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Ruthenium(II) polypyridyl complexes continue to raise increasing interest for the encouraging results in several biomedical areas. Considering their vast chemical‐physical repertoire, in particular the possibility to switch from the sensitization of reactive oxygen species (ROS) to ROS‐scavenging abilities by tuning the nature of their ligands, it is therefore surprising that their potential as antioxidants has not been largely investigated so far. Herein, we explored the antioxidant behaviour of the novel ruthenium compound [Ru(dbpy)(2,3‐DAN)Cl]PF6 (Ru1), featuring a benzoxazole derivative (dpby=2,6‐bis(4‐methyl‐2‐benzoxazolyl)pyridine) and the non‐innocent 2,3‐diamminonaftalene (2,3‐DAN) ligand, along with the reference tpy‐containing analogue [Ru(tpy)(2,3‐DAN)Cl]PF6 (Ru2) (tpy=2,2':6',2"‐terpyridine). Following the synthesis and the electrochemical characterization, chemical antioxidant assays highlighted the beneficial role of dpby for the ROS‐scavenging properties of Ru1. These data have been corroborated by the highest protective effect of Ru1 against the oxidative stress induced in SH‐SY5Y human neuroblastoma, which exerts pro‐survival and anti‐inflammatory actions. The results herein reported highlight the potential of Ru1 as pharmacological tool in neurodegenerative diseases and specially prove that the antioxidant properties of such compounds are likely the result of a non‐trivial synergetic action involving the bioactive ligands in their chemical architectures. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia, characterized by elevated low‐density lipoprotein (LDL) cholesterol levels, is a significant risk factor for cardiovascular disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a crucial role in cholesterol metabolism by regulating LDL receptor degradation, making it a therapeutic target for mitigating hypercholesterolemia‐associated risks. In this context, we aimed to engineer human H ferritin as a scaffold to present 24 copies of a PCSK9‐targeting domain. The rationale behind this protein nanoparticle design was to disrupt the PCSK9–LDL receptor interaction, thereby attenuating the PCSK9‐mediated impairment of LDL cholesterol clearance. The N‐terminal sequence of human H ferritin was engineered to incorporate a 13‐amino acid linear peptide (Pep2‐8), which was previously identified as the smallest PCSK9 inhibitor. Exploiting the quaternary structure of ferritin, engineered nanoparticles were designed to display 24 copies of the targeting peptide on their surface, enabling a multivalent binding effect. Extensive biochemical characterization confirmed precise control over nanoparticle size and morphology, alongside robust PCSK9‐binding affinity (KD in the high picomolar range). Subsequent efficacy assessments employing the HepG2 liver cell line demonstrated the ability of engineered ferritin's ability to disrupt PCSK9–LDL receptor interaction, thereby promoting LDL receptor recycling on cell surfaces and consequently enhancing LDL uptake. Our findings highlight the potential of ferritin‐based platforms as versatile tools for targeting PCSK9 in the management of hypercholesterolemia. This study not only contributes to the advancement of ferritin‐based therapeutics but also offers valuable insights into novel strategies for treating cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Recurrence after colorectal cancer resection is rarely documented in the general population while a key clinical determinant for patient survival. We identified 8785 patients with colorectal cancer diagnosed between 2010 and 2013 and clinically followed up to 2020 in 15 cancer registries from seven European countries (Bulgaria, Switzerland, Germany, Estonia, France, Italy, and Spain). We estimated world age‐standardized net survival using a flexible cumulative excess hazard model. Recurrence rates were calculated for patients with initially resected stage I, II, or III cancer in six countries, using the actuarial survival method. The proportion of nonmetastatic resected colorectal cancers varied from 58.6% to 78.5% according to countries. The overall 5‐year net survival by country ranged between 60.8% and 74.5%. The absolute difference between the 5‐year survival extremes was 12.8 points for stage II (Bulgaria vs Switzerland), 19.7 points for stage III (Bulgaria vs. Switzerland) and 14.8 points for Stage IV and unresected cases (Bulgaria vs. Switzerland or France). Five‐year cumulative rate of recurrence among resected patients with stage I–III was 17.7%. As compared to the mean of the whole cohort, the risk of developing a recurrence did not differ between countries except a lower risk in Italy for both stage I/II and stage III cancers and a higher risk in Spain for stage III. Survival after colorectal cancer differed across the concerned European countries while there were slight differences in recurrence rates. Population‐based collection of cancer recurrence information is crucial to enhance efforts for evidence‐based management of colorectal cancer follow up. [ABSTRACT FROM AUTHOR]

The paper develops some generalizations of the Burgers and the Oldroyd equations for the dynamics of fluids. To account for compressibility, in addition to viscosity, first the Oldroyd derivative is replaced with the Truesdell derivative. Consequently, the two equations can be given a linear form within the Lagrangian formulation. Furthermore, possible anisotropies are modeled by replacing some (scalar) coefficients with tensors. To emphasize the compressibility property, generalizations are established to allow for nonzero longitudinal viscosity. Next, the thermodynamic consistency is investigated by regarding both types of equations as rate equations, of second order and first order. The requirements on the parameters entering the two equations are derived while the linearity of the two equations allow the free energy potential be quadratic. The Oldroyd equation is found to be compatible via appropriate restrictions of the tensor coefficients, through different pairs of free energy and entropy production. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence of adenomyosis at pathologic examination, and its association with obstetric complications, peripartum maternal clinical characteristics and neonatal birth weight in patients undergoing postpartum hysterectomy due to postpartum hemorrhage (PPH). Methods: A multicenter, observational, retrospective, cohort study was carried out including all women who underwent postpartum hysterectomy due to PPH at gestational week 23+0 or later, between January 2010 and May 2023. Patients were categorized into two groups based on the presence of adenomyosis at pathologic examination, and were compared for obstetric complications, peripartum maternal clinical characteristics, and neonatal birth weight. Results: The histologically‐based prevalence of adenomyosis in patients undergoing postpartum hysterectomy due to PPH was 39.4%. Adenomyosis was associated with a longer hospitalization time (regression coefficient: 4.43 days, 95% CI: 0.34–8.52, P = 0.034) and a higher risk of hypertensive disorders (OR: 5.82, 95% CI: 1.38–24.46, P = 0.016), threatened preterm labor (OR: 3.34, 95% CI: 1.08–10.31, P = 0.036), urgent/emergency C‐section (OR: 24.15, 95% CI: 2.60–223.96, P = 0.005), postpartum maternal complications (OR: 4.96, 95% CI: 1.48–16.67, P = 0.012), maternal intensive care unit admission (OR: 3.56, 95% CI: 1.05–12.05, P = 0.041), and low birth weight neonates (OR: 3.8, 95% CI: 1.32–11.02, P = 0.013). Conclusion: In patients undergoing postpartum hysterectomy due to PPH, adenomyosis is a highly prevalent condition among, and is associated with adverse obstetric, maternal, and neonatal outcomes. Synopsis: In patients undergoing postpartum hysterectomy due to postpartum hemorrhage, adenomyosis shows a histologically‐based prevalence of almost 40% and is associated to several adverse obstetric, maternal, and neonatal outcomes. [ABSTRACT FROM AUTHOR]

With their exceptional optoelectronic properties, CsPbBr3 perovskite nanocrystals (NCs) are promising materials for light‐emitting devices. Elucidating their stimulated emission mechanisms is fundamental to grasp the limitations hindering their use as electrically pumped lasers. In particular, two questions remain open: why the Amplified Spontaneous Emission (ASE) band is significantly shifted from the fluorescence one, and why the former seems to suddenly emerge from, and coexist with, the latter. Here, these questions are addressed through experimental ASE measurements, combined with numerical simulations and a comprehensive assessment of the performance of different analytical expressions used in the literature to retrieve the optical gain from these experiments. This multi‐facet study shows that the ASE behavior in CsPbBr3 NCs thin films stems from four distinctive processes: reabsorption due to a large overlap between the absorption and fluorescence spectra, a strong contribution of excited state absorption within the fluorescence window, the excitation of differently polarized waveguide modes, and the coexistence of short‐ and long‐lived localized excitons. The results in this work delineate the best practices to analyze the optical gain in perovskite samples, help to understand their ASE mechanisms, and provide insights to boost their lasing efficiency. [ABSTRACT FROM AUTHOR]

