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Abstract Background Sturge–Weber Syndrome (SWS) is a rare, sporadic neurocutaneous disorder affecting the skin, brain, and eyes, due to somatic activating mutations in GNAQ or, less commonly, GNA11 gene. It is characterized by at least two of the following features: a facial capillary malformation, leptomeningeal vascular malformation, and ocular involvement. The spectrum of clinical manifestations includes headache, seizures, stroke-like events, intellectual disability, glaucoma, facial asymmetry, gingival hyperplasia, etc. An early diagnosis is crucial to guarantee an appropriate care, which is best performed in reference centres by multidisciplinary teams. The aim of this study was to develop a multidisciplinary expert consensus for diagnosis, treatment, and follow-up of all disease manifestations, according to the recommendations of the Italian Law on Rare Disease Care. Results Through a Delphi consensus methodology, 28 recommendations have been developed concerning (i) dermatological SWS manifestations and related treatment timing and modalities, (ii) neurological referral, diagnosis, pharmacological treatment of neurological signs and symptoms, neurosurgical indications, neurocognitive evaluation and related treatment, psychosocial support and patient follow-up, (iii) diagnosis of ophthalmological manifestations, medical and surgical treatment, and follow-up, (iv) maxillofacial surgical treatment, (v) oral cavity assessment, care and follow-up, and (vi) primary care paediatrician/general practitioner involvement. Conclusions The present consensus developed by a multidisciplinary group of experts from Italian reference centres comprises practical recommendations for SWS global management, including currently controversial issues. Specific statements for all disease aspects, from skin manifestations and neurological and ocular signs and symptoms to oral and maxillofacial care, are provided. They can be exploited to uniform clinical practice in reference centres, but also in other hospitals and outpatient settings. Though this consensus has been developed taking primarily into account the Italian National Health System organization and rules on rare disorders, it could be translated also to other countries.

Abstract The present study aimed to investigate the causal relationships among cognitive impairment, psychopathology, and real-life functioning in a large sample of people with schizophrenia, using a data-driven causal discovery procedure based on partial ancestral graphs (PAGs). This method may provide additional insights for the identification of potential therapeutic targets to promote recovery in people with chronic schizophrenia. State-of-the-art instruments were used to assess the study variables. Two PAGs were generated at baseline and after 4 years of follow-up to model the nature of the causal relationships linking psychopathology, cognition, and functioning. The study sample was composed of more than 600 clinically stable patients with schizophrenia at two time points. The PAGs model indicated that working memory impairment is the first ancestor of the causal links, influencing all the other neurocognitive domains, social cognition, and functional capacity, which in turn affects everyday life functioning. From this domain of functioning a causal link is directed to disorganization and positive symptoms, and another to work skills and interpersonal relationships domains; the latter had a direct link to asociality and the other domains of negative symptoms. The structure of the PAGs did not differ significantly between baseline and follow-up, indicating the stability of the causal relationship model investigated cross-sectionally at both time points. The role of working memory impairment in the pathways to functional outcomes in schizophrenia highlights the importance of implementing integrated pharmacological and cognitive remediation interventions targeting neurocognition. The impact of everyday life and interpersonal functioning on the clinical presentation of schizophrenia suggests that integrated and personalized treatments, promoting relevant skills to improve these functional outcomes, may have a beneficial impact on clinical outcomes.

