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Abstract More than half a century after their discovery in the Ionian Sea near Riace Marina (Italy, 1972 CE), the Riace Bronzes continue to fascinate and interest. They are a pair of statues most likely sculpted in Greece in the mid-5th century and are considered masterpieces of Classical Greek sculpture. Many studies have been conducted, yet there are no morphometric studies that delve into their facial features. The aim of this study is to determine dentofacial characteristics and the presence of golden ratios in the so-called “young-man” warrior statue, equipped with a silver foil to represent the upper teeth. The interpupillar, interalar, intercanthal distances and mesio-distal diameter of the upper central incisors were subjected to virtual photogrammetry (GIMP-GNU Image Manipulation Programme). The presence of vertical and horizontal golden ratios between different landmarks (intercanthal distance: centre of the nose; centre of pupils: base of nose: base of upper incisors; centre of pupil-base of nose: base of upper incisors-base of chin; centre of pupils- base of upper incisors: base of the chin) were analysed using a dedicated software (PhiMatrix). The face and teeth satisfy most of golden canons, as also corroborated by the one-way ANOVA-statistic test (p

Short bowel syndrome (SBS) leads to severe morbidity and mortality. Intestinal adaptation is crucial in improving outcomes. To understand the human gene pathways associated with adaptation, we perform single-cell transcriptomic analysis of human small intestinal organoids explanted from mice with experimental SBS. We show that transmembrane ion pathways, specifically the transepithelial zinc transport pathway genes SLC39A4 and SLC39A5, are upregulated in SBS. This discovery is corroborated by an external dataset, bulk RT-qPCR, and Western blots. Oral zinc supplementation is shown to improve survival and weight gain of SBS mice and increase the proliferation of intestinal crypt cells in vitro. Finally, we identify the upregulation of SLC39A5 and associated transcription factor KLF5 in biopsied intestinal tissue specimens from patients with SBS. Thus, we identify zinc supplementation as a potential therapy for SBS and describe a xenotransplantation model that provides a platform for discovery in other intestinal diseases. SBS leads to severe morbidity and mortality. Here, using a xenotransplantation model, the authors uncover the role of zinc transport pathways in intestinal adaptation in SBS, highlighting the potential of zinc supplementation as a therapeutic approach. [ABSTRACT FROM AUTHOR]

The two main Afrotropical malaria vectors - Anopheles coluzzii and An. gambiae – are genetically distinct and reproductively isolated across West Africa. However, populations at the western extreme of their range are assigned as "intermediate" between the two species by whole genome sequence (WGS) data, and as hybrid forms by conventional molecular diagnostics. By exploiting WGS data from 1190 specimens collected across west Africa via the Anopheles gambiae 1000 Genomes network, we identified a putative taxon in the far-west (provisionally named Bissau molecular form), which did not arise by admixture but rather may have originated at the same time as the split between An. coluzzii and An. gambiae. Intriguingly, this taxon lacks insecticide resistance mechanisms commonly observed in the two main species. These findings lead to a change of perspective on malaria vector species in the far-west region with potential for epidemiological implications, and a new challenge for genetic-based mosquito control approaches. Population genomic analyses of 1,190 Afrotropical malaria vector specimens reveal a putative novel taxon within the Anopheles gambiae complex at the western extremes of its range, which may represent a challenge for genetic-based mosquito control [ABSTRACT FROM AUTHOR]

Owing to their exceptional mechanical, electronic, and phononic transport properties, compositionally complex alloys, including high-entropy alloys, represent an important class of materials. However, the interplay between chemical disorder and electronic correlations, and its influence on electronic structure-derived properties, remains largely unexplored. This is addressed for the archetypal CrMnFeCoNi alloy using resonant and valence band photoemission spectroscopy, electrical resistivity, and optical conductivity measurements, complemented by linear response calculations based on density functional theory. Utilizing dynamical mean-field theory, correlation signatures and damping in the spectra are identified, highlighting the significance of many-body effects, particularly in states distant from the Fermi edge. Electronic transport remains dominated by disorder and potentially short-range order, especially at low temperatures, while visible-spectrum optical conductivity and high-temperature transport are influenced by short quasiparticle lifetimes. These findings improve our understanding of element-specific electronic correlations in compositionally complex alloys and facilitate the development of advanced materials with tailored electronic properties. Compositionally complex alloys have attracted significant attention recently, but the role of electronic correlations in these materials is unknown. Redka et al. study the CrMnFeCoNi alloy using a combination of experimental and theoretical techniques, revealing strong correlation effects far from the Fermi edge. [ABSTRACT FROM AUTHOR]

Over the last two decades, platinum group metals (PGMs) and their alloys have dominated as the materials of choice for electrodes in long-term implantable neurostimulation and cardiac rhythm management devices due to their superior conductivity, mechanical and chemical stability, biocompatibility, corrosion resistance, radiopacity, and electrochemical performance. Despite these benefits, PGM manufacturing processes are extremely costly, complex, and challenging with potential health hazards. Additionally, the volatility in PGM prices and their high supply risk, combined with their scarce concentration of approximately 0.01 ppm in the earth's upper crust and limited mining geographical areas, underscores their classification as critical raw materials, thus, their effective recovery or substitution worldwide is of paramount importance. Since postmortem recovery from deceased patients and/or refining of PGMs that are used in the manufacturing of the electrodes and microelectrode arrays is extremely rare, challenging, and highly costly, therefore, substitution of PGM-based electrodes with other biocompatible materials that can yield electrochemical performance values equal or greater than PGMs is the only viable and sustainable solution to reduce and ultimately substitute the use of PGMs in long-term implantable neurostimulation and cardiac rhythm management devices. In this article, we demonstrate for the first time how the novel technique of "reactive hierarchical surface restructuring" can be utilized on titanium—that is widely used in many non-stimulation medical device and implant applications—to manufacture biocompatible, low-cost, sustainable, and high-performing neurostimulation and cardiac rhythm management electrodes. We have shown how the surface of titanium electrodes with extremely poor electrochemical performance undergoes compositional and topographical transformations that result in electrodes with outstanding electrochemical performance. [ABSTRACT FROM AUTHOR]