The hyperdiverse wood‐inhabiting fungi play a crucial role in the global carbon cycle, but often are threatened by deadwood removal, particularly in temperate forests dominated by European beech (Fagus sylvatica) and Oriental beech (Fagus orientalis). To study the impact of abiotic drivers, deadwood factors, forest management and biogeographical patterns in forests of both beech species on fungal composition and diversity, we collected 215 deadwood‐drilling samples in 18 forests from France to Armenia and identified fungi by meta‐barcoding. In our analyses, we distinguished the patterns driven by rare, common, and dominant species using Hill numbers. Despite a broad overlap in species, the fungal composition with focus on rare species was determined by Fagus species, deadwood type, deadwood diameter, precipitation, temperature, and management status in decreasing order. Shifting the focus on common and dominant species, only Fagus species, both climate variables and deadwood type remained. The richness of species within the deadwood objects increased significantly only with decay stage. Gamma diversity in European beech forests was higher than in Oriental beech forests. We revealed the highest gamma diversity for old‐growth forests of European beech when focusing on dominant species. Our results implicate that deadwood retention efforts, focusing on dominant fungi species, critical for the decay process, should be distributed across precipitation and temperature gradients and both Fagus species. Strategies focusing on rare species should additionally focus on different diameters and on the conservation of old‐growth forests. [ABSTRACT FROM AUTHOR]

Aims: Tumour necrosis and/or increased mitoses define high‐grade papillary thyroid carcinoma (PTC). It is unclear whether angioinvasion is prognostic for PTC. Cut‐offs at five or more mitoses/2 mm2 and four or more angioinvasive foci have been empirically defined based upon data from all forms of aggressive non‐anaplastic thyroid carcinomas. Performance of tumour necrosis, mitoses and vascular invasion in predicting distant metastases when specifically applied to PTC is undefined. Methods: We analysed 50 consecutive PTC cases with distant metastases (DM‐PTC): 16 synchronous and 34 metachronous. A total of 108 non‐metastatic PTC (N‐DM‐PTC, 15.0‐year median follow‐up) were used as controls. Invasive encapsulated follicular variant PTC was excluded. Necrosis, mitoses and angioinvasion were quantified. Receiver operating characteristics (ROC) and area under the curve (AUC) analyses determined best sensitivity and specificity cut‐offs predictive of distant metastases. Results: Metastases correlated with necrosis (any extent = 43.8% all DM‐PTC, 53.1% metachronous DM‐PTC versus 5% N‐DM‐PTC; P < 0.001), mitoses (P < 0.001) and angioinvasion (P < 0.001). Mitoses at five or more per 2 mm2 was the best cut‐off correlating with distant metastases: sensitivity/specificity 42.9%/97.2% all DM‐PTC (AUC = 0.78), 18.8%/97.2% synchronous DM‐PTC (AUC = 0.63), 54.6%/97.2% metachronous DM‐PTC (AUC = 0.85). Angioinvasive foci at five or more was the best cut‐off correlating with distant metastases: sensitivity/specificity 36.2%/91.7% all DM‐PTC (AUC = 0.75), 25%/91.7% synchronous DM‐PTC (AUC = 0.79) and 41.9%/91.7% metachronous DM‐PTC (AUC = 0.73). Positive/negative predictive values (PPV/NPV) were: necrosis 22.6%/98.2%; five or more mitoses 32.3%/98.2%; five or more angioinvasive foci 11.8%/97.9%. After multivariable analysis, only necrosis and mitotic activity remained associated with DM‐PTC. Conclusion: Our data strongly support PTC grading, statistically validating World Health Organisation (WHO) criteria to identify poor prognosis PTC. Angioinvasion is not an independent predictor of DM‐PTC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Red raspberry (Rubus idaeus L.) is an important nectar source for honey production in some specific habitats as well as an important crop, so the definition of the features of this kind of honey is noteworthy. However, due to its rarity on the market, red raspberry honey is poorly characterized. The aim of this work was the phytochemical characterization of honey containing red raspberry from different geographical origins, through melissopalynological analyses concurrently with untargeted metabolomics achieved with different chromatographic techniques coupled to mass spectrometry: solid‐phase micro‐extraction/gas chromatography/mass spectrometry (SPME‐GC–MS) and high‐performance liquid chromatography/Orbitrap mass spectrometry (HPLC‐Orbitrap). RESULTS: Only 4 out of the 12 samples involved in the study contained raspberry pollen as dominant pollen, although these honeys did not group in the hierarchical cluster analysis nor in the classical multidimensional scaling analyses used for data evaluation. The first result was the detection of mislabelling in two samples, which contained raspberry pollen only as minor or important minor pollen. Of the 188 compounds identified by HPLC‐Orbitrap and of the 260 identified by SPME‐GC–MS, 87 and 31 compounds were present in all samples, respectively. The structurally related compounds nicotinaldehyde and nicotinamide, nicotinic acid and nicotinyl alcohol were present in 100% of the samples and correlated with R. idaeus pollen count (r > 0.60, Pearson's correlation analysis). CONCLUSION: This study reveals important aspects about the characterization of red raspberry honey and could give new insights on bee diet and preferences, since niacin compounds resulted interestingly to be related to the presence of red raspberry pollen. © 2024 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Longevity crucially affects demand for pensions, insurance products and annuities. Consistent empirical evidence shows that women have historically experienced lower mortality rates than men. In this article, we study a measure of the gender gap in mortality rates, we call "Gender Gap Ratio", across a wide range of ages and for four countries: France, Italy, Sweden, and USA. We show the stylized facts that characterize the trend of the Gender Gap Ratio, both in its historical evolution and future projection. Focusing on an example temporary life annuity contract, we give a monetary consistency to the Gender Gap Ratio. We show evidence that a Gender Gap Ratio that ranges between 1.5 and 2.5, depending on age, translates into a significant reduction of up to 23% in the benefits from a temporary life annuity contract for women with respect to men, against the same amount invested in the life annuity. The empirical evidence discussed in this article documents the crucial importance of working toward a more widespread demographic literacy, for example, a range of tools and strategies to raise longevity consciousness among individuals and policy‐makers, in the framework of gender equality policies. [ABSTRACT FROM AUTHOR]

Aim: Recent evidence challenges the current standard of offering surgery to patients with ileocaecal Crohn's disease (CD) only when they present complications of the disease. The aim of this study was to compare short‐term results of patients who underwent primary ileocaecal resection for either inflammatory (luminal disease, earlier in the disease course) or complicated phenotypes, hypothesizing that the latter would be associated with worse postoperative outcomes. Method: A retrospective, multicentre comparative analysis was performed including patients operated on for primary ileocaecal CD at 12 referral centres. Patients were divided into two groups according to indication of surgery for inflammatory (ICD) or complicated (CCD) phenotype. Short‐term results were compared. Results: A total of 2013 patients were included, with 291 (14.5%) in the ICD group. No differences were found between the groups in time from diagnosis to surgery. CCD patients had higher rates of low body mass index, anaemia (40.9% vs. 27%, p < 0.001) and low albumin (11.3% vs. 2.6%, p < 0.001). CCD patients had longer operations, lower rates of laparoscopic approach (84.3% vs. 93.1%, p = 0.001) and higher conversion rates (9.3% vs. 1.9%, p < 0.001). CCD patients had a longer hospital stay and higher postoperative complication rates (26.1% vs. 21.3%, p = 0.083). Anastomotic leakage and reoperations were also more frequent in this group. More patients in the CCD group required an extended bowel resection (14.1% vs. 8.3%, p: 0.017). In multivariate analysis, CCD was associated with prolonged surgery (OR 3.44, p = 0.001) and the requirement for multiple intraoperative procedures (OR 8.39, p = 0.030). Conclusion: Indication for surgery in patients who present with an inflammatory phenotype of CD was associated with better outcomes compared with patients operated on for complications of the disease. There was no difference between groups in time from diagnosis to surgery. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of florfenicol (FFC) in green sea and hawksbill sea turtles were evaluated following intramuscular (i.m.) administration at two different dosages of 20 or 30 mg/kg body weight (b.w.). This study (longitudinal design) used 5 green sea and 5 hawksbill sea turtles for the two dosages. Blood samples were collected at assigned times up to 168 h. FFC plasma samples were analyzed using validated high‐performance liquid chromatography equipped with diode array detection. The pharmacokinetic analysis was performed using a non‐compartment approach. The FFC plasma concentrations increased with the dosage. The elimination half‐life was similar between the treatment groups (range 19–25 h), as well as the plasma protein binding (range 18.59%–20.65%). According to the surrogate PK/PD parameter (T > MIC, 2 μg/mL), the 20 and 30 mg/kg dosing rates should be effective doses for susceptible bacterial infections in green sea and hawksbill sea turtles. [ABSTRACT FROM AUTHOR]

