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Summary: Background: Severe and prolonged mpox courses have been described during the 2022–2023 outbreak. Identifying predictors of severe evolution is crucial for improving management and therapeutic strategies. We explored the predictors of mpox severity and tested the association between mpox severity and viral load in biological fluids. We also analysed the predictors of disease duration and kinetics of inflammatory markers and described the viral presence and duration of shedding in biological fluids. Methods: This multicentre historical cohort study included adults diagnosed with laboratory-confirmed mpox diagnosis between May 2022 and September 2023 at 15 Italian centres. Patients were followed up from the day of diagnosis until clinical recovery. Biological fluids (blood, urine, saliva, and oropharyngeal and rectal swabs) were collected from each subgroup during the course of the disease and after healing. The primary outcomes were disease severity (presence of mucosal involvement, extended rash, or need for hospitalisation) and its association with the cycle threshold value (Ct-value, surrogate of viral load) in biological fluids, using standard linear and linear mixed-effect logistic regression models. Among the secondary outcomes, predictors of disease duration were assessed using a linear regression model. Findings: A total of 541 patients were enrolled, including four (0.74%) women, with a median age of 38 years (IQR 33–44). Among the 235 people living with HIV (PLWH) (43.44%), 22 (4.07%) had a CD4 count lower than 350 cells/μL. Severe mpox was reported in 215 patients (39.74%). No patient died. Multivariable analysis showed that, severe mpox was more likely among Caucasians (OR 1.82; 95% CI 1.14–2.90, p = 0.012) and patients who had an onset of fever (1.95; 1.27–2.99, p = 0.002), lymphadenopathy (2.30; 1.52–3.48, p

Abstract Chronic liver disease and cancer are global health challenges. The role of the circadian clock as a regulator of liver physiology and disease is well established in rodents, however, the identity and epigenetic regulation of rhythmically expressed genes in human disease is less well studied. Here we unravel the rhythmic transcriptome and epigenome of human hepatocytes using male human liver chimeric mice. We identify a large number of rhythmically expressed protein coding genes in human hepatocytes of male chimeric mice, which includes key transcription factors, chromatin modifiers, and critical enzymes. We show that hepatitis C virus (HCV) infection, a major cause of liver disease and cancer, perturbs the transcriptome by altering the rhythmicity of the expression of more than 1000 genes, and affects the epigenome, leading to an activation of critical pathways mediating metabolic alterations, fibrosis, and cancer. HCV-perturbed rhythmic pathways remain dysregulated in patients with advanced liver disease. Collectively, these data support a role for virus-induced perturbation of the hepatic rhythmic transcriptome and pathways in cancer development and may provide opportunities for cancer prevention and biomarkers to predict HCC risk.

Abstract Hepatocellular carcinoma (HCC) is the most common liver cancer and is among the leading causes of cancer-related death worldwide. There is no reliable biomarker for the early diagnosis of HCC. Circulating microRNAs (miRNAs) have attracted attention as potential biomarkers of disease. By small-RNA next-generation sequencing, the analysis of serum miRNAs led to the identification of molecular signatures able to discriminate advanced HCC from early HCC (n = 246); advanced HCC from CIRRHOSIS (n = 299); advanced HCC from HEALTHY (n = 320); HEALTHY from early HCC (n = 343); and HEALTHY from CIRRHOSIS (n = 414). Cirrhotic patients and early HCC patients exhibited similar serum miRNA profiles, yet a small number of miRNAs (n = 57) were able to distinguish these two classes of patients. A second objective of the study was to identify serum miRNAs capable of predicting the response to therapy in patients with advanced HCC. All patients were treated with sorafenib as first-line therapy: 24 were nonresponsive and 24 responsive. Analysis of circulating miRNAs revealed a 54 miRNAs signature able to separate the two subgroups. This study suggested that circulating miRNAs could be useful biomarkers for monitoring patients with liver diseases ranging from cirrhosis to advanced HCC and possibly predicting susceptibility to first-line treatment based on sorafenib.

