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Abstract The two-dimensional electron gas (2DEG) at the LaAlO $$_3$$ /SrTiO $$_3$$ (LAO/STO) interface exhibits gate-tunable superconductivity with a dome-like shape of critical temperature as a function of electron concentration. This behavior has not been unambiguously explained yet. Here, we develop a microscopic model based on the Schrödinger–Poisson approach to determine the electronic structure of the LAO/STO 2DEG, which we then apply to study the principal characteristics of the superconducting phase within the real-space pairing mean-field approach. For the electron concentrations reported in the experiment, we successfully reproduce the dome-like shape of the superconducting gap. According to our analysis such behavior results from the interplay between the Fermi surface topology and the gap symmetry, with the dominant extended s-wave contribution. Similarly as in the experimental report, we observe a bifurcation effect in the superconducting gap dependence on the electron density when the 2DEG is electrostatically doped either with the top gate or the bottom gate. Our findings explains the dome-shaped phase diagram of the considered heterostucture with good agreement with the experimental data which, in turn, strongly suggest the appearance of the extended s-wave symmetry of the gap in 2DEG at the LAO/STO interface.

Abstract Apical hypertrophic cardiomyopathy (ApHCM) is an HCM variant, affecting frequently males in midlife. It is characterized by apical obliteration and persistent diastolic contraction, often resulting in microvascular ischaemia. We report five cases of ApHCM, with evidence of intramyocardial calcification on echocardiogram. On cardiac magnetic imaging (MRI), a hypointense component at early gadolinium enhancement (EGE) sequences, compatible with calcium, and a deep layer, with hyperintensity at late gadolinium enhancement (LGE) sequences, referable to fibrosis, suggest an endomyocardial fibrosis (EMF) diagnosis. EMF pathologic hallmark is endocardium and myocardium scarring, evolving to dystrophic calcification. It is found only in few ApHCM patients. Our series is the largest one described until now. Analysing patients' history, coexistent inflammatory triggers were evident in all of them, so their co‐morbidities could represent a further cause of small vessel disease, in the context of ischaemic microvascular stress due to hypertrophy, leading to fibrosis and dystrophic calcification. This series could demonstrate the relation between apical fibrosis/calcification and microvascular ischaemia due to hypertrophy and inflammatory triggers.

Bicuspid aortic valve (BAV) is the most common congenital heart malformation in adults, but it can also cause childhood-onset complications. The presentation and clinical course of young adults who present due to BAV complications are relatively uncharacterized. In a multicenter study, we found that young people who experience significant complications related to BAV disease before age 30 are distinguished from the majority of BAV cases that manifest after age 50 by a relatively severe clinical course, with higher rates of surgical interventions, more frequent second interventions, and a greater burden of congenital heart malformations. These observations highlight the need for prompt recognition, regular lifelong surveillance, and targeted interventions to address the significant health burdens of patients with early-onset BAV complications.

Background Whether the presence of right ventricular (RV) dysfunction may influence the clinical outcome of patients with low‐flow, low‐gradient aortic stenosis (LFLG‐AS) undergoing transcatheter aortic valve replacement (TAVR) has not yet been established. Methods and Results This study included consecutive patients with LFLG‐AS undergoing TAVR at 2 high‐volume Italian centers. RV dysfunction before TAVR procedure was defined as tricuspid annular plane systolic excursion assessed by transthoracic echocardiography lower than

Introdução: O Papilomavírus Humano (HPV) é uma causa significativa de câncer cervical e outras doenças. A prevenção tradicionalmente exige múltiplas doses da vacina, o que é desafiador em áreas com acesso limitado à saúde. Estudos recentes sugerem que uma única dose pode ser eficaz, simplificando a vacinação, reduzindo custos e ampliando a cobertura. Objetivo: Avaliar a eficácia e imunogenicidade de uma dose única da vacina bivalente contra o HPV, comparando-a com regimes de múltiplas doses. O estudo investiga se a dose única oferece proteção comparável, facilitando a implementação em regiões com recursos limitados e reduzindo custos e complexidades logísticas. Também examina o impacto econômico e a aceitabilidade da estratégia. Método: A busca sistemática na base de dados PubMed usou palavras-chave como “HPV”, “dose única” e “eficácia da vacina”. Foram incluídos estudos clínicos randomizados, publicados nos últimos dez anos, que compararam a vacina de dose única com regimes de múltiplas doses. Excluímos estudos sem dados originais ou comparações diretas de dosagem, e os que não focaram nos tipos de HPV das vacinas bivalentes. Revisamos metodologias, consistência dos resultados e possíveis vieses. Resultados: A vacinação com uma dose única produziu respostas de anticorpos estáveis e eficazes por até quatro anos, comparáveis às vacinas de múltiplas doses. Todos os grupos de dose única mantiveram seropositividade para HPV16/18, com titulações de anticorpos elevadas em comparação com a infecção natural, sugerindo proteção de longo prazo semelhante. Conclusão: Uma única dose da vacina contra o HPV pode oferecer proteção de longo prazo, potencialmente transformando as estratégias de vacinação globalmente, especialmente em regiões com acesso limitado à saúde. Isso pode aumentar a cobertura, reduzir custos e melhorar a aceitação da vacina, combatendo efetivamente o câncer cervical.

This opinion paper evaluates the potential of porcine islets as a promising alternative in beta cell replacement therapy for Type 1 Diabetes (T1D), juxtaposed with the current limitations of human donor islets. It analyzes the compatibility of pig islets with human glucose metabolism, their prospects as a limitless and high-quality source of beta cells, and the unique immunogenic challenges they present in xenotransplantation. Additionally, the paper discusses the regulatory and ethical considerations pertinent to the use of porcine islets. By synthesizing current research and expert perspectives, the paper highlights both the opportunities and significant barriers that need addressing to advance pig islets as a viable therapeutic option. The findings advocate for a balanced and forward-looking approach to the integration of pig islets in T1D treatment, underscoring the need for continued research and dialogue in this evolving field.

Background. The development of a hybrid beta-cell replacement approach, referred to as a personalized, transplantable bioartificial pancreas (BAP), holds promise to treat type 1 diabetes (T1D). This interview study aimed to explore patients’ expectations, needs, concerns, and considerations when considering to undergo a BAP transplantation. Research Design and Methods. Semistructured interviews were conducted with 24 participants diagnosed with T1D. Data collection stopped once data saturation was reached. Audio recordings of the interviews were transcribed verbatim. The interviews were independently analyzed by 2 researchers. A qualitative content analysis using an inductive approach was used. Results. Three main themes emerged as follow: (1) hoped-for benefits, (2) concerns and decision-making considerations, and (3) procedural aspects. First, the participants expected benefits across medical, psychological, and social domains. Over these 3 domains, 9 subthemes were identified, including improved clinical outcomes, a cure for diabetes, more headspace, emotional relief, a shift in responsibility, protection of privacy, improved flexibility in daily life, less visible diseases, and improved relationships with others. Second, concerns and considerations about undergoing a BAP transplant comprised adverse events, the functionality of the BAP, the surgery procedure, the biological materials used, the transplant location, and the intrusiveness associated with follow-up care. Finally, procedural considerations included equitable access, patient prioritization, and trust and control. Conclusions. Incorporating insights from this study into the clinical development and implementation of the BAP is crucial to ensure alignment of the product and procedures with the needs and expectations of people with T1D.