Abstract AMoRE-II aims to search for neutrinoless double beta decay ( $$0\nu \beta \beta $$ 0 ν β β ) with an array of 423 $$\hbox {Li}_2^{100}\hbox {MoO}_4$$ Li 2 100 MoO 4 crystals operating in the cryogenic system as the main phase of the Advanced Molybdenum-based Rare process Experiment (AMoRE). AMoRE has been planned to operate in three phases: AMoRE-pilot, AMoRE-I, and AMoRE-II. AMoRE-II is currently being installed at the Yemi Underground Laboratory, located approximately 1000 m deep in Jeongseon, Korea. The goal of the experiment is to reach an exclusion half-life sensitivity to the $$0\nu \beta \beta $$ 0 ν β β of $$^{100}$$ 100 Mo on the level of $$T^{0\nu \beta \beta }_{1/2} > 6 \times 10^{26}$$ T 1 / 2 0 ν β β > 6 × 10 26 year that covers completely the inverted Majorana neutrino mass hierarchy region of (15–46) meV. To achieve this, the background level of the experimental configurations and possible background sources of gamma and beta events should be well understood. We have intensively performed Monte Carlo simulations using the GEANT4 toolkit in all the experimental configurations with potential sources. We report the estimated background level that meets the $$10^{-4}$$ 10 - 4 counts/(keV $$\cdot $$ · kg $$\cdot $$ · year) requirement for AMoRE-II in the Region Of Interest (ROI) and show the projected half-life sensitivity based on the simulation study.

After the Second World War, several years of allied occupation followed for Germany and began the difficult operations of clearing the rubble and counting the damage to the building and infrastructural heritage of the cities. At the same time, many architects began to question possible intervention strategies, giving rise to an interesting debate, in which the theme of the interpretation of the ruins played a central role. After 1949 the socio-political conditions changed: with the birth of two states the priority became to physically rebuild the two new countries. A massive work of reorganization and rebuilding began, which, city by city, resulted in very diversified operational choices, both in terms of restoration of historic buildings and urban and territorial planning. Once this phase was over, after the 1970s, German scholars in the East as well as in the West began to draw up initial critical-compilatory studies of what had been achieved. In the context of these studies, those of Niels Gutschow and Werner Durth, Josef Nipper and Manfred Nutz and Hartwig Beseler and Niels Gutschow are significant. At the beginning of the nineties of the twentieth century, so even before the reunification, the first reconstruction projects were elaborated dove era e come era of buildings destroyed by the war, such as those of the Römerberg Ostzeile in Frankfurt, the Knochenhaueramtshaus in Hildesheim and the Alte Waage in Braunschweig. The proposed contribution intends to illustrate and critically comment on the motivations that led to the reconstruction of these buildings, framing them in the wider debate that has developed in Germany after reunification following the notorius cases of the reconstruction of the Frauenkirke in Dresden and the Berlin Castle, and the well-known exhibition curated in 2010 by Winfried Nerdinger at the Architekturmuseum of the TU München entitled Geschichte der Rekonstruktion – Konstruktion der Geschichte.

Background: Work organization and psychosocial factors influencing sleep patterns may be significant risk factors for developing obesity and metabolic syndrome (MetS). However, the impact on the health of working patterns in the fishing sector is not well characterized. The aim of the study is to determine the prevalence of MetS and its components in fishermen and to analyze occupational-specific risk factors contributing to metabolic alterations. Methods: One hundred forty-three male fishermen from Apulia (Southern Italy) and 93 male university workers age-matched and from the same geographical area were included in this cross-sectional study. A questionnaire was administered to investigate socio-demographic variables, work activity, health status, and dietary habits. All subjects underwent clinical evaluation and blood sampling to depict their metabolic profile. Results: A higher body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (p

