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Canonical histone H3 and histone variant H3.3 are posttranslationally modified with the genomic distribution of these marks denoting different features and these modifications may influence transcription. While the majority of posttranslational modifications occur on histone tails, there are defined modifications within the globular domain, such as acetylation of H3K122/H3.3K122. To understand the function of the amino acid H3.3K122 in transcriptional regulation, we attempted to generate H3.3K122A mouse embryonic stem (mES) cells but were unsuccessful. Through multi-omic profiling of mutant cell lines harboring two or three of four H3.3 targeted alleles, we have uncovered that H3.3K122A is neomorphic and results in lethality. This is surprising as prior studies demonstrate H3.3-null mES cells are viable and pluripotent but exhibit a reduced differentiation capacity. Together, these studies have uncovered a novel dependence of a globular domain residue within H3.3 for viability and broadened our understanding of how histone variants contribute to transcription regulation and pluripotency in mES cells., (© 2024. The Author(s).)

Competing Interests: The authors declare that they have no conflicts of interest with the subject matter of this commentary.

Background: Primary angioplasty is the standard procedure for patients with ST-segment elevation myocardial infarction (STEMI). However, myocardial reperfusion results in additional cell damage. Levosimendan, due to its pleiotropic effects, may be a therapeutic alternative to prevent this damage. The objective of this study was to evaluate whether this drug can reduce infarct size in patients with STEMI., Methods: Patients were randomized to receive a 24-h infusion of either levosimendan (0.1 μg/kg/min) or placebo after the primary angioplasty. The main objective was to assess the size of the infarct by cardiac resonance at 30 days and 6 months after the event. Other variables such as left ventricular ejection fraction (LVEF) and adverse ventricular remodeling (AVR) were assessed by speckle-tracking echocardiography and magnetic resonance. Major adverse cardiovascular events (MACE) were also collected., Results: 157 patients were analysed (levosimendan, n = 79; placebo, n = 78). We found that after 6 months, patients treated with levosimendan had a greater reduction in infarct size (13.19% ± 9.5% vs.11.79% ± 9%, p = 0.001), compared with those in the placebo group (13.35% ± 7.1% vs. 13.43% ± 7.8%, p = 0.38). There were no significant differences in MACE between both groups., Conclusions: Levosimendan is a safe and effective therapeutic option for reducing infarct size in patients with STEMI., (© 2024 The Author(s). Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Competing Interests: The author declares no conflict of interest.

One hundred and forty bitches and their offspring (689 puppies) were involved in this study. The influence of different maternal features such as age, breed (brachycephalic/non-brachycephalic), previous births (primiparous/multiparous), health status (complete/incomplete) and litter size over the type of cesarean sections (scheduled/emergency), the neonatal survival, and the incidence of congenital malformations were also examined. Scheduled cesareans were predominant (104/140), of which 90 % were brachycephalic breeds and females were mostly between 2 and 4 years old (54.8 %), multiparous (88.4 %) and with a correct health status (67.3 %). Emergency cesarean sections mainly involved non-brachycephalic breeds (80 %) and were carried out mostly in females under 4 years of age (72.2 %), primiparous (77.7 %), with incomplete health status and a large litter size (47.2 %). Perinatal mortality was notably higher in emergency C-sections (3.25 % and 13.3 %, scheduled and emergency C-sections, respectively); the highest incidence of neonatal mortality was recorded in young females (<2, 2-4 years old), primiparous and with incomplete health status. Congenital anomalies were observed in 4.50 % (31/689) of the puppies, with anasarca (38.71 %) and cleft palate (29.03 %) being the most frequently observed malformations. A higher incidence of congenital malformations was detected in puppies from dams with incomplete sanitary health and from inbreeding cross. Overall, the study provides valuable insights into the complex interplay between maternal characteristics and cesarean outcomes. Appropriate genetic selection, good sanitary health conditions, and the age of the reproducers, are pivotal factors in planning for gestation and improving the survival of neonates., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Using Patient Reported Outcome Measures (PROMs) in clinical settings can improve patient outcomes by enhancing communication between patient and provider. There has been significant improvements in the development of PROMs, their implementation in routine patient clinical care, training physicians and other healthcare providers to interpret the PROMs results to identify any issues reported by the patient, and to use the PROMs results to provide or modify the treatment., Main Body: Despite the increased use of PROMs, the lack of PROM completion by patients is a major concern in the optimal use of PROMs. Studies have shown several reasons why patients do not complete PROMs and one of the reasons is their lack of understanding of the significance of PROMs and their utility in their clinical care. While examining the various strategies that can be used to improve the uptake of PROM completion by patients, educating patients about the use of PROMs has been recommended. There is less evidence on how patients are trained or educated about PROMs. It may also be possible that the patient education strategies are not reported in the publications. This brings up the question of evaluation of the educational strategies used., Conclusion: Our symposium at the 2023 ISOQOL conference brought together a range of experiences and learning around patient-centered PROMs educational activities used in the Netherlands, Canada, and the UK. This commentary is aimed to describe the lay of the land about educational activities around the use of PROMs in clinical care for patients, recognizing the gaps, and posing questions to be considered by the research and clinical community., (© 2024. The Author(s).)

Background: Previous research has suggested that alternative (respiratory) care providers (ACP) may provide affordable, accessible care for sleep-disordered breathing (SDB) that decreases wait-times and improves clinical outcomes. The objective of this study was to compare ACP-led and sleep physician-led care for SDB on patient reported outcome and experiences, with a focus on general and health-related quality of life, sleepiness, and patient satisfaction., Methods: We conducted a secondary analysis of a randomized trial in which participants with severe SDB were assigned to either ACP-led or physician-led management. We created longitudinal linear mixed models to assess the impacts of treatment arm and timepoint on total and domain-level scores of multiple patient-reported outcome measures and patient-reported experience measures., Results: Patients in both treatment arms (ACP-led n = 81; sleep-physician = 75) reported improved outcomes on the Sleep Apnea Quality of Life Index, Health Utilities Index, and Epworth Sleepiness Scale. Patients in each group had similar and clinically meaningful improvements on domains assessing cognition, emotion, and social functioning. The linear mixed models suggested no significant difference between treatment arms on the patient-reported outcomes. However, scores significantly improved over time., Conclusions: Management of SDB using ACPs was comparable to physician-led care, as measured bypatient-reported outcome and experience measures. While loss to follow-up limits our findings, these results provide some support for the use of this novel health service delivery model to improve access to high quality SDB care., Clinical Trial Registration: This is analysis of data from the study registered Clinicaltrials.gov (NCT02191085)., (© 2024. The Author(s).)

Introduction: Improving survival is the objective of intensive care units. Various factors affect long-term outcomes. The objective was to explore survival and the associated factors 1 year after admission to the intensive care unit., Method: This is an observational, descriptive, and analytical study in a retrospective cohort of adults admitted to an intensive care unit at a regional hospital during the first semester of 2022. Records of 218 patients from an anonymized database were analyzed., Results: The average age was 61 years, and the average APACHE II score was 15 points (24% expected mortality). Survival 1 year after admission was 57.8%. Factors associated with 1-year survival in the Cox regression model were age and APACHE II. The univariate analysis showed that the cancer was significantly associated with lethality after 1 year (OR 10.55; 95%CI 1.99-55.76)., Conclusion: One-year survival after intensive care unit decreases by 16.1%. Factors that significantly reduced survival were old age, severity, and oncologic cause at admission.

