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Background and Purpose: Chemotherapy‐induced peripheral neuropathy (CIPN) is perceived differently by patients and physicians, complicating its assessment. Current recommendations advocate combining clinical and patient‐reported outcomes measures, but this approach can be challenging in patient care. This multicenter European study aims to bridge the gap between patients' perceptions and neurological impairments by aligning both perspectives to improve treatment decision‐making. Methods: Data were pooled from two prospective studies of subjects (n = 372) with established CIPN. Patient and physician views regarding CIPN were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI‐CTCAE), Total Neuropathy Scale–clinical version (TNSc) items, and the disease‐specific quality of life ‐ Chemotherapy‐Induced Peripheral Neuropathy questionnaire (QLQ‐CIPN20) from the European Organization for Research and Treatment of Cancer (EORTC). To identify inherent neurotoxic severity patterns, we employed hierarchical cluster analysis optimized with k‐means clustering and internally validated by discriminant functional analysis. Results: Both NCI‐CTCAE and TNSc demonstrated a significant difference in the distribution of severity grades in relation to QLQ‐CIPN20 scores. However, a proportion of subjects with different neurotoxic severity grades exhibited overlapping QLQ‐CIPN20 scores. We identified three distinct clusters classifying subjects as having severely impaired, intermediately impaired, and mildly impaired CIPN based on TNSc and QLQ‐CIPN20 scores. No differences in demographics, cancer type distribution, or class of drug received were observed. Conclusions: Our results confirm the heterogeneity in CIPN perception between patients and physicians and identify three well‐differentiated subgroups of patients delineated by degree of CIPN impairment based on scores derived from TNSc and QLQ‐CIPN20. A more refined assessment of CIPN could potentially be achieved using the calculator tool derived from the cluster equations in this study. This tool, which facilitates individual patient classification, requires prospective validation. [ABSTRACT FROM AUTHOR]

Electronic and vibrational relaxation processes can be optimized and tuned by introducing alternative pathways that channel excess energy more efficiently. An ensemble of interacting molecular systems can help overcome the bottlenecks caused by large energy gaps between intermediate excited states involved in the relaxation process. By employing this strategy, catenanes composed of mechanically interlocked carbon nanostructures show great promise as new materials for achieving higher efficiencies in electronic devices. Herein, we perform nonadiabatic excited state molecular dynamics on different all‐benzene catenanes. We observe that catenanes experience faster relaxations than individual units. Coupled catenanes present overlapping energy manifolds that include several electronic excited states spatially localized on the different moieties, increasing the density of states that ultimately improve the efficiency in the energy relaxation. This result suggests the use of catenanes as a viable strategy for tuning the internal conversion rates in a quest for their utilization for new optoelectronic applications. [ABSTRACT FROM AUTHOR]

Background: Primary cutaneous lymphomas are neoplasms of the immune system with a distinct tropism for the skin and an absence of extracutaneous manifestations at the time of diagnosis. Studies focusing on cutaneous lymphomas in children and adolescents remain scarce and often do not encompass the rare subtypes. Objectives: To address this knowledge gap by describing the clinical, histological and molecular characteristics of a large group of paediatric patients affected by primary cutaneous lymphoma. We also provided the Paediatric Primary Cutaneous Lymphoma Atlas that illustrates the clinicopathological spectrum of observed presentations, in the hope of supporting other physicians in the diagnostic process. Methods: Retrospective chart review of paediatric patients diagnosed with primary cutaneous lymphomas between 1980 and 2022 at the Paediatric Dermatology Unit of Fondazione IRCCS Ca′ Granda Ospedale Maggiore Policlinico, Milan. Results: A total of 101 patients (58 males, 43 females) met the inclusion criteria. The most common subtypes were lymphomatoid papulosis (n = 48) and mycosis fungoides (n = 31). These were followed by primary cutaneous CD4+ small/medium T‐cell lymphoproliferative disorders (n = 7), primary cutaneous anaplastic large‐cell lymphomas (n = 5), primary cutaneous marginal zone B‐cell lymphomas (n = 3), primary cutaneous follicle centre lymphomas (n = 2), subcutaneous panniculitis‐like T‐cell lymphomas (n = 2), primary cutaneous peripheral T‐cell lymphoma not otherwise specified (n = 1), primary cutaneous precursor B‐lymphoblastic lymphoma (n = 1) and Sézary syndrome (n = 1). Clinical follow‐up data covering a median of 70.8 months (range 1–324) were available for 74 patients, of whom three died due to cutaneous lymphoma. Conclusions: Our findings shed light on the peculiar aspects and long‐term outcomes of paediatric cutaneous lymphomas, particularly emphasizing their distinctive features in comparison to their adult counterparts and exploring the less common subtypes. Further larger‐scale studies are warranted to better characterize these entities and to achieve a more rapid and accurate diagnosis. [ABSTRACT FROM AUTHOR]

Despite extensive research into developing efficient and environmentally friendly catalysts for converting CO2 over the last decade, the search for a robust and cost‐effective catalytic system is ongoing. This study describes developing and applying a new catalytic system using inexpensive ferrate and zincate anions immobilized on easily available commercial ion exchange resins (IER) to produce cyclic carbonates from CO2 with high efficiency and low cost. Two polystyrene‐based anion exchange resins, AmberlystTM A26‐Cl (A26‐Cl) and AmberliteTM IRA‐400‐Cl (IRA400‐Cl), were compared. The results demonstrated the catalysts' remarkable activity under mild conditions and demonstrated the synergistic effect between the polystyrene support and the active ammonium metallates, presenting a scalable, eco‐friendly method for cyclic carbonate production using waste CO2. A Design of Experiment (DoE) approach was implemented to optimize the catalytic cycloaddition of CO2. The reaction scale‐up to produce a 5 g batch of propylene oxide and conducting recycling tests demonstrated that the catalyst retained its activity over four cycles. The research also explored the use of various epoxides and found that terminal epoxides produced very good yields. In summary, this study introduces a cost‐effective, scalable method for converting CO2 into valuable cyclic carbonates, leveraging the synergistic effects of polystyrene supports and active ammonium metallates. [ABSTRACT FROM AUTHOR]

Despite extensive research into developing efficient and environmentally friendly catalysts for converting CO2 over the last decade, the search for a robust and cost‐effective catalytic system is ongoing. This study describes developing and applying a new catalytic system using inexpensive ferrate and zincate anions immobilized on easily available commercial ion exchange resins (IER) to produce cyclic carbonates from CO2 with high efficiency and low cost. Two polystyrene‐based anion exchange resins, AmberlystTM A26‐Cl (A26‐Cl) and AmberliteTM IRA‐400‐Cl (IRA400‐Cl), were compared. The results demonstrated the catalysts' remarkable activity under mild conditions and demonstrated the synergistic effect between the polystyrene support and the active ammonium metallates, presenting a scalable, eco‐friendly method for cyclic carbonate production using waste CO2. A Design of Experiment (DoE) approach was implemented to optimize the catalytic cycloaddition of CO2. The reaction scale‐up to produce a 5 g batch of propylene oxide and conducting recycling tests demonstrated that the catalyst retained its activity over four cycles. The research also explored the use of various epoxides and found that terminal epoxides produced very good yields. In summary, this study introduces a cost‐effective, scalable method for converting CO2 into valuable cyclic carbonates, leveraging the synergistic effects of polystyrene supports and active ammonium metallates. [ABSTRACT FROM AUTHOR]

