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Abstract The multi-phase oxidation of S(IV) plays a crucial role in the atmosphere, leading to the formation of haze and severe pollution episodes. We here contribute to its understanding on a molecular level by reporting experimentally determined pK a values of the various S(IV) tautomers and reaction barriers for SO2 formation pathways. Complementary state-of-the-art molecular-dynamics simulations reveal a depletion of bisulfite at low pH at the liquid-vapor interface, resulting in a different tautomer ratio at the interface compared to the bulk. On a molecular-scale level, we explain this with the formation of a stable contact ion pair between sulfonate and hydronium ions, and with the higher energetic barrier for the dehydration of sulfonic acid at the liquid-vapor interface. Our findings highlight the contrasting physicochemical behavior of interfacial versus bulk environments, where the pH dependence of the tautomer ratio reported here has a significant impact on both SO2 uptake kinetics and reactions involving NO x and H2O2 at aqueous aerosol interfaces.

Abstract Background This retrospective study compares the outcomes of unicompartmental medial fixed-bearing knee arthroplasty (mUKA), involving a cemented metal-backed (MB) or an all-polyethylene (AP) tibial component, performed in obese patients with a body mass index (BMI) > 30 with a follow-up of at least 5 years. Methods The institutional database was mined for primary mUKAs involving an MB or an AP tibial component (MB-UKA and AP-UKA groups, respectively) performed from January 2015 to August 2019. Patient demographics and patient-reported outcome measures (PROMs) were compared and a propensity score matching (PSM) analysis (1:1) using multiple variables was conducted. Results PSM analysis yielded 37 pairs of obese MB-UKA and AP-UKA patients. At 5 years, the Knee Society Function Score (KSFS) was 75.1 ± 10.6 in MB-UKA and 79.4 ± 9.1 in AP-UKA patients (p = 0.029), and the Oxford Knee Score (OKS) was 38.1 ± 4.4 in MB-UKA and 40.6 ± 5.7 in AP-UKA patients (p = 0.011). Conclusion At five-year follow-up, in a matched group of obese MB-UKA and AP-UKA patients, the AP-UKA group achieved better KSFSs and OKSs. Both the AP and the MB tibial components were able to bring about a significant improvement of the most widely used PROMs.

Abstract Background The Subglottic Cysts (SGCs) are a rare cause of respiratory distress in infants. Typical risk factors include male gender, extreme prematurity, gastro-oesophageal reflux and invasive ventilation, the latter being associated with mucosal damage and blockage of the subglottic cysts’ ducts. We describe a case of acquired subglottic cysts in a premature infants presented with respiratory distress. Case presentation A premature male infant was born at 25 weeks + 2 days with a history of monochorionic diamniotic twin pregnancy with twin-to-twin transfusion syndrome. During hospitalization, invasive mechanical ventilation was necessary for a total of 18 days; the patient was discharged at postmenstrual age of 40 weeks + 1 day in good condition. At 43 weeks post-menstrual age, he presented to our department with mixed stridor and worsening of respiratory dynamics. A laryngotracheoscopy evaluation was performed. The exam showed the presence of multiple SGCs causing an almost complete obstruction of the airway. Because of the significant reduction of the airway’s patency, the child underwent a tracheotomy and thereafter cysts’ removal using cold steel microinstruments. A better airway patency was restored although a slight glottic edema persisted. The histopathology confirmed the benign nature of the lesions. Successive controls showed a completely patent airway and absence of SGCs. Conclusion In conclusion, SGCs should be considered in preterm infants with respiratory distress previously intubated, which cannot be explained by the most common causes. Early diagnosis and treatment are fundamental to reducing the morbidity and mortality associated with this disease.

Abstract Viral encephalitis is characterized by a series of immunological reactions that can control virus infection in the brain, but dysregulated responses may cause excessive inflammation and brain damage. Microglia are brain-resident myeloid cells that are specialized in surveilling the local CNS environment and in case of viral brain infection they contribute to the control of the infection and to restriction of viral dissemination. Here, we report that after exposure to neurotropic vesicular stomatitis virus (VSV), murine in vitro microglia cultures showed rapid upregulation of a broad range of pro-inflammatory and antiviral genes, which were stably expressed over the entire 8 h infection period. Additionally, a set of immunomodulatory genes was upregulated between 6 and 8 h post infection. In microglia cultures, the induction of several immune response pathways including cytokine responses was dependent on mitochondrial antiviral-signaling protein (MAVS). Consequently, in Mavs-deficient microglia the control of virus propagation failed as indicated by augmented virus titers and the accumulation of viral transcripts. Thus, in the analyzed in vitro system, MAVS signaling is critically required to achieve full microglia activation and to mediate profound antiviral effects. In Mavs-deficient mice, intranasal VSV instillation caused higher disease severity than in WT mice and virus dissemination was noticed beyond the olfactory bulb. Virus spread to inner regions of the olfactory bulb, i.e., the granular cell layer, correlated with the recruitment of highly inflammatory non-microglia myeloid cells into the olfactory bulb in Mavs −/− mice. Furthermore, increased cytokine levels were detected in the nasal cavity, the olfactory bulb and in other brain regions. Thus, microglial MAVS signaling is critically needed for virus sensing, full microglia activation, and for orchestration of protective immunity in the virus-infected CNS.

Abstract Background The present study investigated the effect of time of day (08h00 vs. 11h00 vs. 14h00 vs. 17h00) and sex (girls vs. boys) on physical (i.e., five jump test (5JT), push-ball test and 5 m shuttle run test (5mSRT)), cognitive (i.e., attention) and mental (i.e., mental flexibility) performances. Methods Thirty schoolchildren, equally divided in girls (n = 15; age: 9.60 ± 0.51 years) and boys (n = 15; age: 9.40 ± 0.51 years) performed the digit cancellation test, the trail making test, the 5JT, the 2 kg push-ball test and the 5mSRT in a counterbalanced and cross over study design at 08h00, 11h00, 14h00 and 17h00 with 48 h of rest in between. Additionally, rating of perceived exertion (RPE) was determined after each repetition of the 5mSRT and the average of the score (i.e., sum of RPE scores divided by 6) was determined. Results Results showed that RPE at the end of the test was significantly higher at 11h00 compared to 08h00 (p = 0.02) and 14h00 (p = 0.001) and average RPE was higher at 11h00 compared to 08h00 (p = 0.001). Likewise, attention was significantly higher at 08h00 compared to 17h00 (p = 0.001) before and after the 5mSRT test only in girls. However, 5JT performance was significantly lower at 17h00, both in girls and boys, compared to at 08h00 (p = 0.02 and p = 0.001 respectively), 11h00 (p = 0.004 and p = 0.001 respectively) and 14h00 (p = 0.001 and p = 0.001 respectively). However, push-ball (p = 0.086) and 5mSRT performances [best distance (p = 0.173), total distance (p = 0.306), mean distance (p = 0.29), fatigue index (p = 0.06)] were time of day independent. Mental flexibility was significantly higher at 08h00, 11h00 and 14h00 compared to 17h00 (p = 0.001). Conclusion Mental flexibility, attention and jump performances were time of day dependent and push-ball test and 5mSRT performances did not change according to the time of day. Also, no clear sex effect was found on the diurnal variation of mental, cognitive and physical performances.

Abstract In multicentric studies, data sharing between institutions might negatively impact patient privacy or data security. An alternative is federated analysis by secure multiparty computation. This pilot study demonstrates an architecture and implementation addressing both technical challenges and legal difficulties in the particularly demanding setting of clinical research on cancer patients within the strict European regulation on patient privacy and data protection: 24 patients from LMU University Hospital in Munich, Germany, and 24 patients from Policlinico Universitario Fondazione Agostino Gemelli, Rome, Italy, were treated for adrenal gland metastasis with typically 40 Gy in 3 or 5 fractions of online-adaptive radiotherapy guided by real-time MR. High local control (21% complete remission, 27% partial remission, 40% stable disease) and low toxicity (73% reporting no toxicity) were observed. Median overall survival was 19 months. Federated analysis was found to improve clinical science through privacy-friendly evaluation of patient data in the European health data space.

