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Spontaneous self-assembly in molecular systems is a fundamental route to both biological and engineered soft matter. Simple micellization, emulsion formation, and polymer mixing are well understood. However, the principles behind emergence of structures with competing length scales in soft matter systems remain unknown. Examples include droplet-inside-droplet assembly in many biomacromolecular systems undergoing liquid-liquid phase separation, analogous multiple emulsion formation in oil-surfactant-water formulations, and polymer core-shell particles with internal structure. We develop here a microscopic theoretical model based on effective interactions between the constituents of a soft matter system to explain self-organization both at single and multiple length scales. The model identifies how spatial ordering at multiple length scales emerges due to competing interactions between the system components, e.g., molecules of different sizes and different chemical properties. As an example of single and multiple length scale assembly, we map out a generic phase diagram for a solution with two solute species differing in their mutual and solvent interactions. We further connect the phase diagram to a molecular system via molecular simulations of a block-copolymer system that has a transition from regular single-core polymer particles to multicore aggregates that exhibit multiple structural length scales. The findings provide guidelines to understanding the length scales rising spontaneously in biological self-assembly but also open venues to the development and engineering of biomolecular and polymeric functional materials and pharmaceutical formulations.

Nanomedicine employs molecular materials for prevention and treatment of disease. Recently, smart nanoparticle (NP)-based drug delivery systems were developed for the advanced transport of drug molecules. Rationally engineered organic and inorganic NP platforms hold the promise of improving drug targeting, solubility, prolonged circulation, and tissue penetration. However, despite great progress in the synthesis of NP building blocks, more interdisciplinary research is needed to understand their self-assembly and optimize their performance as smart nanocarriers. Multi-scale modeling and simulations provide a valuable ally to experiment by mapping the potential energy landscape of self-assembly, translocation, and delivery of smart drug-loaded NPs. Here, we highlight key recent advances to illustrate the concepts, methods, and applications of smart polymer-based NP drug delivery. We summarize the key design principles emerging for advanced multifunctional polymer topologies, illustrating how the unusual architecture and chemistry of dendritic polymers, self-assembling polyelectrolytes and cyclic polymers can provide exceptional drug delivery platforms. We provide a roadmap outlining the opportunities and challenges for the effective use of predictive multiscale molecular modeling techniques to accelerate the development of smart polymer-based drug delivery systems.

Aim Of the Study: Drooling is common in children with neurological disabilities (ND), and constitutes an additional burden with many medical complications in an already socially disadvantaged patient. This study aims to evaluate the effectiveness of bilateral submandibulectomy (BS) to treat drooling with regard to the parental satisfaction grade, complications and recurrence of drooling in children with ND.Patients/material and Methods: A retrospective study was performed of all children with ND and drooling who underwent BS in our Department between January 1996 and November 2008. Data were taken from surgical records and patient files. Parental satisfaction was graded into four classes: A: 75-100% satisfaction (infrequent drooling, small amounts; absence of drooling); B: 50-75% satisfaction (occasional drooling, on and off all day; infrequent drooling, small amounts); C: 25-50% satisfaction (frequent drooling, but not profusely; occasional drooling, on and off all day); D: 0-25% satisfaction (constant drooling, always wet; frequent drooling, but not profusely).Results: BS was performed in 85 patients (38% male; 62% female; median age, 9 years). 35 patients had to be excluded from our study because their medical records were unavailable. Only 3 out of the remaining 50 patients had recurrence. Parental satisfaction grade (PSG) was A in 26 cases (55.3%); B in 15 (31.9%); C in 3 (6.4%) and D in 3 (6.4%). The first follow-up was usually 1 week after surgery (median, 2 weeks). The incidence of post-surgery complications was 4% and all complications were minor.Discussion/conclusions: Assessment of the results achieved was subjective as it was not possible to quantify the amount of drooling precisely before/after surgery. Nevertheless, BS was found to be an easy and safe procedure as the low rate of complications demonstrates. It was also found to be an effective procedure; there were only 3 recurrences, and PSG in 87.2% of cases was either A or B, indicating a minimum improvement in drooling of 50%. [ABSTRACT FROM AUTHOR]

Abstract Background The 8-aminoquinoline (8AQ) drug primaquine (PQ) is currently the only approved drug effective against the persistent liver stage of the hypnozoite forming strains Plasmodium vivax and Plasmodium ovale as well as Stage V gametocytes of Plasmodium falciparum. To date, several groups have investigated the toxicity observed in the 8AQ class, however, exact mechanisms and/or metabolic species responsible for PQ’s haemotoxic and anti-malarial properties are not fully understood. Methods In the present study, the metabolism of PQ was evaluated using in vitro recombinant metabolic enzymes from the cytochrome P450 (CYP) and mono-amine oxidase (MAO) families. Based on this information, metabolite identification experiments were performed using nominal and accurate mass measurements. Results Relative activity factor (RAF)-weighted intrinsic clearance values show the relative role of each enzyme to be MAO-A, 2C19, 3A4, and 2D6, with 76.1, 17.0, 5.2, and 1.7% contributions to PQ metabolism, respectively. CYP 2D6 was shown to produce at least six different oxidative metabolites along with demethylations, while MAO-A products derived from the PQ aldehyde, a pre-cursor to carboxy PQ. CYPs 2C19 and 3A4 produced only trace levels of hydroxylated species. Conclusions As a result of this work, CYP 2D6 and MAO-A have been implicated as the key enzymes associated with PQ metabolism, and metabolites previously identified as potentially playing a role in efficacy and haemolytic toxicity have been attributed to production via CYP 2D6 mediated pathways.

Abstract Background The clinical use of mefloquine (MQ) has declined due to dose-related neurological events. Next generation quinoline methanols (NGQMs) that do not accumulate in the central nervous system (CNS) to the same extent may have utility. In this study, CNS levels of NGQMs relative to MQ were measured and an early lead chemotype was identified for further optimization. Experimental design The plasma and brain levels of MQ and twenty five, 4-position modified NGQMs were determined using LCMS/MS at 5 min, 1, 6 and 24 h after IV administration (5 mg/kg) to male FVB mice. Fraction unbound in brain tissue homogenate was assessed in vitro using equilibrium dialysis and this was then used to calculate brain-unbound concentration from the measured brain total concentration. A five-fold reduction CNS levels relative to mefloquine was considered acceptable. Additional pharmacological properties such as permeability and potency were determined. Results The maximum brain (whole/free) concentrations of MQ were 1807/4.9 ng/g. Maximum whole brain concentrations of NGQMs were 23 - 21546 ng/g. Maximum free brain concentrations were 0.5 to 267 ng/g. Seven (28%) and two (8%) compounds exhibited acceptable whole and free brain concentrations, respectively. Optimization of maximum free brain levels, IC90s (as a measure or potency) and residual plasma concentrations at 24 h (as a surrogate for half-life) in the same molecule may be feasible since they were not correlated. Diamine quinoline methanols were the most promising lead compounds. Conclusion Reduction of CNS levels of NGQMs relative to mefloquine may be feasible. Optimization of this property together with potency and long half-life may be feasible amongst diamine quinoline methanols.

