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The significance of hydrogen energy has grown considerably due to climate change and the depletion of fossil fuels. PEM fuel cells are the key hydrogen technologies. Commercial membranes based on perfluorosulfonic acid (PFSA) with a polymer structure containing fluorine are currently available. However, it has been determined that certain perfluorosulfonic acids (PFSAs) are hazardous, persistent, and bioaccumulative. Advancements in hydrogen technology rely on effective, inexpensive, and perfluorocarbon‐free membranes, specifically proton exchange membranes (PEMs). In this research, a PFSA‐free polyacrylonitrile‐co‐methyl acrylate (PAN‐MA) membrane doped with phosphoric acid is prepared using the electrospinning method and then characterized by SEM, FE‐SEM, XRD, FTIR, TGA, DMA, and EIS. The DMA analysis reveals that the storage modulus of the doped membrane increases from 0.98 to 5.66 MPa at 80 °C. The nanofiber composite membrane, with a thickness of 181 µm, exhibits the highest proton conductivity of 0.306 S m−1 at 20 °C, 1.76 times higher than that of the Nafion 212 membrane. The Nafion 212 membrane has an ionic conductivity of 0.173 S m−1 under the same conditions. These results indicate that the prepared nanofiber membranes are promising materials for evaluating fuel cell applications. [ABSTRACT FROM AUTHOR]

The biochemical and physical properties of a scaffold can be tailored to elicit specific cellular responses. However, it is challenging to decouple their individual effects on cell‐material interactions. Here, we solvent‐cast 3D printed different ratios of high and low molecular weight (MW) poly(caprolactone) (PCL) to fabricate scaffolds with significantly different stiffnesses without affecting other properties. Ink viscosity was used to match processing conditions between inks and generate scaffolds with the same surface chemistry, crystallinity, filament diameter, and architecture. Increasing the ratio of low MW PCL resulted in a significant decrease in modulus. Scaffold modulus did not affect human mesenchymal stromal cell (hMSC) differentiation under osteogenic conditions. However, hMSC response was significantly affected by scaffold stiffness in chondrogenic media. Low stiffness promoted more stable chondrogenesis whereas high stiffness drove hMSC progression toward hypertrophy. These data illustrate how this versatile platform can be used to independently modify biochemical and physical cues in a single scaffold to synergistically enhance desired cellular response. [ABSTRACT FROM AUTHOR]

Synergistic interactions between human herpesvirus 6A (HHV‐6A) and Epstein–Barr virus (EBV) are hypothesized in the etiopathogenesis of multiple sclerosis (MS). This study investigated if HHV‐6A and EBV seroreactivities interact regarding the risk of developing MS. Antibodies against viral antigens were analyzed in biobank samples from 670 individuals who later developed MS and matched controls. Additive interactions were analyzed. A significant interaction between HHV‐6A and EBNA‐1 seroreactivities was observed in study participants above the median age of 24.9 years (attributable proportion due to interaction = 0.45). This finding supports the hypothesis that HHV‐6A and EBV infections interact in MS development. ANN NEUROL 2024;96:302–305 [ABSTRACT FROM AUTHOR]

Cholesterol is an essential membrane component, and the metabolites from cholesterol play important biological functions to intricately support cancer progression and dampen immune responses. Preclinical and clinical studies have demonstrated the role of cholesterol metabolism regulation on inhibiting tumor growth, remodeling the immunosuppressive tumor microenvironment (TME), and enhancing anti‐tumor immunity. In this minireview, we discuss complex cholesterol metabolism in tumors, its important role in cancer progression, and its influences on immune cells in the TME. We provide an overview of recent advances in cancer treatment through regulating cholesterol metabolism. We discuss the design of cholesterol‐altering multifunctional nanomaterials to regulate oxidative stress, modulate immune checkpoints, manipulate mechanical stress responses, and alter cholesterol metabolic pathways. Additionally, we examine the interactions between cholesterol metabolism regulation and established cancer treatments with the aim of identifying efficient strategies to disrupt cholesterol metabolism and synergistic combination therapies for effective cancer treatment. [ABSTRACT FROM AUTHOR]

It has been suggested that time spent at a high fraction of maximal oxygen consumption (%V˙ $\dot{\mathrm{V}}$O2max) plays a decisive role for adaptations to interval training. However, previous studies examining how interval sessions should be designed to achieve a high %V˙ $\dot{\mathrm{V}}$O2max have exclusively been performed in males. The present study compared the %V˙ $\dot{\mathrm{V}}$O2max attained during three different 6 × 8 min interval protocols, in female (n = 11; V˙ $\dot{\mathrm{V}}$O2max, 62.5 (6.4) mL · min−1·kg−1) and male (n = 8; V˙ $\dot{\mathrm{V}}$O2max, 81.0 (5.2) mL · min−1·kg−1) cyclists. Mean power output during work intervals were identical across the three interval protocols, corresponding to the cyclist's 40 min maximal effort (PO40min): (1) 30 s intervals at 118% of PO40min interspersed with 15 s active recovery at 60% (30/15), (2) constant pace at 100% of PO40min (CON), and (3) altering between 60 s intervals at 110% and 60 s at 90% of PO40min (60/60). Additionally, the study explored whether the m. vastus lateralis characteristics of the cyclists (fiber type proportion, capillarization, and citrate synthase activity) were associated with the %V˙ $\dot{\mathrm{V}}$O2max attained during the interval sessions. Overall, mean %V˙ $\dot{\mathrm{V}}$O2max and time ≥90% of V˙ $\dot{\mathrm{V}}$O2max were higher during 30/15 compared to CON (86.7 (10.1)% and 1123 (787) s versus 85.0 (10.4)% and 879 (779) s, respectively; both p ≤ 0.01) and 60/60 (85.6 (10.0)% and 917 (745) s, respectively; both p ≤ 0.05), while no difference was observed between 60/60 and CON (both p ≥ 0.36). During interval sessions, %V˙ $\dot{\mathrm{V}}$O2max and time ≥90% of V˙ $\dot{\mathrm{V}}$O2max did not differ between sexes. Skeletal muscle characteristics were not related to %V˙ $\dot{\mathrm{V}}$O2max during interval sessions. In conclusion, well‐trained cyclists demonstrate highest %V˙ $\dot{\mathrm{V}}$O2max during 30/15, irrespective of sex and skeletal muscle characteristics. Highlights: Among the workload‐matched sessions investigated (30/15, 60/60, and CON), 30/15 intervals resulted in the highest oxygen consumption and longest periods with oxygen consumption above 90% of the participant's maximal oxygen consumption.For each of the three interval sessions investigated, no significant differences between female and male participants were displayed for average fraction of maximal oxygen consumption achieved during the intervals.The m. vastus lateralis fiber type proportion, capillarization and citrate synthase activity of the participants were not related to the average fraction of maximal oxygen consumption achieved during the different interval sessions. [ABSTRACT FROM AUTHOR]

Large surface area applications such as high efficiency >26% solar cells require surface patterning with 1–10 μm periodic patterns at high fidelity over 1–10 cm2$1 - \left(\text{cm}\right)^{2}$ areas (before up scaling to 1 m2$ \left(\text{m}\right)^{2}$) to perform at, or exceed, the Lambertian (ray optics) limit of light trapping. Herein, a pathway is shown to high‐resolution sub‐1 μm etch mask patterning by ablation using direct femtosecond laser writing performed at room conditions (without the need for a vacuum‐based lithography approach). A Bessel beam is used to alleviate the required high surface tracking tolerance for ablation of 0.3–0.8 μm diameter holes in 40 nm alumina Al2O3$\left(\text{Al}\right)_{2} \left(\text{O}\right)_{3}$–mask at high writing speed, 7.5 cm s−1; a patterning rate 1 cm2 per 20 min. Plasma etching protocol was optimized for a zero‐mesa formation of photonic‐crystal‐trapping structures and smooth surfaces at the nanoscale level. The maximum of minority carrier recombination time of 2.9 ms was achieved after the standard wafer passivation etch; resistivity of the wafer was 3.5 Ω cm. Scaling up in area and throughput of the demonstrated approach is outlined. [ABSTRACT FROM AUTHOR]