Amelanotic/hypomelanotic melanoma (AHM) may be difficult to diagnose because of a lack of pigmentation. To evaluate whether dermoscopy can be useful for the diagnosis of early AHM, 133 digital dermoscopic images of lesions histopathologically diagnosed as amelanotic/hypomelanotic superficial spreading melanoma with ≤1 mm thickness (AHSSMs) (n = 27), amelanotic/hypomelanotic non‐melanocytic lesions (AHNMLs) (e.g., seborrhoeic keratosis and basal cell carcinoma) (n = 79), and amelanotic/hypomelanotic benign melanocytic lesions (AHBMLs) (e.g., compound and dermal nevi) (n = 27), were dermoscopically assessed by three blinded dermatologists. Using multivariate analysis, we found a significantly increased risk of diagnosing AHSSM versus AHNML and AHBML when the lesion was characterized by the presence of more than one shade of pink (odds ratio [OR] 37.11), irregular dots/globules (OR 23.73), asymmetric pigmentation (OR 8.85), and structureless pattern (OR 7.33). In conclusion, dermoscopy may improve early AHM detection, discriminating AHSSM from amelanotic/hypomelanotic non melanoma lesions. [ABSTRACT FROM AUTHOR]

Although afforestation is a potential strategy to mitigate climate change by sequestering carbon, its potential biophysical effects on climate, such as regulating surface albedo, evapotranspiration, and energy balance, have not been fully incorporated into climate change mitigation strategies. This is partly due to the challenges associated with modeling the complex bidirectional interactions between vegetation and climate. In this study, we assess the impact of afforestation on low cloud cover using a regional climate model (RCM) and Earth observation data, applying a space‐for‐time approach to overcome limitations that may arise from comparing satellite and RCM results, such as different background climate conditions or different extents of land cover change. Our results show a consistent increase in low cloud cover in Europe due to afforestation in both datasets (3.71% and 3.56% on average, respectively), but the magnitude and direction of this effect depend on various factors, including location, seasonality, and forest type. These results suggest that afforestation can have important feedbacks on the climate system, and that its biophysical effects must be considered in climate change mitigation strategies. Furthermore, we emphasize the role of the modeling community in developing accurate and reliable approaches to assess the biophysical effects of land cover change on climate. Plain Language Summary: Although forests can help combat climate change by capturing carbon dioxide, we haven't fully considered the potential impact they can have on the climate in terms of biophysical factors such as surface reflectivity, evaporation, and energy balance. This is because it's challenging to accurately model the complex interactions between forests and climate. In this study, we used a regional climate model and Earth observation data to examine how forests affect the amount of low‐lying clouds. We used a method that compares satellite and model data to overcome limitations arising from different climate conditions and changes in land cover. Our findings consistently show that forests increase the coverage of low clouds in Europe. However, the specific effects depend on factors such as the location, season, and forest type. These results indicate that forests can have significant impacts on the climate system, and it is important to consider these effects when developing climate change strategies. We also emphasize the need for accurate modeling to better understand how changes in forest cover influence the climate. Key Points: Forests increase the amount of low clouds in EuropeForests impact climate beyond carbon sequestration [ABSTRACT FROM AUTHOR]

Since volcanic activity was first discovered on Io from Voyager images in 1979, changes on Io's surface have been monitored from both spacecraft and ground‐based telescopes. Here, we present the highest spatial resolution images of Io ever obtained from a ground‐based telescope. These images, acquired by the SHARK‐VIS instrument on the Large Binocular Telescope, show evidence of a major resurfacing event on Io's trailing hemisphere. When compared to the most recent spacecraft images, the SHARK‐VIS images show that a plume deposit from a powerful eruption at Pillan Patera has covered part of the long‐lived Pele plume deposit. Although this type of resurfacing event may be common on Io, few have been detected due to the rarity of spacecraft visits and the previously low spatial resolution available from Earth‐based telescopes. The SHARK‐VIS instrument ushers in a new era of high resolution imaging of Io's surface using adaptive optics at visible wavelengths. Plain Language Summary: A new instrument, called SHARK‐VIS, on the Large Binocular Telescope in Arizona, has obtained high spatial resolution, visible wavelength images of Io, the highly volcanic moon of Jupiter. Large multicolored plume deposits were imaged, revealing where the red deposit from a volcano named Pele was covered by another plume deposit from another volcano, named Pillan Patera, the site of a powerful eruption in 2021. SHARK‐VIS ushers in a new age in planetary imaging. Key Points: High resolution images taken with SHARK‐VIS at LBT reveal low and high albedo features obscuring a portion of Pele's red ring on IoThis new eruption deposit likely originated from a powerful eruption in August 2021 located at Pillan PateraSuch images provide a new imaging capability that yields vital context to other observations of planetary surfaces [ABSTRACT FROM AUTHOR]

Motivationally significant events like oddball stimuli elicit both a characteristic event‐related potential (ERPs) known as P300 and a set of autonomic responses including a phasic pupil dilation. Although co‐occurring, P300 and pupil‐dilation responses to oddball events have been repeatedly found to be uncorrelated, suggesting separate origins. We re‐examined their relationship in the context of a three‐stimulus version of the auditory oddball task, independently manipulating the frequency (rare vs. repeated) and motivational significance (relevance for the participant's task) of the stimuli. We used independent component analysis to derive a P300b component from EEG traces and linear modeling to separate a stimulus‐related pupil‐dilation response from a potentially confounding action‐related response. These steps revealed that, once the complexity of ERP and pupil‐dilation responses to oddball targets is accounted for, the amplitude of phasic pupil dilations and P300b are tightly and positively correlated (across participants: r =.69 p =.002), supporting their coordinated generation. Significance Statement: Motivationally significant stimuli may trigger diffuse release of norepinephrine in many cortical regions eventually leading to both a P300 ERP and pupil dilation. However, previous studies repeatedly failed to observe a correlation between these two events. Here, we isolated a component of P300 and pupil‐dilation responses that were specifically related to the occurrence of task‐relevant infrequent events (auditory oddball). This revealed a strong positive association between their amplitude, measured across participants, supporting the hypothesis of a common origin. [ABSTRACT FROM AUTHOR]