Purpose: Videos and images are becoming an educational tool in every domain. The objective was to assess the contribution of short educational endoscopic videos in learning the complex anatomy of the tympanic cavity. Methods: We conducted a prospective study amongst all the otolaryngology residents in 2021 in the greater Paris area (n = 74), from the first year to fifth year. We divided the residents into two groups who had the same 30-min anatomy class based on anatomical drawings. The second group had a 4-min endoscopic educational video at the end, whereas the first group did not. A video test of 10 surgical situations with each time 5 anatomic structures to identify was created. All the residents took the test just after the class, and 1 month later to assess long-term memory. The MERSQI score (design to assess the quality of educational studies) applied to our study was calculated. Results: The two groups were comparable in terms of training. The "video" group had significantly better results in the first test, mean score 24.40/50 (± 11.7) versus 16.74/50 (± 11.1) (p = 0.005) and also at 1 month, mean score 23.25/50 (± 12.3) versus 18.01/50 (± 11.3) (p = 0.035). The score in each group, and the difference between both groups, increased with resident seniority. The MERSQI score of our study was 14.5/18. Conclusion: This study highlights the educational value of videos to help memorise complex 3D anatomy such as in the tympanic cavity. [ABSTRACT FROM AUTHOR]

Assessment of liquefaction susceptibility of sediments in alluvial plains is considered one of the first step for infrastructure planning, hazard mitigation, and land use management in seismically active regions. Subtle geomorphological features resulting from depositional processes could greatly contribute to estimating the liquefaction likelihood since they also dictate the type and distribution of sediments. Our case study is from the Piniada Valley (Greece), where widespread liquefaction phenomena were triggered by the 2021 Mw 6.3, Damasi earthquake. As we compiled a detailed geological map for the purposes of this investigation and correlated it to the spatial distribution of the earthquake-induced liquefaction phenomena, we observed that most of liquefaction surface evidence are related to point bars and abandoned river channels formed the last century. In particular, the areal liquefaction density was estimated at 60.7 and 67.1 manifestations per km2, for the point bars and abandoned channels, respectively. Following this outcome, we propose a refinement of the existing liquefaction susceptibility classifications by including point bar bodies as a distinct category, characterized by a very high susceptibility to liquefaction. In addition, we discuss the correlation between the observed liquefaction manifestations and the shallow lithofacies, sand or mud prone areas, within point bars. The outcome arisen by this research is that most of liquefaction phenomena (> 70%) occurred on the area covered by coarser materials deposited on the upstream part of high sinuosity meanders. [ABSTRACT FROM AUTHOR]

The use of the HVSR (Horizontal-to-Vertical Spectral Ratio) method on single-station microtremor measurements is well documented in small alluvial plains for bedrock mapping. In large sedimentary basins, like the Po Plain, its application is still debated. To shed some light on this issue, we investigated two seismogenic structures buried below the Po Plain Quaternary deposits: the Mirandola and Casaglia anticlines. We acquired and analysed a dense distribution of HVSR data covering the two areas and mapped the frequency and amplitude values of the observed resonance peaks. The top of both anticlines is highlighted by high amplitude peaks picturing E-W elongated sectors with high-impedance contrast, where Quaternary deposits are reduced in thickness to about 60–130 m and directly overlay the Pliocene (Mirandola) and Miocene (Casaglia) marine units. In Mirandola, the high-amplitude peaks also correspond to higher resonance frequencies, while in Casaglia, the distribution of resonance frequencies is relatively uniform suggesting a flatter crestal region and the lateral continuity of the resonance surface. The combination of peak frequency and amplitude information on a dense grid of measurement points is thus confirmed to be useful for identifying and mapping buried geological structures such as structural highs. Further modelling is being carried out to estimate the depth of the surface responsible for the observed resonances, through calibration with borehole information. [ABSTRACT FROM AUTHOR]

The French National Metrology Institute (LNE) initiated a series of events to identify priorities for test methods and their harmonisation that directly address regulatory needs in Nanomedicine. One of these workshops entitled "The International Standardisation Roadmap for Nanomedicine" held in October 2023 (Paris, France) brought together key experts in the characterisation of nanomedicines and medical products containing nanomaterials, including the Joint Research Centre of the European Commission, SINTEF Industry and the metrology institutes of France, the UK, the USA and Canada, two flagship initiatives of the European Commission (PHOENIX and SAFE-n-MEDTECH Open Innovation Test Beds), representatives of a working party on mRNA vaccines at the European Directorate for the Quality of Medicines (EDQM) and members of international standardisation and pre-normative organisations (including CEN, ISO, ASTM, VAMAS). Two take-home message came out from the discussion. First, developing standard test methods and Reference Materials (RMs) for nanomedicines is a key priority for the European Commission and various stakeholders. Furthermore, there was a unanimous recognition of the need for a unified approach between standardisation committees, regulators and the nanomedicine community. At the USA, Canadian and European level, examples of success stories and of future initiative have been discussed. Future perspectives include the creation of a dedicated Working Group under CEN/TC 352 to consolidate efforts and develop a nanomedicine standardisation roadmap. [ABSTRACT FROM AUTHOR]

To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia. Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011. [ABSTRACT FROM AUTHOR]

Introduction: Congenital heart disease (CHD) is the most common congenital anomaly, representing a significant global disease burden. Limitations exist in our understanding of aetiology, diagnostic methodology and screening, with metabolomics offering promise in addressing these. Objective: To evaluate maternal metabolomics and lipidomics in prediction and risk factor identification for childhood CHD. Methods: We performed an observational study in mothers of children with CHD following pregnancy, using untargeted plasma metabolomics and lipidomics by ultrahigh performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS). 190 cases (157 mothers of children with structural CHD (sCHD); 33 mothers of children with genetic CHD (gCHD)) from the children OMACp cohort and 162 controls from the ALSPAC cohort were analysed. CHD diagnoses were stratified by severity and clinical classifications. Univariate, exploratory and supervised chemometric methods were used to identify metabolites and lipids distinguishing cases and controls, alongside predictive modelling. Results: 499 metabolites and lipids were annotated and used to build PLS-DA and SO-CovSel-LDA predictive models to accurately distinguish sCHD and control groups. The best performing model had an sCHD test set mean accuracy of 94.74% (sCHD test group sensitivity 93.33%; specificity 96.00%) utilising only 11 analytes. Similar test performances were seen for gCHD. Across best performing models, 37 analytes contributed to performance including amino acids, lipids, and nucleotides. Conclusions: Here, maternal metabolomic and lipidomic analysis has facilitated the development of sensitive risk prediction models classifying mothers of children with CHD. Metabolites and lipids identified offer promise for maternal risk factor profiling, and understanding of CHD pathogenesis in the future. [ABSTRACT FROM AUTHOR]