AbstractDespite providing objective, benchmark statistics on the condition and progress of U.S. education since 1867, the National Center for Education Statistics has been the center of scrutiny over the last dozen years for its lack of resources and agility as well as for its diminished stature and autonomy. Motivated by the COVID-19 pandemic exposure of NCES’ bureaucratic hurdles, Congress’ interest in reauthorizing the agency and its umbrella organization, and the 2022 National Academies’ report, A Vision and Roadmap for Education Statistics, we explore legislative changes and attendant administrative actions that would contribute to building the trust of respondents who provide data to NCES and users who depend on the agency’s products; our article offers recommendations to that end.

In the recent years there has been a significant increase in the interest surrounding the interconnection of AC and DC networks due to its potential to improve the power systems reliability. Despite the potential advantages, however, the AC and DC grid coexistence can pose challenges if not appropriately managed. In this scenario, this paper presents an enhanced control scheme enabling the use of Virtual Synchronous Generators (VSGs) as elements of interconnection between AC and DC networks. The proposed solution enables VSG operation with both fast dynamics for DC voltage regulation and slow dynamics for AC inertia emulation. This approach accommodates the contrasting requirements arising from the distinct mechanisms of DC voltage regulation and AC frequency regulation. Simulation and experimental results obtained with a 8 kVA three-phase converter prototype are provided to validate the effectiveness of the proposed technique and prove its better performances with respect to the solutions currently presented in literature.

Abstract Liver fat storage, also called hepatic steatosis, is increasingly common and represents a very frequent diagnosis in the medical field. Excess fat is not without consequences. In fact, hepatic steatosis contributes to the progression toward liver fibrosis. There are two main types of fatty liver disease, alcoholic fatty liver disease (AFLD) and nonalcoholic fatty liver disease (NAFLD). Although AFLD and NAFLD are similar in their initial morphological features, both conditions involve the same evolutive forms. Moreover, there are various common mechanisms underlying both diseases, including alcoholic liver disease and NAFLD, which are commonalities. In this Review, the authors explore similar downstream signaling events involved in the onset and progression of the two entities but not completely different entities, predominantly focusing on the gut microbiome. Downstream molecular events, such as the roles of sirtuins, cytokeratins, adipokines and others, should be considered. Finally, to complete the feature, some new tendencies in the therapeutic approach are presented.

The superconducting diode effect, reminiscent of the unidirectional charge transport in semiconductor diodes, is characterized by a nonreciprocal, dissipationless flow of Cooper pairs. This remarkable phenomenon arises from the interplay between symmetry constraints and the inherent quantum behavior of superconductors. Here, we explore the geometric control of the diode effect in a kinked nanostrip Josephson junction based on a two-dimensional electron gas (2DEGs) with Rashba spin-orbit interaction. We provide a comprehensive analysis of the diode effect as a function of the kink angle and the out-of-plane magnetic field. Our analysis reveals a rich phase diagram, showcasing a geometry and field-controlled diode effect. The phase diagram also reveals the presence of an anomalous Josephson effect related to the emergence of trivial zero-energy Andreev bound states, which can evolve into Majorana bound states. Our findings indicate that the exceptional synergy between geometric control of the diode effect and topological phases can be effectively leveraged to design and optimize superconducting devices with tailored transport properties.

Abstract Autophagy is important for the removal, degradation and recycling of damaged organelles, proteins, and lipids through the degradative action of lysosomes. In addition to its catabolic function, autophagy is important in cancer and viral-mediated tumorigenesis, including Human Papillomavirus (HPV) positive cancers. HPV infection is a major risk factor in a subset of head and neck cancer (HNC), for which no targeted therapies are currently available. Herein, we assessed autophagy function in HPV-positive HNC. We showed that HPV-positive HNC cells presented a transcriptional and functional impairment of the autophagic process compared to HPV-negative cells, which were reactivated by knocking down HPV E6/E7 oncoproteins, the drivers of cellular transformation. We found that the oncoprotein c-MYC was stabilized and triggered in HPV-positive cell lines. This resulted in the reduced binding of the MiT/TFE transcription factors to their autophagy targets due to c-MYC competition. Thus, the knock-down of c-MYC induced the upregulation of autophagic and lysosomal genes in HPV-positive HNC cells, as well as the increase of autophagic markers at the protein level. Moreover, HPV oncoprotein E7 upregulated the expression of the phosphatase inhibitor CIP2A, accounting for c-MYC upregulation and stability in HPV+ HNC cells. CIP2A mRNA expression negatively correlated with autophagy gene expression in tumor tissues from HNC patients, showing, for the first time, its implication in a transcriptional autophagic context. Both CIP2A and c-MYC knock-down, as well as pharmacological downregulation of c-MYC, resulted in increased resistance to cisplatin treatment. Our results not only show a novel way by which HPV oncoproteins manipulate the host machinery but also provide more insights into the role of autophagy in chemoresistance, with possible implications for targeted HPV-positive HNC therapy.

Genomic surveillance based on sequencing the entire genetic code of SARS-CoV-2 involves monitoring and studying genetic changes and variations in disease-causing organisms such as viruses and bacteria. By tracing the virus, it is possible to prevent epidemic spread in the community, ensuring a ‘precision public health’ strategy. A peptide-based design was applied to provide an efficacious strategy that is able to counteract any emerging viral variant of concern dynamically and promptly to affect the outcomes of a pandemic at an early stage while waiting for the production of the anti-variant-specific vaccine, which require longer times. The inhibition of the interaction between the receptor-binding domain (RBD) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and one of the cellular receptors (DPP4) that its receptors routinely bind to infect human cells is an intriguing therapeutic approach to prevent the virus from entering human cells. Among the other modalities developed for this purpose, peptides surely offer unique advantages, including ease of synthesis, serum stability, low immunogenicity and toxicity, and small production and distribution chain costs. Here, we obtained a potent new inhibitor based on the rearrangement of a previously identified peptide that has been rationally designed on a cell dipeptidyl peptidase 4 (DPP4) sequence, a ubiquitous membrane protein known to bind the RBD-SPIKE domain of the virus. This novel peptide (named DPP4-derived), conceived as an endogenous “drug”, is capable of targeting the latest tested variants with a high affinity, reducing the VSV* DG-Fluc pseudovirus Omicron’s infection capacity by up to 14%, as revealed by in vitro testing in human Calu-3 cells. Surface plasmon resonance (SPR) confirmed the binding affinity of the new DPP4-derived peptide with Omicron variant RBD.