It has been suggested that time at a high fraction (%) of maximal oxygen uptake (VO2max) plays a decisive role for adaptations to interval training. Yet, no study has, to date, measured the % of VO2max during all interval sessions throughout a prolonged training intervention and subsequently related it to the magnitude of training adaptations. Thus, the present study aimed to investigate the relationship between % of VO2max achieved during an interval training intervention and changes in endurance performance and its physiological determinants in well‐trained cyclists. Twenty‐two cyclists (VO2max 67.1 (6.4) mL·min−1 ·kg−1; males, n = 19; females, n = 3) underwent a 9‐week interval training intervention, consisting 21 sessions of 5 × 8‐min intervals conducted at their 40‐min highest sustainable mean power output (PO). Oxygen uptake was measured during all interval sessions, and the relationship between % of VO2max during work intervals and training adaptations were investigated using linear regression. A performance index was calculated from several performance measures. With higher % of VO2max during work intervals, greater improvements were observed for maximal PO during the VO2max test (R2adjusted = 0.44, p = 0.009), PO at 4 mmol·L−1 [blood lactate] (R2adjusted = 0.25, p = 0.035), the performance index (R2adjusted = 0.36, p = 0.013), and VO2max (R2adjusted = 0.54, p = 0.029). Other measures, such as % of maximal heart rate, were related to fewer outcome variables and exhibited poorer session‐to‐session repeatability compared to % of VO2max. In conclusion, improvements in endurance measures were positively related to the % of VO2max achieved during interval training. Percentage of VO2max was the measure that best reflected the magnitude of training adaptations. Highlights: In the present study, we measured well‐trained cyclists' oxygen uptake during 21 power output‐matched interval sessions throughout a 9‐week training intervention and related it to the magnitude of training adaptations.For the first time, we demonstrate that gains in endurance measures following an interval training intervention are positively related to the fraction of maximal oxygen uptake (V̇O2max) and time spent ≥90% of V̇O2max during interval sessions.Fraction of V̇O2max during sessions demonstrated better session‐to‐session repeatability and displayed stronger associations with improvements in indicators of endurance performance compared to the percentage of maximal heart rate. [ABSTRACT FROM AUTHOR]

Let X$X$ be a random variable and define its concentration function by Qh(X)=supx∈RP(X∈(x,x+h]).$$\begin{equation*} {\mathcal {Q}}_{h}(X)=\sup _{x\in {\mathbb {R}}}{\mathbb {P}}(X\in (x,x+h]). \end{equation*}$$For a sum Sn=X1+⋯+Xn$S_n=X_1+\cdots +X_n$ of independent real‐valued random variables, the Kolmogorov–Rogozin inequality states that Qh(Sn)⩽C∑i=1n(1−Qh(Xi))−12.$$\begin{equation*} {\mathcal {Q}}_{h}(S_n)\leqslant C{\left(\sum _{i=1}^{n}(1-{\mathcal {Q}}_{h}(X_i))\right)}^{-\frac{1}{2}}. \end{equation*}$$In this paper, we give an optimal bound for Qh(Sn)${\mathcal {Q}}_{h}(S_n)$ in terms of Qh(Xi)${\mathcal {Q}}_{h}(X_i)$, which settles a question posed by Leader and Radcliffe in 1994. Moreover, we show that the extremal distributions are mixtures of two uniform distributions each lying on an arithmetic progression. [ABSTRACT FROM AUTHOR]

Exidavnemab is a monoclonal antibody (mAb) with a high affinity and selectivity for pathological aggregated forms of α‐synuclein and a low affinity for physiological monomers, which is in clinical development as a disease‐modifying treatment for patients with synucleinopathies such as Parkinson's disease. Safety, tolerability, pharmacokinetics, immunogenicity, and exploratory biomarkers were assessed in two separate Phase 1 single ascending dose studies, including single intravenous (IV) (100 to 6000 mg) or subcutaneous (SC) (300 mg) administration of exidavnemab in healthy volunteers (HVs). Across the two studies, a total of 98 Western, Caucasian, Japanese, and Han Chinese HVs were enrolled, of which 95 completed the study. Exidavnemab was generally well tolerated. There were no serious adverse events or safety issues identified in laboratory analyses. Headache, asymptomatic COVID‐19, back pain, and post lumbar puncture syndrome were the most frequently reported treatment‐emergent adverse events. Following IV infusion, the pharmacokinetics of exidavnemab was approximately dose linear in the range 100‐6000 mg. The terminal half‐life was approximately 30 days, and the exposure was comparable across Western, Caucasian, Japanese, and Han Chinese volunteers. The absolute SC bioavailability was ∼71%. Cerebrospinal fluid exposure relative to serum after single dose was within the range expected for mAbs (approximately 0.2%). The anti‐drug antibody rates were low and there was no effect of immunogenicity on the pharmacokinetics or safety. Dose‐dependent reduction of free α‐synuclein in plasma was observed. In summary, exidavnemab was found to have an excellent pharmacokinetic profile and was well tolerated in HVs, supporting the continued clinical development. [ABSTRACT FROM AUTHOR]

The European Academy of Dermatology and Venereology (EADV) Task Forces on quality of life (QoL) and patient‐oriented outcomes and on urticaria and angioedema recommendations for the assessment of Health‐related (HR) QoL in all patients with urticaria in research and practice are as follows: to use the DLQI for adults and the CDLQI for children as dermatology‐specific and the CU‐Q2oL as a disease‐specific HRQoL instruments in urticaria; to use generic instruments to provide comparison of data on urticaria with non‐dermatologic diseases, or to compare with healthy volunteers or the general population; to select validated HRQoL instruments with appropriate age limits; to present exact numeric data for HRQoL results; correct title of any HRQoL instrument should be used, along with its correct abbreviation and the reference to its original publication, where possible. The EADV TFs discourage the use of non‐validated HRQoL instruments and modified HRQoL instruments that have not undergone standard validation. [ABSTRACT FROM AUTHOR]

Gliomagenesis induces profound changes in the composition of the extracellular matrix (ECM) of the brain. In this study, we identified a cellular population responsible for the increased deposition of collagen I and fibronectin in glioblastoma. Elevated levels of the fibrillar proteins collagen I and fibronectin were associated with the expression of fibroblast activation protein (FAP), which is predominantly found in pericyte‐like cells in glioblastoma. FAP+ pericyte‐like cells were present in regions rich in collagen I and fibronectin in biopsy material and produced substantially more collagen I and fibronectin in vitro compared to other cell types found in the GBM microenvironment. Using mass spectrometry, we demonstrated that 3D matrices produced by FAP+ pericyte‐like cells are rich in collagen I and fibronectin and contain several basement membrane proteins. This expression pattern differed markedly from glioma cells. Finally, we have shown that ECM produced by FAP+ pericyte‐like cells enhances the migration of glioma cells including glioma stem‐like cells, promotes their adhesion, and activates focal adhesion kinase (FAK) signaling. Taken together, our findings establish FAP+ pericyte‐like cells as crucial producers of a complex ECM rich in collagen I and fibronectin, facilitating the dissemination of glioma cells through FAK activation. [ABSTRACT FROM AUTHOR]