With the advancement of artificial intelligence(AI), platforms like ChatGPT have gained traction in different fields, including Medicine. This study aims to evaluate the potential of ChatGPT in addressing questions related to HIV prevention and to assess its accuracy, completeness, and inclusivity. A team consisting of 15 physicians, six members from HIV communities, and three experts in gender and queer studies designed an assessment of ChatGPT. Queries were categorized into five thematic groups: general HIV information, behaviors increasing HIV acquisition risk, HIV and pregnancy, HIV testing, and the prophylaxis use. A team of medical doctors was in charge of developing questions to be submitted to ChatGPT. The other members critically assessed the generated responses regarding level of expertise, accuracy, completeness, and inclusivity. The median accuracy score was 5.5 out of 6, with 88.4% of responses achieving a score ≥ 5. Completeness had a median of 3 out of 3, while the median for inclusivity was 2 out of 3. Some thematic groups, like behaviors associated with HIV transmission and prophylaxis, exhibited higher accuracy, indicating variable performance across different topics. Issues of inclusivity were identified, notably the use of outdated terms and a lack of representation for some communities. ChatGPT demonstrates significant potential in providing accurate information on HIV-related topics. However, while responses were often scientifically accurate, they sometimes lacked the socio-political context and inclusivity essential for effective health communication. This underlines the importance of aligning AI-driven platforms with contemporary health communication strategies and ensuring the balance of accuracy and inclusivity. [ABSTRACT FROM AUTHOR]

We introduce and analyze a natural class of nonlinear dynamics for spin systems such as the Ising model. This class of dynamics is based on the framework of mass action kinetics, which models the evolution of systems of entities under pairwise interactions, and captures a number of important nonlinear models from various fields, including chemical reaction networks, Boltzmann's model of an ideal gas, recombination in population genetics and genetic algorithms. In the context of spin systems, it is a natural generalization of linear dynamics based on Markov chains, such as Glauber dynamics and block dynamics, which are by now well understood. However, the inherent nonlinearity makes the dynamics much harder to analyze, and rigorous quantitative results so far are limited to processes which converge to essentially trivial stationary distributions that are product measures. In this paper we provide the first quantitative convergence analysis for natural nonlinear dynamics in a combinatorial setting where the stationary distribution contains non-trivial correlations, namely spin systems at high temperatures. We prove that nonlinear versions of both the Glauber dynamics and the block dynamics converge to the Gibbs distribution of the Ising model (with given external fields) in times O (n log n) and O (log n) respectively, where n is the size of the underlying graph (number of spins). Given the lack of general analytical methods for such nonlinear systems, our analysis is unconventional, and combines tools such as information percolation (due in the linear setting to Lubetzky and Sly), a novel coupling of the Ising model with Erdős-Rényi random graphs, and non-traditional branching processes augmented by a "fragmentation" process. Our results extend immediately to any spin system with a finite number of spins and bounded interactions. [ABSTRACT FROM AUTHOR]

Vernal keratoconjunctivitis (VKC) is a chronic, recurrent, inflammatory disease that affects both eyes, often with asymmetric severity, potentially causing major visual complications. The seasonal management of VKC can be challenging, especially when specialists with different diagnostic and therapeutic approaches need to be consulted. The aim of this expert panel was to reach a national consensus among pediatric allergologists and ophthalmologists on the diagnosis and treatment of VKC. This consensus was developed by an expert panel of 17 Italian pediatric allergologists and ophthalmologists with over a decade of experience. Ten statements on VKC diagnosis and treatment formulated after a thorough review of current literature were evaluated by the panelists. The level of agreement was quantitatively assessed using a 5-point Likert scale. Consensus was reached if ≥ 75.0% of panelists agreed to any given statement. The consensus emphasizes the importance of evaluation by multispecialty reference centers or experienced specialists for accurate diagnosis. Prompt diagnosis, especially during active phases, is crucial and should occur before corticosteroid therapy. The Bonini score from 2007 is the preferred tool for VKC assessment, although future revisions may be considered. Short cycles of topical corticosteroids should be preferred over prolonged use, even during immunomodulatory therapy. When cyclosporine fails, tacrolimus should be considered. Conclusion: This is the first consensus on the management of VKC that has gathered the expert opinions of both pediatricians and ophthalmologists. The outcome of this multidisciplinary effort provides a uniform approach to VKC diagnosis and treatment, thereby facilitating patient management across the country. What is Known: • Vernal keratoconjunctivitis (VKC) is a chronic recurrent ocular disease particularly prevalent in the pediatric population. • Despite its relevance, there is a lack of standardized approaches shared between pediatricians and ophthalmologists, leading to notable variations in clinical practice. What is New: • This expert panel, comprising 17 pediatric allergologists and ophthalmologists, has reached a national consensus to provide standardized guidance for VKC management. • The consensus emphasizes the importance of a multidisciplinary approach to managing VKC, ensuring consistent and effective patient care. [ABSTRACT FROM AUTHOR]

Aim: Recently, the relationship between diabetes and mental health has been widely studied. With the advent of continuous glucose monitoring (CGM), some researchers have been interested in exploring the association between glucose-related metrics and psychological aspects. These studies have primarily relied on self-report questionnaires which present some limitations. Therefore, the present multicenter study aims at testing potential associations between CGM metrics and affective processes derived from narratives about using a CGM sensor. Methods: An exploratory correlational design was used. Fifty-eight adults with type 1 diabetes using CGM were enrolled and invited to complete an online survey, where they replied to an open-ended question regarding their personal experience with the CGM sensor. Texts derived from the answers were analyzed through Linguistic Inquiry and Word Count, a widely used text analysis tool that can automatically identify and quantify linguistic patterns related to various psychological dimensions. Psycholinguistic measures were correlated with CGM metrics. Results: Higher levels of sadness/depression correlated with lower %TIR (r = − 339; p <.01) and higher %TAR (r =.342; p <.01). Conclusions: The study highlights the relationship between CGM metrics and psychological variables derived from patients' narratives. In particular, it is possible to hypothesize a positive role of %TIR in reducing depressive feelings in individuals with diabetes, as well as a negative role of depressive feelings in achieving desirable CGM outcomes. Additionally, there is a potential role of glycemic variability, particularly hyperglycemia, in the expression of depressive and sad feelings, which has been less studied compared to the effects of hypoglycemia. [ABSTRACT FROM AUTHOR]