Addressing aviation turbulence not only enhances passenger comfort but also help to reduce fuel consumption and environmental impact, supporting aviation sustainability. By using ERA5 reanalysis data we explore how changing atmospheric circulation, monitored via sea level pressure trends, impacts aviation turbulence over Europe. Our results show coherent climate anomalies, with rising turbulence intensity over the UK and Northern Europe where most events involve clear air turbulence, which occurs unexpectedly and without warning, particularly at flight altitudes. We also highlight a clear seasonal patterns in moderate‐or‐greater turbulence encounters, most frequent and intense in winter, with a key role of wind shears due to the sub‐tropical jet position over Southern Mediterranean. Our approach adds to previous studies on the same topic by analyzing individual atmospheric circulation pattern changes and their effects on turbulence‐related factors. This offers insight into how climate change affecting atmospheric dynamics may contribute to increased aviation turbulence. Plain Language Summary: This study investigates how climate change can affects aviation turbulence over Europe, which is crucial for improving passenger comfort, reducing fuel consumption, and promoting sustainable aviation. Our findings indicate an increase in turbulence, particularly over the UK and Northern Europe with a significant portion of this increase involving clear air turbulence. This is particularly hazardous as it occurs without warning and cannot be detected visually, especially at cruising altitudes. We also found that turbulence is more frequent and intense during winter with a seasonal pattern influenced by wind shears associated with the position of the subtropical jet stream over the Southern Mediterranean. Finding ways to face with turbulence could make flights smoother, safer, and more environmentally friendly. Key Points: Changing atmospheric circulation due to climate change increases turbulence over EuropeTurbulence peaks in winter, linked to wind shears from the subtropical jet stream over the Southern MediterraneanMost increasing episodes are related to clear air turbulence, occurring unexpectedly at flight cruise altitudes [ABSTRACT FROM AUTHOR]

Purpose: To investigate changes in the incidence rate of primary rhegmatogenous retinal detachment (RRD) surgery over time and to determine to what extent these changes can be attributed to pseudophakia. Methods: This nationwide cohort study was based on national patient registries. The study population comprised individuals at risk of RRD aged 40 years and above from 2006 to 2021 in Denmark. The primary outcome was RRD incidence, and the exposure was phacoemulsification surgery. A chart review was conducted to validate and examine the lens status of the outcome. Results: The crude and age‐adjusted incidence rate of RRD in the Danish population increased significantly during the study period. The largest increase in RRD was seen in phakic RRD (phRRD) (65%), whereas pseudophakic RRD (pRRD) accounted for 35% of the total increase. A chart review revealed that 17% of phRRDs were misclassified as pseudophakic, resulting in pRRD accounting for a total of 45% of the increase in RRD. The prevalence of pseudophakia in Denmark grew significantly for all age groups and for both sexes (p = 10−6) from 2006 to 2021, but the 1‐year incidence of pRRD in the pseudophakic population was constant throughout the entire period. Conclusion: The incidence rate of RRD is continuing to increase in Denmark. The increase in phRRD remains undetermined, and while the risk of pRRD seemed to be constant during the study period, 45% of the overall increase in RRD could be attributed to the rise of a growing pseudophakic population. [ABSTRACT FROM AUTHOR]

Background and Aims: Chemotherapy‐induced peripheral neurotoxicity (CIPN), with paraesthesia, numbness, dysesthesia and neuropathic pain ranks among the most common dose‐limiting toxicity of several widely used anticancer drugs. Recent studies revealed the microvascular angiogenesis as a new important actor, beside peripheral neurons, in the neurotoxicity and neuropathic pain development and chronicisation. The aim of this work is to elucidate the role of vascular alterations in CIPN. Methods: We evaluated the severity of CIPN with neurophysiological, behavioural and neuropathological analysis together with the microvascular network in central and peripheral nervous systems of rats in order to correlate the features of the CIPN and the vascular abnormalities. The vascular network was quantitatively evaluated through synchrotron radiation‐based X‐ray phase‐contrast micro‐tomography imaging, measuring four specific parameters: vascular density, vessel diameter, vessel tortuosity and branching. Results: Rats exposed to paclitaxel and affected by a severe painful sensory axonopathy showed an increased vascular density (putative sprouting angiogenesis) in the crucial districts of the central (somatosensory cortex and lumbar spinal cord) and peripheral nervous system (lumbar dorsal root ganglia). In addition, the complexity of the vascular network and the size of neo‐formed vessels were significantly decreased in specific regions. On the other hand, less significant changes were observed in rats exposed to cisplatin, affected by a painless peripheral neuropathy, suggesting a specific involvement of neo‐angiogenesis in the development of severe neurotoxicity and neuropathic pain. Interpretations: These new ground‐breaking results can shed light on new pathogenetic mechanisms and potential novel therapeutic approaches for painful‐CIPN. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) and autosomal dominant polycystic kidney disease (ADPKD) are genetically distinct disorders typically associated with pathogenic variants in TSC1 and TSC2 for the former and PKD1 and PKD2 for the latter. TSC2 and PKD1 lie adjacent to each other, and large deletions comprising both genes lead to TSC2/PKD1 contiguous gene deletion syndrome (CGS). In this study, we describe a young female patient exhibiting symptoms of TSC2/PKD1 CGS in which genetic analysis disclosed two noncontiguous partial gene deletions in TSC2 and PKD1 that putatively are responsible for the manifestations of the syndrome. Further analysis revealed that both deletions appear to be de novo on the maternal chromosome, presumably with a germline origin. Despite extensive analysis, no maternal chromosomal rearrangement triggering these pathogenic variants was detected. This case elucidates a unique pathogenesis for TSC2/PKD1 CGS, diverging from the common contiguous deletions typically observed, marking the first reported instance of TSC2/PKD1 CGS caused by independent, functionally significant partial gene deletions. [ABSTRACT FROM AUTHOR]

2,5‐disubstituted N,N'‐alkylpiperazines represent an interesting target in organic synthesis both for pharmaceutical or agrochemical applications and as a promising class of ligands in coordination chemistry. We report here a microwave‐enhanced synthesis of these compounds starting from non‐activated N‐alkyl aziridines in the presence of catalytic amounts of simple ammonium metallates. A remarkable TOF of 2787.9 h−1 has been observed in the case of [TBA]2[ZnI4] as the catalyst (catalyst loading 0.1 mol %) and with an almost complete selectivity (up to 97 %) in favor of both diastereoisomers (meso and chiral form) of the target 2,5‐disubstituted piperazines, obtained in 1 : 1 ratio. The two isomers are easily separated, because the meso form precipitates in pure from the reaction crude. A stereochemical investigation and the unprecedented isolation of 2,6‐disubstituted N,N'‐alkylpiperazines allowed us to shed light on the reaction mechanism. [ABSTRACT FROM AUTHOR]

The combination of complementary techniques for materials analysis can play a key role in both art conservation and academic research. Nowadays, the correlation of x‐ray fluorescence (XRF) with hyperspectral reflectance imaging in the visible and infrared region has become a valuable tool for palette identification, painting techniques studies and for the diagnostic support dedicated to restoration and conservation. Moreover, both techniques enable researchers to reveal fascinating underpaintings, "pentimenti", or even preparatory drawings offering new details on the creative process of the artist. This background has been a strong motivation for the development of a new multimodal tool for art and conservation: IRIS. IRIS is a mobile and reconfigurable scanner designed to address a wide range of demanding application, exploiting the opportunities given by simultaneous MA‐XRF and hyperspectral reflectance scanning in the visible‐near‐infrared (VNIR) and short‐wave‐infrared (SWIR) range from 400 to 2500 nm. The system has been designed for in‐situ, fast and non‐invasive scanning of the sample without compromising spectral resolution and high throughput performance. The scanner acquires co‐registered XRF/VNIR‐SWIR data, thus allowing the user to obtain the maximum profit from their possible correlated information: the two techniques can provide enhanced or complementary information on the same spot of analysis with minimum effort in terms of data processing and no need for spatial alignment. In the present work, the qualitative and quantitative performance of IRIS are explored, together with the presentation of in‐lab analysis on reference samples and a brief insight on a real case‐study. [ABSTRACT FROM AUTHOR]

