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Abstract Hyperspectral imaging has demonstrated its potential to provide correlated spatial and spectral information of a sample by a non‐contact and non‐invasive technology. In the medical field, especially in histopathology, HSI has been applied for the classification and identification of diseased tissue and for the characterization of its morphological properties. In this work, we propose a hybrid scheme to classify non‐tumor and tumor histological brain samples by hyperspectral imaging. The proposed approach is based on the identification of characteristic components in a hyperspectral image by linear unmixing, as a features engineering step, and the subsequent classification by a deep learning approach. For this last step, an ensemble of deep neural networks is evaluated by a cross‐validation scheme on an augmented dataset and a transfer learning scheme. The proposed method can classify histological brain samples with an average accuracy of 88%, and reduced variability, computational cost, and inference times, which presents an advantage over methods in the state‐of‐the‐art. Hence, the work demonstrates the potential of hybrid classification methodologies to achieve robust and reliable results by combining linear unmixing for features extraction and deep learning for classification.

Background Flow diversion has revolutionized the management of wide‐necked intracranial aneurysms (IAs). We aimed to assess the effectiveness and safety of the new generation 64‐wire Surpass Evolve for the treatment of unruptured small/medium‐sized IAs. Methods and Results This is a subanalysis from the SEASE (Safety and Effectiveness Assessment of the Surpass Evolve) registry, an observational cohort study including 15 academic institutions in North America and Europe between July 2020 and October 2022. Patients with wide‐necked saccular IAs, measuring

Background The presence of an incorporated branch as well as its anatomical relationship to the intracranial aneurysms (IAs) and the parent artery may affect the occlusion outcome following flow diversion. This study evaluated the safety and effectiveness of the cobalt‐chromium Surpass Evolve (Stryker), a 64‐wire flow diversion device for the treatment of IAs with incorporated branches. Methods This subanalysis uses data from the SEASE (Safety and Effectiveness Assessment of Surpass Evolve) registry to retrieve data related to IAs with incorporated branches. Those IAs were classified by a core lab into 4 categories based on their anatomical relationship to the parent artery and branch: (A) sidewall anatomic, (B) sidewall hemodynamic, (C) neck branch, and (D) dome branch. We compared the outcomes based on their incorporated branch's relation to the dome (A–C versus D). Results This study included 67 patients and IAs. Most IAs were in the posterior communicating artery (46.3%), with a median size of 4.35 mm. Age, sex, comorbidities, baseline functional‐status, and IA features were similar between the 2 groups. Among those, 53 (79.1%) had branches emerging from the dome, and 14 (20.9%) had branches originating from other locations (A = 7, B = 2, and C = 5). At a median imaging follow‐up of 10.5 months, complete occlusion was lower in IAs with a branch from the sac compared with those with the neck (60.8% versus 92.9%; P = 0.026), with an overall occlusion of 67.7%. Thromboembolic and hemorrhagic complications, as well as retreatment, were reported in 1.6% and 3.1% of cases, respectively, with no significant differences between groups. Conclusion Our analysis underscores the influence of branch origin on occlusion rates, with the neck‐originating branch demonstrating higher occlusion rates. These insights emphasize the role of anatomical considerations in treatment strategies, follow‐up timelines, and designing future clinical trials. Further studies are warranted to explore these variations across different flow diversion technologies.

Abstract The stability of hybrid organic–inorganic halide perovskite semiconductors remains a significant obstacle to their application in photovoltaics. To this end, the use of low‐dimensional (LD) perovskites, which incorporate hydrophobic organic moieties, provides an effective strategy to improve their stability, yet often at the expense of their performance. To address this limitation, supramolecular engineering of noncovalent interactions between organic and inorganic components has shown potential by relying on hydrogen bonding and conventional van der Waals interactions. Here, the capacity to access novel LD perovskite structures that uniquely assemble through unorthodox S‐mediated interactions is explored by incorporating benzothiadiazole‐based moieties. The formation of S‐mediated LD structures is demonstrated, including one‐dimensional (1D) and layered two‐dimensional (2D) perovskite phases assembled via chalcogen bonding and S–π interactions. This involved a combination of techniques, such as single crystal and thin film X‐ray diffraction, as well as solid‐state NMR spectroscopy, complemented by molecular dynamics simulations, density functional theory calculations, and optoelectronic characterization, revealing superior conductivities of S‐mediated LD perovskites. The resulting materials are applied in n‐i‐p and p‐i‐n perovskite solar cells, demonstrating enhancements in performance and operational stability that reveal a versatile supramolecular strategy in photovoltaics.

Abstract Recovery planning is considered an important policy instrument for the management of threatened species. While recovery planning has led to improvements in the conservation status of some species, the degree of success can vary substantially across different contexts and is dependent on multiple factors. Institutional and organizational factors such as insufficient funding, weak policies, underspecified goals, and lack of knowledge impact the success of recovery planning. But recovery planning can be fall short in achieving desired outcomes even in the absence of these constraints. Recovery planning is also highly reliant on collaboration efforts between local agencies, community organizations, and research institutions—yet studies examining the diversity of factors influencing the success of recovery planning are rare. To address this gap, we take a multilevel perspective that situates recovery planning inside nested layers of institutional, organizational, team, and action‐level processes. We apply this framework and utilize in‐depth interviews and thematic analysis to analyze barriers and enablers in the recovery of two threatened Australian species. Our analysis reveals how team‐level processes interact with their organizational and institutional contexts to influence outcomes. Key findings emphasize the indispensable role of committed individuals, collaboration, and strategic utilization of specialist knowledge in fostering effective teamwork. Furthermore, our findings also emphasize the critical importance of a shared purpose within the team and the need for equilibrium between personal agendas and team objectives. We highlight the need for more studies to deliver a nuanced understanding of how team‐level processes drive successful recovery planning, even when institutional factors, such as appropriate funding and knowledge, are present.

Abstract Objectives The objectives of this real‐life study were to analyze the reversion of chronic migraine (CM) to episodic migraine (EM) with fremanezumab, evaluate its benefit on the symptomatology, and determine the influence of possible clinical features on the reversion. Background The clinical manifestations of CM have a high impact on the quality of life of patients, and monoclonal antibodies such as fremanezumab are used as prophylactic treatment. Methods Diagnosed CM patients treated for at least 3 months with monthly fremanezumab were interviewed. The data to assess efficacy were before treatment and at the time of the interview: monthly headache days (MHDs), daily headache hours (DHHs), monthly symptomatic medication days (MSMDs), percentage of patients with symptomatic medication overuse (SMO), and pain intensity with the numerical rating scale (NRS) score. Possible predictors of reversion were analyzed: percentage of patients treated for at least 12 months, hypertension, diabetes mellitus, depression, anxiety, symptomatic control with non‐steroidal anti‐inflammatory drugs (NSAIDs), triptans or both, and amitriptyline prophylaxis. Results A total of 54 patients were included, of whom 40 (74.1%) were converters to EM. There were significant improvements in converters compared to pre‐treatment in MHDs (28.0 vs. 5.0 days), as well as on the variables DHHs, MSMDs, and SMO. The percentage of erenumab failures was significantly higher in non‐converters than in converters, as was the percentage of patients with anxiety. Conclusions High reversion from CM to EM was achieved with fremanezumab and notable symptomatological improvement, establishing previous failure to erenumab and anxiety as possible detrimental factors for reversion.