Abstract Six-dimensional superconformal field theories (SCFTs) have an atomic classification in terms of elementary building blocks, conformal systems that generalize matter and can be fused together to form all known 6d SCFTs in terms of generalized 6d quivers. It is therefore natural to ask whether 5d SCFTs can be organized in a similar manner, as the outcome of fusions of certain elementary building blocks, which we call 5d conformal matter theories. In this project we begin exploring this idea and we give a systematic construction of 5d generalized “bifundamental” SCFTs, building from geometric engineering techniques in M-theory. In particular, we find several examples of ( e 6 $$ {\mathfrak{e}}_6 $$ , e 6 $$ {\mathfrak{e}}_6 $$ ), ( e 7 $$ {\mathfrak{e}}_7 $$ , e 7 $$ {\mathfrak{e}}_7 $$ ) and ( e 8 $$ {\mathfrak{e}}_8 $$ , e 8 $$ {\mathfrak{e}}_8 $$ ) 5d bifundamental SCFTs beyond the ones arising from (elementary) KK reductions of the 6d conformal matter theories. We show that these can be fused together giving rise to 5d SCFTs captured by 5d generalized linear quivers with exceptional gauge groups as nodes, and links given by 5d conformal matter. As a first application of these models we uncover a large class of novel 5d dualites, that generalize the well-known fiber/base dualities outside the toric realm.

Abstract Machine-learning interatomic potentials (MLIPs) offer a powerful avenue for simulations beyond length and timescales of ab initio methods. Their development for investigation of mechanical properties and fracture, however, is far from trivial since extended defects—governing plasticity and crack nucleation in most materials—are too large to be included in the training set. Using TiB2 as a model ceramic material, we propose a training strategy for MLIPs suitable to simulate mechanical response of monocrystals until failure. Our MLIP accurately reproduces ab initio stresses and fracture mechanisms during room-temperature uniaxial tensile deformation of TiB2 at the atomic scale ( ≈ 103 atoms). More realistic tensile tests (low strain rate, Poisson’s contraction) at the nanoscale ( ≈ 104–106 atoms) require MLIP up-fitting, i.e., learning from additional ab initio configurations. Consequently, we elucidate trends in theoretical strength, toughness, and crack initiation patterns under different loading directions. As our MLIP is specifically trained to modelling tensile deformation, we discuss its limitations for description of different loading conditions and lattice structures with various Ti/B stoichiometries. Finally, we show that our MLIP training procedure is applicable to diverse ceramic systems. This is demonstrated by developing MLIPs which are subsequently validated by simulations of uniaxial strain and fracture in TaB2, WB2, ReB2, TiN, and Ti2AlB2.

Purpose This study examines the financial impact of the COVID-19 pandemic on the Colombian Health System, focusing on the adequacy of reimbursement rates for inpatient stays. The study, based on a cost of illness analysis, aims to evaluate the effectiveness of the reimbursement scheme and identify potential economic losses within the health system.Patients and methods The study protocol outlines the inclusion criteria for patients >18 years with confirmed COVID-19 infection and moderate to critical disease. Patients hospitalised between June 2020 and June 2021 for at least 24 hours were included. Exclusion criteria involved pregnant patients and those initially hospitalised for non-COVID-19.Results The study included 781 patients contributing to 790 hospitalisations. Demographic and clinical characteristics were analysed, with critical illness being the most prevalent category (61%). The overall mortality rate was 20.3%, primarily observed in critically ill patients. In the general ward for moderate cases, the reimbursement rate saw a substantial increase from US$3237 in 2020 to US$6760 in 2021, surpassing median resource utilisation. However, for severe cases in the intermediate care unit, reimbursement rates decreased, indicating potential insufficiency in covering costs. In the intensive care unit for critical cases, despite improved reimbursement rates, median resource utilisation still exceeds the 2021 rate, suggesting financial insufficiency in reimbursement rates.Conclusion Our study underscores the inadequacies of the previous reimbursement system in addressing the varying resource utilisation and costs associated with COVID-19 inpatient care. Our analysis reveals substantial discrepancies between estimated costs and actual resource utilisation, particularly for severe and critical cases. We advocate for government flexibility in revising reimbursement baskets, supported by pilot studies to assess effectiveness. The use of real-world evidence forms a crucial basis for informed adjustments to reimbursement levels in preparation for future pandemics. This proactive approach ensures alignment between reimbursement policies and the actual costs associated.