This study investigated the in vitro antimicrobial and anthelmintic effect of copper nanoparticles (CuNPs) against the bacterium Aeromonas hydrophila, the monogeneans Dactylogyrus minutus, Dactylogyrus extensus, Gyrodactylus cyprini, and the cestode Schyzocotyle acheilognathi, as well as their toxicity to Cyprinus carpio Koi. In the antimicrobial in vitro test, the inhibition zone method and minimum inhibitory concentration (MIC) were performed. In order to determine the time and efficacy of monogenean parasite mortality, the parasites were exposed to CuNP concentrations of 20, 50, 100, 150, 200, and 300 mg L−1, and a control group with tank water and one with copper sulphate pentahydrate (CuSO4.5H2O) at a concentration of 0.3 mg L−1, performed in triplicate. The parasites were observed every 10 min for 300 min, and mortality was recorded. For the cestodes, parasites were immersed in CuNP concentrations of 50, 100, 150, and 300 mg L−1. At the end of the in vitro tests, the anthelmintic efficacy of each treatment was calculated. To assess the tolerance and toxicity in fish, they were exposed to CuNP concentrations of 0.6, 1.25, 2.5, 5, 10, 20, and 50 mg L−1 for 12 h. The MIC demonstrated that CuNPs effectively inhibited the growth of A. hydrophila up to a dilution of 12,500 mg L−1 and showed an inhibition zone of 14.0 ± 1.6 mm for CuNPs. The results of anthelmintic activity showed a dose‐dependent effect of concentration for both groups of parasites, with the most effective concentration being 300 mg L−1 in 120 min. In the toxicity test, the carps showed tolerance to lower concentrations. The study indicated that CuNPs were effective against the studied pathogens. However, it proved to be toxic to fish at high concentrations. The use of low concentrations is recommended still requires further investigation. [ABSTRACT FROM AUTHOR]

Predicting soil water status remotely is appealing due to its low cost and large‐scale application. During drought, plants can disconnect from the soil, causing disequilibrium between soil and plant water potentials at pre‐dawn. The impact of this disequilibrium on plant drought response and recovery is not well understood, potentially complicating soil water status predictions from plant spectral reflectance. This study aimed to quantify drought‐induced disequilibrium, evaluate plant responses and recovery, and determine the potential for predicting soil water status from plant spectral reflectance. Two species were tested: sweet corn (Zea mays), which disconnected from the soil during intense drought, and peanut (Arachis hypogaea), which did not. Sweet corn's hydraulic disconnection led to an extended 'hydrated' phase, but its recovery was slower than peanut's, which remained connected to the soil even at lower water potentials (−5 MPa). Leaf hyperspectral reflectance successfully predicted the soil water status of peanut consistently, but only until disequilibrium occurred in sweet corn. Our results reveal different hydraulic strategies for plants coping with extreme drought and provide the first example of using spectral reflectance to quantify rhizosphere water status, emphasizing the need for species‐specific considerations in soil water status predictions from canopy reflectance. Summary Statement: We developed models to accurately predict rhizosphere water status from hyperspectral imaging of roots and soil. We found canopies cannot always accurately predict rhizosphere water status—as our experiment revealed soil–plant disequilibrium in one species (sweet corn) but not another (peanut). [ABSTRACT FROM AUTHOR]

Objectives: Cluster of differentiation 38 (CD38) is a key target on multiple myeloma (MM) cells. This multi‐centre, Phase 1, single‐agent study (NCT04000282) investigated SAR442085, a novel fragment crystallisable (Fc)‐modified anti‐CD38 monoclonal antibody (mAb), with enhanced affinity towards Fc‐gamma receptor on effector cells in patients with relapsed and/or refractory (RR) MM. Methods: This study comprised two parts: Part‐A (dose‐escalation involving anti‐CD38 mAb pre‐treated and naïve patients) and Part‐B (dose expansion). Primary endpoints were maximum tolerated dose and recommended Phase 2 dose (RP2D). Results: Thirty‐seven heavily pre‐treated patients were treated in Part A. Part‐B (dose‐expansion) was not studied. Seven dose‐limiting toxicities were reported at DL3, DL5, DL6, and DL7. RP2D was determined to be 5–7·5 mg/kg. Most common treatment‐emergent adverse events were infusion‐related reactions in 70·3% (26/37) patients. Grade ≥3 thrombocytopenia was reported in 48·6% (18/37). Overall response rate was 70% in anti‐CD38 mAb naïve and 4% in anti‐CD38 pre‐treated patients, with a median progression‐free survival of 7·62 (95%CI: 2·858; not calculable) months and 2·79 (95%CI: 1·150; 4·172) months and, respectively. Conclusions: The efficacy of SAR442085 was promising in anti‐CD38 mAb naïve patients but did not extend to the larger cohort of anti‐CD38 mAb pre‐treated patients. This observation, along with transient high‐grade thrombocytopenia, could potentially limit its clinical use. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors face high risks of adverse late health effects. Long‐term follow‐up care for childhood cancer survivors is crucial to improve their health and quality of life. However, implementation remains a challenge. To support implementation of high‐quality long‐term follow‐up care, we explored expected barriers and facilitators for establishing this follow‐up care among healthcare providers from four European clinics. Methods: A qualitative study was conducted using four focus groups comprising 30 healthcare providers in total. The semi‐structured interview guide was developed based on the Grol and Wensing framework. Data was analyzed following a thematic analysis, combining both inductive and deductive approaches to identify barriers and facilitators across the six levels of Grol and Wensing: innovation, professional, patient, social, organizational and economic and political. Results: Most barriers were identified on the organizational level, including insufficient staff, time, capacity and psychosocial support. Other main barriers included limited knowledge of late effects among healthcare providers outside the long‐term follow‐up care team, inability of some survivors to complete the survivor questionnaire and financial resources. Main facilitators included motivated healthcare providers and survivors, a skilled hospital team, collaborations with important stakeholders like general practitioners, and psychosocial care facilities, utilization of the international collaboration and reporting long‐term follow‐up care results to convince hospital managers. Conclusion: This study identified several factors for successful implementation of long‐term follow‐up care for childhood cancer survivors. Our findings showed that specific attention should be given to knowledge, capacity, and financial issues, along with addressing psychosocial issues of survivors. [ABSTRACT FROM AUTHOR]

A lot of hope for high‐risk cancers is being pinned on immunotherapy but the evidence in children is lacking due to the rarity and limited efficacy of single‐agent approaches. Here, we aim to assess the effectiveness of multimodal therapy comprising a personalized dendritic cell (DC) vaccine in children with relapsed and/or high‐risk solid tumors using the N‐of‐1 approach in real‐world scenario. A total of 160 evaluable events occurred in 48 patients during the 4‐year follow‐up. Overall survival of the cohort was 7.03 years. Disease control after vaccination was achieved in 53.8% patients. Comparative survival analysis showed the beneficial effect of DC vaccine beyond 2 years from initial diagnosis (HR = 0.53, P =.048) or in patients with disease control (HR = 0.16, P =.00053). A trend for synergistic effect with metronomic cyclophosphamide and/or vinblastine was indicated (HR = 0.60 P =.225). A strong synergistic effect was found for immune check‐point inhibitors (ICIs) after priming with the DC vaccine (HR = 0.40, P =.0047). In conclusion, the personalized DC vaccine was an effective component in the multimodal individualized treatment. Personalized DC vaccine was effective in less burdened or more indolent diseases with a favorable safety profile and synergized with metronomic and/or immunomodulating agents. [ABSTRACT FROM AUTHOR]

Background: Diagnostic tests carry significant risks, and communications are needed to help lay people consider these. The development of communications has been hindered by poor knowledge about how lay people understand and negotiate testing risks. We examined lay Australians' perceptions of diagnostic testing risks and how these risks are managed. Method: We completed 12 semistructured online focus groups with 61 Australian adults (18+) between April and June 2022. Participants were divided into younger/older (> 50 years) and male/female groups. Using semistructured discussion and exploring two hypothetical scenarios, we examined attitudes to diagnostic tests, their risks and how test risks were managed. Themes were identified, subanalysed to identify age and gender differences and mapped to the COM‐B model of behaviour change. Results: The six themes provided detailed accounts of how participants considered themselves able, empowered and assertive when negotiating testing risks and of complex ways in which relationships with health workers, personal experiences and structural factors influenced negotiating testing risks. COM‐B identified multiple opportunities for leveraging these lay beliefs in health promotion. It also identified barriers, including narrow concepts of testing risks, challenges during shared decision‐making and overestimation of personal influence on testing decisions. Significance: Our findings matter because they are a novel, detailed account of testing risk beliefs, linked to a model for behaviour change. This will directly inform development of test risk/benefit communications, which are a research priority. Public Contribution: The study design enabled participants to influence the discussion agenda, and they could comment on the analysis. Participants contributed insights about their needs, beliefs and experiences related to medical testing, and these will be used to shape future patient‐centred decision tools. [ABSTRACT FROM AUTHOR]