Abstract Background The clinical utility for mefloquine has been eroded due to its association with adverse neurological effects. Better-tolerated alternatives are required. The objective of the present study was the identification of lead compounds that are as effective as mefloquine, but exhibit physiochemical properties likely to render them less susceptible to passage across the blood-brain barrier. Methods A library of drug-like non-piperidine analogs of mefloquine was synthesized. These compounds are diverse in structure and physiochemical properties. They were screened in appropriate in vitro assays and evaluated in terms of their potential as lead compounds. The correlation of specific structural attributes and physiochemical properties with activity was assessed. Results The most potent analogs were low molecular weight unconjugated secondary amines with no heteroatoms in their side-chains. However, these compounds were more metabolically labile and permeable than mefloquine. In terms of physiochemical properties, lower polar surface area, lower molecular weight, more freely rotatable bonds and fewer H-bond acceptors were associated with greater potency. There was no such relationship between activity and LogP, LogD or the number of hydrogen bond donors (HBDs). The addition of an H-bond donor to the side-chain yielded a series of active diamines, which were as metabolically stable as mefloquine but showed reduced permeability. Conclusions A drug-like library of non-piperidine analogs of mefloquine was synthesized. From amongst this library an active lead series of less permeable, but metabolically stable, diamines was identified.

Introduction: Evidence regarding the benefit of endovascular therapy (EVT) in patients with acute ischemic stroke (AIS) due to isolated cervical internal carotid artery occlusion (c-ICA-O) is lacking. We assessed the outcomes and safety of EVT in patients with isolated c-ICA-O., Methods: Retrospective multicenter cohort study of patients with an AIS due to isolated c-ICA-O, within 24-h since last-seen-well. Comparisons were made between EVT and best medical therapy (BMT). The primary outcome was 3-months modified Rankin Scale (mRS) ordinal shift. Secondary outcomes included 3-month favorable outcome (mRS 0-2, or return to pre-stroke mRS), symptomatic intracranial hemorrhage (sICH) and any parenchymal hemorrhage. Outcomes were compared combining inverse probability of treatment weighting with regression models and propensity score matching (PSM) as sensitivity analysis., Results: We analyzed 998 patients (66.2% male, mean age 71.1 ± 13.2 years). 487 (48.8%) patients received EVT and 511 (51.2%) received BMT. Patients receiving EVT had a higher admission NIHSS [13 (7-18) vs 5 (2-13)] compared to BMT. There was no difference between EVT and BMT groups in 3-month mRS shift (adjusted common odds ratio [OR], 1.01 [95% CI 0.76-1.34]) and favorable outcome (adjusted OR [aOR] 1.16 [95% CI 0.84-1.60]). No patient (0%) in the BMT group had sICH versus 1.6% in the EVT group. Parenchymal hemorrhage was numerically higher in EVT patients (2.7% vs 0.6%; aOR 3.85 [95% CI 0.98-15.23]). PSM analysis revealed similar results., Discussion and Conclusion: In patients with isolated c-ICA-O, EVT was associated with similar odds of disability and intracranial bleeding compared to BMT. Randomized-controlled clinical trials in patients with isolated c-ICA-O are warranted., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Dietary fatty acids (FA) are crucial to the pathophysiology of inflammatory bowel disease (IBD), influencing systemic and gut inflammatory responses. Dietary FA intake influences the fatty acid profiles of vital cell membranes, which might be a source of inflammatory mediators. Despite their significance, research on dietary FA subtypes and their effects on inflammation and oxidative stress in IBD is limited., Objective: We investigated the association between dietary FA intake, the erythrocyte membrane FA composition (EMFA), and inflammation and oxidative stress markers in patients with mild-moderate luminal Crohn's Disease (CD) participating in the CD Therapeutic Dietary Intervention (CD-TDI)., Design: A cross-sectional analysis was performed on 24 participants (13 CD-TDI, 11 habitual diet controls) from a 13-week randomized controlled trial assessing the efficacy of CD-TDI in inducing clinical and biomarker remission in CD., Methods: EMFA was analyzed using direct-injection gas chromatography, and dietary FA intake was assessed using the ASA 24-h Dietary Assessment Tool ® ., Results: The CD-TDI group showed a significant increase in dietary n-3 polyunsaturated fatty acids (PUFA) at Week 13 ( p  = 0.04) compared to no changes in the control group. Participants on the CD-TDI also demonstrated a significant reduction in total fat, saturated fat, and arachidonic acid (AA) ( p  < 0.01). EMFA analysis revealed lower percentages of AA ( p  = 0.03) in the CD-TDI group. Positive correlations were observed between C-reactive protein, fecal calprotectin, and dietary stearic acid ( p  < 0.05). Inverse correlations were found between malondialdehyde (MDA) and the Mediterranean Diet Score ( r  = -0.67) as well as MDA and the intake of whole fruit, legumes, and nuts/seeds ( r  > -0.50)., Conclusion: The CD-TDI significantly increased dietary n-3 PUFA intake, reduced pro-inflammatory n-6 PUFA (AA), and improved markers of oxidative stress, supporting its potential in CD management. The cell membrane fatty acid profile might be a therapeutic target in CD., Trial Registration: NCT04596566., Competing Interests: DLG: Co-founder and Chief Scientific Officer of Melius MicroBiomics; Honorarium from BioCodex. LMT: Co-founder and Chief Executive Officer of LyfeMD., (© The Author(s), 2025.)

The red palm weevil (RPW; Coleoptera: Curculionidae) is a destructive pest affecting palms worldwide, capable of causing significant economic losses and ecological damage in managed palm ecosystems. Current management heavily relies on synthetic insecticides, but their overuse fosters resistance. Bacillus thuringiensis (Bt) offers a promising alternative, producing toxins selective against various insect orders, including Coleoptera. However, no specific Bt toxin has yet been identified for RPW. This study investigates the toxicity against RPW larvae of the Bt Cry1Ia protoxin, known for its dual activity against Lepidoptera and Coleoptera. A laboratory RPW colony was reared for two generations, ensuring a reliable insect source for bioassays. Cry1Ia was expressed as a 6xHis-tagged fusion protein in Escherichia coli and purified using nickel affinity. Incubation with RPW larval gut proteases for 24 h produced a stable core of ~65 kDa. Diet-incorporation bioassays revealed high Cry1Ia toxicity in neonate larvae. In contrast, the lepidopteran-active Cry1Ac protoxin, used as a robust negative control, was completely degraded after 24 h of in vitro proteolysis and showed no toxicity in bioassays. Cry1Ia-fed larvae exhibited significant midgut cell damage, characteristic of Bt intoxication. These findings highlight Cry1Ia's strong potential for integration into RPW management programs.

Background: The optimal endovascular management of cervical carotid dissection causing tandem occlusion remains uncertain. We investigated the impact of emergent carotid stenting during endovascular treatment (EVT) for acute ischemic stroke (AIS) in patients with tandem occlusion secondary to cervical carotid artery dissection. Methods: This was a secondary analysis of patients treated with EVT for AIS due to occlusive carotid artery dissection and tandem occlusion included in the retrospective international Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection (STOP-CAD) study. We compared patients with and without emergent stenting. The primary efficacy and safety outcomes were 90-day functional independence (modified Rankin Scale 0-2) and symptomatic intracranial hemorrhage (sICH) within 24h after EVT. Procedural outcome was successful intracranial recanalization (mTICI 2b/3). We used mixed-effect logistic regression adjusting for site, age, and NIHSS. In additional analyses, we used inverse probability of treatment weighting and adjusted for ASPECTS. Results: Of the 4023 patients enrolled in STOP-CAD, 328 presented with anterior circulation AIS due to tandem occlusion and underwent EVT. The median age was 51 years (interquartile range 44-58), and 96 patients (29.3%) were female. One hundred fifty patients (45.7%) underwent emergent stenting. There was no significant association between stenting and 90-day functional independence (62.0% vs 59.7%; aOR 1.23, 95% CI 0.82-1.86, p=0.315) or sICH (7.3% vs 7.9%; aOR OR 0.95, 95% CI 0.41-2.2, p=0.913). Emergent carotid stenting was associated with successful intracranial recanalization (81.8% vs 76.6% aOR 2.62, 95% CI 1.52-4.5, p<0.001). Results did not meaningfully change in additional analyses. Conclusion: In patients presenting with an acute anterior circulation tandem occlusion secondary to cervical carotid artery dissection, emergent stenting was associated with a higher likelihood of successful intracranial recanalization but not improved functional outcomes or increased sICH. It remains unclear whether emergent stenting led to successful intracranial recanalization or patients with successful intracranial recanalization were more likely to be stented. Randomized trials are warranted.