Extracellular vesicles (EVs) are membrane-enclosed nanoparticles that transport several biomolecules and are involved in important mechanisms and functions related to the pathophysiology of fungal diseases. EVs from Paracoccidioides brasiliensis , the main causative agent of Paracoccidioidomycosis (PCM), modulate the immune response of macrophages. In this study, we assessed the EVs proteome from a virulent P. brasiliensis isolated from granulomatous lesions and compared their immunomodulatory ability with EVs isolated from the fungus before the animal passage (control EVs) when challenging macrophages and dendritic cells (DCs). Proteome showed that virulent EVs have a higher abundance of virulence factors such as GP43, protein 14-3-3, GAPDH, as well as virulence factors never described in PCM, such as aspartyl aminopeptidase and a SidJ analogue compared with control EVs. Virulent extracellular vesicles induced higher expression of TLR4 and Dectin-1 than control EVs in macrophages and dendritic cells (DCs). In opposition, a lower TLR2 expression was induced by virulent EVs. Additionally, virulent EVs induced lower expression of CD80, CD86 and TNF-α, but promoted a higher expression of IL-6 and IL-10, suggesting that EVs isolated from virulent P. brasiliensis -yeast promote a milder DCs and macrophage maturation. Herein, we showed that EVs from virulent fungi stimulated a higher frequency of Th1/Tc1, Th17, and Treg cells, which gives new insights into fungal extracellular vesicles. Taken together, our results suggest that P. brasiliensis utilizes its EVs as virulence bags that manipulate the immune system in its favour, creating a milder immune response and helping with fungal evasion from the immune system.

(1) Background: Cardiac donation after circulatory death (DCD) is an emerging paradigm in organ transplantation. However, this technique is recent and has only been implemented by highly experienced centers. This study compares the characteristics and outcomes of thoraco-abdominal normothermic regional perfusion (TANRP) and static cold-storage DCD and traditional donation after brain death (DBD) cardiac transplants (CT) in a newly stablished transplant program with restricted donor availability. (2) Method: We performed a retrospective, single-center study of all adult patients who underwent a CT between November 2019 and December 2023, with a follow-up conducted until August 2024. Data were retrieved from medical records. A review of the current literature on DCD CT was conducted to provide a broader context for our findings. The primary outcome was survival at 6 months after transplantation. (3) Results: During the study period, 76 adults (median age 56 years [IQR: 50-63 years]) underwent CT, and 12 (16%) were DCD donors. DCD donors had a similar age (46 vs. 47 years, p = 0.727), were mostly male (92%), and one patient had left ventricular dysfunction during the intraoperative DCD process. There were no significant differences in recipients' characteristics. Survival was similar in the DCD group compared to DBD at 6 months (100 vs. 94%) and 12 months post-CT survival (92% vs. 94%), p = 0.82. There was no primary graft dysfunction in the DCD group (9% in DBD, p = 0.581). The median total hospital stay was longer in the DCD group (46 vs. 21 days, p = 0.021). An increase of 150% in transplantation activity due to DCD was estimated. (4) Conclusions: In a new CT program that utilized older donors and included recipients with similar illnesses and comorbidities, comparable outcomes between DCD and DBD hearts were observed. DCD was rapidly incorporated into the transplant activity, demonstrating an expedited learning curve and significantly increasing the availability of donor hearts.

More than 3550 species of mosquitoes are known worldwide, and only a fraction is involved in the transmission of arboviruses. Mosquitoes in sylvatic and semi-sylvatic habitats may rapidly adapt to urban parks and metropolitan environments, increasing human contact. Many of these mosquitoes have been found naturally infected with arboviruses from the Alphaviridae , Flaviviridae , and Bunyaviridae families, with many being the cause of medically important diseases. However, there is a gap in knowledge about the vector status of newly invasive species and their potential threat to human and domestic animal populations. Due to their rapid distribution, adaptation to urban environments, and anthropophilic habits, some neglected mosquito species may deserve more attention regarding their role as secondary vectors. Taking these factors into account, we focus here on Aedes ( Ochlerotatus ) scapularis (Rondani), Aedes japonicus japonicus (Theobald), and Aedes ( Fredwardsius ) vittatus (Bigot) as species that have the potential to become important disease vectors. We further discuss the importance of these neglected mosquitoes and how factors such as urbanization, climate change, and globalization profoundly alter the dynamics of disease transmission and may increase the participation of neglected species in propagating diseases.

The forest industry produces several low-value by-products, such as bark, sawdust, limbs, and leaves, that are not ultimately disposed of and remain in the forests and sawmill facilities. Among these by-products are leaves, which contain not only cellulose fibers and lignin but also essential oils such as terpenes. These are biosynthesized in a similar way as cis-1,4-polyisoprene. In this context, this work evaluates the use of screened and unscreened dried Eucalyptus nitens leaves in natural rubber. Among the most relevant results of this work is a significant increase in mechanical properties, such as tensile strength and elongation at break, reaching values of 9.45 MPa and 649% of tensile strength and elongation at break, respectively, for a sample of natural rubber containing sieved dried leaves of Eucalyptus nitens. In addition, it is observed that the content of this vegetable filler allows for inhibiting the antibacterial effect of vulcanized rubber against several bacteria, such as Bacillus subtilis, Staphylococcus aureus, Escherichia coli K 12, Escherichia coli FT 17 and Pseudomonas fluorescens. These results are promising because they not only add value to a by-product of the forestry industry, improving the mechanical properties of natural rubber from a sustainable approach but also increase the affinity of rubber with bacterial microorganisms that may play a role in certain ecosystems.

Postoperative delirium (POD) is frequent in older adults and is associated with adverse cognitive and functional outcomes. In the last several decades, there has been an increased interest in exploring tools that easily allow the early recognition of patients at risk of developing POD. The electroencephalogram (EEG) is a widely available tool used to understand delirium pathophysiology, and its use in the perioperative setting has grown exponentially, particularly to predict and detect POD. We performed a systematic review to investigate the use of EEG in the pre-, intra-, and postoperative settings. We identified 371 studies, and 56 met the inclusion criteria. A range of techniques was used to obtain EEG data, from limited 1-4 channel setups to complex 256-channel systems. Power spectra were often measured preoperatively, yet the outcomes were inconsistent. During surgery, the emphasis was primarily on burst suppression (BS) metrics and power spectra, with a link between the frequency and timing of BS, and POD. The EEG patterns observed in POD aligned with those noted in delirium in different contexts, suggesting a reduction in EEG activity. Further research is required to investigate preoperative EEG indicators that may predict susceptibility to delirium., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 International Anesthesia Research Society.)

Amyloidosis are a group of diseases in which soluble proteins aggregate and deposit in fibrillar conformation extracellularly in tissues. The effectiveness of therapeutic strategies depends on the specific protein involved, being crucial to accurately determine its nature. Moreover, following the diagnosis, the search for the mutation within relatives allows the clinical advice. Here we report the precise diagnosis and explored the possible reasons of the structural pathogenicity for a renal amyloidosis related to a fibrinogen Aα-chain variant. Whole-exome sequencing and GATK calling pipeline were leveraged to characterize the protein variant present in a patient with kidney failure. Bioinformatics strategies were applied to suggest potential explanations of the variants aggregation. Our pipeline allowed the identification of a single-point variant of fibrinogen Aα-chain, which opened the possibility of curative transplantation. In silico structural analysis suggested that the pathogenicity of the variant may be attributed to a heightened susceptibility to yield a peptide prone to deposit as an oligomer with a β-sheet structure. Exploiting the comprehensive coverage of whole-genome sequencing, we managed to fill a vacant stage in the diagnosis of hereditary amyloidosis and to stimulate the advancement in biomedicine., (© 2024 Wiley Periodicals LLC.)