Abstract Decompression sickness (DCS) is a systemic syndrome that can occur after an environmental pressure reduction. Previously, we showed that the plasmatic tetrameric form of transthyretin (TTR) nearly disappeared in rats suffering DCS but not in asymptomatic ones. In this pilot study, we assessed whether the resistance to DCS could be associated with polymorphism of the gene of TTR. For this study, Sanger sequencing was performed on purified PCR products from the liver of 14‐week‐old male and female standard and DCS‐resistant rats (n = 5 per group). Hepatic TTR mRNA expression was assessed by RT‐qPCR in 18–19 week‐old male and female standard and resistant rats (n = 6 per group). There is a synonymous single nucleotide polymorphism (SNP) on the third base of codon 46 (c.138 C > T). The thymine allele was present in 90% and 100% of males and females standard, respectively. However, this allele is present in only 30% of DCS‐resistant males and females (p = 0.0002301). In the liver, there is a significant effect of the resistance to DCS (p = 0.043) and sex (p = 0.047) on TTR expression. Levels of TTR mRNA were lower in DCS‐resistant animals. To conclude, DCS resistance might be associated with a SNP and a lower expression of TTR.

Abstract Phenotypic plasticity can buffer organisms against short‐term environmental fluctuations. For example, previous exposure to increased temperatures can increase thermal tolerance in many species. Prior studies have found that acclimation to higher temperature can influence the magnitude of transcriptional response to subsequent acute thermal stress (hereafter, “transcriptional response modulation”). However, mechanisms mediating this gene expression response and, ultimately, phenotypic plasticity remain largely unknown. Epigenetic modifications are good candidates for modulating transcriptional response, as they broadly correlate with gene expression. Here, we investigate changes in DNA methylation as a possible mechanism controlling shifts in gene expression plasticity and thermal acclimation in the reef‐building coral Acropora nana. We find that gene expression response to acute stress is altered in corals acclimated to different temperatures, with many genes exhibiting a dampened response to heat stress in corals pre‐conditioned to higher temperatures. At the same time, we observe shifts in methylation during both acclimation (11 days) and acute heat stress (24 h). We observed that the acute heat stress results in shifts in gene‐level methylation and elicits an acute transcriptional response in distinct gene sets. Further, acclimation‐induced shifts in gene expression plasticity and differential methylation also largely occur in separate sets of genes. Counter to our initial hypothesis no overall correlation between the magnitude of differential methylation and the change in gene expression plasticity. We do find a small but statistically significant overlap in genes exhibiting both dampened expression response and shifts in methylation (14 genes), which could be candidates for further inquiry. Overall, our results suggest transcriptional response modulation occurs independently from methylation changes induced by thermal acclimation.

Abstract The management of wasting in Ethiopia is heavily reliant on the Community‐based Management of Acute Malnutrition (CMAM) programme that has been implemented in more than 18,000 service delivery points scattered across the country. Despite the full‐scale implementation of the CMAM, the number of child death averted, and the cost per child death averted remains unknown. This study aimed to estimate the cost and the number of child death averted by the CMAM programme between 2008 and 2020. Using data from routine monitoring of the CMAM programme, we estimated the excess mortality averted by the programme and estimated the cost per averted child death based on supply and labour. Over the past 13 years between 2008 and 2020, 3.6 million children under 5 years were admitted to the Ethiopian CMAM programme. The yearly average admission of 317,228 was achieved since 2011. On average, ~34,000 child deaths were averted yearly. The CMAM programme was estimated to have saved 437,654 (95% confidence interval [CI]: 320,161; 469,932) child deaths between 2008 and 2020, approximately 12% of the admitted cases. The average cost of the programme per adverted death was estimated at US$762/child death averted (95% CI = 639; 1001). The CMAM programme in Ethiopia is cost‐effective and has continued to avert a significant number of child death. Given the high short‐ and long‐term economic and health consequences of child wasting, concerted multi‐sectoral efforts are needed to accelerate progress not only in its treatment but also in its prevention.

Abstract As the SARS‐CoV‐2 virus spread throughout the world, millions of positive cases of COVID‐19 were registered and, even though there are millions of people already vaccinated against SARS‐CoV‐2, a large part of the global population remains vulnerable to contracting the virus. Massive nasopharyngeal sample collection in Puerto Rico at the beginning of the pandemic was limited by the scarcity of trained personnel and testing sites. To increase SARS‐CoV‐2 molecular testing availability, we evaluated the diagnostic accuracy of self‐collected nasal, saliva, and urine samples using the TaqPath reverse transcription polymerase chain reaction (RT‐PCR) COVID‐19 kit to detect SARS‐CoV‐2. We also created a colorimetric loop‐mediated isothermal amplification (LAMP) laboratory developed test (LDT) to detect SARS‐CoV‐2, as another strategy to increase the availability of molecular testing in community‐based laboratories. Automated RNA extraction was performed in the KingFisher Flex instrument, followed by PCR quantification of SARS‐CoV‐2 on the 7500 Fast Dx RT‐PCR using the TaqPath RT‐PCR COVID‐19 molecular test. Data was interpreted by the COVID‐19 Interpretive Software from Applied Biosystems and statistically analyzed with Cohen's kappa coefficient (k). Cohen's kappa coefficient (k) for paired nasal and saliva samples showed moderate agreement (0.52). Saliva samples exhibited a higher viral load. We also observed 90% concordance between LifeGene‐Biomarks' SARS‐CoV‐2 Rapid Colorimetric LAMP LDT and the TaqPath RT‐PCR COVID‐19 test. Our results suggest that self‐collected saliva is superior to nasal and urine samples for COVID‐19 testing. The results also suggest that the colorimetric LAMP LDT is a rapid alternative to RT‐PCR tests for the detection of SARS‐CoV‐2. This test can be easily implemented in clinics, hospitals, the workplace, and at home; optimizing the surveillance and collection process, which helps mitigate global public health and socioeconomic upheaval caused by airborne pandemics.

Abstract Recent systematic reviews suggest that pharmacists' interventions in asthma patients have a positive impact on health‐related outcomes. Nevertheless, the association is not well established, and the role of clinical pharmacists is poorly represented. The aim of this overview of systematic reviews is to identify published systematic reviews assessing the impact of pharmacists' interventions on health‐related outcomes measured in asthma patients. PubMed, Embase, Scopus, and Cochrane Library were searched from inception to December 2022. Systematic reviews of all study designs and settings were included. Methodological quality was assessed using AMSTAR 2. Two investigators performed study selection, quality assessment and data collection independently. Nine systematic reviews met the inclusion criteria. Methodological quality was rated as high in one, low in two, and critically low in six. Reviews included 51 primary studies reporting mainly quality of life, asthma control, lung capacity, and therapeutic adherence. Only four studies were carried out in a hospital setting and only two reviews stated the inclusion of severe asthma patients. The quality of the systematic reviews was generally low, and this was the major limitation of this overview of systematic reviews. However, solid evidence supports that pharmaceutical care improves health‐related outcomes in asthma patients.

Abstract Ocrelizumab (OCR) is a humanized anti‐CD20 monoclonal antibody approved for treating multiple sclerosis. We present three patients who developed psoriasiform dermatitis (PsD) during OCR treatment and a review of the cases published to date. We hereby report the first exclusive fingernail involvement. Most of the cases had a mild skin involvement and only one case required OCR discontinuation. No association with arthritis, personal or family history of psoriasis was found. Data compiled suggests that PsD tends to appear within the first year of treatment. There are few studies focusing on B‐lymphocytes in psoriasis and several hypotheses attempt to explain their role. The most widely accepted is the depletion of regulatory B‐lymphocytes with immunomodulatory function through interleukin‐10. However, the exact mechanism by which this occurs with OCR remains unclear and the presented case of anti‐CD20‐induced PsD highlights the importance of continuous monitoring of new treatments in terms of dermatological side effects and the induction of skin diseases, in particular psoriasis. There is also a need to inform the professional community about the possibility of psoriasis in patients with multiple sclerosis and the consequences of this condition.