Multi-modal learning has gained significant attention due to its ability to enhance machine learning algorithms. However, it brings challenges related to modality heterogeneity and domain shift. In this work, we address these challenges by proposing a new approach called Relative Norm Alignment (RNA) loss. RNA loss exploits the observation that variations in marginal distributions between modalities manifest as discrepancies in their mean feature norms, and rebalances feature norms across domains, modalities, and classes. This rebalancing improves the accuracy of models on test data from unseen ("target") distributions. In the context of Unsupervised Domain Adaptation (UDA), we use unlabeled target data to enhance feature transferability. We achieve this by combining RNA loss with an adversarial domain loss and an Information Maximization term that regularizes predictions on target data. We present a comprehensive analysis and ablation of our method for both Domain Generalization and UDA settings, testing our approach on different modalities for tasks such as first and third person action recognition, object recognition, and fatigue detection. Experimental results show that our approach achieves competitive or state-of-the-art performance on the proposed benchmarks, showing the versatility and effectiveness of our method in a wide range of applications. [ABSTRACT FROM AUTHOR]

Background: Body image is the mental representation of the body and can be influenced by cognitive, biological, behavioral, sociocultural, and environmental factors. University students often encounter challenges related to it. Objective: This systematic review examined interventions aimed at holistically developing a positive body image within this population. Methods: The PRISMA 2020 guidelines and the PICO method were employed to identify, select, assess, and synthesize studies. The consulted databases included Scopus, Web of Science, and PsycINFO, with inclusion criteria targeting body image interventions for university students aged 18 to 39. Study quality was evaluated using the QATSDD tool. Results: Twenty-one relevant studies were identified, primarily from the United States, mostly employing quantitative methods, with a focus on female participants. Various intervention strategies were utilized, including cognitive-behavioral approaches, media literacy, and physical/resistance training, with a growing use of technology like mobile applications. The majority of studies reported effective outcomes, such as reduced body dissatisfaction and increased self-esteem following interventions. Nevertheless, literature gaps were identified, such as the scarcity of formative interventions and limited use of qualitative approaches. Conclusion: While technology in interventions offers promising opportunities, careful assessments and judicious selection of evaluation instruments are fundamental for reliable results. Future research should focus on addressing identified gaps, such as exploring more formative interventions and incorporating qualitative methodologies to provide a more comprehensive understanding of the effectiveness of body image interventions among university students. Highlights: • The majority of studies reported effective outcomes, such as reduced body dissatisfaction and increased self-esteem following interventions. • Nevertheless, literature gaps were identified, such as the scarcity of formative interventions and limited use of qualitative approaches. • While technology in interventions offers promising opportunities, careful assessments and judicious selection of evaluation instruments are fundamental for reliable results. [ABSTRACT FROM AUTHOR]

Modelling approaches play a crucial role in supporting local public health agencies by estimating and forecasting vector abundance and seasonality. However, the reliability of these models is contingent on the availability of standardized, high-quality data. Addressing this need, our study focuses on collecting and harmonizing egg count observations of the mosquito Aedes albopictus, obtained through ovitraps in monitoring and surveillance efforts across Albania, France, Italy, and Switzerland from 2010 to 2022. We processed the raw observations to obtain a continuous time series of ovitraps observations allowing for an extensive geographical and temporal coverage of Ae. albopictus population dynamics. The resulting post-processed observations are stored in the open-access database VectAbundance.This initiative addresses the critical need for accessible, high-quality data, enhancing the reliability of modelling efforts and bolstering public health preparedness. [ABSTRACT FROM AUTHOR]

Purpose: The aims of the present study were (1) to evaluate the survival of patellofemoral joint (PFJ) arthroplasty in a large cohort of patients using data obtained from an Italian regional arthroplasty registry and (2) to collect clinical outcomes of a subgroup of patients, with a minimum follow‐up of 4 years. The hypotheses were that PFJ arthroplasty is a procedure that had good survival and clinical outcomes, not inferior to those reported in the literature for primary total knee arthroplasty (TKA). Methods: The Register of Orthopaedic Prosthetic Implants (RIPO) of Emilia‐Romagna (ER) (Italy) database was searched for the inclusion of all PFJ arthroplasties implanted between 2003 and 2019. PFJ arthroplasties were excluded if they were implanted in patients who lived outside of the ER. The survival information was extrapolated from the RIPO considering the partial or total revision of the implant as failure; moreover, a subgroup of patients was contacted and interviewed by telephone to collect clinical outcomes. Descriptive statistics were used to summarise the data. The survival curve was calculated and plotted using the Kaplan–Meier method. Results: A total of 126 arthroplasties in 114 patients were included in the final analysis (mean age at surgery 60.1 ± 11.5 years old). The main causes of patellofemoral arthroplasty were primary osteoarthritis (88%) and posttraumatic arthritis (7%). The survival was 90.4 ± 30.6 and 78.8 ± 51.5 at 5 and 10 years of follow‐up, respectively. At the latest follow‐up, 23 implants failed (18.3%). The main cause of revision was osteoarthrosis progression (34.8%). A total of 44 patients were contacted by telephone to collect clinical outcomes: Western Ontario and McMaster Universities Osteoarthritis Index, functional Knee Society Score, Forgotten Joint Score and Oxford Knee Score. These patients reported good to excellent scores at a medium follow‐up of 10.3 ± 4.7 years. Conclusions: The PFJ showed good survival and clinical outcomes and could be considered a valuable option for patients affected by isolated patellofemoral osteoarthritis. Level of Evidence: Level IV. [ABSTRACT FROM AUTHOR]