Trustworthy medical AI requires transparency about the development and testing of underlying algorithms to identify biases and communicate potential risks of harm. Abundant guidance exists on how to achieve transparency for medical AI products, but it is unclear whether publicly available information adequately informs about their risks. To assess this, we retrieved public documentation on the 14 available CE-certified AI-based radiology products of the II b risk category in the EU from vendor websites, scientific publications, and the European EUDAMED database. Using a self-designed survey, we reported on their development, validation, ethical considerations, and deployment caveats, according to trustworthy AI guidelines. We scored each question with either 0, 0.5, or 1, to rate if the required information was “unavailable”, “partially available,” or “fully available.” The transparency of each product was calculated relative to all 55 questions. Transparency scores ranged from 6.4% to 60.9%, with a median of 29.1%. Major transparency gaps included missing documentation on training data, ethical considerations, and limitations for deployment. Ethical aspects like consent, safety monitoring, and GDPR-compliance were rarely documented. Furthermore, deployment caveats for different demographics and medical settings were scarce. In conclusion, public documentation of authorized medical AI products in Europe lacks sufficient public transparency to inform about safety and risks. We call on lawmakers and regulators to establish legally mandated requirements for public and substantive transparency to fulfill the promise of trustworthy AI for health.

Bicuspid aortic valve (BAV), the most common congenital heart defect, is a major cause of aortic valve disease requiring valve interventions and thoracic aortic aneurysms predisposing to acute aortic dissections. The spectrum of BAV ranges from early onset valve and aortic complications (EBAV) to sporadic late onset disease. Rare genomic copy number variants (CNVs) have previously been implicated in the development of BAV and thoracic aortic aneurysms. We determined the frequency and gene content of rare CNVs in EBAV probands (n = 272) using genome-wide SNP microarray analysis and three complementary CNV detection algorithms (cnvPartition, PennCNV, and QuantiSNP). Unselected control genotypes from the Database of Genotypes and Phenotypes were analyzed using identical methods. We filtered the data to select large genic CNVs that were detected by multiple algorithms. Findings were replicated in a BAV cohort with late onset sporadic disease (n = 5040). We identified 3 large and rare (< 1,1000 in controls) CNVs in EBAV probands. The burden of CNVs intersecting with genes known to cause BAV when mutated was increased in case-control analysis. CNVs intersecting with GATA4 and DSCAM were enriched in cases, recurrent in other datasets, and segregated with disease in families. In total, we identified potentially pathogenic CNVs in 9% of EBAV cases, implicating alterations of candidate genes at these loci in the pathogenesis of BAV.

IntroductionBicuspid aortic valve (BAV) is the most common congenital heart disease with an increased risk of infective endocarditis (IE). Few data are available on isolated native BAV-IE. The aim of this study was to compare patients with tricuspid aortic valve (TAV) IE and BAV-IE in terms of characteristics, management and prognosis.Material and methodsWe included 728 consecutive patients with IE on isolated native aortic valve in 3 centres: Amiens and Marseille Hospitals in France and Salerno Hospital in Italy. We studied in hospital and long-term mortality before and after matching for age, sex and comorbidity index. Median follow-up was 67.2 [IQR: 19–120] months.ResultsOf the 728 patients, 123 (16.9%) had BAV. Compared with patients with TAV-IE, patients with BAV-IE were younger, had fewer co-morbidities and were more likely to be male. They presented more major neurological events and perivalvular complications (both p

AbstractWe assess the professional autonomy of the 13 principal U.S. federal statistical agencies. We define six components or measures of such autonomy and evaluate each of the 13 principal statistical agencies according to each measure. Our assessment yields three main findings: (a) Challenges to the objectivity, credibility, and utility of federal statistics arise largely as a consequence of insufficient autonomy. (b) There is remarkable variation in autonomy protections and a surprising lack of statutory protections for many agencies for many of the proposed measures. (c) Many existing autonomy rules and guidelines are weakened by unclear or unactionable language. We conclude that a lack of professional autonomy unduly exposes the principal federal statistical agencies to efforts to undermine the objectivity of their products and that agencies cannot completely rebuff these efforts. Our main recommendations are to strengthen the role of the OMB Chief Statistician and to legislate new statutory autonomy protections, including explicit authorization for the principal federal statistical agencies that currently have no recognition in statute. We also recommend periodic assessments of the health of the federal statistical system, including not only autonomy protections and resources, but also how well agencies are satisfying data needs for the public good and using best methods to do so.

The use of traditional Dye-sensitized solar cells (DSSCs) is limited due to the use of toxic and non-environmentally safe solvents. In this review, water is proposed as a viable alternative to developing green chemistry and sustainable materials for DSSCs. However, water-based DSSCs (WBDSSCs) require improvement in their photovoltaic parameters. The detachment of dye molecules from the semiconductor and the poor solubility of iodine in water are the primary reasons for their low efficiency. This review analyzes the best results achieved by 100% aqueous electrolytes containing synthetic, organic, and natural dyes to identify the best conditions to overcome these limitations. Developing a suitable photoanode/electrolyte interface and finding a compromise in the choice of dye are the main research goals in the coming years. WBDSSCs can contribute significantly to producing clean energy using sustainable and environmentally friendly materials. Furthermore, here we report the state of the art of the emerging technology of underwater dye-sensitized solar cells, which are a promising technology for generating renewable energy in aquatic environments. Recent advancements in material science and device engineering have shown promising results in enhancing their efficiency and durability. Further research and development can make these devices a viable alternative for sustainable energy generation in a wide range of underwater applications.

Abstract Aims Sacubitril/valsartan has changed the treatment of heart failure with reduced ejection fraction (HFrEF), due to the positive effects on morbidity and mortality, partly mediated by left ventricular (LV) reverse remodelling (LVRR). The aim of this multicenter study was to identify echocardiographic predictors of LVRR after sacubitril/valsartan administration. Methods and results Patients with HFrEF requiring therapy with sacubitril/valsartan from 13 Italian centres were included. Echocardiographic parameters including LV global longitudinal strain (GLS) and global peak atrial longitudinal strain by speckle tracking echocardiography were measured to find the predictors of LVRR [= LV end‐systolic volume reduction ≥10% and ejection fraction (LVEF) improvement ≥10% at follow‐up] at 6 month follow‐up as the primary endpoint. Changes in symptoms [New York Heart Association (NYHA) class] and neurohormonal activations [N‐terminal pro‐brain natriuretic peptide (NT‐proBNP)] were also evaluated as secondary endpoints; 341 patients (excluding patients with poor acoustic windows and missing data) were analysed (mean age: 65 ± 10 years; 18% female, median LVEF 30% [inter‐quartile range: 25−34]). At 6 month follow‐up, 82 (24%) patients showed early complete response (LVRR and LVEF ≥ 35%), 55 (16%) early incomplete response (LVRR and LVEF

The optimal management of heart valve disease (HVD) is still debated and many studies are underway to identify the best time to refer patients for the most appropriate treatment strategy (either conservative, surgical or transcatheter interventions). Exercise pulmonary hypertension (PH) can be detected during exercise stress echocardiography (ESE) and has been demonstrated to have an important prognostic role in HVD, by predicting symptoms and mortality. This review article aims to provide an overview on the prognostic role of exercise PH in valvulopathies, and its possible role in the diagnostic-therapeutic algorithm for the management of HVD.