Abstract The gene dosage compensation hypothesis presents a mechanism through which the expression of certain genes is modulated to compensate for differences in the dose of genes when additional chromosomes are present. It is one of the means through which cancer cells actively cope with the potential damaging effects of aneuploidy, a hallmark of most cancers. Dosage compensation arises through several processes, including downregulation or overexpression of specific genes and the relocation of dosage‐sensitive genes. In cancer, a majority of compensated genes are generally thought to be regulated at the translational or post‐translational level, and include the basic components of a compensation loop, including sensors of gene dosage and modulators of gene expression. Post‐translational regulation is mostly undertaken by a general degradation or aggregation of remaining protein subunits of macromolecular complexes. An increasingly important role has also been observed for transcriptional level regulation. This article reviews the process of targeted gene dosage compensation in cancer and other biological conditions, along with the mechanisms by which cells regulate specific genes to restore cellular homeostasis. These mechanisms represent potential targets for the inhibition of dosage compensation of specific genes in aneuploid cancers. This article critically examines the process of targeted gene dosage compensation in cancer and other biological contexts, alongside the criteria for identifying genes subject to dosage compensation and the intricate mechanisms by which cells orchestrate the regulation of specific genes to reinstate cellular homeostasis. Ultimately, our aim is to gain a comprehensive understanding of the intricate nature of a systems‐level property. This property hinges upon the kinetic parameters of regulatory motifs, which we have termed “gene dosage sensor loops.” These loops have the potential to operate at both the transcriptional and translational levels, thus emerging as promising candidates for the inhibition of dosage compensation in specific genes. Additionally, they represent novel and highly specific therapeutic targets in the context of aneuploid cancer.

Abstract Invasive species cause severe threats to biodiversity and the economy, but often across multi‐actor landscapes. Therefore, collaboration among multiple actors across landscapes is often essential for managing invasive species. Deciding whether to collaborate depends on available resources and potential benefits. As such, it is vital to identify how different factors can influence the outcomes of collaborations. We developed and tested a conceptual model that integrates potential process factors and performance measures for outcomes of collaborative invasive species management. We surveyed professionals engaged in invasive species management in Queensland, Australia. We first assessed their perception of the presence of process factors and perception of the performance measures of collaborative invasive species management projects using descriptive methods. Then we tested the associations between process factors and performance measures using structural equation modelling. While confirming that a good collaboration of stakeholders (e.g. communication and trust) is essential to enhance performances, our results suggest that the way collaborative projects are structured (e.g. ability to participate in decision‐making, having shared goals) also significantly influences the performance of the projects, especially in achieving goals. Furthermore, results suggest that achieving long‐term collaborations and outcomes is directly influenced by the extent to which stakeholders support or oppose the collaboration. As such, our study contributes to a significant research gap by establishing a connection between the collaboration process and its outcomes. We conclude that decision‐makers should give equal importance to both designing favourable collaborative project structures and fostering collaborations with stakeholders through different means to enhance the benefits of collaboration in invasive species management. Read the free Plain Language Summary for this article on the Journal blog.

Abstract The United Nations heralds a world population exponential increase exceeding 9.7 billion by 2050. This poses the challenge of covering the nutritional needs of an overpopulated world by the hand of preserving the environment. Extensive agriculture practices harnessed the employment of fertilizers and pesticides to boost crop productivity and prevent economic and harvest yield losses attributed to plagues and diseases. Unfortunately, the concomitant hazardous effects stemmed from such agriculture techniques are cumbersome, that is, biodiversity loss, soils and waters contaminations, and human and animal poisoning. Hence, the so‐called ‘green agriculture’ research revolves around designing novel biopesticides and plant growth‐promoting bio‐agents to the end of curbing the detrimental effects. In this field, microbe–plant interactions studies offer multiple possibilities for reshaping the plant holobiont physiology to its benefit. Along these lines, bacterial extracellular membrane vesicles emerge as an appealing molecular tool to capitalize on. These nanoparticles convey a manifold of molecules that mediate intricate bacteria–plant interactions including plant immunomodulation. Herein, we bring into the spotlight bacterial extracellular membrane vesicle engineering to encase immunomodulatory effectors into their cargo for their application as biocontrol agents. The overarching goal is achieving plant priming by deploying its innate immune responses thereby preventing upcoming infections.

Background Previous studies have shown that women with hypertrophic obstructive cardiomyopathy (HCM) have worse long‐term outcomes irrespective of intervention. However, the outcomes of patients undergoing alcohol septal ablation (ASA) based on sex have not been described. Hence, this study aimed to evaluate pressure changes and long‐term mortality in patients with HCM undergoing ASA based on sex. Methods and Results This is a single‐center retrospective study evaluating hemodynamic changes and long‐term mortality in patients with HCM treated with ASA according to sex. A total of 259 patients were included (aged 68.4±11.9 years, 62.2% women). Women had higher age and baseline pressures at the time of ASA, with a greater percent reduction in mean left atrial pressure (men versus women: 2.2% versus 15.9%, respectively; P=0.02). Women had better survival (median survival rate of men versus women: 8.6 versus 12.5 years, respectively; P=0.011). On Cox multivariable regression, predictors of mortality were age (per group change 80 years; hazard ratio [HR], 1.45 [95% CI, 1.10–1.91], P=0.008), female sex (HR, 0.59 [95% CI, 0.35–0.99], P=0.048), chronic kidney disease (HR, 1.88 [95% CI, 1.06–3.33], P=0.031), and left ventricular outflow tract gradient reduction ≤86% (HR, 1.91 [95% CI, 1.14–3.19], P=0.014). Conclusions Women with HCM undergoing ASA are older and have higher left‐sided baseline pressures compared with men yet have better survival. Further studies exploring the mechanisms of differential outcomes according to sex in patients with HCM undergoing ASA are needed.

Abstract Animals that co‐occur in a region (sympatry) may share the same environment (syntopy), and niche differentiation is expected among closely related species competing for resources. The masked booby (Sula dactylatra) and smaller congeneric red‐footed booby (Sula sula) share breeding grounds. In addition to the inter‐specific size difference, females of both species are also larger than the respective males (reversed sexual size dimorphism). Although both boobies consume similar prey, sometimes in mixed‐species flocks, each species and sex may specialize in terms of their diet or foraging habitats. We examined inter‐ and intra‐specific differences in isotopic values (δ13C and δ15N) in these pelagically feeding booby species during the incubation period at Clarion Island, Mexico, to quantify the degrees of inter‐ and intra‐specific niche partitioning throughout the annual cycle. During incubation, both species preyed mainly on flyingfish and squid, but masked boobies had heavier food loads than red‐footed boobies. There was no overlap in isotopic niches between masked and red‐footed boobies during breeding (determined from whole blood), but there was slight overlap during the non‐breeding period (determined from body feathers). Female masked boobies had a higher trophic position than conspecific males during breeding; however, no such pattern was detected in red‐footed boobies. These results provide evidence of inter‐ and intra‐specific niche partitioning in these tropical seabird species, particularly during the breeding period and in the more‐dimorphic species. Our results suggest that these closely related species use different strategies to cope with the same tropical marine environment.