Periocular sebaceous carcinoma (PSC) is a rare, aggressive, and potentially metastatic adnexal malignancy. Due to the ability of PSC to resemble several benign and malignant conditions, diagnosis is often delayed or mistaken. In addition, even with a known diagnosis, choosing the right treatment is still an open debate. For this reason, we decided to review the most up‐to‐date literature on PSC and propose a dedicated procedural protocol to help clinicians when dealing with PSC. A PubMed search was carried out using the terms "Sebaceous Carcinoma", "Adnexal Periocular Cancer", "Sebaceous Carcinoma AND eyelid", "Periocular Sebaceous Carcinoma", and "Ocular Adnexa". Pertinent studies published in English from 1997 up to December 2022 were compared to the selection criteria and if suitable, included in this review. Through the initial search, 84 articles were selected. Of these, 36 were included in the final study. Several papers explored different diagnostic and therapeutic strategies regarding PSC diagnosis and management. In light of the current literature review and the multidisciplinary experience of three clinical centers, a dedicated procedural protocol is proposed. PSC diagnosis may be achieved through accurate clinical evaluation, but it requires histopathologic confirmation, which can be challenging. Dermoscopy, in vivo reflectance confocal microscopy, and optical coherence tomography may facilitate PSC clinical examination, while immunohistochemistry stains may support histological diagnosis. Appropriate disease staging is necessary before choosing the treatment, as local disease requires radically different treatment compared to advanced disease. In addition, recent innovations in nonsurgical treatments, including radio‐chemotherapy, immunotherapy, and targeted therapy, may be a viable option in the most challenging cases. [ABSTRACT FROM AUTHOR]

Objective: Status epilepticus (SE) is frequently associated with peri‐ictal magnetic resonance imaging (MRI) abnormalities (PMA). However, the anatomical distribution of these alterations has not been systematically studied. The aim of this study was to assess the localization patterns of PMA in patients with SE. Methods: In this prospective case–control study, we compared the distribution and combinations of diffusion‐restricted PMA to diffusion‐restricted lesions caused by other neurological conditions. All patients of the SE group and the control group underwent MRI including a diffusion‐weighted imaging sequence. Patients with SE were imaged within 48 h after its onset. Results: We enrolled 201 patients (51 with SE and 150 controls). The most frequent locations of PMA in SE were cortex (25/51, 49%), followed by hippocampus (20/51, 39%) and pulvinar of thalamus (10/51, 20%). In the control group, the cortex was involved in 80 of 150 (53%), white matter in 53 of 150 (35%), and basal ganglia in 33 of 150 (22%). In the control group, the pulvinar of thalamus was never affected and hippocampal structures were rarely involved (7/150, 5%). Involvement of the pulvinar of thalamus and the hippocampus had high specificity for SE at 100% (95% confidence interval [CI] = 98–100) and 95% (95% CI = 91–98), respectively. The sensitivity, however, was low for both locations (pulvinar of thalamus: 20%, 95% CI = 10–33; hippocampus: 39%, 95% CI = 26–54). Significance: Diffusion‐restricted MRI lesions observed in the pulvinar of thalamus and hippocampus are strongly associated with SE. These changes may help physicians in diagnosing SE‐related changes on MRI in an acute setting, especially in cases of equivocal clinical and electroencephalographic manifestations of SE. [ABSTRACT FROM AUTHOR]

Plant species respond to varying plant species diversity and associated changes in their abiotic and biotic environment with changes in their phenotype. However, it is not clear to what degree this phenotypic differentiation is due to genotype diversity within populations or phenotypic plasticity of plant individuals. We studied individuals of 16 populations of the clonal herb Taraxacum officinale grown in plant communities of different species richness in a 17‐year‐old grassland biodiversity experiment (Jena Experiment). We collected 12 individuals in each population to measure phenotypic traits and identify distinct genotypes using microsatellite DNA markers. Plant species richness did not influence population‐level genotype and trait diversity. However, it affected the expression of several phenotypic traits, e.g. leaf and inflorescence number, maximum leaf length and seed mass, which increased with increasing plant species richness. Moreover, population‐level trait diversity correlated positively with genotype richness for leaf dry matter content (LDMC) and negatively with inflorescence number. For several traits (i.e. seed mass, germination rate, LDMC, specific leaf area (SLA)), a larger portion of variance was explained by genotype identity, while variance in other traits (i.e. number of inflorescences, leaf nitrogen concentration, leaf number, leaf length) resided within genotypes and thus was mostly due to phenotypic plasticity. Overall, our findings show that plant species richness positively affected the population means of some traits related to whole‐plant performance, whose variation was achieved through both phenotypic plasticity and genotype composition of a population. [ABSTRACT FROM AUTHOR]

Along the lower course of the Rioni and several minor rivers, more than 70 settlement mounds (local name: Dikhagudzuba) have been identified by field surveys and remote sensing techniques. They give evidence of a formerly densely populated landscape in the coastal lowlands on the Colchian plain (western Georgia) and have been dated to the Bronze Age. As yet, limited information is available on their internal architecture, the chronology of the different layers and their palaeoenvironmental context. Based on archaeological sources, remote sensing measurements of three mounds and sediment cores from one mound and its closer surroundings, our study presents a review of the relevant literature and reveals the internal structure, distribution and spatial extent of the mounds. Geochemical and sedimentological analyses of element contents (X‐ray fluorescence) and granulometry helped to identify different stratigraphical layers and differentiate between natural facies and anthropogenic deposits; using the Structure‐from‐Motion technique the mounds' dimensions were calculated. The studied settlement mounds had relatively small dimension (varying from 30 to 100 m in diameter) and were similar in their stratigraphy. Measurement of elements that can identify types of human activity, notably metals and phosphorus, suggest changing intensities of human occupation, pastoral agriculture and metalworking through the occupation sequence. According to the 14C chronology, the formation of the settlements occurred during the first half of the second millennium B.C., which confirms the archaeological interpretation of their Bronze Age origin. The narrow age difference between the lowermost and uppermost anthropogenic layers indicates an intentional construction of the mounds, rather than a successive accumulation of construction debris due to the disintegration of loam bricks by weathering. Therefore, they are indeed mounds and not tells. It is most likely that the characteristic circular moats that surround them were the source of their construction material. Fluvial and alluvial processes in a warm and humid climate dominated the environment of the mounds. [ABSTRACT FROM AUTHOR]

The integration of pain management in veterinary practice, driven by heightened animal welfare concerns, extends to avian species where subtle and nonspecific behavioral signs pose challenges. Given that safety concerns with classical NSAIDs highlight the need for more targeted alternatives in birds, this study explores the pharmacokinetic (PK) properties of Deracoxib (DX), a COX‐2 selective NSAID approved for use in dogs, following a single oral administration in geese. Six healthy female geese received 4 mg/kg DX. Blood was drawn from the left wing vein to heparinized tubes at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, and 24 h. Plasma DX concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analyzed using PKanalix™ software in a non‐compartmental approach. The results indicated a terminal half‐life of 6.3 h and a Tmax of 1 h, with no observed adverse effects. While refraining from claiming absolute safety based on a single dose, it is worth highlighting that further safety studies for DX in geese are warranted, suggesting a possibility for intermittent use. In addition, drawing conclusions on efficacy and suitability awaits further research, particularly in understanding COX‐2 selectivity and protein binding characteristics specific to geese. [ABSTRACT FROM AUTHOR]

Metronidazole (MTZ) is a 5‐nitroimidazole anti‐bacterial and anti‐protozoal drug. In human and companion animal medicine, MTZ remains widely used due to its effectiveness against anaerobic bacteria and protozoa. In farm animals, however, MTZ is currently prohibited in several countries due to insufficient data on nitroimidazoles. The purpose of this study was to assess its pharmacokinetics (PK) in geese after single intravenous (IV) and oral (PO) administrations. Fifteen‐month old healthy male geese (n = 8) were used. Geese were subjected to a two‐phase, single‐dose (10 mg/kg IV, 50 mg/kg PO), open, longitudinal study design with a two‐week washout period between the IV and PO phases. Blood was drawn from the left wing vein to heparinized tubes at 0, 0.085 (for IV only), 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 24, and 48 h. Plasma MTZ concentrations were measured using HPLC coupled to an UV detector, and the data were pharmacokinetically analyzed using PKanalix™ software with a non‐compartmental approach. MTZ was still quantifiable and well above the LLOQ at 24 h after both routes of administration. Following IV administration, terminal elimination half‐life, volume of distribution, and total clearance were 5.47 h, 767 mL/kg, and 96 mL/h/kg, respectively. For the PO route, the bioavailability was high (85%), and the mean peak plasma concentration was 60.27 μg/mL at 1 h. When parameters were normalized for the dose, there were no statistically significant differences for any of the PK parameters between the two routes of administration. The study shows that oral administration of MTZ seems to be promising in geese, although comprehensive research on its pharmacodynamics and multiple‐dose studies are necessary before its adoption in geese can be further considered. [ABSTRACT FROM AUTHOR]