Acute coronary syndrome (ACS) is a serious medical condition caused by cardiac muscle ischemia, which can lead to myocardial injury or necrosis. EKG is a critical diagnostic tool for patients with suspected ACS, as it can determine the vascular territory and guide therapy. However, there are various non-cardiac causes of EKG changes that mimic ACS and can lead to misdiagnosis and inappropriate management. We present the case of a 57-year-old lady with an extensive past medical history of coronary artery disease (CAD) who presented to our institution unresponsive and pulseless secondary to a perforated viscus and was found to have ST-segment elevations in inferior leads on the EKG., Competing Interests: Conflict of interest: There is no conflict of interest., (© 2024 Greater Baltimore Medical Center.)

Background: Laboratory test overuse in hospitals is a form of healthcare waste that also harms patients. Developing and evaluating interventions to reduce this form of healthcare waste is critical. We detail the protocol for our study which aims to implement and evaluate the impact of an evidence-based, multicomponent intervention bundle on repetitive use of routine laboratory testing in hospitalized medical patients across adult hospitals in the province of British Columbia, Canada., Methods: We have designed a stepped-wedge cluster randomized trial to assess the impact of a multicomponent intervention bundle across 16 hospitals in the province of British Columbia in Canada. We will use the Knowledge to Action cycle to guide implementation and the RE-AIM framework to guide evaluation of the intervention bundle. The primary outcome will be the number of routine laboratory tests ordered per patient-day in the intervention versus control periods. Secondary outcome measures will assess implementation fidelity, number of all common laboratory tests used, impact on healthcare costs, and safety outcomes. The study will include patients admitted to adult medical wards (internal medicine or family medicine) and healthcare providers working in these wards within the participating hospitals. After a baseline period of 24 weeks, we will conduct a 16-week pilot at one hospital site. A new cluster (containing approximately 2-3 hospitals) will receive the intervention every 12 weeks. We will evaluate the sustainability of implementation at 24 weeks post implementation of the final cluster. Using intention to treat, we will use generalized linear mixed models for analysis to evaluate the impact of the intervention on outcomes., Discussion: The study builds upon a multicomponent intervention bundle that has previously demonstrated effectiveness. The elements of the intervention bundle are easily adaptable to other settings, facilitating future adoption in wider contexts. The study outputs are expected to have a positive impact as they will reduce usage of repetitive laboratory tests and provide empirically supported measures and tools for accomplishing this work., Trial Registration: This study was prospectively registered on April 8, 2024, via ClinicalTrials.gov Protocols Registration and Results System (NCT06359587). https://classic., Clinicaltrials: gov/ct2/show/NCT06359587?term=NCT06359587&recrs=ab&draw=2&rank=1., (© 2024. The Author(s).)

Introduction: This was a multicenter, prospective, longitudinal, observational study involving eight Spanish tertiary hospitals to determine the interobserver reliability of an uveitis disease activity index, (UVEDAI) and assess its sensitivity to change in patients with receiving pharmacologic treatment., Methods: Patients aged ≥ 18 years diagnosed with active noninfectious uveitis were included. A complete baseline assessment was performed by two ophthalmologists who determined ocular inflammatory activity using the UVEDAI index independently of each other. The principal ophthalmologist made a new visit at 4 weeks to determine the change in inflammatory activity. The interobserver reliability analysis was performed by calculating the intraclass correlation coefficient (ICC), with the values of the variables and the UVEDAI obtained by both ophthalmologists in the more active eye at the baseline visit. Sensitivity to change in the UVEDAI index was assessed at 4 weeks from the start of pharmacologic treatment by determining the clinically relevant change, defined as a change in UVEDAI of ≥ 0.8 points over baseline. The mean change between both measures was compared using the repeated-measures t-test., Results: A total of 111 patients were included. In the interobserver reliability analysis, the ICC for the UVEDAI value was 0.9, and, when compared with the mean UVEDAI values obtained by the ophthalmologists, no statistically significant differences were found (p value > 0.05). As for the sensitivity to change in UVEDAI, statistically significant differences (p value = 0.00) were found for the mean values of the index compared with baseline. In all cases, the index value decreased by > 1 point at the 4-week visit., Conclusions: The interobserver reliability of the UVEDAI was high in the total sample. Furthermore, the index was sensitive in determining the change in inflammatory activity after treatment. We believe that UVEDAI is a disease activity index that enables objective comparison of results in clinical practice and trials., (© 2024. The Author(s).)

Objective: The objective of this study was to compare the efficacy of Biosilicate and Duraphat in the treatment of dentin hypersensitivity (DH)., Methods and Materials: This clinical trial was conducted with young adults presenting DH. A visual analogue scale (VAS) was used to assess the level of pain, using volatile and tactile tests. Forty participants presenting two teeth with DH were included, and these teeth were divided into two groups according to the treatment: Biosilicate or Duraphat. Each product was randomly applied on one tooth per participant once a week for 4 weeks and evaluated every 15 days for 60 days after the last application., Results: The mean and standard deviation (SD) of VAS values for the initial volatile sensitivity evaluation were 6.18 (1.99) and 6.08 (1.98) for the Biosilicate and Duraphat groups, respectively, and at the fourth week 0.48 (1.5) and 0.83 (1.58). After 60 days, the volatile sensitivity showed the following values: 0.63 (1.19) for Biosilicate and 1.03 (1.07) for Duraphat. The intragroup comparison showed a significant reduction of mean VAS values for DH-related pain assessed by volatile testing for both groups (p<0.001), and the assessment at the 60-day follow-up showed mean values statistically similar to those obtained at the end of treatment. Initial tactile sensitivity observed was 1.48 (2.39) for the Biosilicate and 1.4 (2.2) for the Duraphat group and at the 60-day follow-up 0.23 (0.73) and 0.15 (0.36), respectively, with significant statistical difference (p<0.002). When the reduction in tactile and volatile sensitivities between both groups was compared, no statistically significant difference was observed., Conclusion: This study indicated that both products were able to promote an important reduction in dentin hypersensitivity with similar results within a 60-day follow-up., (©Operative Dentistry, 2024.)

Purpose: Shear-wave elastography (SWE) provides quantitative and absolute metrics for analyzing the elasticity of soft tissues. Despite the anterior scalene muscle (AS) is a key structure in patients with neck pain and nerve compressive syndromes, the majority of SWE studies only included asymptomatic subjects. This study aimed to analyze the Young's modulus and shear wave speed test-retest reliability in a sample of patients with neck pain symptoms to characterize the AS stiffness., Methods: A diagnostic accuracy study acquiring a set of ultrasound images at C7 level in 42 patients with mechanical neck pain by one experienced examiner. After blinding the participants' identity, trial and side, the Young's modulus and shear wave velocity were measured by an independent experienced rater in randomized order. Intra-class correlation coefficients (ICC), standard error of measurement (SEM), minimal detectable changes (MDC) and coefficient of variation (CV%) were calculated., Results: The sample reported moderate pain intensity (5.9/10 points) and disability (17.38/100 points). AS stiffness metrics assessed showed no significant differences between males and females, left and right side nor painful and non-painful side. (all, p > 0.05). Intra-examiner reliability was excellent for calculating the Young's modulus for shear wave speed (ICC > 0.90)., Conclusion: The results support the use of this procedure for assessing the AS stiffness in populations with mechanical neck pain as excellent reliability estimates were obtained. However, future research should analyze case-control differences and the association between SWE metrics with clinical severity indicators., 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 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background: Diagnosing genetic disorders requires extensive manual curation and interpretation of candidate variants, a labor-intensive task even for trained geneticists. Although artificial intelligence (AI) shows promise in aiding these diagnoses, existing AI tools have only achieved moderate success for primary diagnosis., Methods: AI-MARRVEL (AIM) uses a random-forest machine-learning classifier trained on over 3.5 million variants from thousands of diagnosed cases. AIM additionally incorporates expert-engineered features into training to recapitulate the intricate decision-making processes in molecular diagnosis. The online version of AIM is available at https://ai.marrvel.org. To evaluate AIM, we benchmarked it with diagnosed patients from three independent cohorts., Results: AIM improved the rate of accurate genetic diagnosis, doubling the number of solved cases as compared with benchmarked methods, across three distinct real-world cohorts. To better identify diagnosable cases from the unsolved pools accumulated over time, we designed a confidence metric on which AIM achieved a precision rate of 98% and identified 57% of diagnosable cases out of a collection of 871 cases. Furthermore, AIM's performance improved after being fine-tuned for targeted settings including recessive disorders and trio analysis. Finally, AIM demonstrated potential for novel disease gene discovery by correctly predicting two newly reported disease genes from the Undiagnosed Diseases Network., Conclusions: AIM achieved superior accuracy compared with existing methods for genetic diagnosis. We anticipate that this tool may aid in primary diagnosis, reanalysis of unsolved cases, and the discovery of novel disease genes. (Funded by the NIH Common Fund and others.).