Background Carotid artery stenting (CAS) has emerged as a viable alternative to carotid endarterectomy for managing carotid artery stenosis in high‐risk patients. Although transfemoral arterial access remains the preferred method, it is associated with inherent limitations and potential complications. Consequently, exploring transradial artery access as a potential option becomes crucial in optimizing patient outcomes and procedural success rates. There are limited data comparing the outcomes of the transradial with the transfemoral approach for CAS. This study aimed to systematically review and meta‐analyze the outcomes and complication rates between transradial and transfemoral access for CAS. Methods A systematic electronic search was conducted in 4 databases. Studies with randomized or nonrandomized designs, involving CAS by the transradial or transfemoral approach, were included. Outcomes of interest were stroke, transient ischemic attack, death, myocardial infarction, and access site complications. A meta‐analysis was performed, analyzing pooled odds ratios (ORs) and 95% CIs to assess the effect size. Results Six studies with a total of 6917 patients were included, of whom 602 (8.7%) underwent the transradial approach and 6315 (91.3%) the transfemoral approach. The meta‐analysis showed no significant difference in stroke occurrence between the transradial and transfemoral groups (transradial:1.7% versus transfemoral:1.9%; OR = 0.98 [95% CI, 0.49–1.96]; I2 = 0%). Similarly, no significant difference was found in death (TR:1% versus transfemoral:0.9%; OR = 0.95 [95% CI, 0.38–2.37]; I2 = 0%), myocardial infarction (transradial:0.2% versus transfemoral:0.3%; OR = 1.53 [95% CI, 0.20–11.61]; I2 = 0%), transient ischemic attack (transradial:0.4% versus transfemoral:1%; OR = 0.46 [95% CI, 0.11–1.95]; I2 = 0%), or access site complications (transradial:2.2% versus transfemoral:1%; OR = 0.97 [95% CI, 0.48–1.98]; I2 = 0%). Conclusion No significant differences were observed in stroke, death, myocardial infarction, transient ischemic attack, or access site complications on comparing thetransradial and transfemoral approaches for CAS. The transradial approach shows promise as an alternative method for CAS, offering potential benefits without increased risk of complications. However, further studies are needed to confirm these findings.

Abstract Objective To improve susceptibility profiles of nosocomial bacteria, identifying the difference between infectious complications in patients undergoing endoscopic flexible ureterolithotomy (fURS) with negative urine culture (UC) that received extended antibiotic prophylaxis (EP) compared with standard antibiotic prophylaxis (SP). Methodology This is a retrospective, observational, analytical cohort study, comparing infectious complications between patients undergoing fURS with negative UC who received EP versus SP. We include patients with susccessfull fURS,

Abstract Rural electrification is a crucial component of meeting sustainable development goals. In Pakistan, load shedding and power outages are frequent. According to the current data, Pakistan is experiencing a shortfall of power between 6000 and 6500 MW. Microgrid technology has the potential to provide a solution to this problem in an efficient and low‐cost manner. This paper proposes the development of a hybrid microgrid system (HMGS) for rural communities. For that purpose, a technological analysis of the HMGS system for rural electrification is performed. Solar photovoltaic (PV) and wind resource‐based renewable energy systems are considered in this work for the electrification of rural areas of Pakistan. A hybrid PV/wind system is designed using MATLAB software. Simulation results show that a 230‐V sinusoidal output voltage has been produced by the proposed model. The advantage of this model is that it minimizes the impact of transients and provides a sinusoidal output waveform.

Abstract Aims Patients with heart failure (HF) admitted for decompensation often require high doses of intravenous diuretics. This study aims to analyse whether the use of peripheral ultrafiltration (UF) in patients hospitalized for acute HF with systemic‐predominant congestion results in better hydric control, renal protection, and reduction of hospital stay compared with conventional treatment. Methods and results This study was a retrospective, comparative, single‐centre study of 56 patients admitted for HF with systemic congestion with a poor diuretic response after diuretic escalation. One group underwent peripheral UF (35 patients) and others were maintained on intense diuretic treatment (control group, 21 patients). The diuretic response and days of hospital stay were compared between and within groups. The baseline characteristics of both groups were similar: males with right ventricular failure and renal dysfunction. The inter‐group analysis showed that patients who received UF had better glomerular filtration rate (GFR; UF: 39.2 ± 18.2 vs. control: 28.7 ± 13.4 mL/min; P = 0.031) and higher diuresis (UF: 2184 ± 735 vs. control: 1335 ± 297 mL; P = 0.0001) at hospital discharge despite less need for diuretic drugs. Days of hospital stay were shorter in the UF group (UF: 11.7 ± 10.1 vs. control: 19.1 ± 14.4 days; P = 0.027). Intra‐group analysis showed that patients receiving UF improved GFR, increased diuresis, and reduced weight at discharge (P

Abstract Passive acoustic monitoring is usually presented as a complementary approach to monitoring wildlife communities and assessing ecosystem conditions. Automatic species detection methods support biodiversity monitoring and analysis by providing information on the presence–absence of species, which allows understanding the ecosystem structure. Therefore, different alternatives have been proposed to identify species. However, the algorithms are parameterized to identify specific species. Analysing multiple species would help to monitor and quantify biodiversity, as it includes the different taxonomic groups present in the soundscape. We present an unsupervised methodology for multi‐species call recognition from ecological soundscapes. The proposal is based on a clustering algorithm, specifically the learning algorithm for multivariate data analysis (LAMDA) 3pi algorithm, which automatically suggests the number of clusters associated with the sonotypes. Emphasis was made on improving the segmentation of the audio to analyse the whole soundscape without parameterizing the algorithm according to each taxonomic group. To estimate the performance of our proposal, we used four datasets from different locations, years and habitats. These datasets contain sounds from the four major taxonomic groups that dominate terrestrial soundscapes (birds, amphibians, mammals and insects) in audible and ultrasonic spectra. The methodology presents performances between 75% and 96% in presence–absence species recognition. Using the clusters proposed by our methodology, the whole soundscape biodiversity was measured and compared with the estimate of four acoustic indices (ACI, NP, SO and BI). Our approach performs biodiversity assessments similar to acoustic indices with the advantage of providing information about acoustic communities without the need for prior knowledge of the species present in the audio recordings.

Abstract Objective This systematic review aimed to investigate the role of the C‐X3‐C motif ligand 1/chemokine receptor 1 C‐X3‐C motif (CX3CL1/CX3CR1) axis in the pathogenesis of periodontitis. Furthermore, as a secondary objective, we determine whether the CX3CL1/CX3CR1 axis could be considered complementary to clinical parameters to distinguish between periodontitis and rheumatoid arthritis (RA) and/or systemically healthy subjects. Methods The protocol used for this review was registered in OSF (10.17605/OSF.IO/KU8FJ). This study was designed following Preferred Reporting Items for Systematic Review and Meta‐Analysis guidelines. Records were identified using different search engines (PubMed/MEDLINE, Scopus, Science Direct, and Web of Science) from August 10, 2006, to September 15, 2023. The observational studies on human subjects diagnosed with periodontitis and RA and/or systemically healthy were selected to analyze CX3CL1 and CX3CR1 biomarkers. The methodological validity of the selected articles was assessed using NIH. Results Six articles were included. Biological samples (gingival crevicular fluid [GCF], saliva, gingival tissue biopsies, serum) from 379 subjects (n = 275 exposure group and n = 104 control group) were analyzed. Higher CX3CL1 and CX3CR1 chemokine levels were found in subjects with periodontitis and RA compared with periodontal and systemically healthy subjects. Conclusion Very few studies highlight the role of the CX3CL1/CX3CR1 axis in the pathogenesis of periodontitis; however, increased levels of these chemokines are observed in different biological samples (GCF, gingival tissue, saliva, and serum) from subjects with periodontitis and RA compared with their healthy controls. Future studies should focus on long‐term follow‐up of subjects and monitoring changes in cytokine levels before and after periodontal therapy to deduce an appropriate interval in health and disease conditions.