Psychomotor agitation (PMA) is a prominent clinical issue frequently observed in various psychiatric and neurological conditions, including schizophrenia, bipolar disorder, Parkinson disease, dementia and substance use disorder. Characterized by motor restlessness, anxiety and irritability, PMA can rapidly escalate into aggression and violence, necessitating prompt intervention to ensure patient and caregiver safety. The prevalence of PMA in psychiatric emergency settings ranges from 4.3% to 10%, imposing a substantial burden on healthcare systems. Despite the critical nature of PMA, there is a lack of standardized treatment protocols, particularly concerning the use of liquid formulations of antipsychotics such as liquid promazine, which may offer unique advantages in emergency care. This review aims to provide a comprehensive analysis of the existing literature on the efficacy, safety and tolerability of liquid antipsychotics, with a particular focus on promazine, in the management of PMA. An extensive literature search was conducted across publicly available databases with no time limitations to ensure the inclusion of all relevant articles. The findings suggest that liquid promazine offers several benefits, including ease of administration, rapid onset of action and improved patient compliance, making it a valuable option in acute PMA management. However, the review also highlights the need for future research, particularly long-term studies and head-to-head comparisons with other antipsychotics, to better establish the clinical utility of liquid promazine. Future research should focus on expanding the evidence base for liquid antipsychotic formulations, which will contribute to improved clinical outcomes in the management of PMA.

Sabrina Bimonte,1,* Piergiacomo Di Gennaro,2,* Anna Crispo,2 Sergio Coluccia,2 Assunta Luongo,2 Alfonso Amore,3,4 Egidio Celentano,2 Francesco Del Prato,1 Daniela Schiavo,1 Davide Nocerino,1 Marco Cascella,5 Arturo Cuomo1 1Division of Anesthesia and Pain Medicine, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; 2Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; 3Melanoma and Sarcoma Surgery Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Naples, Italy; 4PhD School of Applied Medical-Surgical Sciences, University of Rome Tor Vergata, Rome, Italy; 5Department of Medicine, University of Salerno, Salerno, Italy*These authors contributed equally to this workCorrespondence: Anna Crispo, Epidemiology and Biostatistics Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. Pascale, Via Mariano Semmola 53, Naples, Italy, Tel +39 081 17770298, Email a.crispo@istitutotumori.na.itPurpose: Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that “breaks through” a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) subtype occurs in the absence of any specific activity. Evidence showed that gender differences exist in pain response sensitivity and clinical pain risk. This analysis aimed to signify the gender differences for the NP-BTcP phenomenon.Patients and Methods: This is a secondary analysis of the Italian Oncologic Pain multiSetting-Multicentric Survey (IOPS-MS), the largest study on BTcP. The subset of NP-BTcP cases for non-gender-specific cancer was considered. Univariable and multivariate analyses were conducted to identify gender differences for the NP-BTcP profile about its intensity, number of episodes per day, and type. A metastatic status-stratified analysis was performed to compare gender with the main clinical variables among the population with NP-BTcP.Results: Males exhibited a higher occurrence of BTcP in the thorax region compared to females (15% vs 11%, respectively, p = 0.03). Males also had a higher onset of BTcP, a higher BTcP therapy dosage (33% vs 28%, p = 0.04, mean: 201 vs 186, p = 0.02) and a lower Karnofsky score (mean: 46.9 vs 49.2, p = 0.03) compared to females. Similar gender differences were found for metastatic patients in the BTcP site (14% vs 8.5%, respectively; p = 0.01), peak onset (33% vs 27%, p = 0.02), BTcP therapy dosage (199 vs 185, p=0.04), and Karnofsky score (mean 47.5 vs 50.4, p = 0.009). Phenotype 2 was more characterized by non-metastatic males (41% vs 23%, p = 0.020) while non-metastatic females presence was predominant among others.Conclusion: In this study, gender differences according to site, onset and dosage of BTcP were found. The phenotype characterization of BTcP needs to be further investigated for a possible useful function in the management of cancer-related pain in non-metastatic patients.Keywords: non-predictable breakthrough cancer pain, gender cancer pain, cluster analysis