Osteosarcoma (OS) cancer treatments include systemic chemotherapy and surgical resection. In the last years, novel treatment approaches have been proposed, which employ a drug‐delivery system to prevent offside effects and improves treatment efficacy. Locally delivering anticancer compounds improves on high local concentrations with more efficient tumour‐killing effect, reduced drugs resistance and confined systemic effects. Here, the synthesis of injectable strontium‐doped calcium phosphate (SrCPC) scaffold was proposed as drug delivery system to combine bone tissue regeneration and anticancer treatment by controlled release of methotrexate (MTX) and doxorubicin (DOX), coded as SrCPC‐MTX and SrCPC‐DOX, respectively. The drug‐loaded cements were tested in an in vitro model of human OS cell line SAOS‐2, engineered OS cell line (SAOS‐2‐eGFP) and U2‐OS. The ability of doped scaffolds to induce OS cell death and apoptosis was assessed analysing cell proliferation and Caspase‐3/7 activities, respectively. To determine if OS cells grown on doped‐scaffolds change their migratory ability and invasiveness, a wound‐healing assay was performed. In addition, the osteogenic potential of SrCPC material was evaluated using human adipose derived‐mesenchymal stem cells. Osteogenic markers such as (i) the mineral matrix deposition was analysed by alizarin red staining; (ii) the osteocalcin (OCN) protein expression was investigated by enzyme‐linked immunosorbent assay test, and (iii) the osteogenic process was studied by real‐time polymerase chain reaction array. The delivery system induced cell‐killing cytotoxic effects and apoptosis in OS cell lines up to Day 7. SrCPC demonstrates a good cytocompatibility and it induced upregulation of osteogenic genes involved in the skeletal development pathway, together with OCN protein expression and mineral matrix deposition. The proposed approach, based on the local, sustained release of anticancer drugs from nanostructured biomimetic drug‐loaded cements is promising for future therapies aiming to combine bone regeneration and anticancer local therapy. [ABSTRACT FROM AUTHOR]

The Journal of Geophysical Research: Atmospheres expresses gratitude to the 2854 scientists who reviewed manuscripts for the journal in 2023. Peer review is essential for maintaining the integrity and rigor of scientific research. The reviews have contributed to the improvement of paper quality, the generation of new ideas, and the advancement of young scientists' careers. The journal acknowledges the reviewers' selfless service and dedication to the scientific community and looks forward to their continued support. [Extracted from the article]

An analysis is presented of the precipitation bias and change signal in an ensemble of regional climate model (RCM) (RegCM4) projections driven by multiple general circulation models (GCMs) over China. RegCM4 is driven by five different GCMs for the 120‐year period 1979–2099 at 25 km grid spacing, under the representative concentration pathway RCP8.5. We find that the GCMs and RegCM4 reproduce the general spatial pattern of precipitation over China in all four seasons, with RegCM4 providing greater spatial detail, especially over areas with complex terrain. The spatial patterns of precipitation bias show common features between the GCMs and RegCM4, characterized by an underestimation in the wetter regions, and an overestimation in the drier ones. Systematic increases of precipitation are projected in northern China, most pronounced in the Northwest basins, by both the GCMs and RegCM4 in all seasons except summer, when more mixed results are found. In addition, weak correlations of the projected change patterns are found in summer between the GCMs and nested RegCM4, indicating the greater role played by the representation of local convection processes during this monsoon season. The projections across the RegCM4 experiments show higher consistency and lower spread compared to the GCM ensemble, again indicating that the nested model physics significantly modulates the change signal deriving from the GCM boundary forcing. Plain Language Summary: China is a vulnerable country to climate change due to its dense population, unbalanced social and economic development, shortage of water resources, and fragile ecosystems. How future precipitation will change over the region is of great concern for the general public and decision makers. This paper presents a first analysis of precipitation simulations from a set of five RCM (RegCM4) 21st century climate change projections, driven by coarse resolution general circulation models (GCMs) over China. We find that the spatial patterns of precipitation bias show common features between the GCMs and RegCM4, characterized by a precipitation underestimation in the wetter regions, and an overestimation in the drier ones. Systematic increases of precipitation are projected in north China by both the GCMs and RegCM4 in all seasons except summer, when, weak correlations of the projected change patterns are found between the GCMs and nested RegCM4, indicating the greater role of the representation of local convection processes during this monsoon season. The projections across the RegCM4 experiments show higher consistency and lower spread compared to the GCM ensemble, again indicating that the nested model physics significantly modulates the change signal deriving from the GCM boundary forcing. Key Points: The spatial patterns of bias show common features between the GCMs and RegCM4RegCM4 provides greater spatial detail of present day precipitation simulation compared to the GCMs and finer structures of future changesThe change patterns across the RegCM4 projections show a high correlation, but not always between each pair of driving GCM and RegCM4 [ABSTRACT FROM AUTHOR]

To determine whether the intensity of prior work is an important contributing factor to the downward shift in the power‐duration relationship. Data were collected from 14 professional cyclists (height 176.3 cm ± 7, body mass 67.3 kg ± 5, CP, 5.3 W·kg−1 ± 0.21). Participants conducted a power profile test three times consisting of a 15s, a 3 min and a 12 min maximal effort trial utilizing a standardized climb. On the first occasion, the power profile test was conducted in a fresh state (Fresh), the subsequent power profile tests were conducted after two different fatiguing protocols: ∼2000 kJ of work at <70% of CP (low‐intensity continuous (LIC)) and following a novel fatiguing protocol consisting of 5 × 8 min at 105%–110% of CP (HI). Participants conducted significantly less work in HI compared with LIC, however, 1 and 15s power were significantly lower post‐HI than LIC. The 3‐min power output was significantly lower post‐HI than Fresh but not significantly lower in LIC than Fresh. The 12‐min power output and CP were not significantly different between conditions. These findings demonstrate the importance of the intensity of prior work in the resultant downward shift in the power‐duration relationship, especially for shorter‐duration efforts and suggest that the total amount of work done is alone not sufficient to describe prior work. Highlights: Professional cyclists demonstrate different levels of durability dependent upon the intensity of prior work.Total work is not sufficient to quantify prior work when assessing durability.It is possible to differentiate between professional cyclists by their degree of durability to prior work including work above the critical power. [ABSTRACT FROM AUTHOR]

Summary: This paper proposes a deep generalisation for income inequality indices. A generalised income inequality index that depends on two parameters and that involves a large set of income inequality indices in the same framework is proposed. The two parameters control the sensitivity of the generalised index to different levels of the income distribution. A thorough investigation of the generalised index paves the way for understanding the influence of the low, middle and high incomes on various income inequality indices and thereby facilitates the choice of multiple indices simultaneously for a better analysis of inequality as advocated by several recent studies. Moreover, two methods for estimating the generalised index in the case of finite populations are shown. A new method for estimating the inequality indices is proposed. [ABSTRACT FROM AUTHOR]