Pesticides are indispensable in agriculture and have become ubiquitous in aquatic environments. Pesticides in natural environments can cause many negative impacts on aquatic species, ranging from mortality to sub-lethal physiological and behavioural changes. The complex sub-lethal impacts of pesticides are routinely tested on model species, with zebrafish (Danio rerio) being regularly used as a behavioural model. Although behavioural ecotoxicology research using zebrafish is increasing rapidly, we lack quantitative evidence to support which pesticides have been tested and how study designs are carried out. This shortcoming not only limits the deliberate planning for future primary studies to fill the knowledge gaps but also hinders evidence synthesis. To provide quantitative evidence of what pesticides are currently studied and what study designs are used, we combined a systematic evidence map approach and bibliometric analysis. This novel method has been coined research weaving and allows us to elicit gaps and clusters in our evidence base, whilst showing connections between authors and institutions. The methodology can be summarised in five primary steps: literature searching, screening, extraction, data analysis and bibliometric analysis. We identified four areas where research on the sub-lethal effects of pesticide exposure on zebrafish is lacking. First, some widely used pesticides, such as neonicotinoids, are understudied. Second, most studies do not report important elements of the study design, namely the sex and the life-stage of the zebrafish. Third, some behaviours, such as impacts of pesticide exposure on zebrafish cognition, are underexplored. And last, we revealed through the bibliometric analysis that most of the research is conducted in developed countries and there is limited cross country co-authorships. Upon identifying these gaps, we offer solutions for each limitation, emphasizing the importance of diverse global research output and cross-country co-authorships. Our systematic evidence map and bibliometric analysis provide valuable insights for helping to guide future research, which can be used to help support evidence-based policy decisions., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Shinichi Nakagawa reports financial support was provided by University of New South Wales. Malgorzata Lagisz reports a relationship with University of New South Wales that includes: funding grants. If there are other authors, they 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.)

Ruthenium(II) complexes containing diimine ligands have contributed to the development of agents for photoactivated chemotherapy. Several approaches have been used to obtain photolabile Ru(II) complexes. The two most explored have been the use of monodentate ligands and the incorporation of steric effects between the bidentate ligands and the Ru(II). However, the introduction of electronic effects in the ligands has been less explored. Herein, we report a systematic experimental, theoretical, and photocytotoxicity study of a novel series of Ru(II) complexes Ru1 - Ru5 of general formula [Ru(phen) 2 (N ∧ N')] 2+ , where N ∧ N' are different minimal strained ligands based on the 1-aryl-4-benzothiazolyl-1,2,3-triazole (BTAT) scaffold, being CH 3 ( Ru1 ), F ( Ru2 ), CF 3 ( Ru3 ), NO 2 ( Ru4 ), and N(CH 3 ) 2 ( Ru5 ) substituents in the R4 of the phenyl ring. The complexes are stable in solution in the dark, but upon irradiation in water with blue light (λ ex = 465 nm, 4 mW/cm 2 ) photoejection of the ligand BTAT was observed by HPLC-MS spectrometry and UV-vis spectroscopy, with t 1/2 ranging from 4.5 to 14.15 min depending of the electronic properties of the corresponding BTAT, being Ru4 the less photolabile (the one containing the more electron withdrawing substituent, NO 2 ). The properties of the ground state singlet and excited state triplet of Ru1-Ru5 have been explored using density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. A mechanism for the photoejection of the BTAT ligand from the Ru complexes, in H 2 O, is proposed. Phototoxicity studies in A375 and HeLa human cancer cell lines showed that the new Ru BTAT complexes were strongly phototoxic. An enhancement of the emission intensity of HeLa cells treated with Ru5 was observed in response to increasing doses of light due to the photoejection of the BTAT ligand. These studies suggest that BTAT could serve as a photocleavable protecting group for the cytotoxic bis-aqua ruthenium warhead [Ru(phen) 2 (OH 2 ) 2 ] 2+ .

Neurodevelopmental disorders are characterized by complex phenotypes that often result from concomitant dysregulation of cell proliferation, differentiation, or other crucial developmental processes. Here, we present a protocol to quantify differentiation of progenitor populations during early stages of neurogenesis in induced pluripotent stem cell (iPSC)-derived cerebral organoids. We describe steps for organoid differentiation and maturation, sample preparation, immunofluorescence, and imaging and analysis using epifluorescence microscopy. This protocol can be used to compare cerebral organoids from control and patient-derived iPSCs. For complete details on the use and execution of this protocol, please refer to Rakotomamonjy et al. (2023). 1 ., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The World Health Organization stresses the need for tailored COVID-19 models of vaccination to meet the needs of diverse populations and ultimately reach high rates of vaccination. However, little evidence exists on how COVID-19 models of vaccination operated in the novel context of the pandemic, how vulnerable populations, such as refugees, experience COVID-19 vaccination systems in high-income countries, and what lessons may be learned from vaccination efforts with vulnerable populations. To address this gap, this study explored COVID-19 vaccine delivery models available to newcomer refugees and immigrants, and refugee experiences across different COVID-19 vaccine delivery models in Calgary, Canada, and surrounding area in 2021 and 2022, to understand the barriers, strengths, and strategies of models to support access to COVID-19 vaccination for newcomer refugees and immigrants., Methods: Researchers conducted structured interviews with Government Assisted Refugees (n = 39), and semi-structured interviews with Privately Sponsored Refugees (n = 6), private refugee sponsors (n = 3), and stakeholders involved in vaccination systems (n = 13) in 2022. Thematic analysis was conducted to draw out themes related to barriers, strengths, and strategies of vaccine delivery models and the intersections with patient experiences., Results: Newcomer refugee and immigrant focused vaccination models and strategies were explored. They demonstrated how partnerships between organizations, multi-pronged approaches, and culturally responsive services were crucial to navigate ongoing and emergent factors, such as vaccine hesitancy, mandates, and other determinants of under-vaccination. Many vaccination models presented through interviews were not specific to refugees and included immigrants, temporary residents, ethnocultural community members, and other vulnerable populations in their design., Conclusions: Increasing COVID-19 vaccine uptake for newcomer refugees and immigrants, is complex and requires trust, ongoing information provision, and local partnerships to address ongoing and emerging factors. Three key policy implications were drawn. First, findings demonstrated the need for flexible funding to offer outreach, translation, cultural interpretation, and to meet the basic needs of patients prior to engaging in vaccinations. Second, the research showed that embedding culturally responsive strategies within services ensures community needs are met. Finally, collaborating with partners that reflect the diverse needs of communities is crucial for the success of any health efforts serving newcomers., (© 2024. The Author(s).)