Sintered gears manufactured through powder metallurgy technology contain residual porosity that can make them inadequate for high power supply. Crack propagation is significantly enhanced by both residual porosity and cyclical stresses involving the teeth. The use of densification processes can highly improve their performances, permitting the reduction of the residual porosity. Among the densification processes, the rolling assumes a key-role. The process permits the densification of the tooth flanks, the most stressed parts of the wheel. However, the performances of the rolled wheel depend on several process parameters, whose setup phase requires several efforts and many experiments. Finite element (FE) model can be a helpful tool, allowing a faster estimation of the process parameters, reducing waste and costs linked to the experimental tests. In this sense, FE modelling techniques discussed in literature only cover the simulation of spur gears densification process, since they consist of in-plane 2D finite elements. In this paper, different numerical modelling techniques, based on 2D finite elements, are proposed to simulate the densification process of spur gears and used to perform a tendency analysis to explore the effects of wheelbase reduction between the forming rollers on the material densification. Material densification appeared higher for reduced wheelbases, but an increasing cavity was observed at the tooth root as the wheelbases decreases. Moreover, a FE model based on 3D finite elements is proposed to reproduce numerically the rolling process of a helical gear. The accuracy of the 3D FE model was measured against the results provided by some experimental tests, herein discussed too. A good agreement between numerical and experimental results was observed. [ABSTRACT FROM AUTHOR]

Spin-orbit coupling in noncentrosymmetric crystals leads to spin-momentum locking – a directional relationship between an electron's spin angular momentum and its linear momentum. Isotropic orthogonal Rashba spin-momentum locking has been studied for decades, while its counterpart, isotropic parallel Weyl spin-momentum locking has remained elusive in experiments. Theory predicts that Weyl spin-momentum locking can only be realized in structurally chiral cubic crystals in the vicinity of Kramers-Weyl or multifold fermions. Here, we use spin- and angle-resolved photoemission spectroscopy to evidence Weyl spin-momentum locking of multifold fermions in the chiral topological semimetal PtGa. We find that the electron spin of the Fermi arc surface states is orthogonal to their Fermi surface contour for momenta close to the projection of the bulk multifold fermion at the Γ point, which is consistent with Weyl spin-momentum locking of the latter. The direct measurement of the bulk spin texture of the multifold fermion at the R point also displays Weyl spin-momentum locking. The discovery of Weyl spin-momentum locking may lead to energy-efficient memory devices and Josephson diodes based on chiral topological semimetals. Spin-momentum locking is a fundamental property of condensed matter systems. Here, the authors evidence parallel Weyl spin-momentum locking of multifold fermions in the chiral topological semimetal PtGa. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to assess the feasibility, acceptability, and satisfaction associated with the MyInspiration intervention, a digital spiritual support tool for patients undergoing cancer surgery. Additionally, we evaluated changes in spiritual well-being and the ability to find meaning in their experience with cancer before and after the intervention. Methods: This was a prospective, single-arm pilot study. Feasibility and acceptability were assessed by ratio of participants who completed all assessments among individuals who had signed consent forms. Satisfaction was assessed with 5 Likert-style questions around user experience. Patient spiritual well-being and finding meaning in their experience with cancer were measured at baseline and post-intervention. Results: Forty patients were enrolled, the majority of whom were female (80.0%) and diagnosed with breast cancer (52.5%), with an average age of 54.4 years (SD = 13.7, range 29.0–82.0). Regarding feasibility and acceptability, 76.9% of patients who consented to participate completed the full study protocol. In assessing satisfaction, 59% of patients were satisfied with the overall experience of MyInspiration. There was no difference in spiritual well-being pre-/post-intervention. There was a difference in pre (M = 1.95, SD =.95) and post (M = 2.23, SD =.86) scores relative to “finding meaning in the cancer experience” with a mean difference of 0.28 (p = 0.008). Conclusion: MyInspiration was feasible and acceptable to patients, and the majority were satisfied with the tool. The intervention was associated with changes in patients’ ability to find meaning within their cancer experience. A randomized control trial is needed to evaluate the efficacy of the tool in a broader population of patients with cancer. [ABSTRACT FROM AUTHOR]

In holometabolous insects, extensive reorganisation of tissues and cells occurs at the pupal stage. The remodelling of the external exoskeleton and internal organs that intervenes during metamorphosis has been traditionally studied in many insect species based on histological or ultrastructural methods. This study demonstrates the use of synchrotron X-ray phase-contrast micro-computed tomography as a powerful, non-destructive tool for in situ morphological observation of anatomical structures at the pupal stage in two Tenebrionid beetles, i.e. Tribolium castaneum and Tenebrio molitor, known as important pests, as well as emerging and promising models in experimental biology. Virtual sections and three-dimensional reconstructions were performed on both males and females at early, intermediate, and late pupal stage. The dataset allowed us to observe the remodelling of the gut and nervous system as well as the shaping of the female and male reproductive system at different pupal ages in both mealworm and red flour beetles. Moreover, we observed that the timing and duration pattern of organ development varied between the species analysed, likely related to the species-specific adaptations of the pre-imaginal stages to environmental conditions, which ultimately affect their life cycle. This research provides new knowledge on the morphological modifications that occur during the pupal stage of holometabolous insects and provides a baseline set of information on beetle metamorphosis that may support future research in forensics, physiology, and ecology as well as an image atlas for educational purposes. [ABSTRACT FROM AUTHOR]

This study investigates the effect of biochar (BC) as a filler for biopolymer blends, with a focus on the effect of the biopolymer weight ratio on the final BC-added blends. The blends studied in this work were obtained by varying the weight ratio of poly-butylene adipate-co-terephthalate (PBAT) and polylactic acid (PLA) due to their great importance in packaging and agricultural fields. BC has been produced in our laboratories by the slow pyrolysis of the digestate obtained from the anaerobic digestion of the organic fraction of municipal solid waste (OFMSW). After pyrolysis, digestate-derived biochar has been milled and sieved to produce a powdery form with diameter of less than 45 μm. In order to better investigate the filler/polymer interactions, biochar particles were dimensionally, morphologically and chemically characterised. The inhomogeneity of the feedstock is responsible for content and high diversity of inorganics in biochar surface. The effect of BC on PBAT and PLA biopolymer matrices is different, and for the blend compositions the relative weight ratio between PBAT and PLA plays an important role. Furthermore, the biocomposite blend has been fully characterised: rheological, morphological, mechanical and dynamic-mechanical characterisations have been carried out, highlighting how the properties results strongly influenced by the presence of BC in the blend. In addition, a study of the viscous molar mass of the two polymer matrices when processed in the presence or absence of BC particless highlighting that a strong chemical interaction occurs between PLA and BC particles, unlike PBAT and BC. [ABSTRACT FROM AUTHOR]