Layered halide perovskites are solution‐processed natural heterostructures where quantum and dielectric confinement down to the nanoscale strongly influence the optical properties, leading to stabilization of bound excitons. Detailed understanding of the exciton properties is crucial to boost the exploitation of these materials in energy conversion and light emission applications, with on‐going debate related to the energy order of the four components of the most stable exciton. To provide theoretical feedback and solve among contrasting literature reports, this work performs ab initio solution of the Bethe–Salpeter equation (BSE) for symmetrized reference Cs2PbX4 (X = I and Br) models, with detailed interpretation of the spectroscopic observables based on group‐theory analysis. Simulations predict the following Edark < Ein‐plane < Eout‐of‐plane fine‐structure assignment, consistent with recent magneto‐absorption experiments and obtain similar increase in dark/bright splitting when going from lead‐iodide to a lead‐bromide composition as found experimentally. The authors further suggest that polar distortions may lead to stabilization of the in‐plane component and end‐up in a bright lowest exciton component, discuss exciton landscape over a broad energy range and clarify the exciton spin‐character, when large spin‐orbit coupling is in play, to rationalize the potential of halide perovskites as triplet sensitizers in combination with organic dyes. [ABSTRACT FROM AUTHOR]

Objective: To describe a case of extrauterine adenomyoma (EA) and review all the cases of EA in the literature. Methods: Pubmed/MEDLINE, Embase, and Google Scholar from 1807 to December 2022. All studies reporting the histologic diagnosis of an EA. We collected the following data: patient's age, size and location of adenomyoma, presence of endometriosis and adenomyosis, past gynecologic treatment, symptoms, diagnostic imaging, surgical intervention, alternative/adjuvant treatment, associated malignancy, and follow up. Results: Sixty‐seven studies with 85 patients were included. Pain was the most frequent symptom (69.5%). Among diagnostic examinations, ultrasonography was used in 60 out of 81 reported cases, with several radiologic features described. EA was located inside the pelvis in 77.6% of patients. Adnexa were the most frequent site of the disease (24, 28.2%). History of endometriosis or adenomyosis was described in 35 patients (35, 41.2%). Uterine tissue morcellation was reported in 6 of the 85 patients (7.1%). Associated malignancy was detected in 9 out of 85 patients with available data (10.6%). There were two recurrences of disease. Conclusion: Specific imaging features of EA are yet to be described in the literature. History of endometriosis and adenomyosis or uterine tissue morcellation may be suggestive of EA. Histologic examination can give a definitive diagnosis and exclude malignant transformation. Synopsis: Extrauterine adenomyoma is a rare disease with a challenging preoperative diagnosis due to its non‐specific clinical characteristics. [ABSTRACT FROM AUTHOR]

Study Aims: The article aims at reiterating the importance of a biopsychosocial approach to mental health, taking stock of the critiques that have been raised and moving forward throughout a reconsideration of the theoretical background of systems thinking and emphasizing the relevance of the concept of thick description for the promotion of an adequate reflection on methodology and case formulation. Literature Review: It is our opinion that the biopsychosocial approach is still a powerful framework for making sense of the growing data collected in the different fields related to mental health and for designing proper treatment plans. A crucial challenge for mental health is that of surpassing the dichotomies and ideological disputes that still contaminate the field with detrimental effects on the advancement of knowledge and on the integration and continuity of different kind of interventions. Conclusions: The time is ripe for building bridges among neuroscience, humanities and social sciences, and this can only happen within the umbrella of a biopsychosocial perspective reinstated into its systems thinking background. [ABSTRACT FROM AUTHOR]

Life span uncertainty (longevity risk) impacts several economic decisions. Individuals can form and revise their survival beliefs making use of behavioral heuristics. We propose a model of sentiment, in which individuals are assumed to switch between optimistic and pessimistic expectations of their health. When optimism is persistent in the face of health shocks, or when individuals are more likely to change their sentiment from pessimistic to optimistic than otherwise, our model predicts survival underestimation at young ages and overestimation at old ages. An empirical analysis based on the longitudinal data from Survey of Health, Ageing and Retirement in Europe validates our model. [ABSTRACT FROM AUTHOR]

We propose a reinforcement learning (RL) algorithm for generating a trading strategy in a realistic setting, that includes transaction costs and factors driving the asset dynamics. We benchmark our algorithm against the analytical optimal solution, available when factors are linear and transaction costs are quadratic, showing that RL is able to mimic the optimal strategy. Then we consider a more realistic setting, including non‐linear dynamics, that better describes the WTI spot prices time series. For these more general dynamics, an optimal strategy is not known and RL becomes a viable alternative. We show that on synthetic data generated from WTI spot prices, the RL agent outperforms a trader that linearizes the model to apply the theoretical optimal strategy. [ABSTRACT FROM AUTHOR]

Connective or muscular tissue crossing the axilla is named axillary arch (of Langer). It is known to complicate axillary surgery and to compress nerves and vessels transiting from the axilla to the arm. Our study aims at systematically researching the frequency, insertions, tissue composition and dimension of axillary arches in a large cohort of individuals with regard to gender and bilaterality. In addition, it aims at evaluating the ability of axillary arches to cause compression of the axillary neurovascular bundle. Four hundred axillae from 200 unembalmed and previously unharmed cadavers were investigated by careful anatomical dissection. Identified axillary arches were examined for tissue composition and insertion. Length, width and thickness were measured. The relation of the axillary arch and the neurovascular axillary bundle was recorded after passive arm movements. Twenty‐seven axillae of 18 cadavers featured axillary arches. Macroscopically, 15 solely comprised muscular tissue, six connective tissue and six both. Their average length was 79.56 mm, width 7.44 mm and thickness 2.30 mm. One to three distinct insertions were observed. After passive abduction and external rotation of the arm, 17 arches (63%) touched the neurovascular axillary bundle. According to our results, 9% of the Central European population feature an axillary arch. Approximately 50% of it bilaterally. A total of 40.74% of the arches have a thickness of 3 mm or more and 63% bear the potential of touching or compressing the neuromuscular axillary bundle upon arm movement. [ABSTRACT FROM AUTHOR]

Study Aims Methods Discussion Conclusion The present paper aimed at discussing how the process of decision‐making should be taken care of in healthcare services.This is a position paper based on a review of the relevant literature about meaning‐making processes in medical encounters and psychotherapy.Authors argued that choice options could be perceived as meaningful by patients if their uncertainties were taken into account and grounded on mutual understanding and reciprocal trust. To this end, any decision‐making process should satisfy the patient's legitimate expectations by making choices and habits compatible.In depht analysis of meaning‐making processes is crucial for better refining good practices of shared decision‐making. [ABSTRACT FROM AUTHOR]

Polymer electrolyte membrane (PEM) water electrolysis is a crucial technology for green hydrogen production. Hydrocarbon membranes are drawing a lot of attention due to potentially superior properties and the fact that common fluorinated polymers might face a potential ban. This study introduces a sulfonated poly(phenylene sulfone) (sPPS) membrane, reinforced with a poly(ether‐ether‐ketone) (PEEK) mesh. The reinforced membrane induces a drastic increase in dimensional stability, enabling direct anode casting—an essential step toward industrial manufacturing. It further exhibits a significant reduction in water uptake (115% vs 294% for pure sPPS) and a 40% lower H2‐crossover (0.18 mA cm−2) compared to the industry standard N115 (0.31 mA cm−2). Due to the lower thickness (74 vs 127 µm) and higher ion exchange capacity (IEC)(1.92 vs 0.89 mmol g−1), the PEEK‐sPPS membrane displays a substantially lower resistance (70 vs 159 mΩ cm2 for N115). This directly translates into a voltage reduction of ≈90 mV at 1 A cm−2 or ≈180 mV at 2 A cm−2, both typical operating current densities. Finally, PEEK‐sPPS exhibits the longest lifetime shown for hydrocarbon membranes with almost 650 h at 1 A cm−2 and a low degradation rate (80 µV h−1). [ABSTRACT FROM AUTHOR]