Seaweed farming is the single largest aquaculture commodity with >30 million tonnes produced each year. Furthermore, the restoration of lost seaweed forests is gaining significant momentum, particularly for kelps in warming temperate areas. Whether in aquaculture settings, following restoration practices, or in the wild, all seaweeds undergo biotic interactions with a diverse range of co‐occurring or cocultured organisms. To date, most research assessing such biotic interactions has focused on the response of the organism interacting with seaweeds, rather than on the seaweeds themselves. However, understanding how seaweeds respond to other organisms, particularly on a molecular scale, is crucial for optimizing outcomes of seaweed farming or restoration efforts and, potentially, also for the conservation of natural populations. In this systematic review, we assessed the molecular processes that seaweeds undergo during biotic interactions and propose priority areas for future research. Despite some insights into the response of seaweeds to biotic interactions, this review specifically highlights a lack of characterization of biomolecules involved in the response to chemical cues derived from interacting organisms (four studies in the last 20 years) and a predominant use of laboratory‐based experiments conducted under controlled conditions. Additionally, this review reveals that studies targeting metabolites (70%) are more common than those examining the role of genes (22%) and proteins (8%). To effectively inform seaweed aquaculture efforts, it will be crucial to conduct larger scale experiments simulating natural environments. Also, employing a holistic approach targeting genes and proteins would be beneficial to complement the relatively well‐established role of metabolites. [ABSTRACT FROM AUTHOR]

Coherent diffractive imaging with X‐ray free‐electron lasers could enable structural studies of macromolecules at room temperature. This type of experiment could provide a means to study structural dynamics on the femtosecond timescale. However, the diffraction from a single protein is weak compared with the incoherent scattering from background sources, which negatively affects the reconstruction analysis. This work evaluates the effects of the presence of background on the analysis pipeline. Background measurements from the European X‐ray Free‐Electron Laser were combined with simulated diffraction patterns and treated by a standard reconstruction procedure, including orientation recovery with the expand, maximize and compress algorithm and 3D phase retrieval. Background scattering did have an adverse effect on the estimated resolution of the reconstructed density maps. Still, the reconstructions generally worked when the signal‐to‐background ratio was 0.6 or better, in the momentum transfer shell of the highest reconstructed resolution. The results also suggest that the signal‐to‐background requirement increases at higher resolution. This study gives an indication of what is possible at current setups at X‐ray free‐electron lasers with regards to expected background strength and establishes a target for experimental optimization of the background. [ABSTRACT FROM AUTHOR]

Tau interacts with multiple heterogeneous nuclear ribonucleoproteins (hnRNPs)—a family of RNA binding proteins that regulate multiple known cellular functions, including mRNA splicing, mRNA transport, and translation regulation. We have previously demonstrated particularly significant interactions between phosphorylated tau and three hnRNPs (hnRNP A1, hnRNP A2B1, and hnRNP K). Although multiple hnRNPs have been previously implicated in tauopathies, knowledge of whether these hnRNPs colocalize with tau aggregates or show cellular mislocalization in disease is limited. Here, we performed a neuropathological study examining the colocalization between hnRNP A1, hnRNP A2B1, hnRNP K, and phosphorylated tau in two brain regions (hippocampus and frontal cortex) in six disease groups (Alzheimer's disease, mild cognitive impairment, progressive supranuclear palsy, corticobasal degeneration, Pick's disease, and controls). Contrary to expectations, hnRNP A1, hnRNP A2B1, and hnRNP K did not colocalize with AT8‐immunoreactive phosphorylated tau pathology in any of the tauopathies examined. However, we did observe significant cellular mislocalization of hnRNP A1, hnRNP A2B1 and hnRNP K in tauopathies, with unique patterns of mislocalization observed for each hnRNP. These data point to broad dysregulation of hnRNP A1, A2B1 and K across tauopathies with implications for disease processes and RNA regulation. [ABSTRACT FROM AUTHOR]

Introduction: Use of albumin is suggested for some patients with shock, but preferences for its use may vary among intensive care unit (ICU) physicians. Methods: We conducted an international online survey of ICU physicians with 20 questions about their use of albumin and their opinion towards a randomised trial among adults with shock comparing the use versus no use of albumin. Results: A total of 1248 respondents participated, with a mean response rate of 37%, ranging from 18% to 75% across 21 countries. Respondents mainly worked in mixed ICUs and 92% were specialists in intensive care medicine. The reported use of albumin in general shock varied as 18% reported 'almost never', 22% 'rarely', 34% 'occasionally', 22% 'frequently' and 4% 'almost always' using albumin. In septic shock, 19% reported 'almost never', 22% 'rarely', 29% 'occasionally', 22% 'frequently' and 7% 'almost always' using albumin. Physicians' preferences were more consistent for haemorrhagic‐ and cardiogenic shock, with more than 45% reporting 'almost never' using albumin. While the reported use of albumin for other purposes than resuscitation was infrequent (40%–85% reported 'almost never' for five other indications), the most frequent other indications were low serum albumin levels and improvement of the efficacy of diuretics. Most respondents (93%) would randomise adult ICU patients with shock to a trial of albumin versus no albumin. Conclusions: In this international survey, the reported preferences for the use of albumin in adult ICU patients with shock varied considerably among surveyed ICU physicians. The support for a future randomised trial was high. [ABSTRACT FROM AUTHOR]

Optimal egg size theory implies that female organisms balance between fecundity and individual offspring investment according to their environment. Past interspecific studies suggest that fishes in large marine systems generally produce smaller eggs than those in small freshwater systems. We tested whether intraspecific egg size variation reflected a similar pattern by comparing egg size among yellow perch (Perca flavescens) populations inhabiting a range of system sizes. In 2018, 2019, and 2023, we collected yellow perch egg samples from 12 locations in systems ranging in surface area from 37 to 5,390,492 ha. First, we found that egg diameter significantly increased with maternal total length in five of eight individually tested populations. After accounting for these maternal effects, we found a significant interaction, where females inhabiting larger lakes, such as the main basins of Lakes Erie and Michigan, produced smaller eggs than those in smaller inland lakes, and the greatest differences were demonstrated among females of greater total length. This egg size variation in the largest females is consistent with interspecific egg size comparisons between marine and freshwater fishes. However, by examining a single species across vastly different environments, we were able to support theoretical expectations that maternal investment in offspring should vary with environmental conditions controlling early‐life resource acquisition and competition. [ABSTRACT FROM AUTHOR]

Objective: To assess comparative effectiveness, safety, and tolerability of off‐label rituximab, compared with frequently used therapies approved for multiple sclerosis (MS). Methods: A Swedish cohort study of persons with relapsing–remitting MS, age 18 to 75 years at inclusion and with a first therapy start or a first therapy switch between 2011 and 2018. Low‐dose rituximab was compared with MS‐approved therapies. Primary outcomes were proportions with 12 months confirmed disability worsening and change in MS Impact Scale‐29 (MSIS‐29) scores, respectively. Secondary endpoints included relapses, therapy discontinuation, and serious adverse events. Analyses used an intention‐to‐treat approach and were adjusted for demographics, MS features, and health characteristics. Results: We included 2,449 participants as first therapy start and 2,463 as first therapy switch. Proportions with disability worsening at 3 years were 9.1% for rituximab as first therapy and 5.1% after therapy switch, with no differences to MS‐approved comparators. Worsening on rituximab was mostly independent of relapses. MSIS‐29 with rituximab at 3 years improved by 1.3/8.4 points (physical/psychological) for first disease‐modifying therapy (DMT) and 0.4/3.6 for DMT switch, and was mostly similar across therapies. Rituximab had lower relapse rates and higher therapy persistence in both groups. The rate of hospital‐treated infections was higher with rituximab after a therapy switch, but not as a first therapy. Interpretation: This population‐based real‐world cohort study found low rates of disability progression, mostly independent of relapses, and without significant differences between rituximab and MS‐approved comparators. Rituximab led to lower rates of inflammatory activity and higher treatment persistence, but was associated with an increased rate of serious infections. ANN NEUROL 2024;96:678–693 [ABSTRACT FROM AUTHOR]