We previously reported short-term outcomes for stenting of aortic coarctation (CoA) (native or re-coarctation) with newer generation low-profile stents (Valeo, Formula, and Begraft stents) in children under 30 kg. We present here the medium-term outcomes of this procedure. Retrospective review of patients weighing under 30 kg who had percutaneous stent treatments for coarctation between 2012 and 2021 was performed. Clinical and procedural data were collected; 19 patients were included. The median age at the time of procedure was 5.1 [4.1–6.4] years and median weight 21.0 [17.3–22.3] kg. One patient had a history of re-coarctation. Thirteen (68%) patients were on anti-hypertensives pre-procedure. Different types of stents were used (14 Valeo™, 4 Formula® 535, 1 BeGraft), which can all be dilated to 18 mm or larger. One patient required a 9 F sheath, all others required a 7 F sheath. The narrowest diameter in the aorta increased from a median of 3.5 [3.0–4.5] to 9.4 [8.9–9.8] mm, p < 0.001; there was a reduction in the median pressure gradient across the coarctation from 35.0 [30.0–43.0] to 5.0 [0–10.0] mmHg, p < 0.001. There were no intra-procedural complications. Follow-up was for a median of 56.0 [13.0–65.0] months. Five (26%) of patients underwent re-intervention after a median time frame of 40.0 [39.5–52.0] months; four had balloon dilation, one had repeat stent implantation. Five (26%) patients were on anti-hypertensive agent(s) post-intervention. Our single centre experience demonstrates that percutaneous stenting for coarctation of aorta in children under 30 kg, with low-profile stents, had no significant complications during the median follow-up time of 56 months. This study demonstrated that the procedure is safe and effective for short and medium-term therapy in this group of patients with a 26% re-intervention rate. A quarter of patients remained on anti-hypertensive medication post stenting, emphasizing the importance of long-term follow-up. [ABSTRACT FROM AUTHOR]

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More than half a century after their discovery in the Ionian Sea near Riace Marina (Italy, 1972 CE), the Riace Bronzes continue to fascinate and interest. They are a pair of statues most likely sculpted in Greece in the mid-5th century and are considered masterpieces of Classical Greek sculpture. Many studies have been conducted, yet there are no morphometric studies that delve into their facial features. The aim of this study is to determine dentofacial characteristics and the presence of golden ratios in the so-called "young-man" warrior statue, equipped with a silver foil to represent the upper teeth. The interpupillar, interalar, intercanthal distances and mesio-distal diameter of the upper central incisors were subjected to virtual photogrammetry (GIMP-GNU Image Manipulation Programme). The presence of vertical and horizontal golden ratios between different landmarks (intercanthal distance: centre of the nose; centre of pupils: base of nose: base of upper incisors; centre of pupil-base of nose: base of upper incisors-base of chin; centre of pupils- base of upper incisors: base of the chin) were analysed using a dedicated software (PhiMatrix). The face and teeth satisfy most of golden canons, as also corroborated by the one-way ANOVA-statistic test (p < 0.05) for repeated measurements by independent expert operators. The virtual golden facial grid should confirm an ovoid face, which should match the same dental shape. The statue design stems from the search for beauty as divine proportion, and a relatively small detail such as teeth seems to have been carefully programmed. [ABSTRACT FROM AUTHOR]

Industrial plants are complex structures, highly vulnerable with respect to seismic loading. Past seismic events have demonstrated the devastating impact and huge economic losses that an industrial plant can experience not only due to physical damage of equipment, but also due to interruption of the production processes. In order to quantify these economic losses, plant seismic resilience evaluation is required. The current paper presents a probabilistic process flow-based framework for assessment of industrial plant resilience and economic losses in case of seismic events. Uncertainties are considered in the ability of plant equipment to withstand the perturbation, and also in the recovery process including equipment recovery durations and recovery costs. Monte Carlo Simulation is used to account for the uncertainties of the model. A black carbon plant is used as a case study to show the applicability of the model. Results and capability of the proposed model shows that it can be a useful tool for decision makers, plant owners, insurance companies, emergency managers and plant designers in their decision making process. [ABSTRACT FROM AUTHOR]