Objectives: Peri‐implant mucositis is a biofilm‐related, reversible inflammatory disease that can evolve into peri‐implantitis if not adequately treated. The aim of the present randomized controlled clinical trial was to evaluate the efficacy of air‐abrasive powder as compared to chlorhexidine (CHX) for the treatment of peri‐implant mucositis, in terms of clinical and patient‐reported outcomes (PROMs) and occurrence of peri‐implantitis 12 months after treatment. Methods: In the control group, full‐mouth calculus and plaque removal was performed with ultrasound and manual devices, and a 1.0% CHX gel was applied; in the test group, supra‐ and subgingival biofilm removal was performed using erythritol powder with a dedicated nozzle and calculus removal was performed with ultrasonic instruments if needed. Bleeding and plaque indexes, peri‐implant probing depth and tissue level were measured at 1 week, and 1, 3, 6 and 12 months after treatment, while PROMs were evaluated up to 7 days after treatment. Results: Among 80 included implants, 70 were analysed at 12 months follow‐up (30 in the test group, 40 in the control group, and 20 subjects). Success rates (implant‐level) in terms of bleeding index were significantly different between the test (96.7%) and control group (92.5%); as for PROMs, only taste sensation was significantly better in the test group. The test group was significantly correlated to the smallest changes in peri‐implant probing depth between baseline and 3 months. Conclusions: The study showed that both treatment strategies are effective. This suggests that the use of air‐abrasive powders could be used as an alternative biofilm removal method instead of adjunctive treatments with antiseptics. [ABSTRACT FROM AUTHOR]

The Mexico City Metropolitan Area (MCMA) stands as one of the most densely populated urban regions globally. To quantify the urban CO2 ${\text{CO}}_{2}$ emissions in the MCMA, we independently assimilated observations from a dense column‐integrated Fourier transform infrared (FTIR) network and OCO‐3 Snapshot Area Map observations between October 2020 and May 2021. Applying a computationally efficient analytical Bayesian inversion technique, we inverted for surface fluxes at high spatio‐temporal resolutions (1‐km and 1‐hr). The fossil fuel (FF) emission estimates of 5.08 and 6.77 GgCO2 ${\text{CO}}_{2}$/hr reported by the global and local emission inventories were optimized to 4.85 and 5.51 GgCO2 ${\text{CO}}_{2}$/hr based on FTIR observations over this 7 month period, highlighting a convergence of posterior estimates. The modeled biogenic flux estimate of −0.14 GgCO2 ${\text{CO}}_{2}$/hr was improved to −0.33 to −0.27 GgCO2 ${\text{CO}}_{2}$/hr, respectively. It is worth noting that utilizing observations from three primary sites significantly enhanced the accuracy of estimates (13.6 ∼ ${\sim} $ 29.2%) around the other four. Using FTIR posterior estimates can improve simulation with the OCO‐3 data set. OCO‐3 shows a similar decreasing trend in FF emissions (from 6.37 GgCO2 ${\text{CO}}_{2}$/hr to 6.36 and 5.04 GgCO2 ${\text{CO}}_{2}$/hr) as FTIR, but its correction trends for biogenic sources differ, changing from 0.37 to 0.48 GgCO2 ${\text{CO}}_{2}$/hr. The primary reason is OCO‐3's lower temporal sampling density. Aligning the FTIR inversion timing with that of OCO‐3 yielded comparable corrections for FF emissions, yet discrepancies in biogenic emissions persisted, which can be attributed to their different sampling locations in the rural region and discrepancy in XCO2 ${\text{CO}}_{2}$ observations. Our findings mark a significant step toward validating OCO‐3 and FTIR inversion results in metropolitan region. Plain Language Summary: Urban areas are significant hotspots for CO2 ${\text{CO}}_{2}$ emissions due to their high energy consumption, prompting a strong push toward ambitious greenhouse gas reduction initiatives. Our study harnessed data from the OCO‐3 satellite and an extensive ground‐based sensor network to map CO2 ${\text{CO}}_{2}$ concentrations on an intra‐city scale, aiming to update outdated emission inventories. We delved into the effects of observed CO2 ${\text{CO}}_{2}$ gradient differences on the optimization results, leveraging these two distinct data sources. Although both OCO‐3 satellite and ground‐based observations offer detailed insights into Mexico City's urban region, they reveal discrepancies in the sampling of rural area data. The local FF inventory, when constrained by ground‐based observations, indicates an 18.73% overestimation, whereas the OCO‐3 data set points to only a 6.44% overestimation. Our findings highlight that utilizing ground‐based observations exclusively during OCO‐3 overpass times aligns the correction from ground‐based data (6.41% overestimation) with that derived from the OCO‐3 data. However, biogenic emissions optimization differs significantly, primarily due to OCO‐3's limited rural observations, the rural sampling locations, and the discrepancies in observed XCO2 ${\text{CO}}_{2}$ values in these data sets. Key Points: A high‐resolution computational inversion system is developed with Fourier transform infrared (FTIR) and OCO‐3 Snapshot Area Map (SAM) observations to improve the urban CO2 emissionsFTIR analysis revealed overestimations in current fossil fuel (FF) and biogenic CO2 emissions over Mexico CityInversion constrained by temporally matched observations from OCO‐3 and FTIR revealed consistent corrections for FF priors [ABSTRACT FROM AUTHOR]

Synthetic cocaine analogs are designer drugs that recently emerged as non‐controlled substitutes for their parent drug. Among them, nitracaine is of particular concern for its psychoactive effect. In this work, we present a thorough characterization of the electrochemical behavior of nitracaine, with a final quantification performed by differential pulse voltammetry (DPV) in ethanol/lithium perchlorate 0.1 M. The selectivity of the method and reproducibility of results were assessed. LOQ of 0.3 μg mL−1 and a linear dynamic range of up to 400 μg mL−1 were obtained. In addition, recoveries from 85 % to 101 % were achieved on both simulated and real samples. For nitracaine analysis in urine, a clean‐up and a preconcentration step by solid phase extraction (SPE) using the adsorbent Florisil have been developed and optimized through the Design of Experiments (DoE) strategy, thus achieving an enrichment factor of 20. [ABSTRACT FROM AUTHOR]

Background: Health care delivery contributes a significant carbon footprint in the United Kingdom, and paradoxically climate change is linked to poorer human health outcomes. New General Medical Council (GMC) requirements mandate medical graduates must be able to apply sustainable care to their practice. Implementation of sustainable health care (SHC) teaching is a new challenge for medical schools, and there are several identified barriers including an overcrowded curriculum, lack of expertise within faculties, lack of institutional support and inadequate assessment techniques. Approach: We established a new SHC curriculum spiralling throughout the overall medical curriculum, and as part of this introduced a sustainable quality improvement (susQI) project to our final year cohort. SusQI considers the environmental, social and financial impacts as well as patient and population outcomes. Our students undertook this in their final year GP assistantships. Evaluation: We sought multi‐sourced data through focus groups, formal end of placement feedback, informal feedback and external feedback. We applied thematic analysis to focus group transcriptions and triangulated with the other data sources. We identified some common themes: First, susQI was enjoyed and valuable; second, it allowed meaningful participation; third, it created a co‐learning environment; and fourth, timing and curriculum placement are important when integrating susQI. Implications: SusQI can implement SHC into the overcrowded medical curriculum in a low cost, low resource manner without the need for experienced faculty. SusQI is empowering for students and grants them an active team role. Expansion into secondary and tertiary care is feasible, and we contend that susQI can be placed in other health care curricula. [ABSTRACT FROM AUTHOR]