Apheresis is performed worldwide for an increasing number of indications. The development of common data elements (CDE) for apheresis related areas may facilitate conduct of new research, enhance quality initiatives including benchmarking, and improve patient care. This report describes the systematic development of the Uniform Apheresis Case Report Form (UACRF) as part of the Apheresis in the United States (ApheresUS) program. A consensus panel of 17 diverse experts in apheresis, related specialties, and electronic case report form (eCRF), and database development was assembled. The panel met via online conferencing from November 17, 2020 to December 1, 2021. A draft document was posted online for public comment from October 11, 2021 to November 10, 2021. Feedback was collected using an online survey tool. The consensus panel revised the UACRF. This version was converted to an eCRF with additional changes made to improve usability in this format. The final version of the UACRF was created on August 24, 2023. The UACRF contains 16 modules: procedure and subject eligibility, patient demographics, general procedure information, laboratory parameters, vascular access, common procedure elements, eight procedure specific modules (mononuclear cell collection and seven therapeutic modalities), outcomes, and site information. A total of 137 data elements were created, including 57 with one or more subelements. The UACRF is the first systematic attempt to develop CDE for therapeutic apheresis and white blood cell collections. Further validation of the UACRF is necessary to confirm the tool's ability to collect the relevant data elements and determine the usability of the form. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of abdominal injuries in war and conflict zones, particularly in low‐ and middle‐income countries (LMICs), presents a significant healthcare challenge. These injuries, often resulting from explosive devices, firearms, and shrapnel, lead to high morbidity and mortality rates due to delayed diagnoses, inadequate medical infrastructure, and limited access to specialised care. This review aims to summarise the literature on conflict‐related abdominal injuries in LMICs, highlighting the impact of such trauma on healthcare systems and patient outcomes, and suggesting strategies for improvement. Methods: A comprehensive narrative review was conducted, focusing on studies from contemporary and historical conflict‐ridden nations. Databases such as PubMed, EMBASE, Google Scholar, the Cochrane Library, and Scopus were searched using specific keywords. Inclusion criteria encompassed various study designs and both paediatric and adult populations, with studies providing raw data prioritised. Exclusions included non‐English articles, non‐peer‐reviewed studies, and those not reporting outcomes or involving high‐income countries. Results: The review identified significant challenges in managing war‐related abdominal trauma in LMICs, including a shortage of healthcare personnel and infrastructure, socio‐political barriers, and research gaps. Clinical implications of such injuries include elevated mortality rates, with surgical and nonsurgical management outcomes varying significantly. Positive advancements in diagnostics and surgical techniques have improved survival rates, yet the need for further infrastructural and workforce enhancements remains critical. Conclusion: Abdominal trauma in conflict‐affected LMICs necessitates focused efforts to improve healthcare delivery, including targeted funding for infrastructure and equipment, development of training programs for trauma specialists, and increased humanitarian aid. Bridging research gaps and fostering collaborative efforts are essential for advancing the management of abdominal trauma and enhancing patient outcomes in these challenging environments. [ABSTRACT FROM AUTHOR]

In recent years, systemic inflammation has emerged as a pivotal player in the development and progression of various degenerative diseases. This complex, chronic inflammatory state, often undetected, can have far‐reaching consequences for the body's physiology. At the molecular level, markers such as C‐reactive protein, cytokines and other inflammatory mediators serve as indicators of systemic inflammation and often act as predictors of numerous musculoskeletal diseases and even certain forms of cancer. The concept of 'meta‐inflammation', specifically referring to metabolically triggered inflammation, allows healthcare professionals to understand inflammatory responses in patients with metabolic syndrome. Driven by nutrient excess and the expansion of adipose tissue, meta‐inflammation is closely associated with insulin resistance, further propagating the metabolic dysfunction observed in many Western societies. Wound persistence, on the other hand, exacerbates the detrimental effects of prolonged inflammation at the local level. Acute inflammation is a beneficial and essential process for wound healing and infection control. However, when inflammation fails to resolve, it can impede the healing process, leading to chronic wounds, excessive scarring and even the activation of fibrotic pathways. This approach significantly reduces the efficacy of regenerative biological therapies. Our review focuses on the vital role of proteins, vitamins and minerals in collagen synthesis and cell proliferation for tissue healing. We also examine hormonal influences on regeneration, noting the negative effects of imbalances, and emphasize glucose regulation's importance in creating a stable environment for chronic wound healing. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries, paragangliomas, and syringomyelia are uncommon diseases. Furthermore, in the absence of any genetic link and with less than five reported adult patients surviving unrepaired rare form of Tetralogy of Fallot, our case shows noteworthiness. The possibility of definitive treatment of these conditions is rendered unsafe due to this persistent defect. Thus, management and ongoing survival of this patient remains complex and challenging. [ABSTRACT FROM AUTHOR]

Multiresonant thermally activated delayed fluorescence (MR‐TADF) emitters have been the focus of extensive design efforts as they are recognized to show bright, narrowband emission, which makes them very appealing for display applications. However, the planar geometry and relatively large singlet–triplet energy gap lead to, respectively, severe aggregation‐caused quenching (ACQ) and slow reverse intersystem crossing (RISC). Here, a design strategy is proposed to address both issues. Two MR‐TADF emitters triphenylphosphine oxide (TPPO)‐tBu‐DiKTa and triphenylamine (TPA)‐tBu‐DiKTa have been synthesized. Twisted ortho‐substituted groups help increase the intermolecular distance and largely suppress the ACQ. In addition, the contributions from intermolecular charge transfer states in the case of TPA‐tBu‐DiKTa help to accelerate RISC. The organic light‐emitting diodes (OLEDs) with TPPO‐tBu‐DiKTa and TPA‐tBu‐DiKTa exhibit high maximum external quantum efficiencies (EQEmax) of 24.4% and 31.0%, respectively. Notably, the device with 25 wt% TPA‐tBu‐DiKTa showed both high EQEmax of 28.0% and reduced efficiency roll‐off (19.9% EQE at 1000 cd m−2) compared to the device with 5 wt% emitter (31.0% EQEmax and 11.0% EQE at 1000 cd m−2). The new emitters were also introduced into single‐layer light‐emitting electrochemical cells (LECs), equipped with air‐stable electrodes. The LEC containing TPA‐tBu‐DiKTa dispersed at 0.5 wt% in a matrix comprising a mobility‐balanced blend‐host and an ionic liquid electrolyte delivered blue luminance with an EQEmax of 2.6% at 425 cd m−2. The high efficiencies of the OLEDs and LECs with TPA‐tBu‐DiKTa illustrate the potential for improving device performance when the DiKTa core is decorated with twisted bulky donors. [ABSTRACT FROM AUTHOR]