Abstract There are millions of river barriers worldwide, ranging from wooden locks to concrete dams, many of which form associated impoundments to store water in small ponds or large reservoirs. Besides their benefits, there is growing recognition of important environmental and social trade-offs related to these artificial structures. However, global datasets describing their characteristics and geographical distribution are often biased towards particular regions or specific applications, such as hydropower dams affecting fish migration, and are thus not globally consistent. Here, we present a new river barrier and reservoir database developed by the Global Dam Watch (GDW) consortium that integrates, harmonizes, and augments existing global datasets to support large-scale analyses. Data curation involved extensive quality control processes to create a single, globally consistent data repository of instream barriers and reservoirs that are co-registered to a digital river network. Version 1.0 of the GDW database contains 41,145 barrier locations and 35,295 associated reservoir polygons representing a cumulative storage capacity of 7,420 km3 and an artificial terrestrial surface water area of 304,600 km2.

Abstract Quasicrystals are of interest because of their unique nonperiodic structures and physical properties. Motivated by naturally occurring icosahedral AlCuFe- and decagonal AlNiFe-phases hosted in a shocked meteorite, different laboratories have undertaken a series of shock recovery experiments to understand their formation mechanism. Shock experiments generate a complex series of processes and conditions, including a near-instantaneous excursion to high pressure and high temperature, large shear stresses, local melting, rapid decompression, fast quenching and post-shock annealing. This highly dynamic scenario offers a very useful but imperfect tool for exploring the stability of novel alloys, such as quasicrystals. So far, all the shock-synthesized quasicrystals differ considerably in composition from any thermodynamically stable or metastable quasicrystals synthesized by metallurgical techniques at low pressure, leaving plenty of questions to be answered about their formation conditions and their nucleation and growth mechanisms occurring during shock experiments. In this Perspective, we summarize the previous studies of shock-synthesized quasicrystals and discuss the advantages and difficulties caused by the experimental complexity. We also propose a few directions for future experiments to better control the shock conditions and understand the properties of quasicrystals.

Abstract Reconstructing premortem DNA methylation levels in ancient DNA has led to breakthrough studies such as the prediction of anatomical features of the Denisovan. These studies rely on computationally inferring methylation levels from damage signals in naturally deaminated cytosines, which requires expensive high-coverage genomes. Here, we test two methods for direct methylation measurement developed for modern DNA based on either bisulfite or enzymatic methylation treatments. Bisulfite treatment shows the least reduction in DNA yields as well as the least biases during methylation conversion, demonstrating that this method can be successfully applied to ancient DNA.

Abstract The occurrence of high stress concentrations in reactor components is a still intractable phenomenon encountered in fusion reactor design. Here, we observe and quantitatively model a non-linear high-dose radiation mediated microstructure evolution effect that facilitates fast stress relaxation in the most challenging low-temperature limit. In situ observations of a tensioned tungsten wire exposed to a high-energy ion beam show that internal stress of up to 2 GPa relaxes within minutes, with the extent and time-scale of relaxation accurately predicted by a parameter-free multiscale model informed by atomistic simulations. As opposed to conventional notions of radiation creep, the effect arises from the self-organisation of nanoscale crystal defects, athermally coalescing into extended polarized dislocation networks that compensate and alleviate the external stress.

Abstract Background Latency remains a major obstacle to finding a cure for HIV despite the availability of antiretroviral therapy. Due to virus dormancy, limited biomarkers are available to identify latent HIV-infected cells. Profiling of individual HIV-infected cells is needed to explore potential latency biomarkers and to study the mechanisms of persistence that maintain the HIV reservoir. Methods Single cell spatial transcriptomic characterization using the CosMx Spatial Molecular Imager platform was conducted to analyze HIV-infected cells in formalin-fixed paraffin-embedded sections of splenic tissue surgically obtained from an HIV-infected humanized mouse model. Regulation of over a thousand human genes was quantified in both viremic and aviremic specimens. In addition, in situ hybridization and immunohistochemistry were performed in parallel to identify HIV viral RNA- and p24-containing cells, respectively. Finally, initial findings from CosMx gene profiling were confirmed by isolating RNA from CD4 + T cells obtained from a person living with HIV on antiretroviral therapy following either PMA/Ionomycin or DMSO treatment. RNA was quantified using qPCR for a panel of targeted human host genes. Results Supervised cell typing revealed that most of the HIV-infected cells in the mouse spleen sections were differentiated CD4 + T cells. A significantly higher number of infected cells, 2781 (1.61%) in comparison to 112 (0.06%), and total HIV transcripts per infected cell were observed in viremic samples compared to aviremic samples, respectively, which was consistent with the data obtained from ISH and IHC. Notably, the expression of 55 genes was different in infected cells within tissue from aviremic animals compared to viremic. In particular, both spleen tyrosine kinase (SYK) and CXCL17, were expressed approximately 100-fold higher. This data was further evaluated against bulk RNA isolated from HIV-infected human primary CD4 + T cells. A nearly 6-fold higher expression of SYK mRNA was observed in DMSO-treated CD4 + T cells compared to those stimulated with PMA/Ionomycin. Conclusion This study found that the CosMx SMI platform is valuable for assessing HIV infection and providing insights into host biomarkers associated with HIV reservoirs. Higher relative expression of the SYK gene in aviremic-infected cells from the humanized mouse HIV model was consistent with levels found in CD4 + T cells of aviremic donors.

Abstract Background Liquid biopsy based on cell-free DNA (cfDNA) analysis holds significant promise as a minimally invasive approach for the diagnosis, genotyping, and monitoring of solid malignancies. Human tumors release cfDNA in the bloodstream through a combination of events, including cell death, active and passive release. However, the precise mechanisms leading to cfDNA shedding remain to be characterized. Addressing this question in patients is confounded by several factors, such as tumor burden extent, anatomical and vasculature barriers, and release of nucleic acids from normal cells. In this work, we exploited cancer models to dissect basic mechanisms of DNA release. Methods We measured cell loss ratio, doubling time, and cfDNA release in the supernatant of a colorectal cancer (CRC) cell line collection (N = 76) representative of the molecular subtypes previously identified in cancer patients. Association analyses between quantitative parameters of cfDNA release, cell proliferation, and molecular features were evaluated. Functional experiments were performed to test the impact of modulating DNA methylation on cfDNA release. Results Higher levels of supernatant cfDNA were significantly associated with slower cell cycling and increased cell death. In addition, a higher cfDNA shedding was found in non-CpG Island Methylator Phenotype (CIMP) models. These results indicate a positive correlation between lower methylation and increased cfDNA levels. To explore this further, we exploited methylation microarrays to identify a subset of probes significantly associated with cfDNA shedding and derive a methylation signature capable of discriminating high from low cfDNA releasers. We applied this signature to an independent set of 176 CRC cell lines and patient derived organoids to select 14 models predicted to be low or high releasers. The methylation profile successfully predicted the amount of cfDNA released in the supernatant. At the functional level, genetic ablation of DNA methyl-transferases increased chromatin accessibility and DNA fragmentation, leading to increased cfDNA release in isogenic CRC cell lines. Furthermore, in vitro treatment of five low releaser CRC cells with a demethylating agent was able to induce a significant increase in cfDNA shedding. Conclusions Methylation status of cancer cell lines contributes to the variability of cfDNA shedding in vitro. Changes in methylation pattern are associated with cfDNA release levels and might be exploited to increase sensitivity of liquid biopsy assays.