In this work, we study the topological phase transitions of a Kitaev chain generalized by the addition of nearest-neighbor Coulomb interaction. We show the presence of a robust topological phase as a function of the interaction strength and of the on-site energy with associated non-zero energy Majorana states localized at the chain edges. We provide an effective mean-field model that allows for the self-consistent computation of the mean value of the local particle number operator, and we also perform Density Matrix Renormalization Group numerical simulations based on a tensor network approach. We find that the two methods show a good agreement in reporting the phase transition between trivial and topological superconductivity. Temperature robustness within a physically relevant threshold has also been demonstrated. These findings shed light on an entire class of topological interacting one-dimensional systems in which the effects of residual Coulomb interactions play a relevant role.

Type 1 diabetes (T1D) presents a persistent medical challenge, demanding innovative strategies for sustained glycemic control and enhanced patient well-being. Beta cells are specialized cells in the pancreas that produce insulin, a hormone that regulates blood sugar levels. When beta cells are damaged or destroyed, insulin production decreases, which leads to T1D. Allo Beta Cell Transplantation has emerged as a promising therapeutic avenue, with the goal of reinstating glucose regulation and insulin production in T1D patients. However, the path to success in this approach is fraught with complex immunological hurdles that demand rigorous exploration and resolution for enduring therapeutic efficacy. This exploration focuses on the distinct immunological characteristics inherent to Allo Beta Cell Transplantation. An understanding of these unique challenges is pivotal for the development of effective therapeutic interventions. The critical role of glucose regulation and insulin in immune activation is emphasized, with an emphasis on the intricate interplay between beta cells and immune cells. The transplantation site, particularly the liver, is examined in depth, highlighting its relevance in the context of complex immunological issues. Scrutiny extends to recipient and donor matching, including the utilization of multiple islet donors, while also considering the potential risk of autoimmune recurrence. Moreover, unanswered questions and persistent gaps in knowledge within the field are identified. These include the absence of robust evidence supporting immunosuppression treatments, the need for reliable methods to assess rejection and treatment protocols, the lack of validated biomarkers for monitoring beta cell loss, and the imperative need for improved beta cell imaging techniques. In addition, attention is drawn to emerging directions and transformative strategies in the field. This encompasses alternative immunosuppressive regimens and calcineurin-free immunoprotocols, as well as a reevaluation of induction therapy and recipient preconditioning methods. Innovative approaches targeting autoimmune recurrence, such as CAR Tregs and TCR Tregs, are explored, along with the potential of stem stealth cells, tissue engineering, and encapsulation to overcome the risk of graft rejection. In summary, this review provides a comprehensive overview of the inherent immunological obstacles associated with Allo Beta Cell Transplantation. It offers valuable insights into emerging strategies and directions that hold great promise for advancing the field and ultimately improving outcomes for individuals living with diabetes.

Currently, there are 2 proposed causes of acute left ventricular ballooning. The first is the most cited hypothesis that ballooning is caused by direct catecholamine toxicity on cardiomyocytes or by microvascular ischemia. We refer to this pathogenesis as Takotsubo syndrome. More recently, a second cause has emerged: that in some patients with underlying hypertrophic cardiomyopathy, left ventricular ballooning is caused by the sudden onset of latent left ventricular outflow tract obstruction. When it becomes severe and unrelenting, severe afterload mismatch and acute supply–demand ischemia appear and result in ballooning. In the context of 2 causes, presentations might overlap and cause confusion. Knowing the pathophysiology of each mechanism and how to determine a correct diagnosis might guide treatment.

Resumen Nuestro objetivo es analizar una serie de estrategias metodológicas basadas en la performance, elaboradas entre 2016-2017 por un grupo coordinado por la autora. Estas estrategias transdisciplinares fueron diseñadas para investigar colectivamente experiencias de violencias vividas principalmente por mujeres y, desde estas genealogías, activar potencias micropolíticas de re-existencia. Especialmente, focalizamos en cómo estas metodologías se inspiraron en nuestros registros sobre las expresiones performáticas y los relatos de las activistas feministas en torno a las Marchas del Ni Una Menos contra la violencia de género, iniciadas en 2015 en la ciudad de Buenos Aires, Argentina. Destacamos las principales contribuciones epistemológicas y políticas de estas metodologías experimentales desplegadas en un territorio aún heterodoxo, en el que la investigación antropológica se entrecruza con la creación artística y el activismo político. Así, intentamos ampliar nuestros modos de conocimiento y compromiso activo con los debates y las disputas de los contextos sociales en los que participamos.

Introduction: CSF Neurofilament light chain(NfL) is a promising biomarker of neurodegeneration, but its utility in discriminating between Alzheimer's disease(AD) and frontotemporal dementia(FTD) is limited. Methods: 105 patients with clinical-biological diagnosis of mild cognitive impairment(MCI) due to AD (N = 72) or clinical diagnosis of FTD (N = 33) underwent neuropsychological assessment and CSF Aβ42/40, p-tau181, total-tau and NfL quantification. Group comparisons, correlations between continuous variables and ROC curve analysis were carried out to assess NfL role in discriminating between MCI due to AD and FTD, exploring the associations between NfL, ATN biomarkers and neuropsychological measures. Results: NfL levels were significantly lower in the AD group, while levels of total-tau were higher. In the FTD group, significant correlations were found between NfL, p-tau181 and total-tau, and between NfL and cognitive performances. In the AD group, NfL levels were directly correlated with total-tau and p-tau181; Aβ42/40 ratio was inversely correlated with total-tau and p-tau181, but not with NfL. Moreover, p-tau181 and t-tau levels were found to be associated with episodic memory and lexical-semantic impairment. Total-tau/NfL ratio differentiated prodromal-AD from FTD with an AUC of 0.951, higher than the individual measures. Discussion & conclusions: The results support that NfL and total-tau levels reflect distinct pathophysiological neurodegeneration mechanisms, independent and dependent of Aβ pathology, respectively, Combining them may enhance both markers reliability, their ratio showing high accuracy in distinguishing MCI due to AD from FTD. Moreover, our results revealed associations between NfL and disease severity in FTD and between tauopathy and episodic memory and lexical-semantic impairment in prodromal-AD.