Abstract Atomic monolayers on semiconductor surfaces represent an emerging class of functional quantum materials in the two-dimensional limit — ranging from superconductors and Mott insulators to ferroelectrics and quantum spin Hall insulators. Indenene, a triangular monolayer of indium with a gap of ~ 120 meV is a quantum spin Hall insulator whose micron-scale epitaxial growth on SiC(0001) makes it technologically relevant. However, its suitability for room-temperature spintronics is challenged by the instability of its topological character in air. It is imperative to develop a strategy to protect the topological nature of indenene during ex situ processing and device fabrication. Here we show that intercalation of indenene into epitaxial graphene provides effective protection from the oxidising environment, while preserving an intact topological character. Our approach opens a rich realm of ex situ experimental opportunities, priming monolayer quantum spin Hall insulators for realistic device fabrication and access to topologically protected edge channels.

Abstract Controlling and understanding electron correlations in quantum matter is one of the most challenging tasks in materials engineering. In the past years a plethora of new puzzling correlated states have been found by carefully stacking and twisting two-dimensional van der Waals materials of different kind. Unique to these stacked structures is the emergence of correlated phases not foreseeable from the single layers alone. In Ta-dichalcogenide heterostructures made of a good metallic “1H”- and a Mott insulating “1T”-layer, recent reports have evidenced a cross-breed itinerant and localized nature of the electronic excitations, similar to what is typically found in heavy fermion systems. Here, we put forward a new interpretation based on first-principles calculations which indicates a sizeable charge transfer of electrons (0.4-0.6 e) from 1T to 1H layers at an elevated interlayer distance. We accurately quantify the strength of the interlayer hybridization which allows us to unambiguously determine that the system is much closer to a doped Mott insulator than to a heavy fermion scenario. Ta-based heterolayers provide therefore a new ground for quantum-materials engineering in the regime of heavily doped Mott insulators hybridized with metallic states at a van der Waals distance.

Abstract Background In the pediatric oncology population, oral mucositis as a consequence of chemotherapy is a highly prevalent complication which strongly affects both the quality of life and treatment possibilities of the patients. Still, the etiopathological mechanisms carrying to its development are not fully understood, although a possible role of oral dysbiosis has been previously investigated with unclear conclusions. The aim of this systematic review was to assess the available evidence on the role of microbiota in the development of oral mucositis. Methods A systematic literature search was performed following PRISMA guidelines. Three electronic databases were searched up until April 2023 and a following manual search included the reference lists of the included studies and reviews. Studies reporting microbiological and clinical data of pediatric patients treated by antineoplastic drugs were included. Results Thirteen studies met the inclusion criteria, reporting an average mucositis prevalence of 57,6%. Candida albicans infections were frequently observed in studies performing microbiological analysis on oral lesions, in contrast with the low rate detection of the Herpes simplex viruses. Bacterial species such as coagulase-negative Staphylococci and Streptococcus viridans were detected more frequently on lesion sites. Studies reporting a quantitative analysis of the general flora did not show comparable results. Risk of bias assessment among studies was generally considered high or very high. Conclusions While the specific role of certain microbiological agents, such as Candida albicans, was frequently reported among studies, data regarding the general dynamics of oral microbiota in the development of oral mucositis are lacking in the current literature. Thus, more studies are needed to provide the knowledge required in order to improve protocols for the prevention and treatment of this threatening complication.