Abstract Background The phylum Nematoda is incredibly diverse and includes many parasites of humans, livestock, and plants. Peptide-activated G protein-coupled receptors (GPCRs) are central to the regulation of physiology and numerous behaviors, and they represent appealing pharmacological targets for parasite control. Efforts are ongoing to characterize the functions and define the ligands of nematode GPCRs, with already most peptide GPCRs known or predicted in Caenorhabditis elegans. However, comparative analyses of peptide GPCR conservation between C. elegans and other nematode species are limited, and many nematode GPCRs remain orphan. A phylum-wide perspective on peptide GPCR profiles will benefit functional and applied studies of nematode peptide GPCRs. Results We constructed a pan-phylum resource of C. elegans peptide GPCR orthologs in 125 nematode species using a semi-automated pipeline for analysis of predicted proteome datasets. The peptide GPCR profile varies between nematode species of different phylogenetic clades and multiple C. elegans peptide GPCRs have orthologs across the phylum Nematoda. We identified peptide ligands for two highly conserved orphan receptors, NPR-9 and NPR-16, that belong to the bilaterian galanin/allatostatin A (Gal/AstA) and somatostatin/allatostatin C (SST/AstC) receptor families. The AstA-like NLP-1 peptides activate NPR-9 in cultured cells and are cognate ligands of this receptor in vivo. In addition, we discovered an AstC-type peptide, NLP-99, that activates the AstC-type receptor NPR-16. In our pan-phylum resource, the phylum-wide representation of NPR-9 and NPR-16 resembles that of their cognate ligands more than those of allatostatin-like peptides that do not activate these receptors. Conclusions The repertoire of C. elegans peptide GPCR orthologs varies across phylogenetic clades and several peptide GPCRs show broad conservation in the phylum Nematoda. Our work functionally characterizes the conserved receptors NPR-9 and NPR-16 as the respective GPCRs for the AstA-like NLP-1 peptides and the AstC-related peptide NLP-99. NLP-1 and NLP-99 are widely conserved in nematodes and their representation matches that of their receptor in most species. These findings demonstrate the conservation of a functional Gal/AstA and SST/AstC signaling system in nematodes. Our dataset of C. elegans peptide GPCR orthologs also lays a foundation for further functional studies of peptide GPCRs in the widely diverse nematode phylum.

Abstract Systemic inflammation significantly increases the risk of short- and long-term mortality in geriatric hospitalized patients. To predict mortality in older patients with various age-related diseases and infections, including COVID-19, inflammatory biomarkers such as the C-reactive protein (CRP) to albumin ratio (CAR), and related scores and indexes, i.e. Glasgow Prognostic Score (GPS), modified GPS (mGPS), and high sensitivity (hs)-mGPS, have been increasingly utilized. Despite their easy affordability and widespread availability, these biomarkers are predominantly assessed for clinical purposes rather than predictive applications, leading to their underutilization in hospitalized older patients. In this study, we investigated the association of CAR, GPS, mGPS, and hs-mGPS with short-term mortality in 3,206 geriatric hospitalized patients admitted for acute conditions, irrespective of admission diagnosis. We observed that unit increases of CAR, and the highest classes of GPS, mGPS, and hs-mGPS were significantly associated with a two- to threefold increased risk of death, even adjusting the risk for different confounding variables. Interestingly, a hs-mGPS of 2 showed the highest effect size. Furthermore, gender analysis indicated a stronger association between all CRP-albumin based parameters and mortality in men, underscoring the gender-specific relevance of inflammation-based circulating parameters in mortality prediction. In conclusion, scores based on serum CRP and albumin levels offer additional guidance for the stratification of in-hospital mortality risk in older patients by providing additional information on the degree of systemic inflammation.

Within a practical course of cytotaxonomy organized in Pisa (Italy) on February 2024 by the Group for Floristics, Systematics and Evolution of the Italian Botanical Society, we tested whether relevant differences in karyotype asymmetry and structure occur in four tetraploid European taxa from Paeonia sect. Paeonia (P. mascula subsp. russoi, P. officinalis subsp. huthii, P. officinalis subsp. italica, and P. peregrina). Our results point towards a homogeneous karyotype asymmetry and structure among studied tetraploid species, with no statistically significant difference among taxa and high overlap in variation highlighted by PCA.

Purpose: Recurrence of hallux valgus (HV) following corrective surgery is a frequent concern. A recent systematic review estimated recurrence of HV in only 4.9%, which may be an underestimation, as most included studies had short- to mid-term follow-up. The purpose of this systematic review and meta-analysis was to synthesize and critically appraise the literature on the long-term outcomes of shaft osteotomies of the first metatarsal (M1) to treat HV without inflammatory disease or degenerative arthritis, and to assess the long-term HV recurrence rates of studies with a minimum follow-up of 5 years. Methods: This systematic review conforms to the PRISMA guidelines. The authors conducted a search using PubMed, Embase®, and Cochrane Central Register of Controlled Trials databases. Studies that report outcomes of shaft osteotomies of the M1 for non-inflammatory and non-degenerative HV having a minimum follow-up of 5 years were included. We found five eligible studies comprising six datasets, all assessed Scarf osteotomies with a mean follow-up that ranged from 8 to 14 years. Results: The HV recurrence rate was 40%, considering the threshold of >15° hallux valgus angle (HVA), 30% having >20°, and 2% having >25°. Conclusion: At a minimum follow-up of 8 years following shaft osteotomies of M1, the HVA was 15.9°, the intermetatarsal angle (IMA) was 7.7°, and the DMAA was 8.3°. Furthermore, the recurrence rates considering the various thresholds of HVA were: 40% having >15°, 20% having >20°, and 2% having >25°. Level of Evidence: Meta-analysis, Level IV

Abstract Objective The aim of this study is to describe the pre‐ and post‐operative developmental and intellectual functions in a cohort of patients who underwent surgery for drug‐resistant epilepsy (DRE) before the age of 5 years. Method We retrospectively reviewed the medical records and neurodevelopmental assessments of a cohort of 80 surgically treated pediatric patients with DRE. We included patients if they had at least one pre‐ and one post‐surgical neuropsychological assessments; 27 met the inclusion criteria. We evaluated Developmental Quotient (DQ) and Intelligence Quotient (IQ) before and after surgery. We identified two groups based on psychological evaluation outcome: Group 1, with stable or improved developmental and intellectual functions, and Group 2, experiencing developmental and intellectual loss. Results The mean age at seizure onset was 1.2 ± 1.0 years, and the mean age at surgery was 2.9 ± 1.2 years. At the last follow‐up (mean 4 years, SD ± 2), 19/27 (70%) patients were seizure‐ and drug‐free; 18/27 patients (67%) fit in Group 1, and 9/27 (33%) fit in Group 2. The mean age at surgery was 2.6 years (SD ± 1.1; range 1.2–5.1) in Group 1 and 3.4 years in Group 2 (SD ± 1.1; range 1.6–5.0). Group 1 had a lower pre‐operative DQ/IQ total score than Group 2 (median DQ/IQ respectively 82 vs 108, p = 0.05). Between pre‐ and post‐assessments, we found that in Group 1, Performance scores improved (82.7 vs 102, p = 0.001), while in Group 2, the Total and Verbal scores worsened (respectively 108 vs 75, p = 0.008, and 100 vs 76, p = 0.021). Significance Our study's results emphasize the positive impact of surgery before the age of 5 years on developmental and intellectual outcomes. Despite limitations such as a small sample size, lack of a control group, and diverse etiologies, our findings support the crucial role of early intervention in preserving or enhancing developmental and intellectual functions in young patients with DRE. Plain Language Summary This retrospective study, conducted at the Bambino Gesù Children Hospital in Italy, reports neuropsychological and developmental and/or cognitive data for children undergoing early epilepsy surgery (before the age of 5). It found that children with lower developmental or cognitive profiles gained the highest scores on post‐operative neuropsychological evaluations. This study provides information on the potential benefits of early surgery in shortening the duration of epilepsy, preventing or arresting deterioration, and enhancing plasticity and recovery.