Adequate levels of pyridoxal 5′‐phosphate (PLP), the catalytically active form of vitamin B6, and its proper distribution in the body are essential for human health. The PLP recycling pathway plays a crucial role in these processes and its defects cause severe neurological diseases. The enzyme pyridox(am)ine 5′‐phosphate oxidase (PNPO), whose catalytic action yields PLP, is one of the key players in this pathway. Mutations in the gene encoding PNPO are responsible for a severe form of neonatal epilepsy. Recently, PNPO has also been described as a potential target for chemotherapeutic agents. Our laboratory has highlighted the crucial role of PNPO in the regulation of PLP levels in the cell, which occurs via a feedback inhibition mechanism of the enzyme, exerted by binding of PLP at an allosteric site. Through docking analyses and site‐directed mutagenesis experiments, here we identified the allosteric PLP binding site of human PNPO. This site is located in the same protein region as the allosteric site we previously identified in the Escherichia coli enzyme homologue. However, the identity and arrangement of the amino acid residues involved in PLP binding are completely different and resemble those of the active site of PLP‐dependent enzymes. The identification of the PLP allosteric site of human PNPO paves the way for the rational design of enzyme inhibitors as potential anti‐cancer compounds. [ABSTRACT FROM AUTHOR]

Now that the chemistry of 1 : 1 host:guest complexes is well‐established, it is surprising to note that higher stoichiometry (oligomeric) complexes, especially those with excess host, remain largely unexplored. Yet, proteins tend to oligomerize, affording new functions for cell machinery. Here, we show that cucurbit[n]uril (CB[n]) macrocycles combined with symmetric, linear di‐viologens form unusual 3 : 2 host:guest complexes exhibiting remarkable dynamic properties, host self‐sorting, and external ring‐translocation. These results highlight the structural tunability of cucurbit[8]uril (CB[8]) based 3 : 2 host:guest complexes in water and their responsiveness toward several stimuli (chemicals, pH, redox). [ABSTRACT FROM AUTHOR]

Within the assumption of Left‐Handed (LH) New Physics (NP), the relations between B(B→K(*)τ+τ−)$\mathcal {B}(B\rightarrow K^{(\ast)} \tau ^+\tau ^-)$ and B(B→K(*)νν¯)$\mathcal {B}(B\rightarrow K^{(\ast)} \nu \bar{\nu })$ for several Beyond the Standard Model (BSM) scenarios are reviewed, commonly considered to explain the Lepton flavor Universality (LFU) violation observed in charged and neutral‐current semileptonic B decays. The latest RD(*)$R_{D^{(\ast)}}$ world averages that include the recent LHCb measurement and assess the possibility of simultaneously explaining B‐anomalies without spoiling current bounds on di‐neutrino and di‐tau modes are employed. This is particularly relevant in light of the upcoming results by Belle II on neutrinos and the continuing improvement in accuracy and sensitivity achieved in tau modes. [ABSTRACT FROM AUTHOR]

Background: Biallelic pathogenic variants in the mitochondrial prolyl‐tRNA synthetase 2 gene (PARS2, OMIM * 612036) have been associated with Developmental and Epileptic Encephalopathy‐75 (DEE‐75, MIM #618437). This condition is typically characterized by early‐onset refractory infantile spasms with hypsarrhythmia, intellectual disability, microcephaly, cerebral atrophy with hypomyelination, lactic acidemia, and cardiomyopathy. Most affected individuals do not survive beyond the age of 10 years. Methods: We describe a patient with early‐onset DEE, consistently showing an EEG pattern of Spike‐and‐Wave Activation in Sleep (SWAS) since childhood. The patient underwent extensive clinical, metabolic and genetic investigations, including whole exome sequencing (WES). Results: WES analysis identified compound heterozygous variants in PARS2 that have been already reported as pathogenic. A literature review of PARS2‐associated DEE, focusing mainly on the electroclinical phenotype, did not reveal the association of SWAS with pathogenic variants in PARS2. Notably, unlike previously reported cases with the same genotype, this patient had longer survival without cardiac involvement or lactic acidosis, suggesting potential genetic modifiers contributing to disease variability. Conclusion: These findings widen the genetic heterogeneity of DEE‐SWAS, including PARS2 as a causative gene in this syndromic entity, and highlight the importance of prolonged sleep EEG recording for the recognition of SWAS as a possible electroclinical evolution of PARS2‐related DEE. [ABSTRACT FROM AUTHOR]

The pharmacokinetics were described of meloxicam (MLX) in green sea turtles (Chelonia mydas), following a single intravenous (i.v.) and intramuscular (i.m.) administrations at one of two dosages of 0.1 or 0.2 mg/kg body weight (b.w.). The sample of 20 green sea turtles was divided into four groups (n = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at pre‐assigned times up to 168 h. MLX in the plasma was cleaned‐up and quantified using a validated high‐performance liquid chromatography method with UV detection. The concentration of MLX in the experimental green sea turtles with respect to time was pharmacokinetically analyzed using a non‐compartment model. MLX plasma concentrations were quantifiable for up to 72 and 120 h after i.v. at dosages of 0.1 and 0.2 mg/kg b.w., respectively, whereas it was measurable for up to 168 h after i.m. administration at both dosages. The long elimination half‐life value of MLX (28 h) obtained in green sea turtles after i.v. administration was consistent with the quite slow clearance rate for both dosages. The average maximum concentration (Cmax) values of MLX were 1.05 μg/mL and 4.26 μg/mL at dosages of 0.1 and 0.2 mg/kg b.w., respectively, with their elimination half‐life values being 37.26 h and 30.64 h, respectively, after i.m. administrations. The absolute i.m. bioavailability was approximately 110%. These results suggested that i.m. administration of MLX at a dosage of 0.2 mg/kg b.w. was likely to be effective for clinical use in green sea turtles (Chelonia mydas). However, further studies are needed to determine the pharmacodynamic properties and clinical efficacy of MLX for the treatment of inflammatory disease after single and multiple dosages. [ABSTRACT FROM AUTHOR]

To date, the pharmacokinetics of fluoroquinolones in estuarine crocodiles (Crocodylus porosus) have been reported for enrofloxacin but not for marbofloxacin (MBF), which is a broad‐spectrum antibiotic used only in veterinary medicine. This study investigated the pharmacokinetics of MBF after intramuscular administration at two difference dosages (2 and 4 mg/kg body weight) in estuarine crocodiles and estimated pharmacokinetic/pharmacodynamic (PK/PD) surrogate parameters for the optimization of dosage regimens. Ten treated estuarine crocodiles were divided into two groups (n = 5) using a randomization procedure according to a parallel study design. Blood samples were collected at assigned times up to 168 h. MBF plasma samples were cleaned up using liquid–liquid extraction and analyzed using a validated high‐performance liquid chromatography method with fluorescence detection. A non‐compartment approach was used to fit the plasma concentration of MBF vs time curve for each crocodile. The plasma concentrations of MBF were quantifiable for up to 168 h in both groups. The elimination half‐life values of MBF were long (33.99 and 39.28 h for 2 and 4 mg/kg, respectively) with no significant differences between the groups. The average plasma protein binding of MBF was 30.85%. According to the surrogated PK/PD parameter (AUC0–24‐to‐MIC ratio >100–125), the 2 and 4 mg/kg dosing rates should be effective for bacteria with MIC values lower than 0.125 μg/mL and 0.35 μg/mL, respectively. [ABSTRACT FROM AUTHOR]