Background Aortic valve calcium score is associated with hemodynamic severity of aortic stenosis. Whether this association is present in calcific mitral stenosis remains unknown. Methods and Results This study was a retrospective analysis of consecutive patients with mitral stenosis secondary to mitral annular calcification (MAC) undergoing transseptal catheterization. All patients underwent invasive mitral valve assessment via direct left atrial and left ventricular pressure measurement. Computed tomography within 1 year of cardiac catheterization and with adequate visualization of the mitral annulus was included. MAC calcium score quantification by Agatston method was obtained offline using dedicated software (Aquarius, TeraRecon, V.4). Median patient age was 66.9±11.2 years, 47% of patients were women, 50% had coronary artery disease, 40% had atrial fibrillation, 47% had prior cardiac surgery, and 33% had prior chest radiation. Median diastolic mitral valve gradient was 9.4±3.4 mm Hg on echocardiography and 8.5±4 mm Hg invasively. Invasive median mitral valve area using the Gorlin formula was 1.87±0.9 cm2. Median MAC calcium score for the cohort was 7280±7937 Hounsfield units. MAC calcium score correlated with the presence of atrial fibrillation (P=0.02) but was not associated with other comorbidities. There was no correlation between MAC calcium score and mitral valve area (r=0.07; P=0.6) or mitral valve gradient (r=−0.03; P=0.8). Conclusions MAC calcium score did not correlate with invasively measured mitral valve gradient and mitral valve area in patients with MAC‐related mitral stenosis, suggesting that calcium score should not be used as a surrogate for invasive hemodynamic parameters.

Abstract Swimmer athletes showed a decreased ventilatory response and reduced sympathetic activation during peripheral hypoxic chemoreflex stimulation. Based on these observations, we hypothesized that swimmers develop a diminished cardiorespiratory coupling due to their decreased hypoxic peripheral response. To resolve this hypothesis, we conducted a study using coherence time‐varying analysis to assess the cardiorespiratory coupling in swimmer athletes. We recruited 12 trained swimmers and 12 control subjects for our research. We employed wavelet time‐varying spectral coherence analysis to examine the relationship between the respiratory frequency (Rf) and the heart rate (HR) time series during normoxia and acute chemoreflex activation induced by five consecutive inhalations of 100% N2. Comparing swimmers to control subjects, we observed a significant reduction in the hypoxic ventilatory responses to N2 in swimmers (0.012 ± 0.001 vs. 0.015 ± 0.001 ΔVE/ΔVO2, and 0.365 ± 0.266 vs. 1.430 ± 0.961 ΔVE/ΔVCO2/ΔSpO2, both p

Abstract Pulmonary mechanics has been traditionally viewed as determined by lung size and physical factors such as frictional forces and tissue viscoelastic properties, but few information exists regarding potential influences of cytokines and hormones on lung function. Concentrations of 28 cytokines and hormones were measured in saliva from clinically healthy scholar children, purposely selected to include a wide range of body mass index (BMI). Lung function was assessed by impulse oscillometry, spirometry, and diffusing capacity for carbon monoxide, and expressed as z‐score or percent predicted. Ninety‐six scholar children (55.2% female) were enrolled. Bivariate analysis showed that almost all lung function variables correlated with one or more cytokine or hormone, mainly in boys, but only some of them remained statistically significant in the multiple regression analyses. Thus, after adjusting by height, age, and BMI, salivary concentrations of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in boys were associated with zR5‐R20 and reactance parameters (zX20, zFres, and zAX), while glucagon inversely correlated with resistances (zR5 and zR20). Thus, in physiological conditions, part of the mechanics of breathing might be influenced by some cytokines and hormones, including glucagon and GM‐CSF. This endogenous influence is a novel concept that warrants in‐depth characterization.

Abstract Introduction Trials of CT‐based screening for lung cancer have shown a mortality advantage for screening in North America and Europe. Before introducing a nationwide lung cancer screening program in Germany, it is important to assess the criteria used in international trials in the German population. Methods We used data from 3623 lung cancer patients from the data warehouse of the German Center for Lung Research (DZL). We compared the sensitivity of the following lung cancer screening criteria overall and stratified by age and histology: the National Lung Screening Trial (NLST), the Danish Lung Cancer Screening Trial (DLCST), the 2013 and 2021 US Preventive Services Task Force (USPSTF), and an adapted version of the Prostate, Lung, Colorectal, and Ovarian no race model (adapted PLCOm2012) with 6‐year risk thresholds of 1.0%/6 year and 1.7%/6 year. Results Overall, the adapted PLCOm2012 model (1%/6 years), selected the highest proportion of lung cancer patients for screening (72.4%), followed by the 2021 USPSTF (70.0%), the adapted PLCOm2012 (1.7%/6 year) (57.4%), the 2013 USPTF (57.0%), DLCST criteria (48.7%), and the NLST (48.5%). The adapted PLCOm2012 risk model (1.0%/6 year) had the highest sensitivity for all histological types except for small‐cell and large‐cell carcinomas (non‐significant), whereas the 2021 USPTF selected a higher proportion of patients. The sensitivity levels were higher in males than in females. Conclusion Using a risk‐based selection score resulted in higher sensitivities compared to criteria using dichotomized age and smoking history. However, gender disparities were apparent in all studied eligibility criteria. In light of increasing lung cancer incidences in women, all selection criteria should be reviewed for ways to close this gender gap, especially when implementing a large‐scale lung cancer screening program.

Abstract This paper presents an adaptive control framework for the flexible and effective management and control of clustered DC nano‐grids (NGs) in an islanded DC microgrid system. It is assumed that each NG contains a photovoltaic (PV) system, a battery energy storage system (BESS), local loads, and a gateway (GW) module. Each NG has a hierarchical control system consisting of a decision‐making module and low‐level controllers. The decision‐making module ensures various desirable features including plug‐and‐play operation of NGs, maximum utilization of PV power generations, and avoiding state of charge (SoC) violation of batteries. Moreover, an adaptive model predictive control (AMPC) strategy is proposed to regulate the voltage of the NG local DC buses in the presence of non‐linear loads. This approach improves the performance of the NG voltage control system and reduces the current ripples of BESSs, thereby enhancing the lifetime of the batteries. In addition, a smart switching consensus‐based control strategy is designed that provides flexible power sharing among the NGs to balance the SoC of BESSs in which the BESSs altogether imitate the behaviour of a single cloud energy storage system (ESS). Finally, the performance of the proposed control system is verified by simulating the DC microgrid in MATLAB/Simulink.