Abstract Climate change is currently one of humanity’s greatest threats. To help scholars understand the psychology of climate change, we conducted an online quasi-experimental survey on 59,508 participants from 63 countries (collected between July 2022 and July 2023). In a between-subjects design, we tested 11 interventions designed to promote climate change mitigation across four outcomes: climate change belief, support for climate policies, willingness to share information on social media, and performance on an effortful pro-environmental behavioural task. Participants also reported their demographic information (e.g., age, gender) and several other independent variables (e.g., political orientation, perceptions about the scientific consensus). In the no-intervention control group, we also measured important additional variables, such as environmentalist identity and trust in climate science. We report the collaboration procedure, study design, raw and cleaned data, all survey materials, relevant analysis scripts, and data visualisations. This dataset can be used to further the understanding of psychological, demographic, and national-level factors related to individual-level climate action and how these differ across countries.

Abstract The calmodulin-binding transcription activator (CAMTA) family contributes to stress responses in many plant species. The Oryza sativa ssp. japonica genome harbors seven CAMTA genes; however, intraspecific variation and functional roles of this gene family have not been determined. Here, we comprehensively evaluated the structure and characteristics of the CAMTA genes in japonica rice using bioinformatics approaches and RT-qPCR. Within the CAMTA gene and promoter sequences, 527 single nucleotide polymorphisms were retrieved from 3,024 rice accessions. The CAMTA genes could be subdivided into 5–14 haplotypes. Association analyses between haplotypes and phenotypic traits, such as grain weight and salt stress parameters, identified phenotypic differences between rice subpopulations harboring different CAMTA haplotypes. Co-expression analyses and the identification of CAMTA-specific binding motifs revealed candidate genes regulated by CAMTA. A Gene Ontology functional enrichment analysis of 690 co-expressed genes revealed that CAMTA genes have key roles in defense responses. An interaction analysis identified 30 putative CAMTA interactors. Three genes were identified in co-expression and interaction network analyses, suggesting that they are potentially regulated by CAMTAs. Based on all information obtained together with the phenotypes of the CRISPR-Cas9 knockout mutant lines of three OskCAMTA genes generated, CAMTA1 likely plays important roles in the response to salt stress in rice. Overall, our findings suggest that the CAMTA gene family is involved in development and the salt stress response and reveal candidate target genes, providing a basis for further functional characterization.

Study on static in-situ curing characteristics of CFRP based on near infrared laser The quick curing method of carbon fibre reinforced plastics (CFRP) is one of the hotspots in current research. A static in-situ curing method for CFRP prepreg based on near-infrared laser was put forward in this study. The in-situ curing structural characteristics and the mechanism of CFRP were investigated through real-time surface temperature measurement, COMSOL temperature field simulation, 3D measurement of curing morphology and resin curing degree test. The thermal conductivity of the CFRP along the fiber direction is considerably higher than that along the perpendicular fiber direction. As a result, the temperature profile in the plane takes on an elliptical shape. During the transfer, the temperature field gradually decreases, resulting in an ellipsoidal 3D high-temperature distribution. The different shrinkage phenomena in the different curing regions between the layers lead to an irregular ellipsoidal solidification morphology of the unidirectional CFRP. The temperature in the center of the heat affected zone increases as a power exponential function with time. The area and depth of the heat-affected zone increases with the laser power, and the curing area is positively correlated with the degree of curing. As a result, curing temperature governing equations based on laser power and layer thickness have been proposed, while relationship equations based on laser power, curing depth and curing morphology have been developed. In addition, prediction equations based on curing morphology have been developed for curing degree, in order to achieve precise curing of CFRP.

Abstract To understand how oncogenes affect genome organization, it is essential to visualize fundamental processes such as DNA replication and transcription at high resolution in intact cells. At the same time, it is important to determine the progression of the cell along the cell cycle, as cell cycle regulation is crucial for the control of cell proliferation and oncogenesis. Here, we present a super-resolution imaging-based method to analyze single cell nuclei sorted according to specific phases of the cell cycle. The sorting is based on the evaluation of the number and the intensity of pixels in the replication foci image and the colocalization analysis is based on image cross-correlation spectroscopy (ICCS). We evaluate the colocalization between replication and transcription, at different cell cycle phases, in a model of PML-RARα oncogene activation. We find that colocalization between replication and transcription is higher in cells in early S phase compared to cells in middle and late S phase. When we turn on the PML-RARα oncogene, this colocalization pattern is preserved but we detect an increase of colocalization between replication and transcription in the early S phase which points to an effect of the PML-RARα oncogene on the coordination between replication and transcription.

Abstract The sound produced by vehicles driving on roadways constitutes one of the dominant noise sources in urban areas. The impact of traffic noise on human activities and the related investigation on modeling, assessment, and abatement strategies fueled the research on the simulation of the sound produced by individual passing vehicles. Simulators enable in fact to promote a perceptual assessment of the nature of traffic noise and of the impact of single road agents on the overall soundscape. In this work, we present TrafficSoundSim, an open-source framework for the acoustic simulation of vehicles transiting on a road. We first discuss the generation of the sound signal produced by a vehicle, represented as a combination of road/tire interaction noise and engine noise. We then introduce a propagation model based on the use of variable length delay lines, allowing to simulate acoustic propagation and Doppler effect. The proposed simulator incorporates the effect of air absorption and ground reflection, modeled via complex-valued reflection coefficients dependent on the road surface impedance, as well as a model of the directivity of sound sources representing the passing vehicles. The source signal generation and the propagation stages are decoupled, and all effects are implemented using finite impulse response filters. Moreover, no recorded data is required to run the simulation, making the framework flexible and independent on data availability. Finally, to validate the framework capability to accurately simulate passing vehicles, a comparison between synthetic and recorded pass-by events is presented. The validation shows that sounds generated with the proposed method achieve a good match with recorded events in terms of power spectral density and psychoacoustics metrics as well as a perceptually plausible result.

Abstract Background Cancer onset and progression are driven by genetic and epigenetic alterations leading to oncogene activation and the silencing of tumor suppressor genes. Among epigenetic mechanisms, DNA methylation (methDNA) is gaining growing interest in cancer. Promoter hypomethylation is associated with oncogene activation while intragenic methDNA can be involved in transcriptional elongation, alternative spicing, and the activation of cryptic start sites. Several genes involved in the modulation of the tumor microenvironment are regulated by methDNA, including the Solute Carrier Family 22 Member 17 (SLC22A17), which is involved in iron trafficking and extracellular matrix remodeling cooperating with the Gelatinase-Associated Lipocalin (NGAL) ligand. However, the exact role of intragenic methDNA in cancer has not been fully investigated. Therefore, the aim of the present study is to explore the role of methDNA in the regulation of SLC22A17 in cutaneous melanoma (CM), used as a tumor model. Methods Correlation and differential analyses between SLC22A17 expression and methDNA were performed using the data contained in The Cancer Genome Atlas and Gene Expression Omnibus databases. Functional studies on melanoma cell lines treated with 5-Azacytidine (5-Aza) were conducted to assess the correlation between methDNA and SLC22A17 expression. A validation study on the diagnostic potential of the in silico-identified SLC22A17 methDNA hotspot was finally performed by analyzing tissue samples obtained from CM patients and healthy controls. Results The computational analyses revealed that SLC22A17 was significantly downregulated in CM, and its expression was related to promoter hypomethylation and intragenic hypermethylation. Moreover, SLC22A17 overexpression and hypermethylation of two intragenic methDNA hotspots were associated with a better clinical outcome in CM patients. The correlation between SLC22A17 methDNA and expression was confirmed in 5-Aza-treated cells. In agreement with in silico analyses, the SLC22A17 promoter methylation hotspot showed higher methDNA levels in CM samples compared to nevi. In addition, the methDNA levels of this hotspot were positively correlated with advanced CM. Conclusions The SLC22A17 methDNA hotspot could represent a promising biomarker for CM, highlighting the regulatory role of methDNA on SLC22A17 expression. These results pave the way for the identification of novel epigenetic biomarkers and therapeutic targets for the management of CM patients.