Introduction: Suicidal behavior is a public health problem worldwide. The World Health Organization estimated 700 000 deaths for the year 2021., Objective: This study aimed to estimate the prevalence of suicidal behavior and describe its related factors in the Coquimbo Region, Chile, between 2018 and 2020., Methods: 2190 suicide attempt notifications from the regional epidemiological surveillance system were analyzed, corresponding to 1781 people, along with 217 reports from the Forensic Medical Service of people who died by suicide., Results: The overall suicide rate for the region during that period was 9.79 deaths per 100 000 inhabitants. The 2018 rates were standardized according to available information, with direct methods for the regional rate (9.55 per 100 000 inhabitants) and indirect methods for the communes. Rural communes presented higher rates than urban ones. Women showed a higher risk of attempts (OR 1.28; 95% CI 1.23 to 1.33) and a lower risk of suicide compared to men (0.086; 0.06 to 0.13). Young people had a higher risk of suicide attempts and a lower risk of suicide compared to older people. The increased suicide rates in older people (70 to 79 years) during 2020 are noteworthy. Basic education level is a risk variable for suicide (2.21; from 1.15 to 4.23), compared to having higher education. Previous suicide attempts and psychiatric pathology are risk factors., Conclusions: Suicide prevalence and related factors are similar to those reported in other studies and national reports, highlighting rurality and higher risk in older male adults. In contrast to suicides, attempts are more frequent in women and young people. A history of mental health problems, previous attempts, and family violence are risk factors for both outcomes. Knowing the patterns of suicidal behavior in the population is fundamental for its prevention., Competing Interests: The authors declare no conflicts of interest related to this manuscript., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background: With the COVID-19 pandemic and the restrictions imposed to contain the spread of SARS-CoV-2, the Brazilian population has increased the time spent at home and watching television (TV). Since food advertising exposure is a key driver of food choices, this study described the content of food advertisements (ads) on Brazilian TV during the COVID-19 pandemic., Methods: This is an exploratory study. A total of 684 h of TV programming comprised of three free-to-air channels and two pay-per-view channels was recorded from 06 a.m. to 12 a.m. for eight non-consecutive days in June 2020. A content analysis of all the food-related ads was carried out. The data collection process followed INFORMAS Protocol for TV food advertising monitoring., Results: The sample was composed of 7,083 ads, 752 (10.6%) of which were food-related and 487 (6.9%) were promoting ultra-processed foods. The content analysis indicated seven thematic categories, all of them with reference to the COVID-19 pandemic: brand and product differentials (79.8%); visual and sound effects (70.2%); thematic campaigns (56.0%); digitization (22.9%); convenience (16.5%); economic benefits (11.9%); and commensality and social interaction (6.1%). Ads content varied according to the day of the week, the time of the day, the length of the ad, and the channel type., Conclusions: The thematic of food advertising on Brazilian TV during the COVID-19 pandemic is aligned with the country's health crisis context and varied during the programming., (© 2024. The Author(s).)

The mechanical, thermal and gamma radiation attenuation properties of ethylene-propylene-diene monomer (EPDM)-based composites containing graphene nanoplatelets (GNs) and bismuth (III) oxide nanoparticles (B) were investigated. The use of polyethylene glycol (PEG) as a compatibilizer to improve the dispersion of the fillers was also investigated. The results showed that the combined use of these fillers resulted in a drastic increase in mechanical properties, reaching 123% and 83% of tensile strength and elongation at break, respectively, compared to those of EPDM. In contrast, the addition of PEG to composites containing EPDM GNs and B resulted in composites with lower values of mechanical properties compared to the EPDM/B/GN-based composite. However, the presence of PEG leads to obtaining a composite (EPDM/B/GNP) with a mass attenuation coefficient to gamma radiation ( 137 Cs, 662 keV) superior to that composite without PEG. In addition, the composite EPDM, B and PEG exhibited an elongation at break 153% superior to unfilled EPDM. Moreover, the binary filler system consisting of 100 phr of bismuth (III) oxide and 10 phr of GN leads to reaching 61% of the linear damping coefficient of the EPDM composite compared to that value of the unfilled EPDM. The study of the morphology and the state of filler dispersion in the polymer matrix, obtained using scanning electron microscopy and energy-dispersive X-ray spectroscopy, respectively, provides a useful background for understanding the factors affecting the gamma radiation attenuation properties. Finally, the results also indicated that by adjusting the formulation, it is possible to tune the mechanical and thermal properties of EPDM composites reinforced with bismuth oxide and graphene nanoplatelets.

Refugee decisions to vaccinate for COVID-19 are a complex interplay of factors which include individual perceptions, access barriers, trust, and COVID-19 specific factors, which contribute to lower vaccine uptake. To address this, the WHO calls for localized solutions to increase COVID-19 vaccine uptake for refugees and evidence to inform future vaccination efforts. However, limited evidence engages directly with refugees about their experiences with COVID-19 vaccinations. To address this gap, researchers conducted qualitative interviews (N = 61) with refugees (n = 45), sponsors of refugees (n = 3), and key informants (n = 13) connected to local COVID-19 vaccination efforts for refugees in Calgary. Thematic analysis was conducted to synthesize themes related to vaccine perspectives, vaccination experiences, and patient intersections with policies and systems. Findings reveal that refugees benefit from ample services that are delivered at various stages, that are not solely related to vaccinations, and which create multiple positive touch points with health and immigration systems. This builds trust and vaccine confidence and promotes COVID-19 vaccine uptake. Despite multiple factors affecting vaccination decisions, a key reason for vaccination was timely and credible information delivered through trusted intermediaries and in an environment that addressed refugee needs and concerns. As refugees placed trust and relationships at the core of decision-making and vaccination, it is recommended that healthcare systems work through trust and relationships to reach refugees. This can be targeted through culturally responsive healthcare delivery that meets patients where they are, including barrier reduction measures such as translation and on-site vaccinations, and educational and outreach partnerships with private groups, community organizations and leaders.

In the field of soft robotics, current materials face challenges related to their load capacity, durability, and sustainability. Innovative solutions are required to address these problems beyond conventional strategies, which often lack long-term ecological viability. This study aims to overcome these limitations using mechanically robust, self-healing, and recyclable ionic elastomers based on carboxylated nitrile rubber (XNBR). The designed materials exhibited excellent mechanical properties, including tensile strengths (TS) exceeding 19 MPa and remarkable deformability, with maximum elongations (EB) over 650%. Moreover, these materials showed high self-healing capabilities, with 100% recovery efficiency of TS and EB at 110 °C after 3 to 5 h, and full recyclability, preserving their mechanical performance even after three recycling cycles. Furthermore, they were also moldable and readily scalable. Tendon-driven soft robotic grippers were successfully developed out of ionic elastomers, illustrating the potential of self-healing and recyclability in the field of soft robotics to reduce maintenance costs, increase material durability, and improve sustainability.