The question of how local adaptation takes place remains a fundamental question in evolutionary biology. The variation of allele frequencies in genes under selection over environmental gradients remains mainly theoretical and its empirical assessment would help understanding how adaptation happens over environmental clines. To bring new insights to this issue we set up a broad framework which aimed to compare the adaptive trajectories over environmental clines in two domesticated mammal species co‐distributed in diversified landscapes. We sequenced the genomes of 160 sheep and 161 goats extensively managed along environmental gradients, including temperature, rainfall, seasonality and altitude, to identify genes and biological processes shaping local adaptation. Allele frequencies at putatively adaptive loci were rarely found to vary gradually along environmental gradients, but rather displayed a discontinuous shift at the extremities of environmental clines. Of the 430 candidate adaptive genes identified, only 6 were orthologous between sheep and goats and those responded differently to environmental pressures, suggesting different putative mechanisms involved in local adaptation in these two closely related species. Interestingly, the genomes of the 2 species were impacted differently by the environment, genes related to signatures of selection were most related to altitude, slope and rainfall seasonality for sheep, and summer temperature and spring rainfall for goats. The diversity of candidate adaptive pathways may result from a high number of biological functions involved in the adaptations to multiple eco‐climatic gradients, and a differential role of climatic drivers on the two species, despite their co‐distribution along the same environmental gradients. This study describes empirical examples of clinal variation in putatively adaptive alleles with different patterns in allele frequency distributions over continuous environmental gradients, thus showing the diversity of genetic responses in adaptive landscapes and opening new horizons for understanding genomics of adaptation in mammalian species and beyond. [ABSTRACT FROM AUTHOR]

From both pharmaceutical and structural perspectives, the large family of prostaglandins represent a truly remarkable class of natural products. Prostaglandin A2 is a tissue hormone naturally found in human seminal plasma and in the sea whip Plexaura homomalla with yet poorly understood biological or therapeutic effects. Herein, a novel strategy for the stereoselective construction of both naturally occurring prostaglandin A2 epimers and first insights into their functional effects on the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) type A receptors (GABAAR) are provided. The synthesis of both epimers was achieved in only 11 steps starting from commercially available 2,5‐dimethoxy‐tetrahydrofuran employing an organocatalytic domino‐aldol reaction, a Mizoroki‐Heck reaction, a Wittig reaction as well as an oxidation‐decarboxylation sequence. The (15R)‐epimer significantly reduced GABA‐induced currents through GABAA receptors while its (15S)‐epimer did not show any significant effect. These data suggest that (15R)‐PGA2 might serve as a novel scaffold for the development of selective GABAA receptor modulators. [ABSTRACT FROM AUTHOR]

From both pharmaceutical and structural perspectives, the large family of prostaglandins represent a truly remarkable class of natural products. Prostaglandin A2 is a tissue hormone naturally found in human seminal plasma and in the sea whip Plexaura homomalla with yet poorly understood biological or therapeutic effects. Herein, a novel strategy for the stereoselective construction of both naturally occurring prostaglandin A2 epimers and first insights into their functional effects on the major inhibitory neurotransmitter γ‐aminobutyric acid (GABA) type A receptors (GABAAR) are provided. The synthesis of both epimers was achieved in only 11 steps starting from commercially available 2,5‐dimethoxy‐tetrahydrofuran employing an organocatalytic domino‐aldol reaction, a Mizoroki‐Heck reaction, a Wittig reaction as well as an oxidation‐decarboxylation sequence. The (15R)‐epimer significantly reduced GABA‐induced currents through GABAA receptors while its (15S)‐epimer did not show any significant effect. These data suggest that (15R)‐PGA2 might serve as a novel scaffold for the development of selective GABAA receptor modulators. [ABSTRACT FROM AUTHOR]

Mogamulizumab is a first‐in‐class IgG1k monoclonal antibody that selectively targets the chemokine receptor type 4. The drug has received Food and Drug administration authorisation for mycosis fungoides and Sézary syndrome following failure of at least one previous course of systemic therapy and now is available in Europe. One of the most common treatment‐related side effects observed has been the mogamulizumab‐associated rash (MAR), which affects up to a quarter of patients and is the most frequent adverse event leading to drug discontinuation. The aim of this study is to perform a systematic review of the literature on patients diagnosed with MAR and other mogamulizumab‐related cutaneous events to describe the clinical and histological characteristics, the management in clinical practice and to assess whether these events have prognostic implications. In total, 2073 records were initially identified through a literature search, 843 of which were duplicates. After screening for eligibility and inclusion criteria, 49 articles reporting mogamulizumab‐associated cutaneous events were included. Totally, 1516 patients were retrieved, with a slight male prevalence as for the available data (639 males and 570 females, i.e. 52.9% vs. 47.1%). Regarding the reported clinicopathological findings of the cutaneous reactions, the five most common patterns were spongiotic/psoriasiform dermatitis (22%), eruptions characterized by the presence of papules and/or plaques (16.1%), cutaneous granulomatosis (11.4%), morbilliform or erythrodermic dermatitis (9.4%) and photodermatitis (7.1%). Our results highlight how the majority of the reported cutaneous adverse events on mogamulizumab are of mild‐to‐moderate entity and generally manageable in clinical practice, though prompt recognition is essential and case‐by‐case assessment should be recommended. Future research will need to focus on the MAR prognostic implications and to identify genomic and molecular markers for a more rapid and accurate diagnosis. [ABSTRACT FROM AUTHOR]

This article presents a unique case of a patient with primary cutaneous follicle centre B-cell lymphoma (PCFCCL) who developed a T-cell pseudolymphoma while receiving secukinumab for psoriasis treatment. The patient initially received local radiotherapy for PCFCCL and subsequently developed psoriasis. After starting secukinumab, the patient experienced rapid growth and ulceration of the previously irradiated lesion, which was biopsied and revealed a residual PCFCCL component along with a dense proliferation of small-to-medium-sized lymphocytes. The authors suggest that the pseudolymphoma may have been triggered by secukinumab. This case highlights the complex interplay between tumor and self-immunity and the role of lymphoma-specific T cells. [Extracted from the article]

The Incubator for Clinical Education Research (ClinEdR) is a UK‐wide network, established with support from the National Institute for Health and Care Research (NIHR), to lead initiatives to build capacity in the field. Our lived experiences as members of the NIHR ClinEdR Incubator and wider literature are woven into this 'How to ...' paper, which outlines what to consider as you seek to grow and develop a ClinEdR team. This paper sets out pragmatic steps to grow an effective ClinEdR team that has a wider impact and mutual benefits for its members and their institution(s). Growing a ClinEdR team requires more than a dynamic character to bring people together. In our view, you can grow a ClinEdR team with other people through a structured, well‐thought‐out approach, in which its members develop through collaborative work to achieve a shared objective. [ABSTRACT FROM AUTHOR]

Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta‐analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta‐analysis was performed using random‐effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower‐middle, 12 in upper‐middle, and only two in high‐income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta‐analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta‐analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high‐income countries. [ABSTRACT FROM AUTHOR]

In this work, the harmonic balance approach is applied to a 2D nonlinear finite‐element magnetic model with motion, coupled to a nonlinear circuit. The case study comprises a six‐pole three‐phase surface‐mounted permanent magnet generator connected to a six‐pulse full‐wave diode bridge rectifier. Simulations are performed at fixed generator speed in two operating cases: with an open‐circuit DC bus and supplying a load resistance. Both time stepping and harmonic balance approaches are deeply discussed focusing on the model under study, along with relevant implementation details. Harmonic balance results are compared with benchmark time stepping simulations in terms of voltage and current waveforms, progressively expanding the harmonic spectrum. The computational cost of the two approaches is reported as well. Simulation accuracy is satisfying with regard to time stepping benchmark results: relative errors on total harmonic distortion and global root‐mean‐square values are lower than 3% and 1%, respectively. However, the time stepping approach outperforms the harmonic balance one, due to the relatively short initial transient of the chosen case study. Further improvements on practical implementation are needed to exploit the potentialities of harmonic balance technique. [ABSTRACT FROM AUTHOR]