Background: The U.S. Centers for Disease Control and Prevention (CDC) has reported increasing rates of alpha‐gal syndrome, an allergic response after meat ingestion (AGS). AGS has been associated with prior exposure to tick bites or other biologics characterized by a life‐threatening immunoglobulin E (IgE)–mediated hypersensitivity to galactose‐alpha‐1,3‐galactose (alpha‐gal) an oligosaccharide structurally similar to the group B antigen on red blood cells (RBC) found in most non‐primate mammalian meat and products derived from these mammals. In 2023, Transfusion reported 3 group O recipients of group B plasma in the Washington, D.C. metropolitan area with no history of meat allergy who had anaphylactic transfusion reactions compatible with AGS. Aims: We investigated allergic reactions in 2 additional patients who received ABO minor‐incompatible blood products at 2 hospitals in the D.C. area during fall 2023. Methods: For both patients, a medical chart review was performed and IgE levels to alpha‐gal were measured. Results: The first patient, a 64‐year‐old, O‐positive patient status post heart transplant with no known allergies, was admitted with acute COVID‐19 induced antibody‐mediated transplant rejection and placed on extracorporeal membrane oxygenation (ECMO). While undergoing plasma exchange (PLEX) (50% albumin/50% fresh frozen plasma (FFP)), the patient tolerated 2 units of group O FFP and 1 unit of group A FFP before becoming hemodynamically unstable during transfusion of 1 unit of B‐positive FFP. PLEX was stopped. The patient later died of sepsis from underlying causes. The second patient, a 57‐year‐old O‐positive man with a history of melanoma and neuro fibromatosis type 1, was undergoing an abdominal resection including transfusion of 3 units of O‐positive RBC when he suffered hypotension and ventricular tachycardia requiring intraoperative code after receiving 2 units of group B FFP. Hiveswere noted after resuscitation. The patient had a history of tick bites but no known allergies. He is alive 5 months after the possible allergic event. Both patients had full transfusion reaction evaluations and immunology testing results above the positive cutoff for anti‐alpha‐gal IgE. Discussion and conclusion: Two patients with O‐positive blood and no known allergies experience danaphyl axis after transfusion with group B FFP. The symptoms cannot definitively be imputed to an allergic transfusion reaction, but the presence of IgE against alpha‐gal supports an association. Medicating patients with antihistamines and IV steroids pre‐transfusion may prevent allergic reactions. Restricting group B plasma‐containing products (plasma, platelets, cryoprecipitate) for patients who experience AGS‐like symptoms may be considered. [ABSTRACT FROM AUTHOR]

The spatiotemporal variability of meteorological droughts, its changes and hot spots location across Africa are analysed for the period spanning 1928–2017 using the Standardized Precipitation Index (SPI) applied to the precipitation products from the Climatic Research Unit (CRU), University of Delaware (UDEL) and Global Precipitation Climatology Centre (GPCC). Spatially, an analysis based on rotational empirical orthogonal function identifies five regions of similar drought variability, namely the Sahel, East Africa, East Southern Africa, West Southern Africa and the Gulf of Guinea. Temporally, the most common periods of drought occurrence are the 1970s, the 1980s and, to a lesser extent, the 1990s. Changes in drought characteristics for the intermediate past (1958–1987) and recent past (1988–2017) compared to the far past (1928–1957) indicate robust increases of drought duration, frequency and severity in the Sahel, and to a lower extent in the Gulf of Guinea, some areas of Central Africa, part of Southern Africa and over Madagascar. These changes are stronger (weaker) along the Sahel during the intermediate past (recent past) and stronger (weaker) over Central and Southern Africa and Madagascar during the recent past (intermediate past). As a consequence, drought hot spots, mostly driven by severity during the regions' wet season, are identified in areas confined in the Sahel during the intermediate past and in regions mainly over Central and Southern Africa and Madagascar during the recent past. Our results are useful for drought disaster risk management across Africa and provide a valuable reference for future drought analysis under global warming conditions. [ABSTRACT FROM AUTHOR]

We apply a methodology to identify and count records (events of unprecedented intensity) in daily precipitation time series to two sets of data: (1) different observational and reanalysis products for recent decades and (2) twenty‐first century projections (RCP8.5 and RCP2.6 scenarios) completed with two regional climate models driven by three global climate models over nine continental‐scale domains. Comparison of the detected (or actual) number of records with the corresponding number theoretically expected in stationary climate conditions (or "reference" number of records) provides indications of trends in daily precipitation extremes, as expected in a changing climate. In particular, we measure deviations from stationary conditions using the ratio of actual to reference records (RAtR) as a basic metric. We find that the observational products provide mixed indications of precipitation record trends across regions, while in the reanalysis products and the model simulations for the historical period the RAtR value shows a prevailing increasing trend with time over most continents. The RAtR shows a consistent and pronounced increase in all RCP8.5 continental‐scale projections, when sustained warming occurs throughout the 21st century, while smaller to no significant trends are found in the RCP2.6 scenario, when the warming stabilizes after about mid‐21st century. These results are indicative of an increase in precipitation extremes with global warming as measured by the higher number of local precipitation events of unprecedented intensity compared to what expected in stationary climate conditions, although a marked variability of this response is found across different regions. Our method can have useful applications in detection and attribution of hydroclimatic extremes and in impact and vulnerability assessment studies. [ABSTRACT FROM AUTHOR]

Summary: Objective: Our primary goal was to measure the accuracy of fully automated absence seizure detection, using a wearable electroencephalographic (EEG) device. As a secondary goal, we also tested the feasibility of automated behavioral testing triggered by the automated detection. Methods: We conducted a phase 3 clinical trial (NCT04615442), with a prospective, multicenter, blinded study design. The input was the one‐channel EEG recorded with dry electrodes embedded into a wearable headband device connected to a smartphone. The seizure detection algorithm was developed using artificial intelligence (convolutional neural networks). During the study, the predefined algorithm, with predefined cutoff value, analyzed the EEG in real time. The gold standard was derived from expert evaluation of simultaneously recorded full‐array video‐EEGs. In addition, we evaluated the patients' responsiveness to the automated alarms on the smartphone, and we compared it with the behavioral changes observed in the clinical video‐EEGs. Results: We recorded 102 consecutive patients (57 female, median age = 10 years) on suspicion of absence seizures. We recorded 364 absence seizures in 39 patients. Device deficiency was 4.67%, with a total recording time of 309 h. Average sensitivity per patient was 78.83% (95% confidence interval [CI] = 69.56%–88.11%), and median sensitivity was 92.90% (interquartile range [IQR] = 66.7%–100%). The average false detection rate was.53/h (95% CI =.32–.74). Most patients (n = 66, 64.71%) did not have any false alarms. The median F1 score per patient was.823 (IQR =.57–1). For the total recording duration, F1 score was.74. We assessed the feasibility of automated behavioral testing in 36 seizures; it correctly documented nonresponsiveness in 30 absence seizures, and responsiveness in six electrographic seizures. Significance: Automated detection of absence seizures with a wearable device will improve seizure quantification and will promote assessment of patients in their home environment. Linking automated seizure detection to automated behavioral testing will provide valuable information from wearable devices. [ABSTRACT FROM AUTHOR]

Objective: Perception and recognition of emotions are fundamental prerequisites of human life. Patients with juvenile myoclonic epilepsy (JME) may have emotional and behavioral impairments that might influence socially desirable interactions. We aimed to investigate perception and recognition of emotions in patients with JME by means of neuropsychological tests and functional magnetic resonance imaging (fMRI). Methods: Sixty‐five patients with JME (median age = 27 years, interquartile range [IQR] = 23–34) were prospectively recruited at the Department of Neurology, Christian Doppler University Hospital, Paracelsus Medical University, Salzburg, Austria. Patients were compared to 68 healthy controls (median age = 24 years, IQR = 21–31), matched for sex, age, and education. All study participants underwent the Networks of Emotion Processing test battery (NEmo), an fMRI paradigm of "dynamic fearful faces," a structured interview for psychiatric and personality disorders, and comprehensive neuropsychological testing. Results: JME patients versus healthy controls demonstrated significant deficits in emotion recognition in facial and verbal tasks of all emotions, especially fear. fMRI revealed decreased amygdala activation in JME patients as compared to healthy controls. Patients were at a higher risk of experiencing psychiatric disorders as compared to healthy controls. Cognitive evaluation revealed impaired attentional and executive functioning, namely psychomotor speed, tonic alertness, divided attention, mental flexibility, and inhibition of automated reactions. Duration of epilepsy correlated negatively with parallel prosodic and facial emotion recognition in NEmo. Deficits in emotion recognition were not associated with psychiatric comorbidities, impaired attention and executive functions, types of seizures, and treatment. Significance: This prospective study demonstrated that as compared to healthy subjects, patients with JME had significant deficits in recognition and perception of emotions as shown by neuropsychological tests and fMRI. The results of this study may have importance for psychological/psychotherapeutic interventions in the management of patients with JME. [ABSTRACT FROM AUTHOR]