Background: Melanoma is the most aggressive skin cancer with ability to recur also after early‐stage tumor surgery. The aim was to identify early‐stage melanoma patients at high risk of recurrence using liquid biopsy, estimating of mutated BRAF ctDNA and the level of tumor marker S100B in plasma. Methods: Eighty patients were enrolled in the study. BRAF V600E mutation was determined in FFPE tissue and plasma samples using ultrasensitive ddPCR with pre‐amplification. The level of S100B was determined in plasma by immunoassay chemiluminescent method. Results: The best prediction of melanoma recurrence after surgery was observed in patients with combined high level of S100B (S100Bhigh) and ctDNA BRAFV600E (BRAFmut) in preoperative (57.1% vs. 12.5%, p = 0.025) as well as postoperative blood samples (83.3% vs. 14.3%, resp., p = 0.001) in comparison with low S100B and BRAF wild‐type. Similarly, patients with preoperative and postoperative S100Bhigh and BRAFmut experienced worse prognosis (DFI p = 0.05, OS p = 0.131 and DFI p = 0.001, OS = 0.001, resp.). Conclusion: We observed the benefit of the estimation of combination of S100B and ctDNA BRAFmut in peripheral blood for identification of patients at high risk of recurrence and unfavorable prognosis. Significance: There is still no general consensus on molecular markers for deciding the appropriateness of adjuvant treatment of early‐stage melanoma. We have shown for the first time that the combined determination of the ctDNA BRAFmut oncogene (liquid biopsy) and the high level of tumor marker S100B in pre‐ and postoperative plasma samples can identify patients with the worst prognosis and the highest risk of tumor recurrence. Therefore, modern adjuvant therapy would be appropriate for these patients with resectable melanoma, regardless of disease stage. [ABSTRACT FROM AUTHOR]

Objective: The pathogenesis of inflammatory myopathies is poorly understood and there is a need to dissect the transcriptome in more granular ways beyond gene expression. Methods: We used a set of muscle RNA‐sequencing data from different myositis subtypes grouped by their specific autoantibodies (n = 152). We quantified annotated RNA transcripts for each myositis subtype and identified uniquely expressed RNA as well as transcriptional similarities among myositis types. In addition, we quantified event‐based alternative splicing with predicted protein changes. And finally, we searched for cryptic exons. Results: We saw considerable overlap in RNA expression among subtypes. In addition, MADCAM1 was previously shown to be uniquely expressed in Mi‐2 myositis; we discovered it was two noncanonical transcripts that predominantly contributed to the observed increased expression. At the transcriptional level, dermatomyositis subtypes were least similar to inclusion body myositis (IBM) or Jo1, followed by HMGCR, then SRP and other dermatomyositis subtype. Additionally, we discovered many alternative splicing events that were unique by myositis subgroup, including events in muscle dystrophy genes and one event in SRP72, which was seen uniquely in SRP myositis. Finally, we looked for previously reported cryptic exons in IBM and did not find them. Conclusion: The large degree of transcriptional overlap among myositis subtypes reinforces the need to use disease (in addition to healthy) controls to find unique features of autoimmune disease. Unique alterations in the transcriptome that are seen in one myositis subtype and not others advance our understanding of distinct disease pathology. [ABSTRACT FROM AUTHOR]

In this study, new statistical copolymers made from dioctyl fumarate (DOF) and styrene (S) with different architectures (linear or branched) were synthesized to assess the impact of this macromolecular characteristic on the modification of Argentine asphalt. Modified asphalts (MA) exhibited good compatibility without evidence of oxidative effect during their manufacturing, as confirmed by fluorescence microscopy and Fourier Transform Infrared spectroscopy assays. The incorporation of copolymers led to an improvement in the basic properties of the MA, and this showed a higher viscosity compared to the base asphalt, with the effect being more pronounced in the MA containing branched copolymer. The last sample exhibits the lowest thermal susceptibility, as determined from the analysis of activation energies. Highlights: New linear and branched copolymers were synthesized using fumaric and styrene monomers.Monomers randomly alternate in copolymer chains.No oxidation during asphalt modification and the polymers are stable.Incorporating branched copolymer doubles asphalt's elastic recovery.Asphalt modified with the branched copolymer exhibits reduced thermal susceptibility. [ABSTRACT FROM AUTHOR]

The dynamicity of the mitochondrial network is crucial for meeting the ever‐changing metabolic and energy needs of the cell. Mitochondrial fission promotes the degradation and distribution of mitochondria, while mitochondrial fusion maintains mitochondrial function through the complementation of mitochondrial components. Previously, we have reported that mitochondrial networks are tubular, interconnected, and well‐organized in young, healthy C. elegans, but become fragmented and disorganized with advancing age and in models of age‐associated neurodegenerative disease. In this work, we examine the effects of increasing mitochondrial fission or mitochondrial fusion capacity by ubiquitously overexpressing the mitochondrial fission gene drp‐1 or the mitochondrial fusion genes fzo‐1 and eat‐3, individually or in combination. We then measured mitochondrial function, mitochondrial network morphology, physiologic rates, stress resistance, and lifespan. Surprisingly, we found that overexpression of either mitochondrial fission or fusion machinery both resulted in an increase in mitochondrial fragmentation. Similarly, both mitochondrial fission and mitochondrial fusion overexpression strains have extended lifespans and increased stress resistance, which in the case of the mitochondrial fusion overexpression strains appears to be at least partially due to the upregulation of multiple pathways of cellular resilience in these strains. Overall, our work demonstrates that increasing the expression of mitochondrial fission or fusion genes extends lifespan and improves biological resilience without promoting the maintenance of a youthful mitochondrial network morphology. This work highlights the importance of the mitochondria for both resilience and longevity. [ABSTRACT FROM AUTHOR]

Diseases and parasites are important drivers of population dynamics in wild mammal populations. Small and endangered populations that overlap with larger, reservoir populations are particularly vulnerable to diseases and parasites, especially in ecosystems highly influenced by climate change. Sarcoptic mange, caused by a parasitic mite Sarcoptes scabiei, constitutes a severe threat to many wildlife populations and is today considered a panzootic. The Scandinavian arctic fox Vulpes lagopus is endangered with a fragmented distribution and is threatened by e.g. red fox Vulpes vulpes expansion, prey scarcity and inbreeding depression. Moreover, one of the subpopulations in Scandinavia has suffered from repeated outbreaks of sarcoptic mange during the past decade, most likely spread by red foxes. This was first documented in 2013 and then again 2014, 2017, 2019, 2020 and 2021. We used field inventories and wildlife cameras to follow the development of sarcoptic mange outbreaks in this arctic fox subpopulation with specific focus on disease transmission and consequences for reproductive output. In 2013–2014, we documented visual symptoms of sarcoptic mange in about 30% of the total population. Despite medical treatment, we demonstrate demographic consequences where the number of arctic fox litters plateaued and litter size was reduced after the introduction of S. scabiei. Furthermore, we found indications that mange likely was transmitted by a few arctic foxes travelling between several dens, i.e. 'super‐spreaders'. This study highlights sarcoptic mange as a severe threat to small populations and can put the persistence of the entire Scandinavian arctic fox population at risk. [ABSTRACT FROM AUTHOR]

The landscape theory of food web architecture (LTFWA) describes relationships among body size, trophic position, mobility, and energy channels that serve to couple heterogenous habitats, which in turn promotes long‐term system stability. However, empirical tests of the LTFWA are rare and support differs among terrestrial, freshwater, and marine systems. Further, it is unclear whether the theory applies in highly altered ecosystems dominated by introduced species such as the Laurentian Great Lakes. Here, we provide an empirical test of the LTFWA by relating body size, trophic position, and the coupling of different energy channels using stable isotope data from species throughout the Lake Michigan food web. We found that body size was positively related to trophic position, but for a given trophic position, organisms predominately supported by pelagic energy had smaller body sizes than organisms predominately supported by nearshore benthic energy. We also found a hump‐shaped trophic relationship in the food web where there is a gradual increase in the coupling of pelagic and nearshore energy channels with larger body sizes as well as higher trophic positions. This highlights the important role of body size and connectivity among habitats in structuring food webs. However, important deviations from expectations are suggestive of how species introductions and other anthropogenic impacts can affect food web structure in large lakes. First, native top predators appear to be flexible couplers that may provide food web resilience, whereas introduced top predators may confer less stability when they specialize on a single energy pathway. Second, some smaller bodied prey fish and invertebrates, in addition to mobile predators, coupled energy from pelagic and nearshore energy channels, which suggests that some prey species may also be important integrators of energy pathways in the system. We conclude that patterns predicted by the LTFWA are present in the face of species introductions and other anthropogenic stressors to a degree, but time‐series evaluations are needed to fully understand the mechanisms that promote stability. [ABSTRACT FROM AUTHOR]