Introduction: This study will test the hypothesis that primary aldosteronism (PA) involves alterations in Na+, K+, and water content in the skin that are corrected by adrenalectomy. Aim and Methods: In skin biopsies, we will measure the content of Na+, K+, water, by physical-chemical methods and the osmotic-stress-responsive transcription factor Tonicity-responsive Enhancer Binding Protein (TonEBP, NFAT5) mRNA copy number by droplet digital PCR, in sex-balanced cohorts of 18 -75-year-old consecutive consenting patients with unilateral and bilateral PA, primary (essential) hypertension, and normotension. Before surgery, the patients with unilateral PA will receive the mineralocorticoid receptor antagonist (MRA) canrenone at doses that correct hypokalemia and high blood pressure values. They will be reassessed in an identical way one month after surgical cure, while off MRA. PA patients not selected for adrenalectomy will similarly be assessed at diagnosis and follow-up while on stable MRA treatment. Since a pilot study showed a direct correlation of dry weight (DW) with skin electrolytes and water content and significant differences of biopsy DW between surgery and follow-up, meaningful comparison of the skin cations and water content and TonEBP mRNA copy number, between specimen obtained at different time points, will require DW- and total mRNA-adjustment, respectively. Conclusion: This study will provide novel information on the skin Na+, K+ and water content in PA, the paradigm of salt-dependent hypertension, and novel knowledge on the effect of surgical cure of hyperaldosteronism. The TonEBP-mediated regulation of Na+, K+ and water content in the skin will also be unveiled. Trail Registry: Trial Registration number: NCT06090617. Date of Registration: 2023-10-19. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the impact of using the subcutaneous fixed-dose combination of pertuzumab + trastuzumab (PH FDC SC) compared with intravenous pertuzumab followed by intravenous trastuzumab (P+T IV) in HER2+ breast cancer patients. Methods: Data from three Italian hospitals were collected to assess the organizational and economic benefits of PH FDC SC versus P+T IV on (i) patient pathway time, (ii) personnel time, (iii) direct costs and (iv) recoverable efficiency for the hospital, and (v) social impact for patient and caregivers. Data from hospitals were averaged when calculating results. Results: PH FDC SC induced a reduction in patients' pathway time (ΔIV→SC: −59 min), driven by the administration phase (ΔIV→SC: −89 min); personnel time (ΔIV→SC: −17 min /patient), and direct costs for hospitals (ΔIV→SC: −125.95€/patient). A complete switch to PH FDC SC would also induce potential productivity gains in terms of additional oncological therapies administered by the hospital (ΔIV→SC: +532/year), together with decreased yearly social indirect costs for patients (−13.3%) and caregivers (−13.5%). Conclusion: Overall, PH FDC SC demonstrated potential economic and organizational advantages for hospitals and patients compared with P+T IV, even though patients treated subcutaneously experienced longer waits between activities, indicating the need for optimized organizational choices. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the changes in gustatory and olfactory sensitivity and dietary habits between healthy lean subjects (LS) and participants affected by overweight (OW), stage I and II obesity and to estimate possible impact of these factors on body mass index (BMI). Methods: After a general and ear–nose–throat evaluation, taste and olfactory function testing by means of taste strips and sniffin' stick tests, respectively, and food habits analysis by means of food frequency questionnaire (FFQ), 221 participants (68 LS [33 female; mean age = 53.01 ± 7.54 years]; 51 OW [26 female; mean age = 51.5 ± 12.16 years]; 50 stage I obesity [24 female; mean age = 50.78 ± 13.71 years] and 52 stage II obesity [24 female; mean age = 52.21 ± 13.35 years]) were enrolled in the study. Results: Significant (p < 0.008) reductions in total and subtest taste and smell scores were found in stage I and II obesity when compared to LS and OW participants. FFQ depicted a progressive intake increase of nutrients along the BMI stages. Significant associations were found between BMI and taste/smell subtests sugar taste carbs, saturated, monounsaturated and polyunsaturated fatty acids. Conclusions: These data demonstrated for the first time a parallel impairment in smell and taste in a large sample size of participants from lean to stage II obesity and could reinforce those previous theories claiming that the greater the ability in taste or smell qualities perception, the lower the preference for them, resulting in a lower intake of specific foods. [ABSTRACT FROM AUTHOR]

The continuous growth of annual production and consumption of polyethylene terephthalate (PET) is coined with increasing waste that leaks into the environment, landfills and oceans as microplastics and nano plastics fragments. Upcycling the recycled PET to make a feedstock for the fast-growing material-extrusion additive manufacturing (MEX-AM) technology can contribute to the solution and supports the concept of sustainable materials. In this work, extrudable filaments comprising recycled polyethylene terephthalate (rPET) with low-cost additives, such as pyromellitic dianhydride (PMDA) as a chain extender, styrene-ethylene-butylene-styrene terpolymer functionalized with maleic anhydride (SEBS-g-MA), a thermal modifier and toughening agent, ethylene-ethyl acrylate-glycidyl methacrylate terpolymer (E-EA-GMA), a functional reactive elastomeric impact modifier and ethylene-ethyl-acrylate (EEA), a non-reactive elastomeric impact modifier, have been fabricated using the twin-screw extruder. The optimum extrusion process parameters for producing uniform filaments of different rPET compounded formulations have been identified, this includes the extrusion die temperature of 280 °C and the screw speed of 150 ± 3 rpm. The compounded filaments are then printed into standard ASTM test specimens for thermal characterization and mechanical characterization, including glass transition and melting temperatures, crystallinity and crystallization temperature, tensile strength, tensile modulus, ductility, flexural strength, and Izod impact energy. Furthermore, the melt flow index for the filaments was measured. More significantly, the experimental data showed that compounding rPET with such additives in the reactive twin-screw extrusion process results in uniform filaments that display advantageous thermal and mechanical properties and can be used as a feedstock in the MEX-AM technology. This study suggests that compounding the recycled PET pellets with low-cost additives while extruding them into filaments for MEX-AM offers excellent potential to make high-value-added customized products from a sustainable polymer feedstock, such as prototyping, tooling, testing components or end-use internal components for small machines and cars. [ABSTRACT FROM AUTHOR]

Miniaturization and electrochemical performance enhancement of electrodes and microelectrode arrays in emerging long-term implantable neural stimulation devices improves specificity, functionality, and performance of these devices. However, surgical site and post-implantation infections are amongst the most devastating complications after surgical procedures and implantations. Additionally, with the increased use of antibiotics, the threat of antibiotic resistance is significant and is increasingly being recognized as a global problem. Therefore, the need for alternative strategies to eliminate post-implantation infections and reduce antibiotic use has led to the development of medical devices with antibacterial properties. In this work, we report on the development of electrochemically active antibacterial platinum-iridium electrodes targeted for use in neural stimulation and sensing applications. A two-step development process was used. Electrodes were first restructured using femtosecond laser hierarchical surface restructuring. In the second step of the process, atomic layer deposition was utilized to deposit conformal antibacterial copper oxide thin films on the hierarchical surface structure of the electrodes to impart antibacterial properties to the electrodes with minimal impact on electrochemical performance of the electrodes. Morphological, compositional, and structural properties of the electrodes were studied using multiple modalities of microscopy and spectroscopy. Antibacterial properties of the electrodes were also studied, particularly, the killing effect of the hierarchically restructured antibacterial electrodes on Escherichia coli and Staphylococcus aureus—two common types of bacteria responsible for implant infections. [ABSTRACT FROM AUTHOR]