ObjectivesIt is uncertain whether concurrent mitral valve repair or replacement for moderate or greater secondary mitral regurgitation at the time of coronary artery bypass graft or aortic valve replacement surgery improves long-term survival.MethodsPatients undergoing coronary artery bypass graft and/or aortic valve replacement surgery with moderate or greater secondary mitral regurgitation were reviewed. The effect of concurrent mitral valve repair or replacement upon long-term mortality was assessed while accounting for patient and operative characteristics and mitral regurgitation severity.ResultsOf 1,515 patients, 938 underwent coronary artery bypass graft or aortic valve replacement surgery alone and 577 underwent concurrent mitral valve repair or replacement. Concurrent mitral valve repair or replacement did not alter the risk of postoperative mortality for patients with moderate mitral regurgitation (hazard ratio = 0.93; 0.75–1.17) or more-than-moderate mitral regurgitation (hazard ratio = 1.09; 0.74–1.60) in multivariable regression. Patients with more-than-moderate mitral regurgitation undergoing coronary artery bypass graft-only surgery had a survival advantage from concurrent mitral valve repair or replacement in the first two postoperative years (P = 0.028) that did not persist beyond that time. Patients who underwent concurrent mitral valve repair or replacement had a higher rate of later mitral valve operation or reoperation over the five subsequent years (1.9% vs. 0.2%; P = 0.0014) than those who did not.ConclusionsThese observations suggest that mitral valve repair or replacement for more-than-moderate mitral regurgitation at the time of coronary artery bypass grafting may be reasonable in a suitably selected coronary artery bypass graft population but not for aortic valve replacement, with or without coronary artery bypass grafting. Our findings are supportive of 2021 European guidelines that severe secondary mitral regurgitation “should” or be “reasonabl[y]” intervened upon at the time of coronary artery bypass grafting but do not support 2020 American guidelines for performing mitral valve repair or replacement concurrent with aortic valve replacement, with or without coronary artery bypass grafting.

Tendons are dense connective tissues with a hierarchical polarized structure that respond to and adapt to the transmission of muscle contraction forces to the skeleton, enabling motion and maintaining posture. Tendon injuries, also known as tendinopathies, are becoming more common as populations age and participation in sports/leisure activities increases. The tendon has a poor ability to self-heal and regenerate given its intrinsic, constrained vascular supply and exposure to frequent, severe loading. There is a lack of understanding of the underlying pathophysiology, and it is not surprising that disorder-targeted medicines have only been partially effective at best. Recent tissue engineering approaches have emerged as a potential tool to drive tendon regeneration and healing. In this review, we investigated the physiochemical factors involved in tendon ontogeny and discussed their potential application in vitro to reproduce functional and self-renewing tendon tissue. We sought to understand whether stem cells are capable of forming tendons, how they can be directed towards the tenogenic lineage, and how their growth is regulated and monitored during the entire differentiation path. Finally, we showed recent developments in tendon tissue engineering, specifically the use of mesenchymal stem cells (MSCs), which can differentiate into tendon cells, as well as the potential role of extracellular vesicles (EVs) in tendon regeneration and their potential for use in accelerating the healing response after injury.

Background There is little evidence about the prognostic role of mitral regurgitation (MR) in patients with low‐flow, low‐gradient aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). The aim of this study was to assess the prevalence and outcome implications of MR severity in patients with low‐flow, low‐gradient aortic stenosis undergoing TAVR, and to evaluate whether MR improvement after TAVR could influence clinical outcome. Methods and Results This study included consecutive patients with low‐flow, low‐gradient aortic stenosis undergoing TAVR at 2 Italian high‐volume centers. The study population was categorized according to the baseline MR severity and to the presence of MR improvement at discharge. The primary outcome was the composite of all‐cause death and hospitalization for worsening heart failure up to 1 year. The study included 268 patients; 57 (21%) patients showed MR >2+. Patients with MR >2+ showed a lower 1‐year survival free from the primary outcome (P2+ was an independent predictor of the primary outcome (P2+, MR improvement was reported in 24 (44%) cases after TAVR. The persistence of MR was associated with a significantly reduced survival free from the primary outcome, all‐cause death, and heart failure hospitalization up to 1 year. Conclusions In this study, the presence of moderately severe to severe MR in patients with low‐flow, low‐gradient aortic stenosis undergoing TAVR portends a worse clinical outcome at 1 year. TAVR may improve MR severity in nearly half of the patients, resulting in a potential outcome benefit after discharge.

Cell therapy for diabetes requires the combination of bioengineering and new sources of beta cells. Here, the authors report a self-assembly platform based on neonatal pig islets, human endothelial cells and native organ extracellular matrix, which improves ex vivo islet maturation and in vivo function in a mouse model of diabetes.

Abstract Aims The angiotensin receptor‐neprilysin inhibitor (ARNI) sacubitril/valsartan (Sac/Val) demonstrated to be superior to enalapril in reducing hospitalizations, cardiovascular and all‐cause mortality in patients with ambulatory heart failure and reduced ejection fraction (HFrEF), in particular when it is maximally up‐titrated. Unfortunately, the target dose is achieved in less than 50% of HFrEF patients, thus undermining the beneficial effects on the outcomes. In this study, we aimed to evaluate the role of Sac/Val and its titration dose on reverse cardiac remodelling and determine which echocardiographic index best predicts the up‐titration success. Methods and results From January 2020 to June 2021, we retrospectively identified 95 patients (65.6 [59.1–72.8] years; 15.8% females) with chronic HFrEF who were prescribed Sac/Val from the HF Clinics of 5 Italian University Hospitals and evaluated the tolerability of Sac/Val high dose (the ability of the patient to achieve and stably tolerate the maximum dose) as the primary endpoint in the cohort. We used a multivariable logistic regression analysis, with a stepwise backward selection method, to determine the independent predictors of Sac/Val maximum dose tolerability, using, as candidate predictors, only variables with a P‐value < 0.1 in the univariate analyses. Candidate predictors identified for the multivariable backward logistic regression analysis were age, sex, body mass index (BMI), chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), dyslipidaemia, atrial fibrillation, systolic blood pressure (SBP), baseline tolerability of ACEi/ARBs maximum dose, left ventricle global longitudinal strain (LVgLS), LV ejection fraction (EF), tricuspid annulus plane systolic excursion (TAPSE), right ventricle (RV) fractional area change (FAC), RV global and free wall longitudinal strain (RVgLS and RV‐FW‐LS). After the multivariable analysis, only one categorical (ACEi/ARBs maximum dose at baseline) and three continuous (younger age, higher SBP, and higher TAPSE), resulted significantly associated with the study outcome variable with a strong discriminatory capacity (area under the curve 0.874, 95% confidence interval (CI) (0.794–0.954) to predict maximum Sac/Val dose tolerability. Conclusions Our study is the first to analyse the potential role of echocardiography and, in particular, of RV dysfunction, measured by TAPSE, in predicting Sac/Val maximum dose tolerability. Therefore, patients with RV dysfunction (baseline TAPSE