Competing Interests: Declaration of competing interest The authors have no competing interests to declare.

Interleukin-4 activated human macrophages [M(IL4)s] promote epithelial wound healing and exert an anticolitic effect in a murine model. Blood monocyte-derived M(IL4)s from healthy donors and individuals with Crohn's disease had increased mRNA expression of the calcitonin gene-related peptide (CGRP) receptor chain, receptor activity modifying protein-1 (RAMP1), raising the issue of neural modulation of the M(IL4)s reparative function. Thus, human M(IL4)s were treated with CGRP and the cells' phagocytotic, epithelial wound repair and anticolitic functions were assessed. Initial studies confirmed upregulation of expression of the CGRP receptor, which was localized to the cell surface and was functional as determined by CGRP-evoked increases in cAMP. M(IL4,CGRP)s had increased mannose receptor (CD206) and FcγRIIa (CD32a) mRNA expression, a subtle, but significant, increase in phagocytosis and decreased chemokine production following the exposure to Escherichia coli . When delivered systemically (10 6 cells IP) to oxazolone-treated rag1 -/- mice, M(IL4,CGRP) had an anticolitic effect superior to M(IL4)s from the same blood donor. Conditioned medium (CM) from M(IL4,CGRP) had increased amounts of transforming growth factor (TGF)-β and increased wound-healing capacity compared with matched M(IL4)-CM in the human CaCo 2 epithelial cell line in-vitro wounding assay. Moreover, M(IL4,CGRP)s displayed increased cyclooxygenase (COX)-1 and prostaglandin D 2 (PGD 2 ), and CM from M(IL4,CGRP)s treated with indomethacin or SC-560 to inhibit COX-1 activity failed to promote repair of wounded CaCo 2 cell monolayers. These data confirm the human M(IL4)s' anticolitic effect that was enhanced by CGRP and may be partially dependent on macrophage COX-1/PGD 2 activity. Thus, input from neurone-derived molecules is a local modifier capable of boosting the anticolitic effect of autologous M(IL4) transfer. NEW & NOTEWORTHY A novel pathway is identified whereby interleukin-4-educated human macrophages [M(IL4)s] exposed to calcitonin gene-related peptide (CGRP) reduce oxazolone-induced colitis and promote epithelial wound healing in vitro through COX1-dependent signaling. Support is provided for the concept of macrophage transfer to treat enteric inflammation where neuroimmune interaction, in this case CGRP neuropeptide, produced under inflammatory conditions will reinforce the anticolitic and wound repair capacity of M(IL4) autologous-based therapy for IBD treatment.

Intestinal cell death is a defining feature of Crohn's disease (CD), a major form of inflammatory bowel disease. The focus on this aspect of enteric inflammation has mainly been on epithelial cells, while other cell types such as stromal and myeloid cells have received less attention. Hypothesising that decreased macrophage viability in an oxidative environment could be a contributing factor to the pathophysiology of CD, we found that monocyte-derived macrophages from individuals with active CD (but not those in clinical disease remission) have increased sensitivity to cell death induced by H 2 O 2 . Molecular biology and pharmacological studies ruled out apoptosis and necroptosis, while increased lipid peroxidation and surface expression of the transferrin receptor implicated ferroptosis as the mechanism of the H 2 O 2 -induced cell death: this was supported by suppression of H 2 O 2 -cytotoxicity by liproxstatin-1, a pharmacological inhibitor of ferroptosis. Selenoproteins are important antioxidants, and selenium deficiency can be a feature of CD. Despite normal dietary intake of selenium, monocyte-derived macrophages and intestinal macrophages in individuals with CD had decreased protein and/or mRNA expression of the selenoprotein, glutathione peroxidase (GPx)-1. Knockdown of GPx1 in macrophages from healthy volunteers resulted in increased H 2 O 2 -induced cell death reminiscent of that observed with macrophages from CD. In summary, monocyte-derived macrophages from individuals with CD have increased susceptibility to H 2 O 2 -induced ferroptosis cell death, that may be facilitated, at least in part, by reduced expression of the antioxidant GPx1. We suggest that reduced GPx1 in monocytes recruited to the gut and intestinal macrophages renders these cells vulnerable to reactive oxygen species-evoked ferroptosis cell death and that unraveling the participation of this pathway in Crohn's disease may reveal novel therapeutic approaches to this chronic condition., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval: Ethics approval was issued by the Conjoint Health Research Ethics Board at the University of Calgary (REB24827, REB15-1270, REB19-0402, and REB 20-1534) and the study was performed under accordance with the Declaration of Helsinki., (© 2024. The Author(s).)

The Portuguese Institute for Quality is responsible for the realization and dissemination of the frequency standard in Portugal. There are several techniques for frequency transfer, but we use a frequency mixer to detect phase variations between two light signals with different wavelengths, traveling along an optical fibre. In this paper, we present the development of a digital twin (DT) that replicates the use of a frequency mixer to improve the frequency transfer problem. A setup was built to train and validate the technique: a frequency mixer was used to determine the phase difference between the two signals, which are caused by temperature gradients in the fibre, together with real-time temperature data from sensors placed along the fibre and on the mixer itself. The DT was trained with two machine learning algorithms, in particular, ARIMA and LSTM networks. To estimate the accuracy of the frequency mixer working as a phasemeter, several sources of uncertainty were considered and included in the DT model, with the goal of obtaining a phase value measurement and its uncertainty in real time. The JCGM 100:2008 and JCGM 101:2008 approaches were used for the estimation of the uncertainty budget. With this work, we merge DT technology with a frequency mixer used for phase detection to provide its value and uncertainty in real time.