Aims: Circadian syndrome (CircS) is considered a better predictor for cardiovascular disease than the metabolic syndrome (MetS). We aim to examine the associations between CircS and MetS with cognition in Chinese adults. Method: We used the data of 8546 Chinese adults aged ≥40 years from the 2011 China Health and Retirement Longitudinal Study. MetS was defined using harmonised criteria. CircS included the components of MetS plus short sleep and depression. The cut‐off for CircS was set as ≥4. Global cognitive function was assessed during the face‐to‐face interview. Results: CircS and MetS had opposite associations with the global cognition score and self‐reported poor memory. Compared with individuals without the CircS and MetS, the regression coefficients (95%CI) for global cognition score were −1.02 (−1.71 to −0.34) for CircS alone and 0.52 (0.09 to 0.96) for MetS alone in men; −1.36 (−2.00 to −0.72) for CircS alone and 0.60 (0.15 to 1.06) for MetS alone in women. Having CircS alone was 2.53 times more likely to report poor memory in men (95%CI 1.80–3.55) and 2.08 times more likely in women (95%CI 1.54–2.81). In contrast, having MetS alone was less likely to report poor memory (OR 0.64 (0.49–0.84) in men and 0.65 (0.52–0.81) in women). People with CircS and MetS combined were more likely to have self‐reported poor memory. Conclusions: CircS is a strong and better predictor for cognition impairment than MetS in Chinese middle‐aged adults. MetS without short sleep and depression is associated with better cognition. [ABSTRACT FROM AUTHOR]

This systematic review and meta‐analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo‐controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta‐analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta‐analysis of SCORAD outcomes was conducted using random‐effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta‐analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well‐designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies. [ABSTRACT FROM AUTHOR]

Question: In productive grasslands highly dominated by a single plant species, herbivores can promote overall plant diversity. Wild boars (Sus scrofa) often decrease species diversity, alter regeneration and change community composition in their native and invader ranges while digging and uprooting vegetation for feeding. In addition, wild guinea pigs (Cavia aperea), a small vertebrate herbivore native to South America, concentrate their feeding activities in open patches where they also affect plant diversity, biomass and composition. In this context, can wild‐boar disturbances promote plant diversity in herbaceous systems characterized by a highly dominant species? Can native wild guinea pigs magnify these impacts? Location: Coastal grasslands and salt marshes of the northeastern part of the temperate Argentine pampas, that are dominated by native or exotic herbaceous species. Methods: We first analyzed alpha‐ and beta‐diversity of plant assemblies in three natural coastal herbaceous areas, invaded by wild boars, through samplings (comparing disturbed and undisturbed areas) and experiments (using exclosures and control plots). Then, we analyzed whether wild guinea pigs could affect patch recovery (alpha‐ and beta‐diversity) after wild‐boar disturbances in one site. Results: Wild boars enhanced alpha‐diversity (compared to undisturbed areas) but had no significant effect on beta‐diversity. Nevertheless, wild guinea pigs feeding on wild‐boar disturbances increased between‐patch heterogeneity in species composition (i.e., beta‐diversity). Conclusion: Wild boars remove vegetation in patches that, without subsequent wild‐guinea‐pig herbivory, dominant species rapidly recover. Wild‐guinea‐pig herbivory allows different subordinate species to peak at different disturbed patches, contributing to larger species richness at larger scales in areas otherwise occupied by highly dominant plant species. In a wider context, these results imply that the joint action of different‐sized exotic and native herbivores can help to maintain plant species diversity in highly plant‐dominated grasslands. [ABSTRACT FROM AUTHOR]

Urban evolutionary ecology is inherently interdisciplinary. Moreover, it is a field with global significance. However, bringing researchers and resources together across fields and countries is challenging. Therefore, an online collaborative research hub, where common methods and best practices are shared among scientists from diverse geographic, ethnic, and career backgrounds would make research focused on urban evolutionary ecology more inclusive. Here, we describe a freely available online research hub for toolkits that facilitate global research in urban evolutionary ecology. We provide rationales and descriptions of toolkits for: (1) decolonizing urban evolutionary ecology; (2) identifying and fostering international collaborative partnerships; (3) common methods and freely‐available datasets for trait mapping across cities; (4) common methods and freely‐available datasets for cross‐city evolutionary ecology experiments; and (5) best practices and freely available resources for public outreach and communication of research findings in urban evolutionary ecology. We outline how the toolkits can be accessed, archived, and modified over time in order to sustain long‐term global research that will advance our understanding of urban evolutionary ecology. [ABSTRACT FROM AUTHOR]

Over the years, human dihydroorotate dehydrogenase (hDHODH), which is a key player in the de novo pyrimidine‐biosynthesis pathway, has been targeted in the treatment of several conditions, including autoimmune disorders and acute myelogenous leukaemia, as well as in host‐targeted antiviral therapy. A molecular exploration of its inhibitor‐binding behaviours yielded promising candidates for innovative drug design. A detailed description of the enzymatic pharmacophore drove the decoration of well‐established inhibitory scaffolds, thus gaining further in vitro and in vivo efficacy. In the present work, using X‐ray crystallography, an atypical rearrangement was identified in the binding pose of a potent inhibitor characterized by a polar pyridine‐based moiety (compound 18). The crystal structure shows that upon binding compound 18 the dynamics of a protein loop involved in a gating mechanism at the cofactor‐binding site is modulated by the presence of three water molecules, thus fine‐tuning the polarity/hydrophobicity of the binding pocket. These solvent molecules are engaged in the formation of a hydrogen‐bond mesh in which one of them establishes a direct contact with the pyridine moiety of compound 18, thus paving the way for a reappraisal of the inhibition of hDHODH. Using an integrated approach, the thermodynamics of such a modulation is described by means of isothermal titration calorimetry coupled with molecular modelling. These structural insights will guide future drug design to obtain a finer Kd/logD7.4 balance and identify membrane‐permeable molecules with a drug‐like profile in terms of water solubility. [ABSTRACT FROM AUTHOR]

Satellite measurements of urban CO2 plumes offer a global approach to track CO2 emissions for large cities. To examine and to quantify the feasibility of space‐based monitoring, an intensive measurement campaign (MERCI‐CO2) using seven solar‐tracking Fourier transform infrared (FTIR) spectrometers has been conducted over the Mexico City Metropolitan Area (MCMA) to monitor urban emissions and to evaluate Snapshot Area Map (SAM) observations from the NASA's Orbiting Carbon Observatory‐3 (OCO‐3) mission. Once adjusted for their respective averaging kernels, we diagnosed a positive difference between OCO‐3 and FTIR column measurements (1.06 ppm). Thanks to this unprecedented amount of column observations over a large city, we demonstrate that XCO2 gradients within OCO‐3 SAMs align with the inter‐calibrated FTIR measurements (mean bias of 0.3 ppm), confirming the potential to track CO2 emissions from space over large metropolitan areas. XCO2 urban‐rural differences across the FTIR network, show a strong correlation with observed gradients, with Pearson's correlation coefficients (R) around 0.92. The correlation is significantly lower when considering intra‐urban gradients, where R drop to around 0.24. Simulated XCO2 enhancements (ΔXCO2) based on X‐STILT for both FTIR and OCO‐3 show relatively high correlations (R is around 0.6) using high‐resolution footprints and two gridded inventories. Spatial correlations with OCO‐3 improve when aggregating satellite retrievals at coarser resolutions (10 km). Our study demonstrates the capabilities of detecting urban gradients by FTIR network and OCO‐3 SAM observations over MCMA, a promising result to evaluate the evolution of MCMA's emissions over the coming decade. Plain Language Summary: Despite the fact that large metropolitan areas across the world account for a significant fraction of the global CO2 emissions from fossil fuels, city‐scale CO2 emissions estimates from inventories remain highly uncertain and usually lag real time by several years. Observations obtained from satellites and ground‐based sensors are expected to improve the quantification of CO2 emissions in urban regions. Observed CO2 gradients (site‐to‐site differences) over urban areas is essential for quantifying CO2 emissions. In this study, we assess intra‐urban CO2 gradients over the Mexico City Metropolitan Area utilizing dense observations from both space and ground. Our analysis reveals that space and ground observations exhibit greater consistency when comparing urban‐to‐rural gradients, as opposed to gradients observed exclusively within urban areas. Furthermore, simulated urban gradients based on inventories show good coherence with our observed gradients, underscoring the potential for utilizing both space and ground spatial gradients in city‐scale CO2 emissions estimation. Key Points: Validating fine‐scale XCO2 gradients observed by NASA's OCO‐3 Snapshot Area Map through an unprecedented deployment of dense ground‐based sensorsIntroducing a correction method in a coarser global model to establish reliable background valuesDemonstrating consistency between inventory‐simulated urban gradients and observed data from FTIR and OCO‐3 [ABSTRACT FROM AUTHOR]