Objective: We aimed to assess feasibility and functional correlates of left atrial volume index (LAVI) changes during exercise stress echocardiography (ESE). Methods: ESE on a bike or treadmill was performed in 363 patients with heart failure with preserved ejection fraction (HFpEF, n = 173), reduced ejection fraction (HFrEF, n = 59), or hypertrophic cardiomyopathy (HCM, n = 131). The LAVI stress-rest increase ≥6.8 ml/m2 was defined as dilation. Results: LAVI measurements were feasible in 100%. LAVI did not change in HFrEF being at rest 32 (25-45) vs at stress 36 (24-54) ml/m2, P = NS and in HCM at rest 35 (26-48) vs at stress 38 (28-48) ml/m2, P = NS, whereas it decreased in HFpEF from 30 (24-40) to 29 (21-37) ml/m2 at stress, P = 0.007. LA dilation occurred in 107 (30%) patients (27% with treadmill vs 33% with bike ESE, P = NS): 26 with HFpEF (15%), 26 with HFrEF (44%), and 55 with HCM (42%) with P 14 at rest with odds ratio (OR) 4.4, LVEF

Nonalcoholic fatty liver disease, recently re-named metabolic dysfunction-associated steatotic fatty liver disease, is considered the most prevalent liver disease worldwide. Its molecular initiation events are multiple and not always well-defined, comprising insulin resistance, chronic low-grade inflammation, gut dysbiosis, and mitochondrial dysfunction, all of them acting on genetic and epigenetic grounds. Nowadays, there is a growing public health threat, which is antibiotic excessive use and misuse. This widespread use of antibiotics not only in humans, but also in animals has led to the presence of residues in derived foods, such as milk and dairy products. Furthermore, antibiotics have been used for many decades to control certain bacterial diseases in high-value fruit and vegetables. Recently, it has been emphasised that antibiotic-induced changes in microbial composition reduce microbial diversity and alter the functional attributes of the microbiota. These antibiotic residues impact human gut flora, setting in motion a chain of events that leads straight to various metabolic alterations that can ultimately contribute to the onset and progression of NAFLD.

We provide one of the most comprehensive metallicity studies at z ∼ 4 by analyzing the UV/optical Hubble Space Telescope photometry and rest-frame Very Large Telescope (VLT)/FORS2 UV and VLT/XSHOOTER optical spectra of J0332−3557, a gravitationally lensed galaxy magnified by a factor of 20. With a 5 σ detection of the auroral O iii ] λ 1666 line, we are able to derive a direct gas metallicity estimate for our target. We find Z _gas $=12+\mathrm{log}({\rm{O}}/{\rm{H}})=8.26\pm 0.06$ , which is compatible with an increase of both the gas fraction and the outflow metal loading factor from z ∼ 0 to z ∼ 4. J0332−3557 is the most metal-rich individual galaxy at z ∼ 4 for which the C/O ratio has been measured. We derive a low log(C/O) = −1.02 ± 0.2, which suggests that J0332−3557 is in the early stages of interstellar medium carbon enrichment driven mostly by massive stars. The low C/O abundance also indicates that J0332−3557 is characterized by a low star formation efficiency, higher yields of oxygen, and longer burst duration. We find that EW _C _III _]1906,9 is as low as ∼3 Å, and the main drivers of the low EW _C _III _]1906,9 are the higher gas metallicity and the low C/O abundance. J0332−3557 is characterized by one diffuse and two more compact regions ∼1 kpc in size. We find that the carbon emission mostly originates in the compact knots. Our study on J0332−3557 serves as an anchor for studies investigating the evolution of metallicity and C/O abundance across different redshifts.

Abstract Background Children’s exposure to toxic stress (e.g., parental depression, violence, poverty) predicts developmental and physical health problems resulting in health care system burden. Supporting parents to develop parenting skills can buffer the effects of toxic stress, leading to healthier outcomes for those children. Parenting interventions that focus on promoting parental reflective function (RF), i.e., parents’ capacity for insight into their child’s and their own thoughts, feelings, and mental states, may understand help reduce societal health inequities stemming from childhood stress exposures. The Attachment and Child Health (ATTACHTM) program has been implemented and tested in seven rapid-cycling pilot studies (n = 64) and found to significantly improve parents’ RF in the domains of attachment, parenting quality, immune function, and children’s cognitive and motor development. The purpose of the study is to conduct an effectiveness-implementation hybrid (EIH) Type II study of ATTACHTM to assess its impacts in naturalistic, real-world settings delivered by community agencies rather than researchers under more controlled conditions. Methods The study is comprised of a quantitative pre/post-test quasi-experimental evaluation of the ATTACHTM program, and a qualitative examination of implementation feasibility using thematic analysis via Normalization Process Theory (NPT). We will work with 100 families and their children (birth to 36-months-old). Study outcomes include: the Parent Child Interaction Teaching Scale to assess parent-child interaction; the Parental Reflective Function and Reflective Function Questionnaires to assess RF; and the Ages and Stages Questionnaire – 3rd edition to examine child development, all administered pre-, post-, and 3-month-delayed post-assessment. Blood samples will be collected pre- and post- assessment to assess immune biomarkers. Further, we will conduct one-on-one interviews with study participants, health and social service providers, and administrators (total n = 60) from each collaborating agency, using NPT to explore perceptions and experiences of intervention uptake, the fidelity assessment tool and e-learning training as well as the benefits, barriers, and challenges to ATTACHTM implementation. Discussion The proposed study will assess effectiveness and implementation to help understand the delivery of ATTACHTM in community agencies. Trial registration Name of registry: https://clinicaltrials.gov/. Registration number: NCT04853888 . Date of registration: April 22, 2021.

Background Assessment of psychological reactions to delays in fertility treatment have often utilized single clinic samples during the time that fertility treatments were paused. We, therefore, assessed emotional reactions to treatment cancelations due to COVID-19 in infertility patients across the United States after treatments had begun to resume. Study design Cross-sectional survey emailed on 27 May 2020 and closed on 30 June 2020, to 53,600 FertilityIQ.com website users inquiring about their experience since the COVID-19 pandemic. A subset of FertilityIQ users (n = 13,490) opened the survey invitation and 1806 respondents participated in the survey (13.4% response rate). Results The majority of respondents (female, 67.4%; male, 61.7%) were 31-40 years old; most were planning to start treatment immediately (women, 42.6%; men, 44.7%) or were undergoing treatment (women, 34.9%; men, 29.8%) at the time of treatment cancelation. Patients (women, 21.1%; men 19.1%) or clinics (women, 57.7%; men, 40.4%) canceled treatment. Most clinics had resumed treatment at the time of the study (women, 90.0%; men, 73.7%). Cancelation resulted in sadness (women, 83.9%; men 86.7%) and anger (women, 45.4%; men, 36.7%); greater than half of the participants whose treatment was canceled (women: 66.8%, n = 630; men: 73.7%, n = 14) agreed with cancelations. Greater than 70% of respondents were at least somewhat concerned about reproductive chances (women, 84.7%; men, 72.4%) and exclusion of partners (women, 73.3%; men, 72.4%). Distress/concern was associated with clinic cancelation, disagreement with delays, age, diagnosis, and concern about delays and pregnancy chances (p

This paper analyzes how special relativity changes the equation for the many-body-induced current density starting from the Foldy–Wouthuysen diagonalization of the Dirac–Coulomb Hamiltonian. This current density differs from that obtained with the Gordon decomposition due to the presence of a spin-orbit coupling contribution not considered before for many-body molecular systems. This contribution diverges on atomic nuclei due to the nature of the point charges considered in the nonrelativistic approach, demonstrating that conventionally used nonrelativistic methods are not suitable for dealing with spin effects such as spin-orbit coupling or effects smaller than α2, with α the fine structure constant, and that a fully relativistic approach with a finite charge should be used. Despite the singularity, the spin-orbit coupling current becomes an important contribution to the total current in open-shell systems with high-spin multiplicity and a high atomic number in the nuclear proximity. On long ranges, this contribution is overcome by the Coulomb potential and the derived electric field which decays very quickly for small distances from nuclear charges. An evaluation of this spin-orbit current has been performed in the linear response approach at the HF/DFT level of theory.