In beef cattle, the selection for higher weights at young ages has been questioned with the argument that this criterion may increase the adult weight of cows, resulting in higher costs. Therefore, selection criteria should be employed to increase weights at young ages with minimal impact on the adult weight of cows. Additionally, the relationship between measures of cow production efficiency and other well-established selection criteria in breeding programs remains poorly understood. The objective of this study was to longitudinally evaluate the relationship between the weaning index (WIndex) as a measure of efficiency and growth traits of the cows. Possible changes over time in WIndex due to selection applied for yearling weight (YW) were also investigated. The WIndex was proposed to maximize genetic response in the weaning weight of the calf while maintaining genetic gain in BW of the cow at zero. A random regression model was adopted to estimate correlations between WIndex, BW, hip height (HH), and body condition score (BCS) using records of Nelore cows from three lines. Genetic trends were calculated for the control line (NeC) and lines selected for greater YW (NeS and NeT). The age of 3 years was the most critical for the weaning efficiency of the cows. At this stage, young cows are still growing and wean lighter calves than their adult counterparts. The genetic correlation estimates between WIndex and BW (-0.58 to 0.04), HH (-0.05 to -0.34), and BCS (-0.51 to -0.17) were close to zero or negative. BW and HH were strongly correlated genetically across all ages (0.73-0.76). In general, HH exhibited a weak and negative genetic relationship with BCS. The genetic correlation between BW and BCS was stronger for advanced ages (0.45-0.68). In lines selected for YW, important increases in WIndex were observed. However, NeS has been selected since the 1980s until the present for YW, and thus, it showed a more pronounced trend of increasing BW and, consequently, a more modest trend of increasing WIndex compared to NeT. In contrast, WIndex exhibited a trend close to zero for NeC. In this context, monitoring HH and BCS can be useful to avoid losses in the weaning efficiency of cows. Furthermore, we suggest that one way to mitigate efficiency losses in calf production could involve stabilizing the BW of cows and increasing the weaning weight of calves using the WIndex., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: This meta-analysis investigated the prevalence of post-COVID symptoms two-years after SARS-CoV-2 infection., Methods: Electronic literature searches on PubMed, MEDLINE, CINAHL, EMBASE, Web of Science databases, and on medRxiv/bioRxiv preprint servers were conducted up to October 1, 2023. Studies reporting data on post-COVID symptoms at two-years after infection were included. Methodological quality was assessed using the Newcastle-Ottawa Scale. Random-effects models were used for meta-analytical pooled prevalence of each symptom., Results: From 742 studies identified, twelve met inclusion criteria. The sample included 7912 COVID-19 survivors (50.7% female; age: 59.5, SD: 16.3). Post-COVID symptoms were assessed at a follow-up of 722.9 (SD: 51.5) days after. The overall methodological quality of studies was moderate (mean: 6/10, SD: 1.2 points). The most prevalent post-COVID symptoms two-years after SARS-CoV-2 infection were fatigue (28.0%, 95%CI 12.0-47.0), cognitive impairments (27.6%, 95%CI 12.6-45.8), and pain (8.4%, 95%CI 4.9-12.8). Psychological disturbances such as anxiety (13.4%, 95%CI 6.3-22.5) and depressive (18.0%, 95%CI 4.8-36.7) levels as well as sleep problems (20.9%, 95%CI 5.25-43.25) were also prevalent. Pooled data showed high heterogeneity (I 2 ≥ 75%)., Conclusion: This meta-analysis shows the presence of post-COVID symptoms in 30% of patients two-years after COVID-19. Fatigue, cognitive disorders, and pain were the most prevalent post-COVID symptoms. Psychological disturbances as well as sleep problems were still present two-years after COVID-19., 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 © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Inclusiveness, Support, Mutual Respect and Co-Build are the four pillars of patient engagement according to the Strategy for Patient-Oriented Research (SPOR). The aim of this manuscript is to describe the operationalization of these principles through the creation of a Patient Advisory Council (PAC) for the research study titled 'Re-Purposing the Ordering of Routine laboratory Tests (RePORT)'., Methods: Researchers collaborated with the Alberta SPOR SUPPORT Unit (AbSPORU) Patient Engagement Team to create a diverse PAC. Recruitment was intentional and included multiple perspectives and experiences. PAC meetings were held monthly, and patient research partners received support to function as co-chairs of the PAC. Patient research partners were offered training, support and tailored modalities of compensation to actively engage with the PAC. Regular member check-ins occurred through reflexivity and a formal evaluation of PAC member engagement., Results: The PAC included between 9 and 11 patient research partners, principal investigator, research study coordinator, improvement scientist, resident physician and support members from the AbSPORU team. Twelve monthly PAC meetings were held during the first phase of the project. The PAC made course-changing contributions to study design including study objectives, recruitment poster, interview guide and development of codes for thematic analysis. Patient research partners largely felt that their opinions were valued. Diversity in the PAC membership enhanced access to diverse patient participants. Furthermore, support for co-chairs and patient research partner members enabled active engagement in research. In addition, a culture of mutual respect facilitated patient partner engagement, and co-design approaches yielded rich research outputs., Conclusions: Collaboration between research teams and Patient Engagement Teams can promote effective patient engagement through a PAC. Deliberate and flexible strategies are needed to manage the PAC to create an ecology of Inclusiveness, Support, Mutual Respect, and Co-Build for meaningful patient engagement., Patient or Public Contribution: Patient research partners were involved in the decision to write this manuscript and collaborated equitably in the conception and development of this manuscript, including providing critical feedback. Patient research partners were active members of the PAC and informed the research project design, participant recruitment strategies, data collection and analysis, and will be involved in the implementation and dissemination of results. They are currently involved in the co-development of a patient engagement strategy using a Human-Centered Design process., (© 2023 The Authors. Health Expectations published by John Wiley & Sons Ltd.)

The non-canonical BAF complex (ncBAF) subunit BRD9 is essential for acute myeloid leukemia (AML) cell viability but has an unclear role in leukemogenesis. Because BRD9 is required for ncBAF complex assembly through its DUF3512 domain, precise bromodomain inhibition is necessary to parse the role of BRD9 as a transcriptional regulator from that of a scaffolding protein. To understand the role of BRD9 bromodomain function in regulating AML, we selected a panel of five AML cell lines with distinct driver mutations, disease classifications, and genomic aberrations and subjected these cells to short-term BRD9 bromodomain inhibition. We examined the bromodomain-dependent growth of these cell lines, identifying a dependency in AML cell lines but not HEK293T cells. To define a mechanism through which BRD9 maintains AML cell survival, we examined nascent transcription, chromatin accessibility, and ncBAF complex binding genome-wide after bromodomain inhibition. We identified extensive regulation of transcription by BRD9 bromodomain activity, including repression of myeloid maturation factors and tumor suppressor genes, while standard AML chemotherapy targets were repressed by inhibition of the BRD9 bromodomain. BRD9 bromodomain activity maintained accessible chromatin at both gene promoters and gene-distal putative enhancer regions, in a manner that qualitatively correlated with enrichment of BRD9 binding. Furthermore, we identified reduced chromatin accessibility at GATA, ETS, and AP-1 motifs and increased chromatin accessibility at SNAIL-, HIC-, and TP53-recognized motifs after BRD9 inhibition. These data suggest a role for BRD9 in regulating AML cell differentiation through modulation of accessibility at hematopoietic transcription factor binding sites., Significance: The bromodomain-containing protein BRD9 is essential for AML cell viability, but it is unclear whether this requirement is due to the protein's role as an epigenetic reader. We inhibited this activity and identified altered gene-distal chromatin regulation and transcription consistent with a more mature myeloid cell state., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Background: Transcription factors bind DNA in specific sequence contexts. In addition to distinguishing one nucleobase from another, some transcription factors can distinguish between unmodified and modified bases. Current models of transcription factor binding tend not to take DNA modifications into account, while the recent few that do often have limitations. This makes a comprehensive and accurate profiling of transcription factor affinities difficult., Results: Here, we develop methods to identify transcription factor binding sites in modified DNA. Our models expand the standard A/C/G/T DNA alphabet to include cytosine modifications. We develop Cytomod to create modified genomic sequences and we also enhance the MEME Suite, adding the capacity to handle custom alphabets. We adapt the well-established position weight matrix (PWM) model of transcription factor binding affinity to this expanded DNA alphabet. Using these methods, we identify modification-sensitive transcription factor binding motifs. We confirm established binding preferences, such as the preference of ZFP57 and C/EBPβ for methylated motifs and the preference of c-Myc for unmethylated E-box motifs., Conclusions: Using known binding preferences to tune model parameters, we discover novel modified motifs for a wide array of transcription factors. Finally, we validate our binding preference predictions for OCT4 using cleavage under targets and release using nuclease (CUT&RUN) experiments across conventional, methylation-, and hydroxymethylation-enriched sequences. Our approach readily extends to other DNA modifications. As more genome-wide single-base resolution modification data becomes available, we expect that our method will yield insights into altered transcription factor binding affinities across many different modifications., (© 2023. The Author(s).)