This article discusses the comparison between indolent systemic mastocytosis (ISM) and clonal mast cell disease that does not meet the World Health Organization (WHO) diagnostic criteria. ISM is a rare neoplasm characterized by abnormal mast cell proliferation, while clonal mast cell disease refers to cases with clonal markers but not all diagnostic criteria for ISM. The study collected data from 530 patients diagnosed with ISM or clonal mast cell disease and compared their clinical features, outcomes, and therapeutic needs. The results showed that the two groups had similar symptom burden, outcomes, and treatment requirements, suggesting that clonal criteria in the appropriate clinical context may be sufficient for diagnosing a "low-burden SM." The authors recommend similar management for both groups to prevent severe complications. [Extracted from the article]

Questions: What is the relative importance of interspecific and intraspecific trait variation and their covariation in the herb layer of European temperate beech forests, and how do they vary with elevation? Is there evidence of interspecific trait convergence at higher elevations, as postulated by the habitat‐filtering hypothesis, and is this convergence enhanced or counteracted by intraspecific variation? Location: National Park "Foreste Casentinesi, Monte Falterona and Campigna", Italy. Methods: We measured four functional traits – plant height, specific leaf area (SLA), leaf dry matter content (LDMC) and leaf area – across 775 individuals from 60 herb‐layer species in 28 forest plots (10 m × 10 m) spanning an 800 m elevation gradient. For each trait in each plot, we computed community‐weighted means (CWMs) and the standardized effect size of functional diversity (SES‐FD). We decomposed total trait variation into its interspecific and intraspecific components, and their covariation. We run linear regression models to assess the impact of elevation on these three components of functional variation. Lastly, we investigated whether higher elevation communities exhibited lower SES‐FD, indicating functional convergence that could hint to a stronger habitat filtering. Results: Interspecific trait variation was more important than the intraspecific counterpart both for CWMs and SES‐FD. Only CWMs calculated for plant height and LDMC showed a significant relationship with elevation. Low‐elevation communities featured taller, more‐conservative species, whereas shorter, faster‐growing species were more common at higher elevations. SES‐FD remained consistently negative for species turnover and total variation, suggesting stable functional convergence across the gradient. Conclusions: Our findings suggest that interspecific and intraspecific trait variability can be decoupled along an elevation gradient, stressing the importance of individually considering each component of trait variation when studying community composition. Elevation significantly influenced various components of plant community trait variation, with habitat filtering playing a substantial role in selecting plants with specific traits across elevations. [ABSTRACT FROM AUTHOR]

Objectives. The aims of this study were to assess the morphologic features of peri-implant defects, as measured on 2D intraoral radiographs, and to investigate the possible correlation between such morphology and other parameters related to the position and characteristics of the implant or the implant-supported prosthesis. Materials and Methods. Implants with peri-implantitis were included in this retrospective study. Data collected were related both to the patients and to the position/characteristics of the implants and the implant-supported prosthesis. Measurements of the morphologic defects were performed by two operators on digitalized intraoral periapical radiographs. Results and Conclusion. In total, 73 implants in 27 patients were included. The measurements of the periapical radiograph suggested that the most common defect conformation was crateriform, with both intraosseous and horizontal components. An inverse correlation was found between the extension of the peri-implant lesion and the time between the radiographic assessment and the implant placement. The total lesion area was strongly correlated to oral hygiene levels. No correlations between lesion extension and smoking, diabetes, history of periodontal were found. In conclusion, the results from this 2D radiographic study showed the prevalence of crateriform peri-implant defects, with a hygiene-correlated extension, perceptible on the mesial and distal aspects; 3D imaging could be used when available for further research and clinical investigation. [ABSTRACT FROM AUTHOR]

In this study, the optical behavior of lead‐free Bi‐based low‐dimensional perovskite single crystals (Cs3Bi2Cl9, Cs3Bi2Br9, Cs3Bi2I9, and MA3Bi2I9) is investigated by spectroscopic ellipsometry, supported by X‐ray diffraction and density functional theory calculations. All materials exhibit a strong excitonic peak resulting from photogenerated electron–hole Coulomb interactions, whereas the threshold of continuous absorption is found at higher energies. The resonances of the excitonic and continuous bands, along with exciton binding energies, are extracted through Critical Point Analysis of the ellipsometric data over a wide temperature range (from −90 °C to 90 °C), revealing subtle variations in the optical characteristics for each single crystal. These materials can be applied in optoelectronics as photodetectors because of their high stability and lower toxicity compared to their Pb‐based perovskites. [ABSTRACT FROM AUTHOR]

The Salado and Verde streams constitute the two main seasonally available freshwater courses that flow into the Atlantic coast of the Río Negro province (continental Patagonia, Argentina, 42° South). This would have favored their use in the past as corridors for human circulation between the coast and the interior. This paper presents the results of the technomorphological and geochemical analyses of the obsidian artifacts recovered in the area to constrain mobility. The results allow us to propose the existence of toolkit reconditioning or replacement activities, and the identification of different sources of provenance of the obsidians (Sacanana, Telsen, and Portada Covunco, distant up to 800 km from the study area), reinforcing the hypothesis of a coast–inland circulation, with the possible existence of circuits of exchange of this raw material. [ABSTRACT FROM AUTHOR]

Objective: This work investigates cortical thickness (CT) and gyrification patterns in Anorexia Nervosa (AN) before and after short‐term weight restoration using graph theory tools. Methods: 38 female adolescents with AN underwent structural magnetic resonance imaging scans at baseline and after ‐ on average ‐ 3.5 months following short‐term weight restoration while 53 age‐matched healthy controls (HCs) were scanned once. Graph measures were compared between groups and longitudinally within the AN group. Associations with clinical measures such as age of onset, duration of illness, BMI standard deviation score (BMI‐SDS), and longitudinal weight changes were tested via stepwise regression. Results: Cortical thickness graphs of patients with acute AN displayed lower modularity and small‐world index (SWI) than HCs. Modularity recovered after weight gain. Reduced global efficiency and SWI were observed in patients at baseline compared to HCs based on gyrification networks. Significant associations between local clustering of CT at admission and BMI‐SDS, and clustering/global efficiency of gyrification and duration of illness emerged. Conclusions: Our results indicate a shift towards less organised CT networks in patients with acute AN. After weight recovery, the disarrangement seems to be partially reduced. However, longer‐term follow‐ups are needed to determine whether cortical organizational patterns fully return to normal. Highlights: Patients with acute Anorexia Nervosa (AN) displayed a shift towards less organised cortical networks.After a short‐term weight restoration, alterations in cortical architecture seems to partially recover, suggesting the beneficial consequences of adequate nutritional programs on the brain structure.The associations between the organization of morphological patterns and clinical indices such as BMI standard deviation score (BMI‐SDS) and duration of the disorder support and emphasise the importance of an early and thorough weight rehabilitation in the treatment of AN. [ABSTRACT FROM AUTHOR]