Tendon injuries caused by overuse or age-related deterioration are frequent. Incomplete knowledge of somatic tendon cell biology and their progenitors has hindered interventions for the effective repair of injured tendons. Here, we sought to compare and contrast distinct tendon-derived cell populations: type I and II tendon stem cells (TSCs) and tenocytes (TNCs). Porcine type I and II TSCs were isolated via the enzymatic digestion of distinct membranes (paratenon and endotenon, respectively), while tenocytes were isolated through an explant method. Resultant cell populations were characterized by morphology, differentiation, molecular, flow cytometry, and immunofluorescence analysis. Cells were isolated, cultured, and evaluated in two alternate oxygen concentrations (physiological (2%) and air (21%)) to determine the role of oxygen in cell biology determination within this relatively avascular tissue. The different cell populations demonstrated distinct proliferative potential, morphology, and transcript levels (both for tenogenic and stem cell markers). In contrast, all tendon-derived cell populations displayed multipotent differentiation potential and immunophenotypes (positive for CD90 and CD44). Type II TSCs emerged as the most promising tendon-derived cell population for expansion, given their enhanced proliferative potential, multipotency, and maintenance of a tenogenic profile at early and late passage. Moreover, in all cases, physoxia promoted the enhanced proliferation and maintenance of a tenogenic profile. These observations help shed light on the biological mechanisms of tendon cells, with the potential to aid in the development of novel therapeutic approaches for tendon disorders.

The NOTCH ligands JAG1 and JAG2 have been correlated in vitro with multiple myeloma (MM) cell proliferation, drug resistance, self-renewal and a pathological crosstalk with the tumor microenvironment resulting in angiogenesis and osteoclastogenesis. These findings suggest that a therapeutic approach targeting JAG ligands might be helpful for the care of MM patients and lead us to explore the role of JAG1 and JAG2 in a MM in vivo model and primary patient samples. JAG1 and JAG2 protein expression represents a common feature in MM cell lines; therefore, we assessed their function through JAG1/2 conditional silencing in a MM xenograft model. We observed that JAG1 and JAG2 showed potential as therapeutic targets in MM, as their silencing resulted in a reduction in the tumor burden. Moreover, JAG1 and JAG2 protein expression in MM patients was positively correlated with the presence of MM cells in patients’ bone marrow biopsies. Finally, taking advantage of the Multiple Myeloma Research Foundation (MMRF) CoMMpass global dataset, we showed that JAG2 gene expression level was a predictive biomarker associated with patients’ overall survival and progression-free survival, independently from other main molecular or clinical features. Overall, these results strengthened the rationale for the development of a JAG1/2-tailored approach and the use of JAG2 as a predictive biomarker in MM.

Abstract Background Head and Neck cancer (HNC) is a fatal malignancy with poor prognosis. Human Papillomavirus (HPV) infection is becoming the prominent cause of HNC in the western world, and studying the molecular mechanisms underlying its action in cancers is key towards targeted therapy. To replicate, HPV regulates the host DNA damage repair (DDR) pathway. SMAD4 is also involved in the regulation of the DDR machinery and likely plays important role in maintaining cell viability upon genotoxic stress. In this study, we investigated the role of HPV in the upregulation of SMAD4 to control the DDR response and facilitate its lifecycle. Methods SMAD4, Rad51 and CHK1 expression was assessed in HPV-positive and HPV-negative HNC using TCGA data, a panel of 14 HNC cell lines and 8 fresh tumour tissue samples from HNC patients. HPV16 expression was modulated by E6/E7 siRNA knock-down or transduction in HPV-positive HNC cell lines and Human Primary keratinocytes respectively. SMAD4 half-life was assessed by cycloheximide treatment in HNC cell lines, together with βTRCP1-dependent SMAD4 ubiquitination. SMAD4 siRNA knock-down was used to determine its role in HPV-mediated regulation of DDR machinery and to assess cisplatin sensitivity in HPV-positive HNC cell lines. Results We found that HPV increases SMAD4 expression is both HPV-positive HNC tumours and cell lines, impairing its degradation which is mediated by the E3 ubiquitin ligase βTRCP1. SMAD4 expression highly correlates with the expression of two main players of the DDR pathway, CHK1 and Rad51, which expression is also upregulated by the presence of HPV. In particular, we demonstrate that HPV stabilizes SMAD4 to increase CHK1 and Rad51 expression. In addition, SMAD4-deficient HPV-positive cells have increased sensitivity to cisplatin treatment. Conclusions Our results give a clear molecular mechanism at the basis of HPV regulation of the DDR pathway. In particular, we show how HPV stabilizes SMAD4 to promote DDR protein expression, which may be used to facilitate viral replication and HNC onset. Moreover, we found that SMAD4 silencing in HPV-positive HNC cell lines increases sensitivity to cisplatin treatment, suggesting that HPV-positive HNC with low SMAD4 expression may be preferentially susceptible to similar treatments.

Abstract Two-dimensional SrTiO3-based interfaces stand out among non-centrosymmetric superconductors due to their intricate interplay of gate-tunable Rashba spin-orbit coupling and multi-orbital electronic occupations, whose combination theoretically prefigures various forms of non-standard superconductivity. By employing superconducting transport measurements in nano-devices we present strong experimental indications of unconventional superconductivity in the LaAlO3/SrTiO3 interface. The central observations are the substantial anomalous enhancement of the critical current by small magnetic fields applied perpendicularly to the plane of electron motion, and the asymmetric response with respect to the magnetic field direction. These features cannot be accommodated within a scenario of canonical spin-singlet superconductivity. We demonstrate that the experimental observations can be described by a theoretical model based on the coexistence of Josephson channels with intrinsic phase shifts. Our results exclude a time-reversal symmetry breaking scenario and suggest the presence of anomalous pairing components that are compatible with inversion symmetry breaking and multi-orbital physics.