Abstract In the distribution system, decentralized generation is incorporated to maximize the system reliability and economic stability, and to avoid redundancy in system. The efficient implementation of distributed‐generations (DGs) in a distribution‐system (DS) can be done by employing demand‐side management (DSM). In this research proposal, location and size selection of DGs in a DS considering DSM is accomplished using a hybrid Jaya‐Luus‐Jaakola (JLJ) algorithm. The hybridization of Jaya algorithm (JA) with Luus‐Jaakola algorithm (LJA) is done with a view to improving the rate of convergence of the algorithm. Three design objectives of minimization of active power loss and voltage deviation along with maximization of voltage stability index are considered in this research proposal. These design objectives under consideration are integrated together to form a problem of a single objective by assignments of weights. The formulated problem is minimized using proposed hybrid algorithm subjected to system constraints such as balance of power, limits on bus voltage and line capacity, and generation level of DGs. A static penalty is added to the formulated problem in case of any constraint violations. A photo‐voltaic‐based DG is used in the 33‐bus standard radial‐distribution‐system (RDS). A DSM scenario is created by shifting some loads of peak hours to off‐peak hours in view of minimizing the total cost of generation. The potency and superiority of the proposed algorithm is validated with the help of comparison of the results obtained by exploiting proposed method with results acquired from available state‐of‐art algorithms in literature. The comparison proves the comparative superior performance of the proposed algorithm.

Abstract Dispatchable energy storage system (ESS) plays a critical role in the smart grid through energy shift and power support. However, it exhibits different operational strategies and economic benefits in different application scenarios due to its inherent degradation behaviour. This paper aims to explore the technical and economic feasibility of the flexible traction power supply system (FTPSS) integrating ESS and renewable energy sources (RES) based on the traction load characteristics. First, a battery degradation model applicable in its frequent charging and discharging operating conditions is derived. Then this paper develops an operational‐sizing co‐optimization framework for the ESS in the FTPSS, where the operation decisions are made considering the degradation costs varying with the sizes and energy throughput. To solve this large‐scale non‐linear intertemporal decision‐making problem, an iterative method with a linear programming (LP) core is proposed to achieve the trade‐off between computational efficiency and accuracy. The results of the extensive comparative cases show that the proposed approach can achieve approximately 10% higher economic benefits than the existing bi‐level sizing strategies for FTPSS.

Introduction Burnout in medicine is an occupational hazard and has emerged as a pressing concern in recent years. Organizational changes can be impactful in countering burnout (1). The factors leading to burnout in medicine are multifaceted, encompassing organizational factors such as workload, inadequate support, and inefficient administrative systems. The purpose of this study is to investigate current organizational measures to support physician well‐being. This study was an initiative led by the SVIN wellness committee. Methods A 39‐question online survey investigating current organizational well‐being practices was distributed to physicians both nationally and internationally practicing stroke, neurocritical care, and interventional neurology. Data analysis was performed using Python, utilizing the libraries “pandas” and “sklearn”. Results This study analyzed burnout among 109 healthcare professionals, predominantly from the U.S. (93.6%) and Canada (6.4%). The majority were neurointerventional specialists (53.2%), aged 35‐44 years (52.3%), and male (62.4%). Burnout frequency was measured on a 0 (Never) to 4 (Every day) scale. Using a Random Forest model, the study identified key burnout predictors from questions, which covered organizational leadership, wellness resources, compensation, and workload. The most influential predictors were: adequacy of compensation relative to specialty, workload, and stress (17.7% importance); leadership accountability for workforce wellbeing (9.1%); and establishment of wellness or burnout as a critical metric (7.5%). Other factors included provision of wellness screenings (7.1%), and dedication of resources toward professional well‐being (4.9%). Conclusion The study identifies compensation, leadership accountability, and wellness resources as key predictors of burnout among healthcare professionals. These findings highlight the need for targeted organizational strategies to enhance physician well‐being and mitigate burnout. Further research is warranted to validate and expand upon these findings.

Introduction Tandem Lesions (TLs) pose unique challenges in the endovascular management of acute ischemic stroke.(1) The absence of anterograde blood flow in the carotid occluded segment may limit the effectiveness of endovascular interventions, resulting in delayed reperfusion or suboptimal recanalization.(2,3) Thus, the presence of unpaired blood flow through the ICA in the context of TLs is believed to exacerbate the extension of ischemic lesions. (4,5) This study compared the clinical and procedural outcomes of patients with TLs and extracranial internal carotid artery occlusion versus those with stenosis. Methods A retrospective analysis was performed on a multicenter cohort of patients with TLs who underwent endovascular treatment. The patients were categorized into two groups: those with extracranial ICA stenosis and those with occlusion. Clinical outcomes, including functional independence, hemorrhagic events, and procedural time metrics including puncture to reperfusion time were assessed. Sensitivity analyses were conducted to evaluate these differences segregating patients according to varying degrees of stenosis, and in pre‐specified subgroups. Results A total of 513 patients with TLs were included in the study. 281 (54.8%) presented with ICA occlusion, and 232 (45.2%) presented stenosis >=70% (Table 1). The comparison between the stenosis and occlusion groups revealed no significant differences in the main outcomes, including mTICI 2c‐3 (47.5% vs. 50.6%, aOR 1.07, 95% CI 0.70‐1.64, p=.751) (Figure 1), mRS 0‐2 at 90 days (43.6% vs. 48.9%, aOR 0.79, 95% CI 0.52‐1.20, p=.271), sICH rates (4.7% vs. 5.6%, aOR 0.72, 95% CI 0.31‐1.71, p=.458), and puncture to reperfusion time (58 [40‐80.5] vs. 52.5 [35.2‐80], ratio 1.04, 95% CI 0.88‐1.23, p=.64). Similar analyses performed comparing different degrees of stenosis and occlusion, and in patients treated with the antegrade approach only, did not show significant differences either. Conclusion Our findings indicate that although more severe degrees of stenosis or occlusion of the ICA prolong the time from puncture to reperfusion, no significant differences in clinical outcomes exist. The clinical implications of these findings need to be further evaluated to fully comprehend the specific needs of patients affected by TLs.

Introduction Carotid artery stenting (CAS) has emerged as a viable alternative to carotid endarterectomy for managing carotid artery stenosis in high‐risk patients (1). While the transfemoral arterial approach (TF) remains the preferred method, it is associated with inherent limitations and potential complications (2‐4). Consequently, exploring the transradial artery access (TR) as a potential option becomes crucial in optimizing patient outcomes and procedural success rates. Limited data exists comparing the outcomes of TR approach in CAS to TF approach. This study aims to systematically review and meta‐analyze the outcomes and complication rates between TR and TF access for CAS. Methods A systematic electronic search was conducted in four databases up to May 10th, 2023. Studies with randomized or non‐randomized designs, involving CAS through TR or TF approach, were included. Outcomes of interest were stroke, transient ischemic attack (TIA), death, myocardial infarction (MI), and access site complications. A meta‐analysis was performed, analyzing pooled odds ratios (ORs) and 95% confidence intervals (CI) to assess the effect size of the vascular access approaches. Results Six studies with a total of 6,917 patients were included, out of which 602 (8.7%) underwent the TR approach, and 6,315 (91.3%) underwent the TF approach. Meta‐analysis results showed no significant difference in stroke occurrence between TR and TF groups (TR: 1.7% vs. TF: 1.9%; OR = 0.98; 95% CI 0.49 – 1.96; I2 = 0%). Similarly, no significant difference was found in death (TR: 1% vs. TF: 0.9%; OR = 0.95; 95% CI 0.38 – 2.37; I2 = 0%), MI (TR: 0.2% vs. TF: 0.3%; OR = 1.53; 95% CI 0.20 – 11.61; I2 = 0%), TIA (TR: 0.4% vs. TF: 1%; OR = 0.46; 95% CI 0.11 – 1.95; I2 = 0%), and access site complications (TR: 2.2% vs. TF: 1%; OR = 0.97; 95% CI 0.48 – 1.98; I2 = 0%). Conclusion In the comparison of TR and TF approaches for CAS, no significant differences were observed in stroke, death, MI, TIA, or access site complications. TR approach shows promise as an alternative method for CAS, offering potential benefits without increased risk of complications. However, further studies are needed to confirm these findings and establish guidelines for optimal access site selection.