Vadadustat is an oral hypoxia‐inducible factor prolyl hydroxylase inhibitor for treating anemia in chronic kidney disease (CKD). Single ascending dose (SAD) and multiple ascending dose (MAD) studies assessed pharmacokinetics (PK), pharmacodynamics (PD), and safety of vadadustat in healthy volunteers. A single‐dose, open‐label study was conducted in patients with CKD stages 3 and 4 not on dialysis. In the SAD study, 48 healthy adult men (n = 8/cohort) received single doses of vadadustat (80–1,200 mg) or placebo. In the MAD study, 34 healthy adult men (n = 8–9/cohort) received daily vadadustat (500–900 mg) or placebo for 10 days. In the single‐dose CKD study, 22 male and female patients with CKD (stage 3: n = 10; stage 4: n = 12) received single doses of vadadustat (500 mg). PK parameters included plasma vadadustat; PD biomarkers were measured, including erythropoietin (EPO) levels, reticulocytes, and others. Plasma vadadustat peaked 3–4 hours after single or multiple dosing in healthy volunteers, with a mean t1/2 of approximately 4.5 hours. In patients with CKD, plasma vadadustat peaked at 5–6 hours, with a mean t1/2 of 7.2 (stage 3) and 8.5 (stage 4) hours. Vadadustat AUC∞ and Cmax increased dose proportionally in SAD and MAD trials. In all trials, EPO concentrations increased in a dose‐related manner and returned approximately to baseline by 24 hours. Adverse events were mild and considered not study drug related. The PK and PD results of these studies were utilized for further clinical development of vadadustat for treatment of anemia in CKD patients. [ABSTRACT FROM AUTHOR]

Depletion of veins for dialysis access is a challenging life threatening situation for patients in need of haemodialysis. The utilisation of intracardiac catheter is a rare procedure with scarce reported experience. We describe the case of a 68‐year‐old male that contributes to the limited knowledge of performing a life‐saving intracardiac catheter placement for emergency haemodialysis in a patient without immediate alternative renal replacement therapy available. We also retrospectively analyse the experience reported so far and summarise complications and outcomes. In our case, the patient was able to pursue haemodialysis after intracardiac catheter placement without any complications. Two weeks later, the patient successfully received a kidney transplant from a deceased donor and has a serum creatinine of 1.7 mg/dL after 2 years of follow‐up. There are only four reported cases of kidney transplantation after the procedure, including our own. Intracardiac catheter is an emerging option that could be considered in certain patients as the last resort. Further investigation with regards to patient candidacy and procedure security are necessary. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis (MS) is a demyelinating disease affecting millions of people worldwide. Hereditary susceptibility and environmental factors contribute to disease risk. Infection with Epstein–Barr virus (EBV) and human herpesvirus 6A (HHV‐6A) have previously been associated with MS risk. Other neurotropic viruses, such as rubella virus (RV), are possible candidates in MS aetiopathogenesis, but previous results are limited and conflicting. Methods: In this nested case–control study of biobank samples in a Swedish cohort, we analysed the serological response towards RV before the clinical onset of MS with a bead‐based multiplex assay in subjects vaccinated and unvaccinated towards RV. The association between RV seropositivity and MS risk was analysed with conditional logistic regression. Results: Seropositivity towards RV was associated with an increased risk of MS for unvaccinated subjects, even when adjusting for plausible confounders including EBV, HHV‐6A, cytomegalovirus and vitamin D (adjusted odds ratio [AOR] = 4.0, 95% confidence interval [CI] 1.8–8.8). Cases also had stronger antibody reactivity towards rubella than controls, which was not seen for other neurotropic viruses such as herpes simplex or varicella zoster. Furthermore, we observed an association between RV seropositivity and MS in vaccinated subjects. However, this association was not significant when adjusting for the aforementioned confounders (AOR = 1.7, 95% CI 1.0–2.9). Conclusions: To our knowledge, these are the first reported associations between early RV seropositivity and later MS development. This suggests a broadening of the virus hypothesis in MS aetiology, where molecular mimicry between rubella epitopes and human central nervous system molecules could be an attractive possible mechanism. [ABSTRACT FROM AUTHOR]

The Pantanal is considered the largest continuous freshwater wetland in the world, and its sustainable use requires a unified conceptual framework. The lengthy process to establish public policies has contributed to the increasing vulnerability of the Pantanal. Given the need for a conceptual basis to help this process, we elaborate a list of eight basic principles based on the accumulated scientific evidence: (i) Consider the Paraguay River Basin a management unity; (ii) Establish rules that follow the concept of restricted use approach; (iii) Ensure the ecologically sustainable use of the Pantanal; (iv) Maintain the environmental heterogeneity and functionality in the Pantanal landscapes; (v) Maintain the hydrological integrity and connectivity; (vi) Ensure the environmental representativeness of the protected areas network; (vii) Provide economic incentives for conservationist use of the land; and (viii) Recognize and protect traditional people, their values, resources, and way of living. However, the elaboration of public policies should be a participatory and inclusive decision‐making process towards a more just and sustainable future. [ABSTRACT FROM AUTHOR]

How the timing of development is linked to organismal size is a longstanding question. Although numerous studies have reported a correlation of temporal and spatial traits, the developmental or selective constraints underlying this link remain largely unexplored. We address this question by studying the periodic process of embryonic axis segmentation in-vivo in Oryzias fish. Interspecies comparisons reveal that the timing of segmentation correlates to segment, tissue and organismal size. Segment size in turn scales according to tissue and organism size. To probe for underlying causes, we genetically hybridised two closely related species. Quantitative analysis in ~600 phenotypically diverse F2 embryos reveals a decoupling of timing from size control, while spatial scaling is preserved. Using developmental quantitative trait loci (dev QTL) mapping we identify distinct genetic loci linked to either the control of segmentation timing or tissue size. This study demonstrates that a developmental constraint mechanism underlies spatial scaling of axis segmentation, while its spatial and temporal control are dissociable modules. Synopsis: The molecular relationships that link developmental timing and organismal size remain underexplored. Here, a cross-species analysis in Oryzias fish measures the timing of embryonic body axis segmentation and overall organismal size, providing evidence that timing and size control are dissociable modules. Real-time imaging of the segmentation clock in F2 embryos from interspecies crosses of Oryzias fish reveals a broad phenotypic spectrum. F2 embryos exhibit a linear relationship between PSM and somite size, indicating that a developmental constraint mechanism underlies spatial scaling. developmental quantitative trait loci (dev QTL) analysis of F2 embryos identifies distinct genomic loci correlated with segmentation timing and tissue size, respectively. Interspecies comparison in rice fish (Orzyias spp.) shows that both the rate and size of embryonic segmentation increase in proportion to fish size but are regulated by independent mechanisms. [ABSTRACT FROM AUTHOR]

Summary: Plants rely on solar energy to synthesize ATP and NADPH for photosynthetic carbon fixation and all cellular need. Mitochondrial respiration is essential in plants, but this may be due to heterotrophic bottlenecks during plant development or because it is also necessary in photosynthetically active cells.In this study, we examined in vivo changes of cytosolic ATP concentration in response to light, employing a biosensing strategy in the moss Physcomitrium patens and revealing increased cytosolic ATP concentration caused by photosynthetic activity.Plants depleted of respiratory Complex I showed decreased cytosolic ATP accumulation, highlighting a critical role of mitochondrial respiration in light‐dependent ATP supply of the cytosol. Consistently, targeting mitochondrial ATP production directly, through the construction of mutants deficient in mitochondrial ATPase (complex V), led to drastic growth reduction, despite only minor alterations in photosynthetic electron transport activity.Since P. patens is photoautotrophic throughout its development, we conclude that heterotrophic bottlenecks cannot account for the indispensable role of mitochondrial respiration in plants. Instead, our results support that mitochondrial respiration is essential for ATP provision to the cytosol in photosynthesizing cells. Mitochondrial respiration provides metabolic integration, ensuring supply of cytosolic ATP essential for supporting plant growth and development. [ABSTRACT FROM AUTHOR]