Modern cyber-physical systems are becoming increasingly complex to model, thus motivating data-driven techniques such as reinforcement learning (RL) to find appropriate control agents. However, most systems are subject to hard constraints such as safety or operational bounds. Typically, to learn to satisfy these constraints, the agent must violate them systematically, which is computationally prohibitive in most systems. Recent efforts aim to utilize feasibility models that assess whether a proposed action is feasible to avoid applying the agent’s infeasible action proposals to the system. However, these efforts focus on guaranteeing constraint satisfaction rather than the agent’s learning efficiency. To improve the learning process, we introduce action mapping, a novel approach that divides the learning process into two steps: first learn feasibility and subsequently, the objective by mapping actions into the sets of feasible actions. This paper focuses on the feasibility part by learning to generate all feasible actions through self-supervised querying of the feasibility model. We train the agent by formulating the problem as a distribution matching problem and deriving gradient estimators for different divergences. Through an illustrative example, a robotic path planning scenario, and a robotic grasping simulation, we demonstrate the agent’s proficiency in generating actions across disconnected feasible action sets. By addressing the feasibility step, this paper makes it possible to focus future work on the objective part of action mapping, paving the way for an RL framework that is both safe and efficient.

Abstract Tailoring vacancies is a feasible way to improve the mechanical properties of ceramics. However, high concentrations of vacancies usually compromise the strength (or hardness). We show that a high elasticity and flexural strength could be achieved simultaneously using a nitride superlattice architecture with disordered anion vacancies up to 50%. Enhanced mechanical properties primarily result from a distinctive deformation mechanism in superlattice ceramics, i.e., unit-cell disturbances. Such a disturbance substantially relieves local high-stress concentration, thus enhancing deformability. No dislocation activity involved also rationalizes its high strength. The work renders a unique understanding of the deformation and strengthening/toughening mechanism in nitride ceramics.

Abstract Long-range electronic ordering descending from a metallic parent state constitutes a rich playground to study the interplay of structural and electronic degrees of freedom. In this framework, kagome metals are in the most interesting regime where both phonon and electronically mediated couplings are significant. Several of these systems undergo a charge density wave transition. However, to date, the origin and the main driving force behind this charge order is elusive. Here, we use the kagome metal ScV6Sn6 as a platform to investigate this problem, since it features both a kagome-derived nested Fermi surface and van-Hove singularities near the Fermi level, and a charge-ordered phase that strongly affects its physical properties. By combining time-resolved reflectivity, first principles calculations and photo-emission experiments, we identify the structural degrees of freedom to play a fundamental role in the stabilization of charge order, indicating that ScV6Sn6 features an instance of charge order predominantly originating from phonons.

Background and Objectives: To achieve success in endodontic treatment, it is essential to properly perform the steps of shaping, cleansing and obturation. Determining the working length of the canal is, therefore, a process that must be precise and accurate. Electronic apex locators are a useful tool for the clinician to best perform this step of endodontic treatment. Materials and Methods: The purpose of the following umbrella review is to evaluate, through data in the literature, the degree of accuracy of apex locators. Results: Seven systematic reviews were included in the following umbrella review. Five compare the accuracy of apex locators versus radiographic techniques, two compare different types of electronic apex locators, and two analyze the determination of working length in primary teeth. Conclusions: From the results obtained from the following umbrella review, albeit at low levels of evidence, the methods for determining working length using electronic apex locators and other methods, particularly using radiographic evaluation, are equally valid.