Introduction Tandem lesions (TLs) are present in up to 15% of patients with stroke due to acute large vessel occlusions.(1) Nevertheless, published research on endovascular treatment outcomes in this population is scarce. Although TLs are most commonly of atherosclerotic etiology, some patients present with dissection of the ICA.(2, 3) In this study, we compared the clinical outcomes of TL patients with the two etiologies. Methods A retrospective analysis was performed on a multicenter cohort of patients with TLs who underwent endovascular treatment. The patients were categorized into two groups according to the etiology of the ICA lesion: atherosclerosis and dissection. Patients were matched by baseline characteristics. Clinical outcomes, including recanalization success, functional independence and hemorrhagic events were assessed with multivariable analyses. Results Of 691 patients from the database, 526 met the inclusion criteria of this study. 467 (88.8%) patients presented with atherosclerosis of the ICA, and 59 (11.2%) patients presented dissection. Univariable differences were found in median age (69 y. [IQR 61 ‐ 76] vs. 52 y. [IQR 44 ‐ 63], p

Background Procedural intravenous cangrelor has been proposed as an effective platelet inhibition strategy for stenting in acute ischemic stroke. We aimed to compare the safety profile of low‐dose intravenous cangrelor versus dual oral antiplatelet therapy (DAPT) loading in patients with acute cervical tandem lesions. Methods We retrospectively identified cases from an international multicenter cohort who underwent intraprocedural administration of intravenous cangrelor (15 μg/kg followed by an infusion of 2 μg/kg per min) or DAPT loading during acute tandem lesions intervention. Safety outcomes included rates of symptomatic intracranial hemorrhage, parenchymal hematoma type 2, petechial hemorrhage, and in‐stent thrombosis. Inverse probability of treatment weighting matching was used to reduce confounding. Results From 691 patients, we included 195 patients, 30 of whom received intravenous cangrelor and 165 DAPT. The DAPT regimens were aspirin+clopidogrel (93.3%) or aspirin+ticagrelor (6.6%). After inverse probability of treatment weighting, the patients treated with cangrelor were not at greater odds of symptomatic intracranial hemorrhage (odds ratio [OR], 1.30 [95% CI, 0.09–17.3]; P=0.837), symptomatic intracranial hemorrhage–parenchymal hematoma type 2 (OR, 0.54 [95% CI, 0.05–4.98]; P=0.589), or petechial hemorrhage (OR, 1.11 [95% CI, 0.38–3.28]; P=0.836). Similarly, the rate of in‐stent thrombosis was not significantly different between the 2 groups (1.8% versus 0%; P=0.911). Conclusion Cangrelor at the half dose of the myocardial infarction protocol showed a similar safety profile compared with the commonly used DAPT loading protocols in patients with acute tandem lesions. Further studies with larger samples are warranted to elucidate the safety of antiplatelet therapy in tandem lesions.

Abstract Introduction Waning immunity after vaccination justifies the need for additional effective COVID‐19 treatments. Immunomodulation of local immune response at the oropharyngeal mucosa could hypothetically activate mucosal immunity, which can prevent SARS‐CoV‐2 main immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections using an enteral route, which point to potential effects on time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID‐19. Summary This pilot clinical trial investigated the effect of buccopharyngeal administered high polyphenolic olive oil on COVID‐19 incidence, duration, and severity. Importance Waning immunity after vaccination justifies the need of further research for additional effective treatments for COVID‐19. Objective Immunomodulation of local immune response at the buccopharyngeal mucosa could hypothetically activate mucosal immunity, which would in turn difficult SARS‐CoV‐2 immune evasion mechanisms in early stages of the disease and send an effective warning to other components of immune system. Olive polyphenols are biologically active compounds with immunomodulatory activity. There are previous studies based on immunomodulation with olive polyphenols and respiratory infections, using an enteral route, which suggest potential shortening of time to resolution of symptoms. The investigators sought to determine whether participants following immunomodulation with tiny quantities of high polyphenolic olive oil administered through an oromucosal route could have a better outcome in COVID‐19. Design, Setting, and Participants Double blind, randomized pilot clinical trial conducted at a single site, Talavera de la Reina, Spain. Potential study participants were identified by simple random sampling from the epidemiological database of contact patients recently diagnosed of COVID‐19 during the study period. A total of 88 adult participants were enrolled and 84 completed the 3‐month study, conducted between July 1, 2021 and August 31, 2022. Intervention Participants were randomized to receive oromucosal administered high polyphenolic olive oil, 2 mL twice a day for 3 months or no treatment. Main Outcome and Measures Primary outcomes were incidence, duration, and severity of COVID‐19 after intervention. Results There were no differences in incidence between both groups but there were significant differences in duration, the median time to resolution of symptoms was 3 days in the high polyphenolic olive oil group compared with 7 days in the no‐treatment group. Although time to resolution is directly related to severity, this study did not find any differences in severity. Conclusion and Relevance Among full‐vaccinated adults recent infected with COVID‐19, a daily intake of tiny quantities of oromucosal administered high polyphenolic olive oil before infection significantly improved the time to symptom resolution. This finding strongly support the appropriateness of further deep research on the use of oromucosal administered high polyphenolic olive oil as an effective immune strategy against COVID‐19.

Abstract Chromatin homeostasis mediates essential processes in eukaryotes, where histone chaperones have emerged as major regulatory factors during DNA replication, repair, and transcription. The dynamic nature of these processes, however, has severely impeded their characterization at the molecular level. Here, fluorescence optical tweezers are applied to follow histone chaperone dynamics in real time. The molecular action of SET/template‐activating factor‐Iβ and nucleophosmin 1—representing the two most common histone chaperone folds—are examined using both nucleosomes and isolated histones. It is shown that these chaperones present binding specificity for fully dismantled nucleosomes and are able to recognize and disrupt non‐native histone‐DNA interactions. Furthermore, the histone eviction process and its modulation by cytochrome c are scrutinized. This approach shows that despite the different structures of these chaperones, they present conserved modes of action mediating nucleosome remodeling.