Background: T 2 mapping is valuable to evaluate pathophysiology in kidney disease. However, variations in T 2 relaxation time measurements across MR scanners and vendors may occur requiring additional correction., Purpose: To harmonize renal T 2 measurements between MR vendor platforms, and use an extended-phase-graph-based fitting method ("StimFit") to correct stimulated echoes and reduce between-vendor variations., Study Type: Prospective., Subjects: 8 healthy "travelling" volunteers (37.5% female, 32 ± 6 years) imaged on four MRI systems across three vendors at four sites, 10 healthy volunteers (50% female, 32 ± 8 years) scanned multiple times on a given MR scanner for repeatability evaluation. ISMRM/NIST system phantom scanned for evaluation of T 2 accuracy., Field Strength/sequence: 3T, multiecho spin-echo sequence., Assessment: T 2 images fit using conventional monoexponential fitting and "StimFit." Mean absolute percentage error (MAPE) of phantom measurements with reference T 2 values. Average cortex and medulla T 2 values compared between MR vendors, with masks obtained from T 2 -weighted images and T 1 maps. Full-width-at-half-maximum (FWHM) T 2 distributions to evaluate local homogeneity of measurements., Statistical Tests: Coefficient of variation (CV), linear mixed-effects model, analysis of variance, student's t-tests, Bland-Altman plots, P-value <0.05 considered statistically significant., Results: In the ISMRM/NIST phantom, "StimFit" reduced the MAPE from 4.9%, 9.1%, 24.4%, and 18.1% for the four sites (three vendors) to 3.3%, 3.0%, 6.6%, and 4.1%, respectively. In vivo, there was a significant difference in kidney T 2 measurements between vendors using a monoexponential fit, but not with "StimFit" (P = 0.86 and 0.92, cortex and medulla, respectively). The intervendor CVs of T 2 measures were reduced from 8.0% to 2.6% (cortex) and 7.1% to 2.8% (medulla) with StimFit, resulting in no significant differences for the CVs of intravendor repeat acquisitions (P = 0.13 and 0.05). "StimFit" significantly reduced the FWHM of T 2 distributions in the cortex and whole kidney., Data Conclusion: Stimulated-echo correction reduces renal T 2 variation across MR vendor platforms., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 1., (© 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Dietary intervention is a subject of growing interest in the management of inflammatory bowel disease (IBD), as new incident cases across the globe are rapidly rising, suggesting environmental factors as contributing elements. Dietary components and micronutrients have been associated with IBD pathogenesis or reductions in disease severity. Selenium, a diet-derived essential micronutrient that is important for proper immune system function, has received limited attention in the context of IBD. Selenium deficiency is a common finding in patients with IBD, but few clinical trials have been published to address the consequences of this deficiency. Here, we review the physiological and immunological roles of selenium and its putative role in IBD, and draw attention to knowledge gaps and unresolved issues, with the goal of stimulating more research on selenium in IBD.

Mobile genetic elements shape microbial gene repertoires and populations. Recent results reveal that many, possibly most, microbial mobile genetic elements require helpers to transfer between genomes, which we refer to as Hitcher Genetic Elements (hitchers or HGEs). They may be a large fraction of pathogenicity and resistance genomic islands, whose mechanisms of transfer have remained enigmatic for decades. Together with their helper elements and their bacterial hosts, hitchers form tripartite networks of interactions that evolve rapidly within a parasitism-mutualism continuum. In this emerging view of microbial genomes as communities of mobile genetic elements many questions arise. Which elements are being moved, by whom, and how? How often are hitchers costly hyper-parasites or beneficial mutualists? What is the evolutionary origin of hitchers? Are there key advantages associated with hitchers' lifestyle that justify their unexpected abundance? And why are hitchers systematically smaller than their helpers? In this essay, we start answering these questions and point ways ahead for understanding the principles, origin, mechanisms, and impact of hitchers in bacterial ecology and evolution., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ares-Arroyo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Stroke is considered one of the greatest public health challenges worldwide, with the ischemic subtype being the most prevalent. Various acute stroke clinical guidelines recommend early rehabilitation interventions, including very early mobilization. However, despite the studies conducted in recent years regarding when to initiate mobilization after an acute stroke, there are few systematic and personalized protocols based on the factors for which patient mobilization should ideally be performed. We aim to conduct an umbrella review of systematic reviews and meta-analyses to study the early mobilization decision after an acute ischemic stroke in comparison with conventional care and correlate the different approaches with patient clinical outcomes., Methods and Analysis: We will perform a systematic search on PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Epistemonikos and Web of Science Core Collection databases. Retrieved studies will be independently reviewed by two authors and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. We will use the 16-item Assessment of Multiple Systematic Reviews 2 (AMSTAR2) checklist as the critical appraisal tool to assess cumulative evidence and risk of bias of the different studies. This will be the first umbrella review that compares early mobilization approaches in post-acute ischemic stroke. This study may help to define the optimal early mobilization strategy in stroke patients. PROSPERO registration number: CRD42023430494.

Members of the genus Lysinibacillus attract attention for their mosquitocidal, bioremediation, and plant growth-promoting abilities. Despite this interest, comprehensive studies focusing on genomic traits governing plant growth and stress resilience in this genus using whole-genome sequencing are still scarce. Therefore, we sequenced and compared the genomes of three endophytic Lysinibacillus irui strains isolated from Canary Island date palms with the ex-type strain IRB4-01. Overall, the genomes of these strains consist of a circular chromosome with an average size of 4.6 Mb and a GC content of 37.2%. Comparative analysis identified conserved gene clusters within the core genome involved in iron acquisition, phosphate solubilization, indole-3-acetic acid biosynthesis, and volatile compounds. In addition, genome analysis revealed the presence of genes encoding carbohydrate-active enzymes, and proteins that confer resistance to oxidative, osmotic, and salinity stresses. Furthermore, pathways of putative novel bacteriocins were identified in all genomes. This illustrates possible common plant growth-promoting traits shared among all strains of L. irui. Our findings highlight a rich repertoire of genes associated with plant lifestyles, suggesting significant potential for developing inoculants to enhance plant growth and resilience. This study is the first to provide insights into the overall genomic signatures and mechanisms of plant growth promotion and biocontrol in the genus Lysinibacillus. KEY POINTS: • Pioneer study in elucidating plant growth promoting in L. irui through comparative genomics. • Genome mining identified biosynthetic pathways of putative novel bacteriocins. • Future research directions to develop L. irui-based biofertilizers for sustainable agriculture., (© 2024. The Author(s).)

The metathesis reaction has been an important tool in both organic and inorganic synthetic chemistry. More specifically in polymer chemistry, ring opening metathesis polymerization (ROMP), via the formation of an active metal-carbene species (MCHR), has been widely used. The elucidation of the mechanism for ROMP opened the way for the development of well-defined catalysts, suited to local conditions. In the present study, we employed density functional theory (DFT) to investigate three reaction pathways for the formation of a species capable of activating ROMP. The active species is formed from the [RuCl 2 (PPh 3 ) 2 (pip)] complex in the presence of norbornadiene (NBD) and the carbene source ethyl diazoacetate (EDA). Formation of a hexacoordinated intermediate [RuCl 2 (PPh 3 ) 2 (pip)(NBD)] is favored in the first step, with NBD doubly coordinated to the [RuCl 2 (PPh 3 ) 2 (pip)] moiety. Analysis of donation (X → Ru) and back-donation (Ru → X) processes in the [RuCl 2 (PPh 3 ) 2 (pip)(NBD)] complex shows that piperidine behaves as a σ donor, while NBD behaves as a π donor and the PPh 3 groups act as π acceptors. The intensity of the orbital component is predominant in relation to the steric component in the complex. Thus, we propose that the reaction occurs through the formation of a hexacoordinated complex, followed by the dissociation of a PPh 3 group, thus forming a complex where NBD is doubly coordinated to the metal center. Coordination of EDA leads finally to the catalyst capable of forming the metallocyclobutane intermediate required for the ROMP reaction.

