated by the forest. Cloud layer thickness and immersion frequency on the mountain slope correlated with antecedent rainfall, linking recycled terrestrial moisture to the formation of mountain clouds; and cloud-base altitude rose during drought stress and posthurricane defoliation. Changes in diurnal cycles of temperature and vapor-pressure deficit and an increase in sensible versus latent heat flux quantified local meteorological response to forest disturbances. Temperature and water vapor anomalies along the mountain slope persisted for at least 12 mo posthurricane, showing that understory recovery did not replace intact forest canopy function. In many similar settings around the world, prolonged drought, increasing temperatures, and deforestation could affect orographic cloud precipitation and the humans and ecosystems that depend on it., Competing Interests: The authors declare no competing interest.

The use of aminals in dynamic covalent chemistry is slightly underexplored, probably due to their inherent instability. Here we report the spontaneous [2+2] macrocyclization of tetrakis(aminals). Their unexpected stability and structural modularity, the dynamic nature of the connections and their water tolerance make them appealing systems for future applications as stimulus-responsive materials.

The reaction mechanism of the intramolecular [2 + 2] cycloaddition from a jatrophane precursor to the gaditanane skeleton, an unprecedented 5/6/4/6-fused tetracyclic ring framework recently isolated from Euphorbia spp., was studied using the bond reactivity indices approach. Furthermore, six diterpenoids, including three undescribed jatrophanes isolated from E. gaditana Coss, were described. The structures of these compounds were deduced by a combination of 2D NMR spectroscopy and ECD data analysis., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A protocol for the induction of hairy roots on somatic embryos of rhizoclones from Typha domingensis seedlings grown in hydroponic rhizotron systems was established for the first time. Rhizogenesis was induced through the agrotransformation of somatic embryos in oblong and scutellar states of development using the K599, LBA9402, and A4 strains of Agrobacterium rhizogenes . The transfection to the embryos was performed by cocultivation of rhizoclones on a Murashige and Skoog mineral medium at 50% strength (MS0.5), in the dark, at 28 ± 2 °C for 72 h. In contrast to nontransformed embryos that did not exhibit any root tissue, transformed embryos presented hairy roots that varied in number, length, and density depending on the bacterial strain, and K599 was the most effective strain. After analysis via optical microscopy, the transformed embryos were collected and transferred to fresh culture media supplemented with 400 mg mL -1 cefotaxime and 10 mg L -1 ascorbic acid. The efficiency of transformation and survival of the oblong and scutellar embryos were similar among the three bacterial strains. The results show that agrotransformation of somatic embryos of rhizoclones from T. domingensis is a novel and viable strategy for the generation of genetic transformants of Typha that have potential applications in bioremediation technologies.