Hole‐transporting layer‐free mesoporous carbon (mC) architectures represent a printable, low‐cost, and stable solution for the future commercialization of perovskite solar cells (PSCs). CsPbI3 perovskite is attracting attention for its inorganic structure, which yields higher structural stability compared to hybrid counterparts and allows reversibility of its photoactive phase. Here the photovoltaic performance of large‐area (144 mm2) devices infiltrated with CsPbI3:EuCl3 is systematically evaluated, using AVA‐MAPbI3 mC‐PSCs as a reference. Measured and simulated J–V curves acquired at various scan rates show a significantly reduced hysteresis for Eu‐doped CsPbI3 with respect to AVA‐MAPbI3 mC‐PSCs. The synergic comparison between experiments and simulations reveals the complex interplay between ionic and electronic charges in the two mC‐PSCs, supporting the argument that cation migration is suppressed in CsPbI3:EuCl3. This also agrees with steady‐state photoconversion efficiency measured and simulated at fixed bias, which is constant over time in CsPbI3:EuCl3, contrary to what occurs in AVA‐MAPbI3 where a decay arises from enhanced ionic migration. In addition, CsPbI3:EuCl3 mC‐PSCs maintain their initial efficiency up to 250 h at 55 °C under continuous illumination during maximum power point tracking measurements. The possibility of reusing the CsPbI3:EuCl3 mC‐PSCs multiple times is demonstrated, pointing out the superiority of this inorganic perovskite in terms of sustainability. [ABSTRACT FROM AUTHOR]

Background and Aims: Chemotherapy‐induced peripheral neurotoxicity (CIPN) is one of the most common dose‐limiting side effects of paclitaxel (PTX) treatment. Many age‐related changes have been hypothesized to underlie susceptibility to damage or impaired regeneration/repair after nerve injury. The results of these studies, however, are inconclusive and other potential biomarkers of nerve impairment need to be investigated. Methods: Twenty‐four young (2 months) and 24 adult (9 months) Wistar male rats were randomized to either PTX treatment (10 mg/kg i.v. once/week for 4 weeks) or vehicle administration. Neurophysiological and behavioral tests were performed at baseline, after 4 weeks of treatment and 2‐week follow‐up. Skin biopsies and nerve specimens collected from sacrificed animals were examined for intraepidermal nerve fiber (IENF) density assessment and nerve morphology/morphometry. Blood and liver samples were collected for targeted metabolomics analysis. Results: At the end of treatment, the neurophysiological studies revealed a reduction in sensory nerve action potential amplitude (p <.05) in the caudal nerve of young PTX‐animals, and in both the digital and caudal nerve of adult PTX‐animals (p <.05). A significant decrease in the mechanical threshold was observed only in young PTX‐animals (p <.001), but not in adult PTX‐ones. Nevertheless, both young and adult PTX‐rats had reduced IENF density (p <.0001), which persisted at the end of follow‐up period. Targeted metabolomics analysis showed significant differences in the plasma metabolite profiles between PTX‐animals developing peripheral neuropathy and age‐matched controls, with triglycerides, diglycerides, acylcarnitines, carnosine, long chain ceramides, sphingolipids, and bile acids playing a major role in the response to PTX administration. Interpretation: Our study identifies for the first time multiple related metabolic axes involved in PTX‐induced peripheral neurotoxicity, and suggests age‐related differences in CIPN manifestations and in the metabolic profile. [ABSTRACT FROM AUTHOR]

Background and Aims: Chemotherapy‐induced peripheral neurotoxicity (CIPN) is a common and long‐lasting adverse event of several anticancer compounds, for which treatment has not yet been developed. To fill this gap, preclinical studies are warranted, exploiting highly translational outcome measure(s) to transfer data from bench to bedside. Nerve excitability testing (NET) enables to test in vivo axonal properties and can be used to monitor early changes leading to axonal damage. Methods: We tested NET use in two different CIPN rat models: oxaliplatin (OHP) and paclitaxel (PTX). Animals (female) were chronically treated with either PTX or OHP and compared to respective control animals. NET was performed as soon as the first injection was administered. At the end of the treatment, CIPN onset was verified via a multimodal and robust approach: nerve conduction studies, nerve morphometry, behavioural tests and intraepidermal nerve fibre density. Results: NET showed the typical pattern of axonal hyperexcitability in the 72 h following the first OHP administration, whereas it showed precocious signs of axonal damage in PTX animals. At the end of the month of treatment, OHP animals showed a pattern compatible with a mild axonal sensory polyneuropathy. Instead, PTX cohort was characterised by a rather severe sensory axonal polyneuropathy with minor signs of motor involvement. Interpretation: NET after the first administration demonstrated the ongoing OHP‐related channelopathy, whereas in PTX cohort it showed precocious signs of axonal damage. Therefore, NET could be suggested as an early surrogate marker in clinical trials, to detect precocious changes leading to axonal damage. [ABSTRACT FROM AUTHOR]

Drawing upon representative bureaucracy theory, this study investigates the relationship between passive and symbolic representation by examining the extent to which a more passively representative public organization would be attractive as an employer. The study involved a randomized survey experiment of members of the public in the US and UK. Overall, and contrary to the theory of representative bureaucracy, results show that women found a male‐dominated police department more attractive. The explanation for the results of the study may lie in bureaucratic reputation as a boundary condition of symbolic representation. [ABSTRACT FROM AUTHOR]

Electron density (Ne) and electron temperature (Te) observations collected by Langmuir Probes on board the European Space Agency (ESA) Swarm B satellite are used to characterize their correlation in the topside ionosphere at an altitude of about 500 km. Spearman correlation coefficient values (RSpearman) are calculated on joint probability distributions between Ne and Te for selected conditions. The large data set of Swarm B observations at 2‐Hz rate, covering the years 2014–2022, allowed investigating the correlation properties of the topside ionospheric plasma on a global scale, for different diurnal and seasonal conditions, with both a coverage and a detail never reached before. Results are given as maps of RSpearman as a function of the Quasi‐Dipole (QD) magnetic latitude and magnetic local time (MLT) coordinates. The characterization of the correlation at high latitudes, along with the description of the diurnal trend at all latitudes, are the new findings of this study. The main correlation features point out a negative correlation at the morning overshoot, during daytime at mid latitudes, and during nighttime at the ionospheric trough and subauroral latitudes. Conversely, a positive correlation dominates the nighttime hours at mid and low latitudes and, to a minor extent, the low latitudes from 09 MLT onwards. A seasonal dependence of the correlation is noticeable only at very high latitudes where the general pattern of the negative correlation does not hold around ±75° QD latitude in the summer season. Results from Swarm B have been statistically compared and discussed with observations from the Arecibo, Jicamarca, and Millstone Hill incoherent scatter radars. Key Points: The correlation between the electron density and temperature in the topside ionosphere has been investigated through 9 years of Swarm B in‐situ observationsThe latitudinal, diurnal, and seasonal variations of the correlation have been studied on a global scale at an unprecedented spatial and temporal resolutionFirst ever study of the correlation at high latitudes, which highlighted a general pattern of negative correlation except for the summer season at the polar cusp [ABSTRACT FROM AUTHOR]