IntroductionIn the last two decades, a more aggressive approach has been encouraged to treat patients with acute type A aortic dissection (ATAAD), extending the repair to the aortic arch and proximal descending thoracic aorta with the frozen elephant trunk (FET) implantation. Here, we report our single-centre experience with the FET technique for the systematic treatment of emergency type A aortic dissection.Materials and methodsBetween December 2017 and January 2022, 69 consecutive patients were admitted with ATAAD; of those, 66 patients (62.9 ± 10.2 years of age, 81.8% men) underwent emergency hybrid aortic arch and FET repair with the multibranched Thoraflex hybrid graft and were enrolled in the study. Primary endpoints were 30 days- and in-hospital mortality. Secondary endpoints were postoperative morbidity and follow-up survival. To better clarify the impact of age on surgical outcomes, we have divided the study population into two groups: group A for patients

Objectives Although inherited retinal disorders (IRDs) related to the gene encoding the retinal pigment epithelium 65kD protein (RPE65) significantly impact the vision-related quality of life (VRQoL), their emotional and social aspects remain poorly investigated in Italy. Narrative Medicine (NM) reveals the more intimate aspects of the illness experience, providing insights into clinical practice.Design and setting This NM project was conducted in Italy between July and December 2020 and involved five eye clinics specialised in IRDs. Illness plots and parallel charts, together with a sociodemographic survey, were collected through the project’s website; remote in-depth interviews were also conducted. Narratives and interviews were analysed through NVivo software and interpretive coding.Participants 3 paediatric and 5 adult patients and eight caregivers participated in the project; 11 retinologists globally wrote 27 parallel charts; 5 professionals from hospital-based multidisciplinary teams and one patient association member were interviewed.Results Findings confirmed that RPE65-related IRDs impact VRQoL in terms of activities and mobility limitations. The emotional aspects emerged as crucial in the clinical encounter and as informative on IRD management challenges and real-life experiences, while psychological support was addressed as critical from clinical diagnosis throughout the care pathway for both patients and caregivers; the need for an IRDs ‘culture’ emerged to acknowledge these conditions, and therefore, promoting diversity within society.Conclusions The project was the first effort to investigate the impact of RPE65-related IRDs on the illness experience through NM, concomitantly addressing the perspectives of paediatric and adult patients, caregivers and healthcare professionals and provided preliminary insights for the knowledge of RPE65-related IRDs and the clinical practice.

Regenerative medicine (RM) is changing how we think and practice transplant medicine. In regenerative medicine, the aim is to develop and employ methods to regenerate, restore or replace damaged/diseased tissues or organs. Regenerative medicine investigates using tools such as novel technologies or techniques, extracellular vesicles, cell-based therapies, and tissue-engineered constructs to design effective patient-specific treatments. This review illustrates current advancements in regenerative medicine that may pertain to transplant medicine. We highlight progress made and various tools designed and employed specifically for each tissue or organ, such as the kidney, heart, liver, lung, vasculature, gastrointestinal tract, and pancreas. By combing both fields of transplant and regenerative medicine, we can harbor a successful collaboration that would be beneficial and efficacious for the repair and design of de novo engineered whole organs for transplantations.

Despite the availability on the market of different anti-SARS-CoV-2 vaccines, there are still unanswered questions on whether they can stimulate long-lasting protection. A deep understanding of adaptive immune response to SARS-CoV-2 is important for optimizing both vaccine development and pandemic control measures. Among cytokines secreted by lymphocytes in response to viral infection, IFN-γ plays a pivotal role both in innate and adaptive immunity. In this study, we report on 28 naïve-to-SARS-Cov-2-infection and unvaccinated subjects, having reported a close and prolonged contact with COVID-19-positive patients. Samples were tested for defective genetic variants in interferon pathway genes by whole exome sequencing and anti-IFN autoantibodies production was investigated. Subject T-cells were cultured and infected with pseudotype particles bearing the S proteins and in parallel stimulated with two S-peptides designed on the RBD region of the spike protein. Our results showed that one of these peptides, RBD 484–508, induces a significant increase in IFN-γ gene expression and protein production in T-cells, comparable to those obtained in cells infected by SARS-CoV-2 pseudovirus. This work deepens our understanding of immune response and highlights the selected peptide as a reasonable approach to induce broad, potent, and variant concern-independent T-cell responses.

Abstract Aims Acute pulmonary disorders are known physical triggers of takotsubo syndrome (TTS). This study aimed to investigate prevalence of acute pulmonary triggers in patients with TTS and their impact on outcomes. Methods and results Patients with TTS were enrolled from the International Takotsubo Registry and screened for triggering factors and comorbidities. Patients were categorized into three groups (acute pulmonary trigger, chronic lung disease, and no lung disease) to compare clinical characteristics and outcomes. Of the 1670 included patients with TTS, 123 (7%) were identified with an acute pulmonary trigger, and 194 (12%) had a known history of chronic lung disease. The incidence of cardiogenic shock was highest in patients with an acute pulmonary trigger compared with those with chronic lung disease or without lung disease (17% vs. 10% vs. 9%, P = 0.017). In‐hospital mortality was also higher in patients with an acute pulmonary trigger than in the other two groups, although not significantly (5.7% vs. 1.5% vs. 4.2%, P = 0.13). Survival analysis demonstrated that patients with an acute pulmonary trigger had the worst long‐term outcome (P = 0.002). The presence of an acute pulmonary trigger was independently associated with worse long‐term mortality (hazard ratio 2.12, 95% confidence interval 1.33–3.38; P = 0.002). Conclusions The present study demonstrates that TTS is related to acute pulmonary triggers in 7% of all TTS patients, which accounts for 21% of patients with physical triggers. The presence of acute pulmonary trigger is associated with a severe in‐hospital course and a worse long‐term outcome.

Functional loss of E-cadherin is frequent during tumor progression and occurs through a variety of mechanisms, including proteolytic cleavage. E-cadherin downregulation leads to the conversion of a more malignant phenotype promoting Epithelial to Mesenchymal Transition (EMT). The UBC9/SUMO pathway has been also shown to be involved in the regulation of EMT in different cancers. Here we found an increased expression of UBC9 in the progression of Head and Neck Cancer (HNC) and uncovered a role for UBC9/SUMO in hampering the HPV-mediated E-cadherin cleavage in HNC.

(1) Background: The principal aim of our research was to explore the relationship between digital devices use and fine motor skills in children aged three to six years and to explore the effect of some socio-demographic factors. (2) Methods: we enrolled 185 children aged between three to six years. The parents of all the participants fulfilled a questionnaire to explore the digital device use, and their children performed a standardized test to assess fine motor skills (APCM-2). We performed the Spearman correlation test to explore the relationship between different variables. (3) Results: the children spent an average of 3.08 ± 2.30 h/day on digital devices. We did not find a significant association between the time of use of digital devices and fine motor skills (p = 0.640; r = −0.036). The youngest children experienced digital tools earlier than older ones (p < 0.001; r = 0.424) and they were also the ones who used digital tools more time afterwards (p = 0.012; −0.202). The children who had working parents spent more time on digital devices (p = 0.028; r = 0.164/p = 0.037; r = 0.154) and used digital devices earlier (p = 0.023; r = 0.171). (4) Conclusions: This data suggest that it would be useful to monitor the use of digital tools, especially in the very first years of life. Future studies are needed to further explore this topic.