Reprogramming of amino acid metabolism, sustained by oncogenic signaling, is crucial for cancer cell survival under nutrient limitation. Here we discovered that missense mutant p53 oncoproteins stimulate de novo serine/glycine synthesis and essential amino acids intake, promoting breast cancer growth. Mechanistically, mutant p53, unlike the wild-type counterpart, induces the expression of serine-synthesis-pathway enzymes and L-type amino acid transporter 1 (LAT1)/CD98 heavy chain heterodimer. This effect is exacerbated by amino acid shortage, representing a mutant p53-dependent metabolic adaptive response. When cells suffer amino acids scarcity, mutant p53 protein is stabilized and induces metabolic alterations and an amino acid transcriptional program that sustain cancer cell proliferation. In patient-derived tumor organoids, pharmacological targeting of either serine-synthesis-pathway and LAT1-mediated transport synergizes with amino acid shortage in blunting mutant p53-dependent growth. These findings reveal vulnerabilities potentially exploitable for tackling breast tumors bearing missense TP53 mutations. Mutant p53 induces serine/glycine synthesis and essential amino acids intake. Under amino acid restriction, mutant p53 is stabilized and activates a transcriptional program that sustains a metabolic adaptive response promoting breast cancer cells growth [ABSTRACT FROM AUTHOR]

Lifelogging was introduced as the process of passively capturing personal daily events via wearable devices. It ultimately creates a visual diary encoding every aspect of one's life with the aim of future sharing or recollecting. In this paper, we present LifeSeeker, a lifelog image retrieval system participating in the Lifelog Search Challenge (LSC) for 3 years, since 2019. Our objective is to support users to seek specific life moments using a combination of textual descriptions, spatial relationships, location information, and image similarities. In addition to the LSC challenge results, a further experiment was conducted in order to evaluate the power retrieval of our system on both expert and novice users. This experiment informed us about the effectiveness of the user's interaction with the system when involving non-experts. [ABSTRACT FROM AUTHOR]

Background: Zonulin is involved in the integrity and functioning of both intestinal-epithelial barrier and blood–brain barrier (BBB) by regulating tight junction molecular assembly. Aim: Since changes in microbiota and BBB may play a role in neurodegenerative disorders, we aimed to determine whether serum zonulin levels change in older patients affected by different types of dementia or mild cognitive impairment (MCI). Methods: We evaluated serum zonulin levels in patients with late-onset AD (LOAD), vascular dementia (VAD), MIXED (AD + VAD) dementia, amnestic MCI, and in healthy controls. Results: Compared with controls, serum zonulin increased in LOAD, MIXED dementia, and aMCI but not in VAD, independent of potential confounders (ANCOVA p = 0.01; LOAD vs controls, p = 0.01; MIXED vs. controls, p = 0.003; aMCI vs. controls, p = 0.04). Notably, aMCI converting to dementia showed significantly higher levels of zonulin compared with stable aMCI (p = 0.04). Serum zonulin inversely correlated with the standardized Mini-Mental State Examination (MMSE) score (p < 0.05), regardless of potential confounders. Discussion: We found increased serum zonulin levels in patients with aMCI, LOAD and MIXED dementia, but not in VAD; moreover, zonulin levels were higher in aMCI converting to AD compared with stable ones. Conclusions: Our findings suggest that a dysregulation of intestinal-epithelial barrier and/or BBB may be an early specific event in AD-related neurodegeneration. [ABSTRACT FROM AUTHOR]

Actin, tropomyosin and troponin, the proteins that comprise the contractile apparatus of the cardiac thin filament, are highly conserved across species. We have used cryo-EM to study the three-dimensional structure of the zebrafish cardiac thin and actin filaments. With 70% of human genes having an obvious zebrafish orthologue, and conservation of 85% of disease-causing genes, zebrafish are a good animal model for the study of human disease. Our structure of the zebrafish thin filament reveals the molecular interactions between the constituent proteins, showing that the fundamental organisation of the complex is the same as that reported in the human reconstituted thin filament. A reconstruction of zebrafish cardiac F-actin demonstrates no deviations from human cardiac actin over an extended length of 14 actin subunits. Modelling zebrafish homology models into our maps enabled us to compare, in detail, the similarity with human models. The structural similarities of troponin-T in particular, a region known to contain a hypertrophic cardiomyopathy 'hotspot', confirm the suitability of zebrafish to study these disease-causing mutations. [ABSTRACT FROM AUTHOR]

Mitochondrial dysfunction has pleiotropic effects and is frequently caused by mitochondrial DNA mutations. However, factors such as significant variability in clinical manifestations make interpreting the pathogenicity of variants in the mitochondrial genome challenging. Here, we present APOGEE 2, a mitochondrially-centered ensemble method designed to improve the accuracy of pathogenicity predictions for interpreting missense mitochondrial variants. Built on the joint consensus recommendations by the American College of Medical Genetics and Genomics/Association for Molecular Pathology, APOGEE 2 features an improved machine learning method and a curated training set for enhanced performance metrics. It offers region-wise assessments of genome fragility and mechanistic analyses of specific amino acids that cause perceptible long-range effects on protein structure. With clinical and research use in mind, APOGEE 2 scores and pathogenicity probabilities are precompiled and available in MitImpact. APOGEE 2's ability to address challenges in interpreting mitochondrial missense variants makes it an essential tool in the field of mitochondrial genetics. APOGEE 2 is a machine-learning tool for assessing the fragility of the mitochondrial genome, evaluating genetic variant pathogenicity and ultimately enhancing our understanding of the clinical heterogeneity of mitochondrial genetic diseases. [ABSTRACT FROM AUTHOR]

Purpose of Review: The purpose of this review is to overview the most relevant and recent knowledge regarding medical management in pulmonary arterial hypertension (PAH). Recent Findings: Evidence has shown that PAH patients' quality of life and prognosis depend on the capability of the RV to adapt to increased afterload and to fully recover in response to substantially reduced pulmonary vascular resistance obtained with medical therapy. Data from recent clinical studies show that more aggressive treatment strategies, especially in higher risk categories, determine larger afterload reductions, consequentially increasing the probability of achieving right heart reverse remodeling, therefore improving the patients' survival and quality of life. Remarkable progress has been observed over the past decades in the medical treatment of PAH, related to the development of drugs that target multiple biological pathways, strategies for earlier and more aggressive treatment interventions. Summary: New hopes for treatment of patients who are unable to achieve low-risk status have been derived from the phase 2 trial PULSAR and the phase 3 trial STELLAR, which show improvement in the hemodynamic status of patients treated with sotatercept on top of background therapy. Promising results are expected from several ongoing clinical trials targeting new pathways involved in the pathophysiology of PAH. [ABSTRACT FROM AUTHOR]