The interplay of dynamical correlations and electronic ordering is pivotal in shaping phase diagrams of correlated quantum materials. In magic-angle twisted bilayer graphene, transport, thermodynamic, and spectroscopic experiments pinpoint a competition between distinct low-energy states with and without electronic order, as well as between localized and delocalized charge carriers. In this study, we utilize dynamical mean-field theory on the topological heavy fermion model of twisted bilayer graphene to investigate the emergence of electronic correlations and long-range order in the absence of strain. We contrast moment formation, Kondo screening, and ordering on a temperature basis and explain the nature of emergent correlated states based on three central phenomena: (i) the formation of local spin and valley isospin moments around 100 K, (ii) the ordering of the local isospin moments around 10 K preempting Kondo screening, and (iii) a cascadic redistribution of charge between localized and delocalized electronic states upon doping. At integer fillings, we find that low-energy spectral weight is depleted in the symmetric phase, while we find insulating states with gaps enhanced by exchange coupling in the zero-strain ordered phases. Doping away from integer filling results in distinct metallic states: a “bad metal” above the ordering temperature, where scattering off the disordered local moments suppresses electronic coherence, and a “good metal” in the ordered states with coherence of quasiparticles facilitated by isospin order. This finding reveals coherence from order as the microscopic mechanism behind the Pomeranchuk effect observed experimentally by Rozen et al. [Nature (London) 592, 214 (2021)NATUAS0028-083610.1038/s41586-021-03319-3] and by Saito et al. [Nature (London) 592, 220 (2021)NATUAS0028-083610.1038/s41586-021-03409-2]. Upon doping, there is a periodic charge reshuffling between localized and delocalized electronic orbitals leading to cascades of doping-induced Lifshitz transitions, local spectral weight redistributions, and periodic variations of the electronic compressibility ranging from nearly incompressible to negative. Our findings highlight the essential role of charge transfer, hybridization, and ordering in shaping the electronic excitations and thermodynamic properties in twisted bilayer graphene and provide a unified understanding of the most puzzling aspects of scanning tunneling spectroscopy, transport, and compressibility experiments.

MAB phases (MABs) are atomically-thin laminates of ceramic/metallic-like layers, having made a breakthrough in the development of 2D materials. Though offering a vast chemical and phase space, relatively few MABs have been synthesised. To guide experiments, we perform high-throughput ab initio screening of MABs that combine group 4–7 transition metals (M); Al, Si, Ga, Ge, or In (A); and boron (B) focusing on their phase stability trends and mechanical properties. Considering the 1:1:1, 2:1:1, 2:1:2, 3:1:2, 3:1:3, and 3:1:4 M:A:B ratios and 10 phase prototypes, synthesisability of a single-phase compound for each elemental combination is estimated through formation energy spectra of competing dynamically stable MABs. Based on the volumetric proximity of energetically-close phases, we identify systems in which volume-changing deformations may facilitate transformation toughening. Subsequently, chemistry- and phase-structure-related trends in the elastic stiffness and ductility are predicted using elastic-constants-based descriptors. The analysis of directional Cauchy pressures and Young's moduli allows comparing mechanical response parallel and normal to M–B/A layers. The suggested promising MABs include Nb3AlB4, Cr2SiB2, Mn2SiB2 or the already synthesised MoAlB.

Abstract Doped Mott insulators are the starting point for interesting physics such as high temperature superconductivity and quantum spin liquids. For multi-band Mott insulators, orbital selective ground states have been envisioned. However, orbital selective metals and Mott insulators have been difficult to realize experimentally. Here we demonstrate by photoemission spectroscopy how Ca2RuO4, upon alkali-metal surface doping, develops a single-band metal skin. Our dynamical mean field theory calculations reveal that homogeneous electron doping of Ca2RuO4 results in a multi-band metal. All together, our results provide evidence for an orbital-selective Mott insulator breakdown, which is unachievable via simple electron doping. Supported by a cluster model and cluster perturbation theory calculations, we demonstrate a type of skin metal-insulator transition induced by surface dopants that orbital-selectively hybridize with the bulk Mott state and in turn produce coherent in-gap states.