Abstract Introduction Infection is a significant complication of cardiac implantable electronic device (CIED) therapy. The European TauroPace™ Registry investigates the safety and efficacy of TauroPace™ (TP), an antimicrobial solution containing taurolidine, designed to prevent CIED infections. Methods This multicenter study included patients undergoing CIED procedures at participating centers where TP was used as a disinfectant for external hardware surfaces and an antiseptic for irrigating surgical sites. All patients eligible for CIED placement with adjunctive TP as the standard of care were included. Other aspects of CIED procedures adhered to current guidelines. Data on CIED-related infective endocarditis, CIED pocket infection, device and procedure-related complications, adverse events, and all-cause mortality were prospectively collected for 12 months. In cases of revision, the previous procedure was censored, and a new procedure was created. Binomial and Kaplan–Meier statistics were employed to analyze event rates. Results From January 2020 to November 2022, TP was used in 822 out of 1170 CIED procedures. Among patients who completed the 3-month follow-up, no CIED pocket infections were observed, and one case of CIED-related infective endocarditis was reported. In the 12-month follow-up cohort, two additional local pocket CIED infections were observed, resulting in a total of three major CIED infections within 1 year after the CIED placement procedure. The 3-month and 12-month major CIED infection rates were 0.125% and 0.51%, respectively. During the observation a complication rate of 4.4% was reported. No adverse events related to TP were observed. Conclusions TP appears to be effective and safe in preventing CIED infections. ClinicalTrials.gov Identifier: NCT04735666.

Abstract The presence of plastics and microplastics in water environments has raised concerns for potential negative impacts. The broader ecological implications for ecosystem functioning are, however, still unknown. The interaction between phytoplankton community and plastics has, for example, been overlooked. Here, we investigated the role of plastic as a substrate for biofilm growth and how this affects the dispersal of terrestrial microalgae, potentially altering the assembly of pelagic communities. When exposing an artificially assembled microalgae community to pristine and biofouled plastic under laboratory-controlled conditions, we found that only biofouled plastic affected the final community structure and the content of available nutrients in water. This is due to the exchanged algal species between the biofilm and the pelagic community. The results from this batchwise pilot scale study indicate that plastic can act as a substrate for benthic and pelagic species, potentially affecting ecosystem functions, which have been overlooked so far.

Abstract Over the past five decades, a large number of wild animals have been individually identified by various observation systems and/or temporary tracking methods, providing unparalleled insights into their lives over both time and space. However, so far there is no comprehensive record of uniquely individually identified animals nor where their data and metadata are stored, for example photos, physiological and genetic samples, disease screens, information on social relationships. Databases currently do not offer unique identifiers for living, individual wild animals, similar to the permanent ID labelling for deceased museum specimens. To address this problem, we introduce two new concepts: (1) a globally unique animal ID (UAID) available to define uniquely and individually identified animals archived in any database, including metadata archived at the time of publication; and (2) the digital ‘home’ for UAIDs, the Movebank Life History Museum (MoMu), storing and linking metadata, media, communications and other files associated with animals individually identified in the wild. MoMu will ensure that metadata are available for future generations, allowing permanent linkages to information in other databases. MoMu allows researchers to collect and store photos, behavioural records, genome data and/or resightings of UAIDed animals, encompassing information not easily included in structured datasets supported by existing databases. Metadata is uploaded through the Animal Tracker app, the MoMu website, by email from registered users or through an Application Programming Interface (API) from any database. Initially, records can be stored in a temporary folder similar to a field drawer, as naturalists routinely do. Later, researchers and specialists can curate these materials for individual animals, manage the secure sharing of sensitive information and, where appropriate, publish individual life histories with DOIs. The storage of such synthesized lifetime stories of wild animals under a UAID (unique identifier or ‘animal passport’) will support basic science, conservation efforts and public participation.

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and Methods:Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 coun-tries were analyzed descriptively, with a Delphi process used for expert recommendations. Results:Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoosper-mia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differ-entiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions:Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

Backgroundobjective: Post-oncological nasal reconstruction presents both aesthetic and functional challenges. While established methods exist for quantitatively evaluating functional results following surgery, equivalent systems for assessing aesthetic outcomes are lacking. Three-dimensional (3D) photogrammetry, already used in maxillofacial and orthodontic surgery for aesthetic evaluation, overcomes some limitations of traditional methods like direct anthropometry. However, its applicability in oncological facial reconstruction has not yet been explored. In our study, we applied the 3dMDtrio™ system for the quantitative analysis of line and surface modifications following nasal reconstruction. Methods: We conducted a prospective observational study enrolling patients with skin neoplasms located on the nose undergoing surgical excision and reconstruction. Using the 3dMDtrio™ system, we measured the dimensions and projections of nasal surfaces and the positions of specific landmarks before and after surgery. The surface measurements were then correlated with aesthetic evaluations performed by three plastic surgeons, not involved in the procedure, using a 5-point Likert scale. Results: We included 33 patients with a mean age of 71 years, ranging from 40 to 94. We obtained complete documentation of all postoperative measurements for 21 patients. We observed significant changes in the positions of the landmarks post-surgery, limited to the right ala and nasion. The average nasal surface area was 4674.41 mm2 ± 477.24 mm2 before surgery and 4667.95 mm2 ± 474.12 mm2 after surgery, with no significant discrepancies. The evaluation using the Likert scale revealed an average score of 3.04 ± 0.48, with a significant negative correlation to the measured surface changes. Conclusion: Our findings suggest that 3D photogrammetry can be considered a valid method for objectively assessing volumetric changes associated with post-oncological nasal reconstructive surgery.

Abstract Aims The initial bundle of cares strongly affects haemodynamics and outcomes in acute decompensated heart failure cardiogenic shock (ADHF‐CS). We sought to characterize whether 24 h haemodynamic profiling provides superior prognostic information as compared with admission assessment and which haemodynamic parameters best predict in‐hospital death. Methods and results All patients with ADHF‐CS and with available admission and 24 h invasive haemodynamic assessment from two academic institutions were considered for this study. The primary endpoint was in‐hospital death. Regression analyses were run to identify relevant predictors of study outcome. We included 127 ADHF‐CS patients [65 (inter‐quartile range 52–72) years, 25.2% female]. Overall, in‐hospital mortality occurred in 26.8%. Non‐survivors were older, with greater CS severity. Among admission variables, age [odds ratio (OR) = 1.06; 95% confidence interval (CI): 1.02–1.11; Padj = 0.005] and CPIRAP (OR = 0.62 for 0.1 increment; 95% CI: 0.39–0.95; Padj = 0.034) were found significantly associated with in‐hospital death. Among 24 h haemodynamic univariate predictors of in‐hospital death, pulmonary elastance (PaE) was the strongest (area under the curve of 0.77; 95% CI: 0.68–0.86). PaE (OR = 5.98; 95% CI: 2.29–17.48; Padj

Abstract Aims The identification of subjects at higher risk for incident heart failure (HF) with preserved ejection fraction (EF) suitable for more intensive preventive programmes remains challenging. We applied phenomapping to the DAVID‐Berg population, comprising subjects with preclinical HF, aiming to refine HF risk stratification. Methods The DAVID‐Berg study prospectively enrolled 596 asymptomatic outpatients with EF > 40% with hypertension, diabetes mellitus or known cardiovascular disease. In this cohort, we performed an unsupervised cluster analysis on 591 patients, including clinical, laboratory, electrocardiographic and echocardiographic parameters. We tested the association between each cluster and a composite outcome of HF/death. Results The median age was 70 years, 55.5% were males and the median EF was 61.0%. Phenomapping provided three different clusters. Subjects in Cluster 3 were the oldest and had the highest prevalence of atrial fibrillation, the lowest estimated glomerular filtration rate (eGFR), the highest N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and the largest left atrium. During a median follow‐up of 5.7 years, 13.4% of subjects experienced HF/death events (N = 79). Compared with Clusters 1 and 2, Cluster 3 had the worst prognosis (log‐rank test: Cluster 3 vs. 1 P 40% who deserve more efforts to prevent clinical HF.