Background: Small, randomized trials of patients with cervical artery dissection showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with cervical artery dissection treated with antiplatelets versus anticoagulation., Methods: This is a multicenter observational retrospective international study (16 countries, 63 sites) that included patients with cervical artery dissection without major trauma. The exposure was antithrombotic treatment type (anticoagulation versus antiplatelets), and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with inverse probability of treatment weighting to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an as-treated crossover approach and only included outcomes occurring with the above treatments., Results: The study included 3636 patients (402 [11.1%] received exclusively anticoagulation and 2453 [67.5%] received exclusively antiplatelets). By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with inverse probability of treatment weighting, compared with antiplatelet therapy, anticoagulation was associated with a nonsignificantly lower risk of subsequent ischemic stroke by day 30 (adjusted hazard ratio [HR], 0.71 [95% CI, 0.45-1.12]; P =0.145) and by day 180 (adjusted HR, 0.80 [95% CI, 0.28-2.24]; P =0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR, 1.39 [95% CI, 0.35-5.45]; P =0.637) but was by day 180 (adjusted HR, 5.56 [95% CI, 1.53-20.13]; P =0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR, 0.40 [95% CI, 0.18-0.88]; P interaction =0.009)., Conclusions: Our study does not rule out the benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings., Competing Interests: Disclosures Disclosures provided by Dr Nguyen in compliance with American Heart Association annual Journal Editor Disclosure Questionnaire are available at https://www.ahajournals.org/editor-coi-disclosures. Dr Arnold reports compensation from Boehringer Ingelheim, AstraZeneca, Bayer, Bristol-Myers Squibb, Covidien, Daiichi Sankyo, Novartis, Sanofi, Pfizer, Medtronic, Novo Nordisk, and Amgen for consultant services. Dr Lester reports a provisional patent for Methods and compositions for disrupting tau aggregates. Dr Touze reports compensation from Elsevier for other services and employment by Caen. J.E. Kaufman reports grants from Goldschmidt Jacobson-Stiftung. Dr Traenka reports travel support from Bayer Healthcare. Dr Aguiar de Sousa reports compensation from Daiichi Sankyo, Bayer, AstraZeneca, Johnson & Johnson, and Fundação Bial for other services; compensation from the University of British Columbia for data and safety monitoring services; compensation from Organon & Co for consultant services. Dr Rosa reports grants from Merck Sharp & Dohme Corporation. Dr Field reports compensation from HLS Therapeutics, AstraZeneca Canada, and Roche for consultant services; service as a board member for Destine Health; and compensation from the Canadian Medical Protective Association for expert witness services; and grants from Bayer. Dr Leker reports compensation from Medtronic, Ischemaview, Bayer, Abbott Diabetes Care, Biogen, Janssen Biotech, and Boehringer Ingelheim for other services. Dr Nolte reports compensation from Daiichi Sankyo Europe GmbH, Boehringer Ingelheim, Pfizer, Bristol-Myers Squibb, and Alexion Pharmaceuticals for consultant services; and compensation from AstraZeneca, Abbott Canada, Deutsches Zentrum für Neurodegenerative Erkrankungen, Novartis, Portola Pharmaceuticals, Deutsches Zentrum für Herz-Kreislaufforschung, and Novartis for other services. Dr Poppe reports grants from Foundation Brain Canada, Heart and Stroke Foundation of Canada, and Stryker; and compensation from Roche for other services. Dr Liebeskind reports compensation from Medtronic, Genentech, Cerenovus, Stryker, and Rapid Medical Ltd, for consultant services. B. Mac Grory reports grants from the National Institutes of Health; employment by Duke University Medical Center; compensation from Bayer for other services; grants from the American Heart Association, Duke Bass Connections, and the Duke Office of Physician Scientist Development. Dr Al Kasab reports compensation from Stryker for other services and employment by Medical University of South Carolina. Dr Kicielinski reports compensation from Stryker, Penumbra Inc, Medtronic, and MicroVention Inc, for other services; travel support from MicroVention Inc; and employment by Medical University of South Carolina and Elsevier. Dr de Havenon reports stock options in TitinKM and Certus; grants from the National Institutes of Health; and compensation from Novo Nordisk for consultant services. Dr Siegler reports grants from Philips and employment by the University of Chicago. Dr Willey reports compensation from Edwards Lifesciences Corporation and Abbott Fund for end point review committee services; compensation from Uptodate for other services; and compensation from the Abbott Laboratories for consultant services. Dr Sharma reports a provisional patent for a stroke etiology classifier algorithm and grants from the National Institutes of Health Clinical Center. Dr Martins reports compensation from Pfizer, Medtronic, Servier Affaires Medicales, Daiichi Sankyo, Bayer, Novo Nordisk, Novartis, Penumbra Inc, and Boehringer Ingelheim for other services. Dr Simpkins reports grants from the National Institutes of Health. Dr Stretz reports grants from Massachusetts General Hospital. Dr Furie reports compensation from Janssen Biotech for consultant services. The other authors report no conflicts

Introduction: After several uncontrolled studies and one randomized clinical trial, there is still uncertainty regarding the role of endovascular treatment (EVT) in cerebral venous thrombosis (CVT). This study aims to describe and assess different acute management strategies in the treatment of CVT., Methods: We performed a retrospective analysis of an international two-center registry of CVT patients admitted since 2019. Good outcome was defined as a return to baseline modified Rankin scale at three months. We described and compared EVT versus no-EVT patients., Results: We included 61 patients. Only one did not receive systemic anticoagulation. EVT was performed in 13/61 (20%) of the cases, with a median time from diagnosis to puncture of 4.5 h (1.25-28.5). EVT patients had a higher median baseline NIHSS [6 (IQR 2-17) vs 0 (0-2.7), p  = 0.002)] and a higher incidence of intracerebral hemorrhage (53.8% vs 20.3%, p  = 0.03). Recanalization was achieved in 10/13 (77%) patients. Thrombectomy was performed in every case with angioplasty in 7 out of 12 patients and stenting in 3 cases. No postprocedural complication was reported. An improvement of the median NIHSS from baseline to discharge [6 (2-17) vs 1(0-3.75); p  < 0.001] was observed in EVT group. A total of 31/60 patients (50.8%) had good outcomes. Adjusting to NIHSS and ICH, EVT had a non-significant increase in the odds of a good outcome [aOR 1.42 (95%CI 0.73-2.8, p  = 0.307)]., Conclusions: EVT in combination with anticoagulation was safe in acute treatment of CVT as suggested by NIHSS improvement. Selected patients may benefit from this treatment., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Embryonic diapause in mammals is a temporary developmental delay occurring at the blastocyst stage. In contrast to other diapausing species displaying a full arrest, the blastocyst of the European roe deer (Capreolus capreolus) proliferates continuously and displays considerable morphological changes in the inner cell mass. We hypothesised that developmental progression also continues during this period. Here we evaluate the mRNA abundance of developmental marker genes in embryos during diapause and elongation. Our results show that morphological rearrangements of the epiblast during diapause correlate with gene expression patterns and changes in cell polarity. Immunohistochemical staining further supports these findings. Primitive endoderm formation occurs during diapause in embryos composed of around 3,000 cells. Gastrulation coincides with elongation and thus takes place after embryo reactivation. The slow developmental progression makes the roe deer an interesting model for unravelling the link between proliferation and differentiation and requirements for embryo survival., (© 2024. The Author(s).)

Phage satellites are bacterial genetic elements that co-opt phage machinery for their own dissemination. Here we identify a family of satellites, named Phage-Inducible Chromosomal Minimalist Islands (PICMIs), that are broadly distributed in marine bacteria of the family Vibrionaceae. A typical PICMI is characterized by reduced gene content, does not encode genes for capsid remodelling, and packages its DNA as a concatemer. PICMIs integrate in the bacterial host genome next to the fis regulator, and encode three core proteins necessary for excision and replication. PICMIs are dependent on virulent phage particles to spread to other bacteria, and protect their hosts from other competitive phages without interfering with their helper phage. Thus, our work broadens our understanding of phage satellites and narrows down the minimal number of functions necessary to hijack a tailed phage., (© 2024. The Author(s).)