Objective: Performance indicators are used to evaluate the quality of healthcare services. The majority of these, however, are derived solely from administrative data and rarely incorporate feedback from patients who receive services. Recently, our research team developed person-centred quality indicators (PC-QIs), which were co-created with patients. It is unknown whether these PC-QIs are associated with unplanned healthcare use following discharge from hospital., Design: A retrospective, cross-sectional study., Methods: Survey responses were obtained from April 2014 to September 2020 using the Canadian Patient Experiences Survey - Inpatient Care instrument. Logistic regression models were used to predict the link between eight PC-QIs and two outcomes; unplanned readmissions within 30 days and emergency department visits within 7 days., Results: A total of 114 129 surveys were included for analysis. 6.0% of respondents (n=6854) were readmitted within 30 days, and 9.9% (n=11 287) visited an emergency department within 7 days of their index discharge. In adjusted models, 'top box' responses for communication between patients and physicians (adjusted OR (aOR)=0.82, 95% CI: 0.77 to 0.88), receiving information about taking medication (aOR=0.86, 95% CI: 0.80 to 0.92) and transition planning at hospital discharge (aOR=0.79, 95% CI: 0.73 to 0.85) were associated with lower odds of emergency department visit.Likewise, 'top box' responses for overall experience (aOR=0.87, 95% CI: 0.82 to 0.93), communication between patients and physicians (aOR=0.73, 95% CI: 0.67 to 0.80) and receiving information about taking medication (aOR=0.90, 95% CI: 0.83 to 0.98), were associated with lower odds of readmission., Conclusions: This study demonstrates that patient reports of their in-hospital experiences may have value in predicting future healthcare use. In developing the PC-QIs, patients indicated which elements of their hospital care matter most to them, and our results show agreement between subjective and objective measures of care quality. Future research may explore how current readmission prediction models may be augmented by person-reported experiences., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

International guidelines strongly advise about the frequent and varied intake of plant in diet. In this scenario, the consumption of fruits is closely related to health benefits due to the abundant presence of bioactive substances. Accordingly, the production of tropical fruits has stood out worldwide, reaching records since the past decade. However, to ensure that phenolic substances are indeed used by the body, they need to be accessible for absorption. For this purpose, several methods are used to assess the phenomenon of bioaccessibility. We provide information on i) in vitro methods for the evaluation of the bioaccessibility of phenolic compounds in tropical fruits, including their derivatives and by-products; ii) a study performed using a semi-dynamic in vitro digestion model; iii) simulated digestion with a dialysis membrane step, polyphenol transport/uptake using cell culture, and in vitro colonic fermentation process. Although standardized static and semi-dynamic in vitro digestion methods already exist, few studies use these protocols to assess the bioaccessibility of polyphenols in tropical fruits. To guarantee that in vitro digestion assays reproduce consistent results compared to in vivo reference methods, it is essential to universalize standardized methods that allow the comparison between results, enabling the validation of in vitro digestion methods.

Aedes aegypti is a vector of various disease-causing arboviruses. Chemical insecticide-based methods for mosquito control have increased resistance in different parts of the world. Thus, alternative control agents such as the entomopathogenic fungi are excellent candidates to control mosquitoes as part of an ecofriendly strategy. There is evidence of the potential of entomopathogenic fungal conidia and blastospores for biological control of eggs, larval and adult stages, as well as the pathogenicity of fungal microsclerotia against adults and eggs. However, there are no studies on the pathogenicity of microsclerotia against either aquatic insects or insects that develop part of their life cycle in the water, such as the A. aegypti larvae. In this study, we assayed the production of microsclerotia and their pathogenicity against A. aegypti larvae of two isolates of Metarhizium robertsii, i.e., CEP 423 isolated in La Plata, Argentina, and the model ARSEF 2575. Both isolates significantly reduced the survival of A. aegypti exposed to their microsclerotia. The fungus-larva interaction resulted in a delayed response in the host. This was evidenced by the expression of some humoral immune system genes such as defensins and cecropin on the 9th day post-infection, when the fungal infection was consolidated as a successful process that culminates in larvae mortality. In conclusion, M. robertsii microsclerotia are promising propagules to be applied as biological control agents against mosquitoes since they produce pathogenic conidia against A. aegypti larvae., 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 © 2023. Published by Elsevier B.V.)

This study examined the relationship between weight stigma and disordered eating behaviors in university students during the COVID-19 pandemic, considering individuals with and without overweight. A national sample of 738 college students completed an online questionnaire at three time points between July 2020 and December 2021, reporting their experiences of weight stigma, perceived increase in weight stigma during the pandemic, internalized weight stigma, and disordered eating behaviors. The findings showed that the trajectories of disordered eating behaviors varied depending on participants' anthropometric status. Among those with overweight, there was a decrease over time in binge eating, food restriction, and purging. Conversely, the non-overweight group experienced a slight increase in binge eating from T2 to T3. Using the Generalized Estimating Equations model, the study revealed that weight stigma predicted disordered eating behaviors in both weight spectrums during the pandemic. Experiences of weight stigma and the perceived increase in weight stigma significantly increased the likelihood of engaging in binge eating, food restriction, and purging among individuals with overweight. Furthermore, the internalization of weight stigma was longitudinally associated with all examined eating behaviors, regardless of anthropometric status. These findings highlight the importance of addressing weight stigma to prevent disordered eating in college students., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to declare., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Cancer disparities are a major public health concern in Canada, affecting racialized communities of Latin American and African descent, among others. This is evident in lower screening rates, lower access to curative, and palliative-intent treatments, higher rates of late cancer diagnoses and lower survival rates than the general Canadian population. We will develop an Access to Palliative Care Strategy informed by health equity and patient-oriented research principles to accelerate care improvements for patients with advanced cancer of African and Latin American descent., Methods: This is a community-based participatory research study that will take place in two Canadian provinces. Patients and community members representatives have been engaged as partners in the planning and design of the study. We have formed a patient advisory council (PAC) with patient partners to guide the development of the Access to Palliative Care Strategy for people of African and Latin American descent. We will engage100 participants consisting of advanced cancer patients, families, and community members of African and Latin American descent, and health care providers. We will conduct in-depth interviews to delineate participants' experiences of access to palliative care. We will explore the intersections of race, gender, socioeconomic status, language barriers, and other social categorizations to elucidate their role in diverse access experiences. These findings will inform the development of an action plan to increase access to palliative care that is tailored to our study population. We will then organize conversation series to examine together with community partners and healthcare providers the appropriateness, effectiveness, risks, requirements, and convenience of the strategy. At the end of the study, we will hold knowledge exchange gatherings to share findings with the community., Discussion: This study will improve our understanding of how patients with advanced cancer from racialized communities in Canada access palliative care. Elements to address gaps in access to palliative care and reduce inequities in these communities will be identified. Based on the study findings a strategy to increase access to palliative care for this population will be developed. This study will inform ways to improve access to palliative care for racialized communities in other parts of Canada and globally., (© 2023. The Author(s).)

Herpes simplex virus type 2 (HSV-2) is the most common agent of sexually transmitted infections around the world. Currently, no vaccine is available, and acyclovir is the reference compound in treatment HSV-2 infections. However, the emergence of resistant strains has reduced the efficacy in treatment. Several studies have shown marine seaweed biological activities, but there are no studies yet about the activity anti-HSV-2 of two its secundary metabolites, atomaric acid (1) and marine dolastane (2), isolated from Stypopodium zonale and Canistrocarpus cervicornis respectively. Therefore, we evaluated the anti-HSV-2 activity of compounds 1 and 2. Both compounds showed anti-HSV-2 activity with low cytotoxicity and compound 1 inactivated 90% of the viral particles at 50 µM. Both compounds inhibited the penetration and results in silico indicated the compound 1 as possible therapy alternative anti -HSV-2.