The Advanced Fuels Campaign's Fission Accelerated Steady State Testing (FAST) approach at Idaho National Laboratory creates a benchmark for evaluating accelerated irradiation via control rodlets and advanced metal fuel alloys for sodium-cooled fast reactors (SFRs). FAST experiments have been developed to generate prototypic temperature conditions during steady state irradiations of scaled geometric fuel pins. This approach helps to attain higher burn ups at a much faster rate than previous irradiation tests. For this study, the results from profilometry, fission gas release, and metallography of a FAST experiment are presented. Profilometry determined 0 % effective strain in the rodlets. The fission gas release fraction was measured from puncture/collection analysis. Constituent redistribution was observed in two specimens despite the peak fuel temperatures being below the normal ranges in which redistribution is expected. Metallography of the two higher temperature specimens showed typical swelling with the solid pin closing the fuel-cladding gap and the annular specimen having a fully closed annulus. Additionally, metallography indicated no swelling, no redistribution, and a homogenous microstructure for specimens with lower irradiation temperature. Post irradiation examination of FAST rodlets generally showed the expected representative behavior of metallic fuels within SFRs.

Background and objective: More than 10% of patients with negative clinical metastatic status (cN0M0) on conventional imaging for prostate cancer (PCa) harbor lymph node involvement (pN+) at final pathology following radical prostatectomy (RP) and lymphadenectomy. Our aim was to assess outcomes of initial observation for cN0M0 pN+ PCa and identify prognostic factors that may help in clinical decision-making. Methods: We performed a retrospective multicenter study of patients with cN0M0 PCa on conventional imaging (computed tomography and/or magnetic resonance imaging, and a bone scan) who were found to have pN+ disease at RP between 2000 and 2021. Biochemical recurrence (BCR) and systemic progression/recurrence were the primary outcomes. Kaplan-Meier curves and Cox proportional hazards model were used for survival and multivariate analysis. Key findings and limitations: A total of 469 men were included in this retrospective multicenter trial. Median prostate-specific antigen (PSA) was 10.1 ng/ml (interquartile range [IQR] 6.6–18.0). Among these patients, 56% had grade group ≥4, 53.7% had stage ≥pT3b, 42.6% had positive margins, and 19.6% had PSA persistence. The median number of positive nodes and of nodes removed were 1 (IQR 1–3) and 20 (14–28), respectively. At median follow-up of 41 mo, 48.5% experienced BCR. The 5-yr BCR-free survival rate was 31.7% (95% confidence interval [CI] 26.33–37.1%). Salvage treatments were needed in 211 patients and included radiotherapy (RT; n = 53), RT + androgen deprivation therapy (ADT; n = 88), ADT alone (n = 68), and salvage lymphadenectomy (n = 2). The 5-yr estimated survival rates were 66.3% (95% CI 60.4–72.1) for metastasis-free survival, 97.7% (95% CI 95.5–99.8%) for cancer-specific survival, and 95.3% (95% CI 92.4–98.1%) for overall survival. On multivariable analysis, PSA persistence was an independent predictor of BCR (odds ratio [OR] 51.8, 95% CI 12.2–219.2), exit from observation (OR 8.5, 95% CI 4.4–16.5), and systemic progression (OR 3.0, 95% CI 1.771–4.971). Conclusions: Initial observation in the management of pN+ cN0M0 PCa is feasible and has excellent survival rates in the intermediate term. Patients with worse disease features, especially PSA persistence, have a higher likelihood of recurrence and progression and may be candidates for more aggressive upfront management. Patient summary: We investigated the value of initial observation for men with prostate cancer with negative scan findings for metastasis who were then found to have positive lymph nodes after surgery to remove the prostate. Our results show that initial observation is a good option for patients with less aggressive prostate cancer features.

Abstract Introduction Despite an improved understanding of its pathogenesis, dry eye disease (DED) remains relatively underestimated and its treatment challenging. A better alignment between the clinical evaluation and the patient self-assessment also requires capturing the whole patient experience of DED. This project aimed to unveil this experience through narrative medicine (NM). Methods The project involved 38 expert centres in Italy and one in San Marino, targeting adult patients with DED, their informal caregivers and their treating ophthalmologists. Written narratives and sociodemographic and quality of life (QoL)-related data were anonymously collected through the project’s webpage. Narratives were analysed through MAXQDA (VERBI Software, Berlin, Germany), NM classifications and content analysis. Results A total of 171 patients with DED, 37 informal caregivers and 81 ophthalmologists participated in the research. DED was defined as a disabling condition by 19% of patients and 35% of caregivers; 70% of patients reported that a therapeutic alliance is an integral part of DED treatment and 32% hope for more effective therapies. Forty-four per cent of patients assessed their own QoL as good; however, DED emerged as importantly impacting work performance and social events. DED physical, emotional and economic burden and the cruciality of a trusting care relationship represent the main themes that emerged across all narratives, while empathy and effective treatment are among the factors favouring coping with DED. Conclusion This project marked a pioneering initiative investigating the lived experience of patients with DED through NM, simultaneously involving all viewpoints involved in the care pathway. NM enabled the unveiling of factors favouring the ability to cope with DED and its associated QoL implications and provided valuable insights to improve the therapeutic alliance.

Background: Listening difficulties may frequently occur in school settings, but so far there were no tools to identify them for both hearing and hearing-impaired Italian students. This study performed cross-cultural adaptation and validation of the Listening Inventory for Education-Revised for Italian students (LIFE-R-ITA). Methods: The study procedure followed the stages suggested by the Guidelines for the Process of Cross-cultural Adaptation of Self-Report Measures. For the content validation, six cochlear implanted students (8–18 years old) pre-tested the initial version. Whenever any situation did not occur in Italy, the item was adapted to more typical listening situations in Italy. The final version of LIFE-R-ITA was administered to a sample of 223 hearing students from different school settings and educational degrees in order to collect normative data. Results: For the LIFE-R-ITA, hearing students showed an average score of 72.26% (SD = 11.93), reflecting some listening difficulties. The subscales (LIFE total, LIFE class, and LIFE social) indicated good internal consistency. All items were shown to be relevant. Most challenging situations happened when listening in large rooms, especially when other students made noise. LIFE social scores were significantly worse than those of LIFE class (p < 0.001). Conclusions: The present study provides cross-cultural adaptation and validation for the LIFE-R-ITA along with the normative data useful to interpret the results of students with hearing loss. The LIFE-R-ITA may support teachers and clinicians in assessing students’ self-perception of listening at school. Such understanding may help students overcome their listening difficulties, by planning and selecting the most effective strategies among classroom interventions.

Foot structure can be influenced by various factors, such as footwear, body weight and physical activity. A change in foot structure can alter shock absorption and force transition. The main objective of this study is to investigate the effect of the long-term use of military boots on foot shape parameters. Thirty military and thirty non-military subjects participated in this case-control study. All participants had been regularly wearing military boots for the past 12 years. After introducing the experiment, static and dynamic footprints were recorded via paper and ink while standing and walking. The footprints were analysed using ImageJ software to extract foot width indices, area indices, truncated arch index, footprint index and arch angle index. The findings indicated no significant difference in comparison static and dynamic variables in the military and non-military groups (p ≥ 0.05). However, there was a significant difference between the two groups in both static (midfoot area, arch index (AI), truncated arch index, footprint index and arch angle index) and dynamic (midfoot width, Staheli Index (SAI), truncated arch index and arch angle index) conditions, when static and dynamic variable were compared (p < 0.05). Findings revealed the military personnel have low arch, making them susceptible to musculoskeletal disorders. To mitigate this risk, it is recommended that military boots be reassessed or that insoles be used. Furthermore, it is suggested that military boots be limited to specific activities and fewer hours of usage to avoid potential health issues.