Background: The optimal imaging method for detecting distal medium vessel occlusions (DMVOs) remains undefined., Purpose: The objective of this study is to compare the diagnostic performance of CTA with CTP in detecting DMVOs., Data Sources: We searched PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials up to March 31, 2023 (PROSPERO: CRD42022344006)., Study Selection: A total of 12 studies reporting accuracy values of CTA and/or CTP were included, comprising 2607 patients with 479 cases (18.3%) of DMVOs., Data Analysis: Pooled sensitivity and specificity of both imaging methods were compared using a random-effects model. Subgroup analyses were performed based on the technique used in CTA (multi or single-phase) and the subtype of DMVOs (M2-only vs. M2 and other DMVOs). We applied Quality Assessment of Diagnostic Accuracy (QUADAS-2) tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality assessment criteria., Data Synthesis: CTA demonstrated significantly lower sensitivity compared to CTP in detecting DMVOs [0.74, 95%CI (0.63-0.82) vs. 0.89, 95% CI (0.82-0.93), P < 0.01]. When subgrouped into single-phase and multi-phase CTA, multi-phase CTA exhibited higher sensitivity for DMVO detection than single-phase CTA [0.91, 95%CI (0.85-0.94) vs. 0.64, 95%CI (0.56-0.71), P < .01], while reaching similar levels to CTP. The sensitivity of single-phase CTA substantially decreased when extending from M2 to other non-M2 DMVOs [0.74, 95%CI (0.63-0.83) vs. 0.61, 0.95%CI (0.53-0.68), P = .02]., Limitations: We identified an overall high risk of bias and low quality of evidence, attributable to the design and reference standards of most studies., Conclusions: Our findings highlight a significantly lower sensitivity of single-phase CTA compared to multi-phase CTA and CTP in diagnosing DMVOs., (© 2024 by American Journal of Neuroradiology.)

Purpose: Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) are often complicated by vasospasm and ischemia. Monitoring with transcranial color-coded Doppler (TCCD) could be useful, but its role is not established. We studied the incidence of ultrasonographic vasospasm (uVSP) in PRES/RCVS and its relationship with ischemic lesions and clinical outcome., Materials and Methods: We conducted a multicenter retrospective study of all patients with PRES/RCVS from 2008 to 2020 who underwent TCCD and magnetic resonance imaging (MRI). TCCD exams were analyzed for uVSP. Diffusion-weighted MRI was analyzed for positive lesions (DWI-positive). Functional outcome was assessed by modified Rankin scale (mRS) at 90 days. The associations with outcomes were determined by logistic regression., Results: We included 80 patients (mean age of 46 (standard deviation, 17) years; 66% females; 41 with PRES, 28 with RCVS and 11 with overlap phenotype). uVSP was detected in 25 (31%) patients. DWI-positive lesions were more often detected in uVSP-positive than uVSP-negative patients (36% vs. 15%; adjusted odds ratio [aOR] 4.05 [95% CI 1.06 - 15.5], P=0.04). DWI-positive lesions were independently associated with worse functional prognosis (mRS 2-6, 43% vs. 10%; aOR, 10 [95% CI 2.6 - 43], P<0.01). Having additional uVSP further increased the odds of a worse outcome (P interaction=0.03)., Conclusion: Ultrasonographic vasospasm was detected in a third of patients with PRES/RCVS and was associated with brain ischemic lesions. TCCD bedside monitoring can help to stratify patients at risk for cerebral ischemia, a strong predictor of functional outcome., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

General-purpose quantum computation and quantum simulation require multi-qubit architectures with precisely defined, robust interqubit interactions, coupled with local addressability. This is an unsolved challenge, primarily due to scalability issues. These issues often derive from poor control over interqubit interactions. Molecular systems are promising materials for the realization of large-scale quantum architectures, due to their high degree of positionability and the possibility to precisely tailor interqubit interactions. The simplest quantum architecture is the two-qubit system, with which quantum gate operations can be implemented. To be viable, a two-qubit system must possess long coherence times, the interqubit interaction must be well defined and the two qubits must also be addressable individually within the same quantum manipulation sequence. Here results are presented on the investigation of the spin dynamics of chlorinated triphenylmethyl organic radicals, in particular the perchlorotriphenylmethyl (PTM) radical, a mono-functionalized PTM, and a biradical PTM dimer. Extraordinarily long ensemble coherence times up to 148 µs are found at all temperatures below 100 K. Two-qubit and, importantly, individual qubit addressability in the biradical system are demonstrated. These results underline the potential of molecular materials for the development of quantum architectures., (© 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Longitudinally extensive transverse myelitis (LETM) is a debilitating inflammatory spinal cord lesion involving several spinal segments. There are several possible etiologies, with spinal cord sarcoidosis being a rare cause of LETM. Spinal cord sarcoidosis is, in itself, a rare manifestation of sarcoidosis that can be difficult to diagnose, especially in patients with no prior history of systemic sarcoidosis, frequently leading to a delayed diagnosis. We report the case of a 53-year-old man who developed LETM as the first manifestation of sarcoidosis. The patient presented with progressive lower limb weakness, urinary retention, sensory disturbances, and muscle spasms. Imaging studies showed hyperintense lesions extending over multiple spinal segments. After the exclusion of other causes and a lymph node biopsy showing non-caseating granulomas, the diagnosis of LETM secondary to sarcoidosis was confirmed., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Rodrigues et al.)

Jejunal gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors of the gastrointestinal (GI) tract and a rare cause of massive GI bleeding. Due to this rarity and non-specific presentation, diagnosis and treatment may be difficult and often delayed. Urgent surgical intervention is crucial for controlling the source of bleeding and total tumor excision. Herein, we present the case of a 40-year-old male who presented to the emergency room (ER) with features of upper GI bleeding. He referred astheny and black stools, and was pale, sweaty, and tachycardic despite normal blood pressure. Rectal examination revealed melena, and laboratory findings revealed decreased hemoglobin (Hb) and elevated blood urea. Upper endoscopy was normal, and the Hb level dropped again to 6.9 g/dL; therefore, blood transfusion was required during ER observation. For further investigation, the patient underwent an angio-computed tomography scan, which revealed a lesion located in a jejunal loop as the probable bleeding source. Emergency exploratory laparotomy revealed a jejunal loop tumor. Segmental enterectomy containing the tumor was performed and the post-operative period was uneventful. The anatomopathological examination was compatible with low-risk GIST, and the multidisciplinary board agreed that surveillance was the best ongoing treatment. Due to the rarity of jejunal GIST as the cause of massive GI bleeding, diagnosis may be challenging, delaying prompt treatment with bleeding source control. In such cases, surgery may be both lifesaving and curative. Therefore, these tumors should not be forgotten when managing patients with occult GI bleeding with an atypical presentation to prevent delays in treatment and severe outcomes., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Martins et al.)

Background: Blood-brain barrier permeability (BBBp) is a key process involved in ischemic stroke pathophysiology. However, there is a lack of consensus on how BBBp evolves after the ischemia injury, and its clinical relevance at different timepoints post stroke., Aims: The main objective of this study is to assess BBBp evolution through stroke phases and its implications on patient outcomes., Methods: We screened PubMed/MEDLINE, Embase, Web of Science, Scopus, and Cochrane Central Register of Controlled Trials up to 31 December 2021. We included research quantitatively using neuroimaging to assess BBBp in stroke patients. BBBp in the different phases was evaluated by a random-effect model based on the standardized mean difference (SMD) between the ipsilateral and contralateral sides of the brain. We performed a subgroup analysis on clinical outcome, reperfusion treatment, haemorrhagic transformation, and imaging method., Results: We identified 3761 studies, of which 22 (1592 patients and 1787 evaluations) were included in our study. Overall, 17 studies reported BBBp for the hyperacute phase, 8 for the acute, 5 for the subacute, and 2 for the chronic phase. All phases were associated with increased BBBp: 0.74 (0.48-0.99), 1.68 (0.94-2.42), 1.98 (0.96-3.00), and 1.00 (0.45-1.55), respectively. An increase in BBBp was associated with hemorrhagic transformation in the hyperacute phase and with improved functional outcomes in the late subacute phase., Conclusion: BBBp is persistently increased after stroke, peaking in the acute and subacute phases. The degree of BBBp influences patient outcomes depending on stroke phase. Our findings support the clinical relevance of BBBp dynamics in stroke care.