Background Data are rare about the incidence of severe Fontan‐associated liver disease (FALD) and its association with mortality. We sought to: (1) estimate the probability of developing severe FALD in patients who undergo the Fontan procedure (Fontan patients), compared with severe liver complications in patients with a ventricular septal defect; (2) assess the severe FALD‐mortality association; and (3) identify risk factors for developing severe FALD. Methods and Results Using the Quebec Congenital Heart Disease database, a total of 512 Fontan patients and 10 232 patients with a ventricular septal defect were identified. Kaplan‐Meier curves demonstrated significantly higher cumulative risk of severe FALD in Fontan patients (11.95% and 52.24% at 10 and 35 years, respectively), than the risk of severe liver complications in patients with a ventricular septal defect (0.50% and 2.75%, respectively). At 5 years, the cumulative risk of death was 12.60% in patients with severe FALD versus 3.70% in Fontan patients without FALD (log‐rank P=0.0171). Cox proportional hazard models identified significant associations between the development of severe FALD and congestive heart failure and supraventricular tachycardia, with hazard ratios (HRs) of 2.36 (95% CI, 1.38–4.02) and 2.45 (95% CI, 1.37–4.39), respectively. More recent Fontan completion was related to reduced risks of severe FALD, with an HR of 0.95 (95% CI, 0.93–0.97) for each more recent year. Conclusions This large‐scale population‐based study documents that severe FALD in Fontan patients was associated with a >3‐fold increase in mortality. The risk of FALD is time‐dependent and can reach >50% by 35 years after the Fontan operation. Conditions promoting poor Fontan hemodynamics were associated with severe FALD development.

Abstract Introduction Social support is a protective factor in the mental health of autistic people. Furthermore, prejudice regarding autistic people is a constraint for the development of social support programmes by autistic peers. Methods The objective of this study is to describe the anticipated acceptability of structured peer support programmes for and by autistic persons. Fifteen key stakeholders (six autistic adults, four caregivers and five service providers) participated in in‐depth semistructured interviews. A qualitative thematic analysis of the content of the verbatim was carried out. Findings We found that while a structured peer social support programme is acceptable to autistic people and caregivers, there was no consensus among service providers. The latter expressed doubts about the ability of autistic people to offer support. The framing of discussions between peers, the training of peer helpers, the support for autistic leadership and an organization that considers the communicational and sensory characteristics of autistic persons, could influence adherence to such a programme. Moreover, a space without service providers is an important condition for the acceptability of a peer support programme. Conclusion A structured peer support service for and by autistic persons could be an innovative way to answer the unmet support needs of autistic people. It seems essential to anticipate potential barriers and facilitators and to communicate among health professionals to promote this approach and reduce possible prejudice about the ability of autistic people to offer support to their peers. More studies are necessary. Patient or Public Contribution Fifteen key stakeholders who are involved in autistic people's trajectory of service and support participated in this research. We are a research team composed of healthcare professionals and researchers, in addition to one member of our team being an autistic advocate and a mental health peer‐support mentor. Two members of our team are also parents of autistic children. The comprehensibility of the questions for the interview was consulted and discussed with one autistic advocate‐collaborator.

Abstract Aim The study aimed to establish the impact of high‐fidelity simulation (HFS) in the objective structured clinical examination (OSCE) of nursing students enrolled in four undergraduate courses (medical‐surgical, critical‐care, maternal‐health and paediatric nursing). Design This quasi‐experimental research study was performed during the midterm and final OSCEs of nursing students at the institution, and their OSCE performance was assessed. Methods The students were divided into two: those who were exposed to HFS in addition to their clinical training and the other group who underwent clinical training without HFS exposure. Results The combined mean midterm and final OSCE results of the group of nursing students with HFS exposure and those without HFS exposure were 92.58 and 82.66, respectively, with a mean between‐group difference of 9.92% (p

Abstract Introduction Stage III non‐small‐cell lung cancer (NSCLC) management is challenging given the heterogeneous nature of the disease. The LATAM subset of the real‐world, global KINDLE study reported the treatment patterns and clinical outcomes for LATAM from the pre‐immuno‐oncology era. Methods The study was conducted in seven countries (Argentina, Chile, Colombia, Dominican Republic, Mexico, Peru and Uruguay) in stage III NSCLC (American Joint Committee on Cancer, 7th edition) diagnosed between January 2013 and December 2017. Retrospective data from patients' medical records (index date to the end of follow‐up) were collected. Summary statistics, Kaplan–Meier survival estimates and a two‐sided 95% confidence interval (CI) were provided. Cox proportional hazard model was used for univariate and multi‐variate analyses. Results A total of 231 patients was enrolled, the median age was 65.0 years (range 21.0–89.0), 60.6% were males, 76.6% had smoking history, 64.0% had adenocarcinoma and 28.7% underwent curative resection. Multiple treatment regimens (>25) were used; chemotherapy alone was the most common (24.8%). The overall median progression‐free survival (mPFS) and median overall survival (mOS) were 14.8 months (95% CI, 12.1–18.6) and 48.6 months (95% CI, 34.7 to not calculable). Significantly better mPFS and mOS were observed for stage IIIA with curative surgery and resectable tumours and stage IIIB with an Eastern Cooperative Oncology Group score of 0/1, female gender, resectable tumours, adenocarcinoma and curative surgery (p

Objective Evobrutinib is a highly selective, orally administered Bruton's tyrosine kinase (BTK) inhibitor. The objective of this phase II, multicenter, randomized, double‐blind, placebo‐controlled trial was to evaluate the efficacy and safety of evobrutinib in patients with active autoantibody‐positive systemic lupus erythematosus (SLE). Methods Patients were diagnosed with SLE by either the Systemic Lupus International Collaborating Clinics criteria or at least four American College of Rheumatology criteria 6 months or more prior to screening, had an SLE Disease Activity Index‐2000 score of 6 or more, were autoantibody‐positive and on standard‐of‐care therapy. Randomization was 1:1:1:1 to oral evobrutinib 25 mg once daily (QD), 75 mg QD, 50 mg twice daily, or placebo. Primary efficacy endpoints were SLE responder index (SRI)‐4 response at week 52 and SRI‐6 response at week 52 in the high disease activity subpopulation. Safety endpoints included treatment‐emergent adverse events (TEAEs). Results A total of 469 patients were randomized and received at least one dose of evobrutinib or placebo at the time of primary analysis. Mean (SD) age at baseline was 40.7 (±12.3) years; 94.9% of patients were female. Neither primary efficacy endpoint was met. All doses of evobrutinib were well tolerated, and there was no clear dose effect on the incidence of reported TEAEs, or serious TEAEs, including severe infections. Conclusion This phase II, dose‐ranging trial in SLE failed to show a treatment effect of evobrutinib versus placebo at any dose. Evobrutinib was generally well tolerated, with no dose effect observed for TEAEs. These results suggest that BTK inhibition does not appear to be an effective therapeutic intervention for patients with SLE.

Abstract The transport sector is in all probability the one that emits the greatest amounts of CO2 and other harmful gases into the atmosphere. Therefore, the emission of greenhouse gases from the combustion of fossil fuels must be significantly reduced to mitigate their harmful effects on the environment. In this sense, bio‐fuels obtained from lignocellulosic biomass are a solution to partially replace fuels from petroleum. However, the biggest challenge facing the scientific community is to decrease the amount of oxygen in bio‐fuels through catalytic hydrodeoxygenation (HDO) reactions. This review offers a broad perspective on the catalytic systems used so far in the HDO processes of model compounds present in bio‐fuels, analyzing in detail the advantages and disadvantages of each system to give a vision towards the future.

Abstract Locoregional recurrence of differentiated thyroid cancer (DTC) occurs in 20% of thyroid cancer patients. Currently, there are many strategies for management of locoregional recurrence of DTC that lead to local control of the disease. The introduction of lenvatinib into the therapeutic armamentarium provides a new option for the treatment of radioiodine‐refractory DTC (RR‐DTC). However, results for simultaneous treatment with lenvatinib and locoregional therapies are unknown in patients with RR‐DTC. This paper reviews the current status of this approach and gives recommendations on the management of lenvatinib during concomitant locoregional procedures.