Historically, several classification systems have been used for brachytherapy, and they were based on the type of clinical purpose, type of implant and timing of the implant, dose-rate, and type of loading for treatment delivery. However, over the last decades, there have been some major technological advancements, including the introduction of image-guidance and possibility to modulate the dose delivered, which have led several authors (in order to highlight the differences between old technique and new approach) to label it in a different way by replacing “brachytherapy” with “interventional radiotherapy”. Modern interventional procedures involve several key aspects, which contribute to the complexity of implant phase, such as implant type, imaging used during the procedure, and role of multi-disciplinary team in operating room. By assigning scores to these procedural elements, it is possible to classify the procedure’s complexity using a COMIRI classification (COMplexity Index of interventional Radiotherapy Implants). The aim of the COMIRI classification system is to appropriately highlight the need for suitable resources based on the complexity level of different procedures in terms of personnel expertise, equipment availability, and multi-disciplinary teamwork.

Background and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P

Abstract Background The integration of nuclear mitochondrial DNA (mtDNA) into the mammalian genomes is an ongoing, yet rare evolutionary process that produces nuclear sequences of mitochondrial origin (NUMT). In this study, we identified and analysed NUMT inserted into the pig (Sus scrofa) genome and in the genomes of a few other Suinae species. First, we constructed a comparative distribution map of NUMT in the Sscrofa11.1 reference genome and in 22 other assembled S. scrofa genomes (from Asian and European pig breeds and populations), as well as the assembled genomes of the Visayan warty pig (Sus cebifrons) and warthog (Phacochoerus africanus). We then analysed a total of 485 whole genome sequencing datasets, from different breeds, populations, or Sus species, to discover polymorphic NUMT (inserted/deleted in the pig genome). The insertion age was inferred based on the presence or absence of orthologous NUMT in the genomes of different species, taking into account their evolutionary divergence. Additionally, the age of the NUMT was calculated based on sequence degradation compared to the authentic mtDNA sequence. We also validated a selected set of representative NUMT via PCR amplification. Results We have constructed an atlas of 418 NUMT regions, 70 of which were not present in any assembled genomes. We identified ancient NUMT regions (older than 55 million years ago, Mya) and NUMT that appeared at different time points along the Suinae evolutionary lineage. We identified very recent polymorphic NUMT (private to S. scrofa, with

Abstract We show how to encode the radiative degrees of freedom in 4-dimensional asymptotically AdS spacetimes, using the boundary Cotton and stress tensors. Background radiation leads to a reduction of the asymptotic symmetry group, in contrast to asymptotically flat spacetimes, where a non-vanishing news tensor does not restrict the asymptotic symmetries. Null gauges, such as Λ-BMS, provide a framework for AdS spacetimes that include radiation in the flat limit. We use this to check that the flat limit of the radiative data matches the expected definition in intrinsically asymptotically flat spacetimes. We further dimensionally reduce our construction to the celestial sphere, and show how the 2-dimensional celestial currents can be extracted from the 3-dimensional boundary data.

Abstract Background Patellar instability is a well-known pathology in which kinematics can be investigated using metrics such as tibial tuberosity tracheal groove (TTTG), the bisect offset (BO), and the lateral patellar tilt (LPT). We used dynamic computed tomography (CT) to investigate the patellar motion of healthy subjects in weight-bearing conditions to provide normative values for TTTG, BO, and LPT, as well as to define whether BO and LPT are affected by the morphology of the trochlear groove. Methods Dynamic scanning was used to acquire images during weight-bearing in 21 adult healthy volunteers. TTTG, BO, and LPT metrics were computed between 0° and 30° of knee flexion. Sulcus angle, sulcus depth, and lateral trochlear inclination were calculated and used with the TTTG for simple linear regression models. Results All metrics gradually decreased during eccentric movement (TTTG, -6.9 mm; BO, -12.6%; LPT, -4.3°). No significant differences were observed between eccentric and concentric phases at any flexion angle for all metrics. Linear regression between kinematic metrics towards full extension showed a moderate fit between BO and TTTG (R 2 0.60, β 1.75) and BO and LPT (R 2 0.59, β 1.49), and a low fit between TTTG and LPT (R 2 0.38, β 0.53). A high impact of the TTTG distance over BO was shown in male participants (R 2 0.71, β 1.89) and patella alta individuals (R 2 0.55, β 1.91). Conclusion We provided preliminary normative values of three common metrics during weight-bearing dynamic CT and showed the substantial impact of lateralisation of the patella tendon over patella displacement. Relevance statement These normative values can be used by clinicians when evaluating knee patients using TTTG, BO, and LPT metrics. The lateralisation of the patellar tendon in subjects with patella alta or in males significantly impacts the lateral displacement of the patella. Key Points Trochlear groove morphology had no substantial impact on motion prediction. The lateralisation of the patellar tendon seems a strong predictor of lateral displacement of the patella in male participants. Participants with patella alta displayed a strong fit between the patellar lateral displacement and tilt. TTTG, BO, and LPT decreased during concentric movement. Concentric and eccentric phases did not show differences for all metrics. Graphical Abstract

Abstract Background Regular disease monitoring with low-dose high-resolution (LD-HR) computed tomography (CT) scans is necessary for the clinical management of people with cystic fibrosis (pwCF). The aim of this study was to compare the image quality and radiation dose of LD-HR protocols between photon-counting CT (PCCT) and energy-integrating detector system CT (EID-CT) in pwCF. Methods This retrospective study included 23 pwCF undergoing LD-HR chest CT with PCCT who had previously undergone LD-HR chest CT with EID-CT. An intraindividual comparison of radiation dose and image quality was conducted. The study measured the dose-length product, volumetric CT dose index, effective dose and signal-to-noise ratio (SNR). Three blinded radiologists assessed the overall image quality, image sharpness, and image noise using a 5-point Likert scale ranging from 1 (deficient) to 5 (very good) for image quality and image sharpness and from 1 (very high) to 5 (very low) for image noise. Results PCCT used approximately 42% less radiation dose than EID-CT (median effective dose 0.54 versus 0.93 mSv, p

Abstract Purpose Childhood Cancer Survivors (CCSs) have an increased risk for treatment-related chronic health conditions, but the adherence to long-term follow-up (LTFU) care decreases over time. We therefore assessed the CCSs’ development of cancer knowledge, cancer worries, self-management skills, and expectations for LTFU care in a structured, cancer center-based transition model—a crucial part for maintaining adherence. Methods Using questionnaire-based surveys, we compared the CCSs’ cancer knowledge with medical record data and assessed cancer worries (6 questions), self-management skills (15 questions), and expectations (12 questions) longitudinally by validated scales. We used descriptive statistics for presenting our results. Results We analyzed 17 CCSs, 71% were female, had a median age of 8 years at diagnosis and 21 years at study enrollment. The knowledge about late effects increased during the transition process, except for the risk of secondary malignancies. Leukemia survivors had a decrease in cancer worries. At least 75% of the CCSs agreed to 11 of 15 self-management questions before and after transition, with the highest increase over time in less parental involvement. The CCSs expected the most, that physicians know the CCSs’ cancer history, that the visit starts on time, and that physicians can always be called in case of questions. Conclusions Our transition model improved cancer knowledge, especially the risk for late effects, decreased cancer worries, and identified expectations for LTFU care which should be considered in the future. A structured transition process with evidence-based tools further increases the knowledge of CCS for LTFU through empowerment.