Phoretic mites attach to different body parts of the red palm weevil (RPW), Rhynchophorus ferrugineus (Olivier, 1790), to disperse. However, the question of how the patterns of attachment sites are formed remains intriguing. Here, we examined RPW-associated phoretic mites in four districts in Northern Portugal (macrohabitat), and investigated the patterns of mite distribution on six body parts of RPW (microhabitat). At the macrohabitat level, we detected seven phoretic mite taxa using the RPW host in each of the four studied districts, all documented for the first time in association with this invasive exotic species in Portugal. However, their relative abundance (species evenness) varied between districts, as did species diversity. All examined weevils carried mites, and the prevalence of the different taxa did not differ between districts or sex of weevils. Measured by mean abundance and degree of aggregation, Centrouropoda sp. proved to be the dominant taxon, while Acarus sp. and Curculanoetus rhynchophorus were considered common subordinate taxa and Uroovobella sp., Mesostigmata, Nenteria extremica and Dendrolaelaps sp. sparse taxa. At the microhabitat level, all taxa were present on all body parts of the RPW; the highest abundance was in a region encompassing the inner surface of the elytra and the membranous hind wings (subelytral space). Analysis of niche overlap revealed that the distribution patterns of phoretic mite taxa on the RPW were not randomly structured. In the subelytral space, interspecific coexistence of mites increased as a function of body size difference with the dominant Centrouropoda sp. We found that in the subelytral space the large dominant species Centrouropoda sp. displaced the larger species Uroobovella sp. and the similarly sized species Nenteria extremica , but coexisted with smaller taxa., Competing Interests: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses or interpretation of data; in the writing of the manuscript; or in the decision to publish the results., (© 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)

Background: Twitter is a social media platform popularly used by health practitioners, a trend that has been followed by medical journals. The impact of Twitter in bibliometrics of stroke-related literature is yet to be determined., Aims: We aimed to qualitatively assess the usage of Twitter by stroke journals and study the relationship between Twitter activity and citation rates of stroke articles., Methods: We used Journal Citation Reports to identify stroke journals. We collected the 2021 Impact Factor (IF) and the top 50 articles contributing to each journal IF. Relevant metrics were collected through Twitonomy, Altmetric, and Web of Science. The association between Twitter activity and citation rates was tested by a negative binomial regression model adjusted to journal's IF. A bivariate correlation and a log-linear regression model adjusted to journal's IF tested the relationship between number of tweets, tweeters, and the number of citations., Results: We collected 450 articles across nine stroke-dedicated journals, five of which had a Twitter account. Only 95 (21%) articles had no Twitter mentions. The median number of citations in articles with versus without Twitter activity was 19 (10-39) versus 11(7-17) ( P < 0.001). Twitter activity was associated with higher citation rates controlling for the IF (odds ratio (OR): 2.7, 95% confidence interval (CI) 2.12-3.38, P < 0.001). We found number of tweets to be predicted by the number of citations controlling for the IF (B = 0.33, 95% CI 0.29-0.40, β = 0.54, P < 0.001)., Conclusions: Tweeted stroke articles tend to have higher citation rates which can be predicted by the number of tweets.

Background: Distal medium vessel occlusions (DMVOs) represent 25-40% of all acute ischemic strokes (AIS). DMVO clinical syndromes are heterogenous, but as eloquent brain regions are frequently involved, they are often disabling. Since current intravenous fibrinolytic therapies may fail to recanalize up to two-thirds of DMVOs, endovascular treatment is progressively being considered in this setting. Nevertheless, the optimal imaging method for diagnosis remains to be defined. Stroke centers that use computed tomography as a routine stroke imaging approach rely on either isolated computed tomography angiography (CTA) or combined perfusion (CTP) studies. Despite a simplified non-CTP-dependent approach seeming reasonable for large vessel occlusion AIS diagnosis, CTP may still hold advantages for DMVOs workup. Therefore, this systematic review aims to compare the diagnostic performance of CTA and CTP in detecting DMVOs., Methods: We will perform a systematic search in PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials. In addition, grey literature and ClinicalTrials.gov will be scanned. We will include any type of study that presents data on the diagnostic accuracy of CTA and/or CTP for detecting DMVOs. Two authors will independently review retrieved studies, and any discrepancies will be resolved by consensus or with a third reviewer. Reviewers will extract the data and assess the risk of bias in the selected studies. Data will be combined in a quantitative meta-analysis following the guidelines provided by the Cochrane Handbook for Systematic Reviews of Interventions. We will assess cumulative evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach., Discussion: This will be the first systematic review and meta-analysis that compares two different imaging approaches for detecting DMVOs. This study may help to define optimal acute ischemic stroke imaging work-up., Trial Registration: PROSPERO registration: CRD42022344006., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Sousa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Coronary artery disease (CAD), characterized by an atherogenic process in the coronary arteries, is one of the leading causes of death in Madeira. The GENEMACOR (GENEs in MAdeira and CORonary Disease) study sought to investigate the main risk factors - environmental and genetic - and estimate whether a genetic risk score (GRS) improves CAD prediction, discrimination and reclassification., Methods: Traditional risk factors and 33 CAD genetic variants were considered in a case-control study with 3139 individuals (1723 patients and 1416 controls). The multivariate analysis assessed the likelihood of CAD. A multiplicative GRS (mGRS) was created, and two models (with and without mGRS) were prepared. Two areas under receiver operating characteristic curve (area under curve (AUC)) were analyzed and compared to discriminate CAD likelihood. Net reclassification improvement (NRI) and integrated discrimination index (IDI) were used to reclassify the population., Results: All traditional risk factors were strong and independent predictors of CAD, with smoking being the most significant (OR 3.25; p<0.0001). LPA rs3798220 showed a higher CAD likelihood (odds ratio 1.45; p<0.0001). Individuals in the fourth mGRS quartile had an increased CAD probability of 136% (p<0.0001). A traditional risk factor-based model estimated an AUC of 0.73, rising to 0.75 after mGRS inclusion (p<0.0001), revealing a better fit. Continuous NRI better reclassified 28.1% of the population, and categorical NRI mainly improved the reclassification of the intermediate risk group., Conclusions: CAD likelihood was influenced by traditional risk factors and genetic variants. Incorporating GRS into the traditional model improved CAD predictive capacity, discrimination and reclassification. These approaches may provide helpful diagnostic and therapeutic advances, especially in the intermediate risk group., (Copyright © 2022 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.)

Hepatocellular carcinoma (HCC) accounts for most of the hepatic neoplasms and can also occur in ectopic liver tissue. We present a case of a 55-year-old male complaining of weight loss. The imaging studies reported a 2.9 cm nodule in the pancreatic body, with a neuroendocrine tumor diagnosis by cytology. A corpo-caudal pancreatectomy was performed. Pathology showed a well-differentiated HCC developed in ectopic liver tissue with free margins and no lymph node metastases. HCC presenting in ectopic liver tissue is rare. In this case, the preoperative study did not establish the diagnosis, warranting the need for suspicion of this neoplasm.