We report the case of a 12‐year‐old girl and her father who both had marked postnatal tall stature, camptodactyly and clinodactyly, scoliosis and juvenile‐onset hearing loss. The CATSHL (CAmptodactyly – Tall stature – Scoliosis – Hearing Loss syndrome) syndrome was suspected, and molecular analysis revealed a hitherto unreported, monoallelic variant c.1861C>T (p.Arg621Cys) in FGFR3. This variant affects the same residue, but is different than, the variant p.Arg621His reported in the two families with dominant CATSHL described so far. Interestingly, peg‐shaped incisors were observed in the proband, a feature never reported in CATSHL but typical of another FGFR3‐related condition, LADD (Lacrimo – Auricolo – Dento – Digital) syndrome. The FGFR3 p.Arg621Cys variant seems to be a newly identified cause of CATSHL syndrome with some phenotypic overlap with the LADD syndrome. [ABSTRACT FROM AUTHOR]

Aim: To determine the relationships between the functional trait composition of forest communities and environmental gradients across scales and biomes and the role of species relative abundances in these relationships. Location: Global. Time period: Recent. Major taxa studied: Trees. Methods: We integrated species abundance records from worldwide forest inventories and associated functional traits (wood density, specific leaf area and seed mass) to obtain a data set of 99,953 to 149,285 plots (depending on the trait) spanning all forested continents. We computed community‐weighted and unweighted means of trait values for each plot and related them to three broad environmental gradients and their interactions (energy availability, precipitation and soil properties) at two scales (global and biomes). Results: Our models explained up to 60% of the variance in trait distribution. At global scale, the energy gradient had the strongest influence on traits. However, within‐biome models revealed different relationships among biomes. Notably, the functional composition of tropical forests was more influenced by precipitation and soil properties than energy availability, whereas temperate forests showed the opposite pattern. Depending on the trait studied, response to gradients was more variable and proportionally weaker in boreal forests. Community unweighted means were better predicted than weighted means for almost all models. Main conclusions: Worldwide, trees require a large amount of energy (following latitude) to produce dense wood and seeds, while leaves with large surface to weight ratios are concentrated in temperate forests. However, patterns of functional composition within‐biome differ from global patterns due to biome specificities such as the presence of conifers or unique combinations of climatic and soil properties. We recommend assessing the sensitivity of tree functional traits to environmental changes in their geographic context. Furthermore, at a given site, the distribution of tree functional traits appears to be driven more by species presence than species abundance. [ABSTRACT FROM AUTHOR]

Objective: There is growing evidence that ketogenic dietary therapy (KDT) can be safely and efficiently used in young children, but little evidence exists on its use in newborns. Developmental and epileptic encephalopathies starting in the neonatal period or early infancy usually present a poor prognosis. The aim of this study was to evaluate effectiveness, safety, and survival of infants younger than 3 months of age with drug‐resistant epilepsy in whom KDT was used. Methods: A retrospective study was conducted to evaluate neonates and infants younger than 3 months who started KDT for drug‐resistant developmental and epileptic encephalopathies at three referral centers. Data were collected on demographic features, time of epilepsy onset, epilepsy syndrome, seizure type, seizure frequency at diet onset, etiology, details regarding diet initiation, type of ketogenic formula, breastfeeding, route of administration, blood ketones, growth, length of NICU stay, and survival. Results: Nineteen infants younger than 12 weeks of life who received KDT with a minimum follow‐up of 1 month were included; 13 had early‐infantile developmental and epileptic encephalopathy, four epilepsy of infancy with migrating focal seizures, and two focal epilepsy. A >50% response was observed in 73.7% at 1 month on the diet; 37% achieved a > 75% seizure reduction, and 10.5% became seizure free. At 3 months, a >50% decrease in seizure frequency was observed in 72.2%; 15.8% had a >75% reduction; 21% became seizure free. Overall survival was 76% at 1 year on diet. Incidence of acute and late adverse effects was low and most adverse effects were asymptomatic and manageable. Significance: Our experience suggests that KDT is safe and effective in newborns and very young infants; however, further studies on the management of the diet in this vulnerable age group are necessary. [ABSTRACT FROM AUTHOR]

Background. Meningeal solitary fibrous tumors (SFTs) are rare, malignant, mesenchymal tumors of the central nervous system. While surgical gross total resection is widely accepted as a positive prognostic factor for local control (LC), the role of postoperative radiotherapy (PORT) remains controversial. We sought to report our institutional experience with a particular focus on outcomes after PORT. Materials and Methods. In this single-center, retrospective cohort study, 20 patients with the primary diagnosis of histopathologically confirmed meningeal SFT were analyzed. Data on patient characteristics, imaging, treatment modalities, histopathology, and oncological outcomes were collected. LC and overall survival (OS) were assessed using the Kaplan–Meier estimator. Results. The median follow-up time was 95.8 months. After surgery only, 9 out of 11 patients (81.8%) developed a local recurrence while, after surgery and PORT, 3 out of 9 patients (33.33%) showed local failure. The 5- and 10-year LC rates were 50.5% and 40.4% in the surgery-only group and 80% at both time points in the surgery with the PORT group. In the surgery-only group, 4 out of 11 patients (36.4%) died, and 4 out of 9 patients (44.4%) died in the surgery and PORT group. OS rates after 5 and 10 years were 88.9% and 66.7% in the surgery-only group and 88.9% and 76.2% in the surgery with PORT group. Conclusions. Our findings suggest that PORT may improve LC in patients with meningeal SFT. The low incidence of meningeal SFT impedes prospective studies and requires further international collaborative efforts to exploit retrospective datasets and molecular analysis to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Summary: The practice of aging beverages, such as fruit liqueur, incorporates phenolic compounds from wood, contributing to sensorial enhancement with new aromas and flavours. The apple liqueurs were prepared with 100 g L−1 of sugar, 20°GL and the addition of oak chips (toasted or untoasted) was previously treated with ultrasound (bath or probe). The content of total and individual phenolic compounds, antioxidant activity (FRAP, DPPH and ABTS) and colour were evaluated. A Ranking Descriptive Analysis was performed to evaluate the characteristics of each apple liqueur. The apple liqueur that received chips pre‐treated with an ultrasonic probe presented 116.5% more phenolic compounds, on average 4.9 times more antioxidant activity, and greater variation in total colour ΔE 7.03 than the control apple liqueur. The pre‐treatment with an ultrasonic probe accelerated the extraction process in approximately 60 days. The untoasted chips contributed by adding 17.4% more total phenols than the toasted chips, due to the significant presence of gallic acid. The pre‐treatment on wood chips accelerated the aging of apple liqueurs, increased phenolics compounds. Sensorially, the woody descriptors (taste, aroma and residual) were more intensely perceived and with the best acceptance scores among the judges. [ABSTRACT FROM AUTHOR]

Memory and learning allow animals to appropriate certain properties of nature with which they can navigate in it successfully. Memory is acquired slowly and consists of two major phases, a fragile early phase (short‐term memory, <4 h) and a more robust and long‐lasting late one (long‐term memory, >4 h). Erythropoietin (EPO) prolongs memory from 24 to 72 h when animals are trained for 5 min in a place recognition task but not when training lasted 3 min (short‐term memory). It is not known whether it promotes the formation of remote memory (≥21 days). We address whether the systemic administration of EPO can convert a short‐term memory into a long‐term remote memory, and the neural plasticity mechanisms involved. We evaluated the effect of training duration (3 or 5 min) on the expression of endogenous EPO and its receptor to shed light on the role of EPO in coordinating mechanisms of neural plasticity using a single‐trial spatial learning test. We administered EPO 10 min post‐training and evaluated memory after 24 h, 96 h, 15 days, or 21 days. We also determined the effect of EPO administered 10 min after training on the expression of arc and bdnf during retrieval at 24 h and 21 days. Data show that learning induces EPO/EPOr expression increase linked to memory extent, exogenous EPO prolongs memory up to 21 days; and prefrontal cortex bdnf expression at 24 h and in the hippocampus at 21 days, whereas arc expression increases at 21 days in the hippocampus and prefrontal cortex. [ABSTRACT FROM AUTHOR]