Metarhizium robertsii microsclerotia are fungal aggregates composed of compacted, pigmented hyphae. As they are highly tolerant to desiccation and produce infective conidia, they are promising candidates to be formulated as bioinsecticides. Despite this potential, the nature of the pigments within these structures remains unclear. In this study, routine culture media used for the differentiation of M. robertsii microsclerotia were supplemented with four melanin inhibitors, and the resulting propagules were characterized. Inhibitors of the 1,8-dihydroxynaphthalene (DHN)-melanin biosynthetic pathway such as tricyclazole and guaiacol induced significant phenotypic and molecular modifications in the obtained M. robertsii propagules, which exhibited a more spherical shape, reduced size, and increased susceptibility to desiccation, heat, and oxidative stress than microsclerotia obtained without inhibitors. Additionally, genes encoding for a polyketide synthase (Mrpks2) and a putative 1,3,6,8-tetrahydroxynaphthalene reductase (Mrthnr), potentially involved in the DHN-melanin biosynthetic pathway, were upregulated in fungi grown in the inhibitor-added media. In conclusion, M. robertsii microsclerotia contain melanins of type DHN that might play a role in both microsclerotia differentiation and environmental stress tolerance.

Background: Visible blue light (wavelength 400-495 nm) is a promising new treatment option for both psoriasis and atopic dermatitis (AD). Whilst previous clinical trials featured various devices and blue light at a variety of wavelengths, none of these interventions were challenged in objective clinical criteria., Patients and Methods: Eighty-seven patients diagnosed with AD were enrolled in AD-Blue, an international, prospective, double-blinded, three-armed (415 nm vs. 450 nm vs. sham control), randomized trial designed to investigate the safety and efficacy of prototype full-body blue light devices., Results: Full-body irradiation with 450 nm blue light but not 415 nm had a significant impact on itch (Itch-VAS, -1.6 ± 2.3; p  =  0.023 vs. sham irradiation). PO-SCORAD values also decreased significantly in response to irradiation at 415 nm (-11.5 ± 18.4; p = 0.028 vs. sham irradiation). None of the other outcome measures (EASI, SCORAD, IGA, DLQI) changed significantly. No safety signals were observed. Evaluation of skin transcriptomes, cytokine levels in serum, and ELISpots from peripheral blood mononuclear cells isolated from a subset of patients revealed moderate decreases in IL-31 in response to irradiation with blue light., Conclusions: Despite its favorable safety profile and moderate reductions in itch and IL-31 levels, full-body blue light irradiation did not lead to an amelioration of any of the objective measures of AD., (© 2023 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Amazonian strains of Cyathus spp. and Geastrum spp. were studied for the ability to discolor the trypan blue azo dye and reduce its toxicity. Discoloration of trypan blue dye (0.05%) was evaluated in solid and aqueous medium over different periods. The reduction of dye toxicity after treatment was assessed by seed germination and the development of lettuce seedlings (Lactuca sativa L.) and toxicity test in Artemia salina (L.) larvae. All evaluated strains showed the potential to reduce the color intensity of trypan blue dye. Cyathus strains reached 96% discoloration, and C. albinus and C. limbatus also reduced dye toxicity. Geastrum strains showed a high efficiency degree in color reduction, reaching 98% discoloration, however, the by-products generated during the process presented toxicity and require further investigation. For the first time, Amazonian strains of gasteroid fungi degrading trypan blue are reported, some even reducing its toxicity. Thus, making them promising sources of enzymes of interest to bioremediation scenarios involving synthetic dyes.

Background: Melanoma is one of the deadliest tumors in the world. Early detection is critical for first-line therapy in this tumor pathology and it remains challenging due to the need for histological analysis to ensure correctness in diagnosis. Therefore, multiple computer-aided diagnosis (CAD) systems working on melanoma images were proposed to mitigate the need of a biopsy. However, although the high global accuracy is declared in literature results, the CAD systems for the health fields must focus on the lowest false negative rate (FNR) possible to qualify as a diagnosis support system. The final goal must be to avoid classification type 2 errors to prevent life-threatening situations. Another goal could be to create an easy-to-use system for both physicians and patients., Results: To achieve the minimization of type 2 error, we performed a wide exploratory analysis of the principal convolutional neural network (CNN) architectures published for the multiple image classification problem; we adapted these networks to the melanoma clinical image binary classification problem (MCIBCP). We collected and analyzed performance data to identify the best CNN architecture, in terms of FNR, usable for solving the MCIBCP problem. Then, to provide a starting point for an easy-to-use CAD system, we used a clinical image dataset (MED-NODE) because clinical images are easier to access: they can be taken by a smartphone or other hand-size devices. Despite the lower resolution than dermoscopic images, the results in the literature would suggest that it would be possible to achieve high classification performance by using clinical images. In this work, we used MED-NODE, which consists of 170 clinical images (70 images of melanoma and 100 images of naevi). We optimized the following CNNs for the MCIBCP problem: Alexnet, DenseNet, GoogleNet Inception V3, GoogleNet, MobileNet, ShuffleNet, SqueezeNet, and VGG16., Conclusions: The results suggest that a CNN built on the VGG or AlexNet structure can ensure the lowest FNR (0.07) and (0.13), respectively. In both cases, discrete global performance is ensured: 73% (accuracy), 82% (sensitivity) and 59% (specificity) for VGG; 89% (accuracy), 87% (sensitivity) and 90% (specificity) for AlexNet., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Standard Palm Oil (SPO) is widely used as a food ingredient partially due to its unique thermophysical properties. However, the American Heart Association recommends a saturated fat consumption of <5% of the caloric intake per day. The OxG Palm hybrid yields oil known as "palm oil with a higher content of oleic acid" (HOPO), with <35% SFA and >50% oleic acid. Characterizing novel high oleic oils is the starting point to find processes that can functionalize them such as oleogelation. This study compared the thermophysical properties of HOPO to SPO using Differential Scanning Calorimetry, shear rheology, polarized light microscopy, and texture analysis to characterize the differences between these oils. HOPO had a lower onset crystallization temperature (Δ7 °C) and its rheological behavior followed similar trends to SPO; however, large viscosity offsets were observed and were correlated to differences in crystallization temperatures. The maximum peak force of SPO was an order of magnitude higher than that of HOPO. Overall similar trends between the oils were observed, but differences in firmness, crystal morphology, and viscosity were not linearly correlated with the offset in crystallization temperature. This study quantified differences between these oils that will better enable industry to use HOPO in specific applications.

Protocadherins (PCDHs) are cell adhesion molecules that regulate many essential neurodevelopmental processes related to neuronal maturation, dendritic arbor formation, axon pathfinding, and synaptic plasticity. Biallelic loss-of-function variants in PCDH12 are associated with several neurodevelopmental disorders (NDDs). Despite the highly deleterious outcome resulting from loss of PCDH12, little is known about its role during brain development and disease. Here, we show that PCDH12 loss severely impairs cerebral organoid development, with reduced proliferative areas and disrupted laminar organization. 2D models further show that neural progenitor cells lacking PCDH12 prematurely exit the cell cycle and differentiate earlier when compared with wild type. Furthermore, we show that PCDH12 regulates neuronal migration and suggest that this could be through a mechanism requiring ADAM10-mediated ectodomain shedding and/or membrane recruitment of cytoskeleton regulators. Our results demonstrate a critical involvement of PCDH12 in cortical organoid development, suggesting a potential cause for the pathogenic mechanisms underlying PCDH12-related NDDs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)