Abstract The biological aspects of infancy within late Upper Palaeolithic populations and the role of southern refugia at the end of the Last Glacial Maximum are not yet fully understood. This study presents a multidisciplinary, high temporal resolution investigation of an Upper Palaeolithic infant from Grotta delle Mura (Apulia, southern Italy) combining palaeogenomics, dental palaeohistology, spatially-resolved geochemical analyses, direct radiocarbon dating, and traditional anthropological studies. The skeletal remains of the infant – Le Mura 1 – were directly dated to 17,320-16,910 cal BP. The results portray a biological history of the infant’s development, early life, health and death (estimated at ~72 weeks). They identify, several phenotypic traits and a potential congenital disease in the infant, the mother’s low mobility during gestation, and a high level of endogamy. Furthermore, the genomic data indicates an early spread of the Villabruna-like components along the Italian peninsula, confirming a population turnover around the time of the Last Glacial Maximum, and highlighting a general reduction in genetic variability from northern to southern Italy. Overall, Le Mura 1 contributes to our better understanding of the early stages of life and the genetic puzzle in the Italian peninsula at the end of the Last Glacial Maximum.

Abstract Background The prolificacy of sows (litter size at birth) has markedly increased, leading to higher post-natal mortality. Heat stress can exacerbate this issue. Arginine plays an important role in several physiological pathways; its effect on gestating sows can depend on the period of supplementation. This study evaluated the effects of arginine supplementation on the productive performance and physiological status of sows during different gestation periods and seasons, using a multi-omics approach. Methods A total of 320 sows were divided into 4 groups over 2 seasons (warm/cold); a control group (CO) received a standard diet (including 16.5 g/d of arginine) and 3 other groups received the standard diet supplemented with 21.8 g/d of arginine (38.3 g/d of arginine) either during the first 35 d (Early35), the last 45 d (Late45) or throughout the entire gestation period (COM). The colostrum was analyzed for nutritional composition, immunoglobulins and metabolomic profile. Urine and feces were analyzed on d 35 and 106 for the metabolomic and microbial profiles. Piglet body weight and mortality were recorded at birth, d 6, d 26, and on d 14 post-weaning. Results Interactions between arginine and season were never significant. The Early35 group had a lower percentage of stillborn (P

Abstract Background Chronic pain and inflammation are common features of rheumatic conditions such as Psoriatic Arthritis (PsA) and Axial Spondyloarthritis (axSpA), often needing prolonged medication treatment for effective management. Maintaining drug retention is essential for both achieving disease control and improving patients' quality of life. This study investigates the influence of pain catastrophizing, a psychological response to pain, on the drug retention rates of PsA and axSpA patients. Methods A two-year prospective multicenter observational study involved 135 PsA and 71 axSpA patients. Pain Catastrophizing Scale (PCS) was employed to assess pain catastrophizing. Univariable and multivariable regression analyses were utilized to identify factors associated with drug retention. Results In the PsA group, patients early discontinuing therapy showed higher baseline disease activity as well as higher incidence of comorbid fibromyalgia. Notably, pain catastrophizing, specifically the domains of Helplessness, Magnification, and Rumination, were significantly elevated in PsA patients who interrupted the treatment. Multivariable analysis confirmed pain catastrophizing as an independent predictor of drug suspension within two years. In axSpA, drug discontinuation was associated with female gender, shorter disease duration, higher baseline disease activity as well as elevated levels of pain catastrophizing. Univariable analysis supported the role of pain catastrophizing, including its domains, as predictors of treatment interruption. However, limited events in axSpA patients precluded a multivariate analysis. Conclusion This prospective study emphasizes the impact of pain catastrophizing on drug retention in patients with PsA and axSpA.

Abstract Using effective field theory methods, we derive the Carrollian analog of the geodesic action. We find that it contains both “electric” and “magnetic” contributions that are in general coupled to each other. The equations of motion descending from this action are the Carrollian pendant of geodesics, allowing surprisingly rich dynamics. As an example, we derive Carrollian geodesics on a Carroll–Schwarzschild background and discover an effective potential similar to the one appearing in geodesics on Schwarzschild backgrounds. However, the Newton term in the potential turns out to depend on the Carroll particle’s energy. As a consequence, there is only one circular orbit localized at the Carroll extremal surface, and this orbit is unstable. For large impact parameters, the deflection angle is half the value of the general relativistic light-bending result. For impact parameters slightly bigger than the Schwarzschild radius, orbits wind around the Carroll extremal surface. For small impact parameters, geodesics get reflected by the Carroll black hole, which acts as a perfect mirror.

Abstract Background The integration of telemedicine in pain management represents a significant advancement in healthcare delivery, offering opportunities to enhance patient access to specialized care, improve satisfaction, and streamline chronic pain management. Despite its growing adoption, there remains a lack of comprehensive data on its utilization in pain therapy, necessitating a deeper understanding of physicians’ perspectives, experiences, and challenges. Methods A survey was conducted in Italy between January 2024 and May 2024. Specialist center members of the SIAARTI were sent an online questionnaire testing the state of the art of telemedicine for pain medicine. Results One-hundred thirty-one centers across Italy reveal varied adoption rates, with 40% routinely using telemedicine. Regional disparities exist, with Northern Italy showing higher adoption rates. Barriers include the absence of protocols, resource constraints, and bureaucratic obstacles. Despite challenges, telemedicine has shown positive impacts on service delivery, with increased service volume reported. Technological capabilities, including image sharing and teleconsultation with specialists, indicate promising interdisciplinary potential. Conclusions The integration of advanced telemedicine software utilizing artificial intelligence holds promise for enhancing telemonitoring and alert systems, potentially leading to more proactive and personalized pain management strategies.

Abstract Micronuclei (MN) can form through many mechanisms, including the breakage of aberrant cytokinetic chromatin bridges. The frequent observation of MN in tumors suggests that they might not merely be passive elements but could instead play active roles in tumor progression. Here, we propose a mechanism through which the presence of micronuclei could induce specific phenotypic and functional changes in cells and increase the invasive potential of cancer cells. Through the integration of diverse in vitro imaging and molecular techniques supported by clinical samples from patients with prostate cancer (PCa) defined as high-risk by the D’Amico classification, we demonstrate that the resolution of chromosome bridges can result in the accumulation of Emerin and the formation of Emerin-rich MN. These structures are negative for Lamin A/C and positive for the Lamin-B receptor and Sec61β. MN can act as a protein sinks and result in the pauperization of Emerin from the nuclear envelope. The Emerin mislocalization phenotype is associated with a molecular signature that is correlated with a poor prognosis in PCa patients and is enriched in metastatic samples. Emerin mislocalization corresponds with increases in the migratory and invasive potential of tumor cells, especially in a collagen-rich microenvironment. Our study demonstrates that the mislocalization of Emerin to MN results in increased cell invasiveness, thereby worsening patient prognosis.

Gathering citizens, research organizations, companies, policymakers and practitioners is often considered sufficient for creating a Living-lab aimed at change towards food system sustainability.However, sustainability remains a social construct calling for a deliberation about the values that must be prioritised. These values need to be debated at each level of the food chain, from the choice of crops (neglected vs. main crops) and seeds (commons vs. intellectual property) through production (organic vs. weak agroecology) and processing (small-scale vs. industrial) to food supply and retail (local vs. global).The DIVINFOOD project’s Living-labs create favorable conditions for the emergence of such debates, in a food democracy perspective. Further to farmers, processors and researchers, they all aim to engage, around neglected and underutilized agrobiodiversity, groups of stakeholders that are still too rarely represented in participatory research approaches, such as teachers and students of agricultural schools, chefs, marginalized people, gardeners and citizen-led organisations.All actors are regularly invited into:● farmer’s fields to observe, evaluate and comment on cultivated biodiversity, and Genotype-Environment (GxE) interactions,● chefs’ kitchens to taste, co-create recipes,● laboratories to analyze, raise research questions, discuss results,● micro-enterprises to co-conduct diagnosis,● neighborhood associations to increase awareness about sustainable food systems,● meetings with policy-makers to co-develop short food chains and territorial networks.Each of the 9 Living-labs acts in its own territory. Bringing them together allows to shape a meta-Living-lab in which changes are studied, debated, observed, documented, initiated, and reflected.The connection of Living-labs makes it possible to think these changes locally and act globally for their realisation. By making collective decisions to give voice to very small structures in each region, this meta-living lab contributes to profound changes for the sustainability and diversity of the global food system.