The existence of a selective blood-brain barrier (BBB) and neurovascular coupling are two unique central nervous system vasculature features that result in an intimate relationship between neurons, glia, and blood vessels. This leads to a significant pathophysiological overlap between neurodegenerative and cerebrovascular diseases. Alzheimer's disease (AD) is the most prevalent neurodegenerative disease whose pathogenesis is still to be unveiled but has mostly been explored under the light of the amyloid-cascade hypothesis. Either as a trigger, bystander, or consequence of neurodegeneration, vascular dysfunction is an early component of the pathological conundrum of AD. The anatomical and functional substrate of this neurovascular degeneration is the BBB, a dynamic and semi-permeable interface between blood and the central nervous system that has consistently been shown to be defective. Several molecular and genetic changes have been demonstrated to mediate vascular dysfunction and BBB disruption in AD. The isoform ε4 of Apolipoprotein E is at the same time the strongest genetic risk factor for AD and a known promoter of BBB dysfunction. Low-density lipoprotein receptor-related protein 1 (LRP-1), P-glycoprotein, and receptor for advanced glycation end products (RAGE) are examples of BBB transporters implicated in its pathogenesis due to their role in the trafficking of amyloid-β. This disease is currently devoid of strategies that change the natural course of this burdening illness. This unsuccess may partly be explained by our misunderstanding of the disease pathogenesis and our inability to develop drugs that are effectively delivered to the brain. BBB may represent a therapeutic opportunity as a target itself or as a therapeutic vehicle. In this review, we aim to explore the role of BBB in the pathogenesis of AD including the genetic background and detail how it can be targeted in future therapeutic research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sousa, Bernardes, Bernardo-Castro, Lino, Albino, Ferreira, Brás, Guerreiro, Tábuas-Pereira, Baldeiras, Santana and Sargento-Freitas.)

The preparation of monolayers based on an organic radical and its diamagnetic counterpart has been pursued on hydrogen-terminated silicon surfaces. The functional monolayers have been investigated as solid-state metal/monolayer/semiconductor (MmS) junctions showing a characteristic diode behavior which is tuned by the electronic characteristics of the organic molecule. The eutectic gallium-indium liquid metal is used as a top electrode to perform the transport measurements and the results clearly indicate that the SOMO-SUMO molecular orbitals impact the device performance. The junction incorporating the radical shows an almost two orders of magnitude higher rectification ratio ( R (| J 1V / J -1V |) = 10 4.04 ) in comparison with the nonradical one ( R (| J 1V / J -1V |) = 10 2.30 ). The high stability of the fabricated MmS allows the system to be interrogated under irradiation, evidencing that at the wavelength where the photon energy is close to the band gap of the radical there is a clear enhancement of the photoresponse. This is translated into an increase of the photosensitivity ( S ph ) value from 68.7 to 269.0 mA/W for the nonradical and radical based systems, respectively.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, 10.1016/j.repc.2022.10.005. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal., (Copyright © 2022. Publicado por Elsevier España, S.L.U.)

Objetives: Time is relative in large-vessel occlusion acute ischemic stroke (LVO-AIS). We aimed to evaluate the rate of inter-hospital ASPECTS decay in patients transferred from a primary (PSC) to a comprehensive stroke center (CSC); and to identify patients that should repeat computed tomography (CT) before thrombectomy., Materials and Methods: This was a retrospective cohort study of consecutive anterior circulation LVO-AIS transferred patients. The rate of ASPECTS decay was defined as (PSC-ASPECTS - CSC-ASPECTS)/hours elapsed between scans. Single-phase CT angiography (CTA) at the PSC was used to classify the collateral score. We compared patients with futile versus useful CT scan re-evaluation., Results: We included 663 patients, of whom 245 (37.0%) repeated CT at a CSC. The median rate of ASPECTS decay was 0.4/h (0.0-0.9). Patients excluded from thrombectomy after a CT scan repeat (n=64) had a median ASPECTS decay rate of 1.18/h (0.83-1.61). Patients with absent collateral circulation had a median rate of 1.51(0.65-2.19). The collateral score was an independent predictor of the ASPECTS decay rate (aβ = -0.35; 95%CI -0.45 - -0.19, p<0.001). Age (aOR: 1.04 95% CI 1.02-1.07, p<0.001), NIHSS (aOR: 1.11 95% CI 1.06-1.15, p<0.001), PSC ASPECTS (aOR: 0.74 95% CI 0.60-0.91, p=0.006) and the CTA collateral score (aOR: 0.14 95% CI 0.08-0.22, p<0.001) were independent predictors of the usefulness of a CT scan repeat., Conclusions: The rate of ASPECTS decay can be predicted by the CTA collateral score, helping in the selection of patients that would benefit from repeating a CT assessment on arrival at the CSC., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In this work, antibiotic pyrazinamide (PZA) photodegradation on palygorskite (Pal), NiWO 4 crystals, and NiWO 4 -Pal (2, 6, and 10%) nanocomposites was evaluated under polychromatic irradiation. In the characterization of the samples, XRD patterns displayed good crystallinity for NiWO 4 crystals and nanocomposites. In addition, the diffractograms were used in the Rietveld refinement for phase indexing, revealing a wolframite-type monoclinic structure with the space group P2/c. The active vibrational modes related to the characteristic groups of the samples were identified using Raman and FTIR spectroscopy. Photoluminescence (PL) spectra revealed that NiWO 4 and NiWO 4 -Pal (2%) nanocomposite have the highest electron-hole pair recombination rate, and the contribution of the green component in the NiWO 4 -Pal (2%) nanocomposite indicates a greater contribution of deep energy levels to the PL profile. DRS in the UV-visible region indicated that NiWO 4 crystals have indirect band-gap energy (E gap ) 2.64 eV; NiWO 4 -Pal (2, 6, and 10%) nanocomposites have 2.62, 2.58, and 2.59 eV, respectively; and Pal has 2.83 eV. The catalytic tests showed that the NiWO 4 -Pal (2%) nanocomposite samples, under polychromatic radiation, exhibit greater efficiency in photodegradation at 110 min, with yield of 98.5%. The ROS tests indicated that the studied reactive species play a similar role in PZA photodegradation., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Radiopacity is sometimes an essential characteristic of biomaterials that can help clinicians perform follow-ups during pre- and post-interventional radiological imaging. Due to their chemical composition and structure, most bioceramics are inherently radiopaque but can still be doped/mixed with radiopacifiers to increase their visualization during or after medical procedures. The radiopacifiers are frequently heavy elements of the periodic table, such as Bi, Zr, Sr, Ba, Ta, Zn, Y, etc., or their relevant compounds that can confer enhanced radiopacity. Radiopaque bioceramics are also intriguing additives for biopolymers and hybrids, which are extensively researched and developed nowadays for various biomedical setups. The present work aims to provide an overview of radiopaque bioceramics, specifically crystalline, non-crystalline (glassy), and nanostructured bioceramics designed for applications in orthopedics, dentistry, and cancer therapy. Furthermore, the modification of the chemical, physical, and biological properties of parent ceramics/biopolymers due to the addition of radiopacifiers is critically discussed. We also point out future research lacunas in this exciting field that bioceramists can explore further.

Primary cardiac lymphomas are extremely rare and involve mainly the pericardium. We present the case of a 77-year-old man with a germinal center diffuse large B-cell lymphoma causing severe right ventricular inflow obstruction. Clinical presentation of isolated dyspnea and severe desaturation and cyanosis were, otherwise, unexpected. ( Level of Difficulty: Beginner. )., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 Published by Elsevier on behalf of the American College of Cardiology Foundation.)