The evolution of Sb2Se3 heterojunction devices away from CdS electron transport layers (ETL) to wide bandgap metal oxide alternatives is a critical target in the development of this emerging photovoltaic material. Metal oxide ETL/Sb2Se3 device performance has historically been limited by relatively low fill factors, despite offering clear advantages with regards to photocurrent collection. In this study, TiO2 ETLs are fabricated via direct current reactive sputtering and tested in complete Sb2Se3 devices. A strong correlation between TiO2 ETL processing conditions and the Sb2Se3 solar cell device response under forward bias conditions is observed and optimized. Numerical device models support experimental evidence of a spike‐like conduction band offset, which can be mediated, provided a sufficiently high conductivity and low interfacial defect density can be achieved in the TiO2 ETL. Ultimately, a SnO2:F/TiO2/Sb2Se3/P3HT/Au device with the reactively sputtered TiO2 ETL delivers an 8.12% power conversion efficiency (η), the highest TiO2/Sb2Se3 device reported to‐date. This is achieved by a substantial reduction in series resistance, driven by improved crystallinity of the reactively sputtered anatase‐TiO2 ETL, whilst maintaining almost maximum current collection for this device architecture. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusion Overall, the prognosis of patients with chronic lymphocytic leukemia (CLL) in the early phase of the disease (Rai 0, Binet A) is favorable; some patients never require therapy. However, some patients require intervention shortly after diagnosis. In the past decade, several risk scores (RS) have been developed to predict disease progression, yet some patients are misclassified. On the other hand, IGHV subset 2 (IGHV2) predicts poor outcomes.A retrospective and multicentric study was conducted to compare the accuracy of five different RS (IPS‐E, CR0, AIPS‐E, CLL‐IPI, and Barcelona‐Brno) to predict disease progression in 781 stage A previously untreated patients with CLL. As an exploratory analysis, it was further investigated whether the inclusion of the IGHV2 as a poor prognostic parameter improved the accuracy of RS.All the scores identified a similar group of patients with CLL in early stage with low‐, intermediate‐, and high‐risk progression. Discrimination was high and similar in all RS (c‐index = 0.74–0.79, area under the curve = 0.7–0.75), as well as calibration (p = .98) and parsimony, although CLL‐IPI showed the best results (Akaike information criterion = 441). A total of 34.4% of patients were categorized within the same RS and concordance was at least moderate between RS.Moreover, the results suggest that IGHV2 may improve the accuracy of RS. [ABSTRACT FROM AUTHOR]

An in‐depth investigation was conducted on a promising composite material (BiVO4/TiO2), focusing on its potential toxicity, photoinduced catalytic properties, as well as its antibiofilm and antimicrobial functionalities. The preparation process involved the synthesis of 2D TiO2 using the lyophilization method, which was subsequently functionalized with sphere‐like BiVO4 through wet impregnation. Finally, we developed BiVO4/TiO2 S‐scheme heterojunctions which can greatly promote the separation of electron‐hole pairs to achieve high photocatalytic performance. The evaluation of concentration‐ and time‐dependent viability inhibition was performed on human lung carcinoma epithelial A549 cells. This assessment included the estimation of glutathione levels and mitochondrial dehydrogenase activity. Significantly, the BiVO4/TiO2 composite demonstrated minimal toxicity towards A549 cells. Impressively, the BiVO4/TiO2 composite exhibited notable photocatalytic performance in the degradation of rhodamine B (k=0.135 min−1) and phenol (k=0.016 min−1). In terms of photoinduced antimicrobial performance, the composite effectively inactivated both gram‐negative E. coli and gram‐positive E. faecalis bacteria upon 60 minutes of UV‐A light exposure, resulting in a significant log 6 (log 10 CFU/mL) reduction in bacterial count. In addition, a 49 % reduction of E. faecalis biofilm was observed. These promising results can be attributed to the unique 2D morphology of TiO2 modified by sphere‐like BiVO4, leading to an increased generation of (intracellular) hydroxyl radicals, which plays a crucial role in the treatments of both organic pollutants and bacteria. This research has significant potential for various applications, particularly in addressing environmental contamination and microbial infections. [ABSTRACT FROM AUTHOR]

Medium‐chain fatty acids (MCFAs), particularly decanoic acid (C10) and octanoic acid (C8), have garnered attention in recent years for their potential antiepileptic properties. A previous study from our laboratory demonstrated that C10 targets the PPARγ nuclear receptor, increasing the activity of the antioxidant enzyme catalase and thereby possibly modulating peroxisomal content. Here, we examined markers of peroxisomal content and activity in response to C10 and C8 exposure in neuronal‐like SH‐SY5Y cells. SH‐SY5Y were treated with 250 mM C10 or C8 for a period of 6 days. Following this, biochemical markers of peroxisomal content and function were assessed, including acyl‐coA oxidase activity, peroxisomal gene expression and peroxisomal VLCFA β‐oxidation. Our findings revealed that C10 treatment augments acyl‐CoA oxidase 1 (ACOx1) activity by 129% in comparison to control cells. An exploration into genes related to peroxisomal biosynthesis showed 23% increased expression of PEX11α upon C10 exposure, implying peroxisomal proliferation. Furthermore, it was observed that C10 exposure not only elevated ACOx1 activity but also enhanced peroxisomal β‐oxidation of docosanoic acid (C22). Our findings bolster the premise that C10 functions as a peroxisome proliferator, influencing peroxisomal content and function. Further investigations are required to fully understand the mechanistic details as to how this may be beneficial in epilepsy and the potential implications with regards to peroxisomal disease. [ABSTRACT FROM AUTHOR]

Circular supply chains (CSCs) prioritize resource efficiency by reusing, remanufacturing, and recycling materials, offering environmental benefits and competitive advantages. However, they are facing various risks and organizational challenges that hinder their efficiency. To ensure long‐term sustainability, this study identifies the key risks and introduces a prioritization model for risk management in CSC strategies proposing a framework for the risk evaluation based on the set of criteria and prioritization model using a combination of three multicriteria decision‐making (MCDM) methods. The model applies fuzzy Delphi‐based analytical hierarchy process (AHP) method to determine the criteria weights and fuzzy axial distance‐based aggregated measurement (ADAM) method for ranking the alternatives. The findings of this study allow for the identification of the most important risks associated with CSC enabling stakeholders to allocate resources strategically and focus efforts on crucial areas. Results highlight that the most important risks are supply chain complexity, resource availability, and quality and technological challenges. The most important contributions are the identification of the most relevant risks that threaten the resilience and sustainability of CSCs, the establishment of the framework for their evaluation, and the development of a novel hybrid MCDM model for their ranking. These contributions are also the main theoretical implications of the study. On a practical level, it enables organizations to strategically manage risks, standardize risk assessment, and improve their competitive advantage by enhancing resilience, reducing disruptions, and lowering operational costs. [ABSTRACT FROM AUTHOR]

We examine whether estimates of hedge fund performance reported in prior empirical research are affected by publication bias. Using a sample of 1019 intercept terms from regressions of hedge fund returns on risk factors (the "alphas") collected from 74 studies published between 2001 and 2021, we show that the selective publication of empirical results does not significantly contaminate inferences about hedge fund returns. Most of our monthly alpha estimates adjusted for the (small) bias fall within a relatively narrow range of 30–40 basis points, indicating positive abnormal returns of hedge funds: Hedge funds generate money for investors. Studies that explicitly control for potential biases in the underlying data (e.g., backfilling and survivorship biases) report lower but still positive alphas. Our results demonstrate that despite the prevalence of publication selection bias in many other research settings, publication may not be selective when there is no strong a priori theoretical prediction about the sign of the estimated coefficients. [ABSTRACT FROM AUTHOR]