Background: The human being is defined as a ‘superorganism’ since it is made up of its own cells and microorganisms that reside inside and outside the human body. Commensal microorganisms, which are even ten times more numerous than the cells present in the body, perform very important functions for the host, as they contribute to the health of the host, resist pathogens, maintain homeostasis, and modulate the immune system. In the mouth, there are different types of microorganisms, such as viruses, mycoplasmas, bacteria, archaea, fungi, and protozoa, often organized in communities. The aim of this umbrella review is to evaluate if there is a connection between the oral microbiome and systematic diseases. Methodology: A literature search was conducted through PubMed/MEDLINE, the COCHRANE library, Scopus, and Web of Science databases without any restrictions. Because of the large number of articles included and the wide range of methods and results among the studies found, it was not possible to report the results in the form of a systematic review or meta-analysis. Therefore, a narrative review was conducted. We obtained 73.931 results, of which 3593 passed the English language filter. After the screening of the titles and abstracts, non-topic entries were excluded, but most articles obtained concerned interactions between the oral microbiome and systemic diseases. Discussion: A description of the normal microbial flora was present in the oral cavity both in physiological conditions and in local pathological conditions and in the most widespread systemic pathologies. Furthermore, the therapeutic precautions that the clinician can follow in order to intervene on the change in the microbiome have been described. Conclusions: This review highlights what are the intercorrelations of the oral microbiota in healthy subjects and in subjects in pathological conditions. According to several recent studies, there is a clear correlation between dysbiosis of the oral microbiota and diseases such as diabetes, cardiovascular diseases, chronic inflammatory diseases, and neurodegenerative diseases.

Abstract The topological classification of electronic band structures is based on symmetry properties of Bloch eigenstates of single-particle Hamiltonians. In parallel, topological field theory has opened the doors to the formulation and characterization of non-trivial phases of matter driven by strong electron-electron interaction. Even though important examples of topological Mott insulators have been constructed, the relevance of the underlying non-interacting band topology to the physics of the Mott phase has remained unexplored. Here, we show that the momentum structure of the Green’s function zeros defining the “Luttinger surface" provides a topological characterization of the Mott phase related, in the simplest description, to the one of the single-particle electronic dispersion. Considerations on the zeros lead to the prediction of new phenomena: a topological Mott insulator with an inverted gap for the bulk zeros must possess gapless zeros at the boundary, which behave as a form of “topological antimatter” annihilating conventional edge states. Placing band and Mott topological insulators in contact produces distinctive observable signatures at the interface, revealing the otherwise spectroscopically elusive Green’s function zeros.

A prosthetic rehabilitation, whether supported by implants, teeth, or mucous membranes, must be functionally and aesthetically adequate, so it is essential that the oral structures are reproduced as accurately as possible. The purpose of this overview is to evaluate the accuracy, time of digital impressions, and patient preference compared to those of conventional high-precision in vivo impressions. This umbrella review was developed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement and was registered in the PROSPERO systematic review registry. The search method and study selection were based on the PEO (Population–Exposure–Outcome) model, a modified version of the PICO model. Systematic reviews regarding the dental impression technique made using an intraoral scanner versus the analog impression technique made with high-precision impression materials were searched electronically up to 1 February 2023 among articles published in English, through numerous registries and databases, such as PROSPERO e, Scopus, MEDLINE/ PubMed, BioMed Central, and Cochrane Library. The records screened totaled 2942, but only 23 systematic reviews were included in this umbrella review. The Assessing the Methodological Quality of Systematic Reviews (AMSTAR) 2 tool was used to evaluate the quality assessment of the systematic reviews included in this umbrella review. Accuracy, time, and patient preference for digital impressions were compared with those of high-precision conventional impressions. A total of 23 systematic reviews were included in this umbrella review. From the analysis of this umbrella review, the data on the accuracy between the two methods of taking the impression are conflicting, especially as regards full-arch rehabilitations. However, the digital impression seems to be preferred over the analog one as regards time and patient preference. However, there is limited high-quality evidence available for studying conventional and digital implant impressions. The results obtained are limited to the type of review performed, and the type of studies included was limited by the settings and study designs. Furthermore, another important limitation highlighted was that the digital scanners analyzed in the various studies are not the same, and the number of missing teeth or implants inserted is not the same. More in vivo clinical studies and RCTs are needed to increase the level of evidence for impression procedures.