Abstract In this study, we evaluated and forecasted the cumulative opportunities for residents to access radiotherapy services in Cali, Colombia, while accounting for traffic congestion, using a new people-centred methodology with an equity focus. Furthermore, we identified 1–2 optimal locations where new services would maximise accessibility. We utilised open data and publicly available big data. Cali is one of South America's cities most impacted by traffic congestion. Methodology: Using a people-centred approach, we tested a web-based digital platform developed through an iterative participatory design. The platform integrates open data, including the location of radiotherapy services, the disaggregated sociodemographic microdata for the population and places of residence, and big data for travel times from Google Distance Matrix API. We used genetic algorithms to identify optimal locations for new services. We predicted accessibility cumulative opportunities (ACO) for traffic ranging from peak congestion to free-flow conditions with hourly assessments for 6–12 July 2020 and 23–29 November 2020. The interactive digital platform is openly available. Primary and secondary outcomes: We present descriptive statistics and population distribution heatmaps based on 20-min accessibility cumulative opportunities (ACO) isochrones for car journeys. There is no set national or international standard for these travel time thresholds. Most key informants found the 20-min threshold reasonable. These isochrones connect the population-weighted centroid of the traffic analysis zone at the place of residence to the corresponding zone of the radiotherapy service with the shortest travel time under varying traffic conditions ranging from free-flow to peak-traffic congestion levels. Additionally, we conducted a time-series bivariate analysis to assess geographical accessibility based on economic stratum. We identify 1–2 optimal locations where new services would maximize the 20-min ACO during peak-traffic congestion. Results: Traffic congestion significantly diminished accessibility to radiotherapy services, particularly affecting vulnerable populations. For instance, urban 20-min ACO by car dropped from 91% of Cali’s urban population within a 20-min journey to the service during free-flow traffic to 31% during peak traffic for the week of 6–12 July 2020. Percentages represent the population within a 20-min journey by car from their residence to a radiotherapy service. Specific ethnic groups, individuals with lower educational attainment, and residents on the outskirts of Cali experienced disproportionate effects, with accessibility decreasing to 11% during peak traffic compared to 81% during free-flow traffic for low-income households. We predict that strategically adding sufficient services in 1–2 locations in eastern Cali would notably enhance accessibility and reduce inequities. The recommended locations for new services remained consistent in both of our measurements. These findings underscore the significance of prioritising equity and comprehensive care in healthcare accessibility. They also offer a practical approach to optimising service locations to mitigate disparities. Expanding this approach to encompass other transportation modes, services, and cities, or updating measurements, is feasible and affordable. The new approach and data are particularly relevant for planning authorities and urban development actors. Video Abstract

A hospital-based school is offered to hospitalised children with the aim of promoting school continuity and preventing disengagement from school; children have the chance to attend a hospital-based school with hospital teachers during long recoveries. The aim of this study is to obtain an in-depth understanding of hospital teaching: which training hospital teachers receive before teaching the hospitalised children and how they work with children in a hospital-based school (i.e. didactical methodologies, student's knowledge evaluation, etc.)? Twenty hospital teachers (N = 2, males; N = 18, females) from the Meyer Children's Hospital in Florence took part in an "ad hoc" semi-structured interview. The thematic analysis through QCAmap highlighted the following aspects: training of hospital teachers is various; no teacher had previously taught in a hospital or had taken part in specific trainings about hospital settings before becoming a hospital teacher; not only didactic but also medical skills are needed; a hospital context requires extremely flexible and personalised teaching and hospital teachers think that the connection with the class group is an important opportunity for the hospitalised child. In the future, it will be necessary to adequately train hospital teachers to carry out this delicate work with the hospitalised children.

IntroductionIn a model of right heart failure secondary to pulmonary artery banding (PAB), a mechanical approach using an elastic, biodegradable epicardial patch with integrated extracellular matrix digest was evaluated for its potential to inhibit disease progression.MethodsAdult male syngeneic Lewis rats aged 6–7 weeks old were used. Biohybrid cardiac patches were generated by co-processing biodegradable poly(ester carbonate urethane) urea (PECUU) and a digest of the porcine cardiac extracellular matrix. Three weeks after PAB, the cardiac patch was attached to the epicardium of the right ventricle (RV). Cardiac function was evaluated using echocardiography and catheterization for 9 weeks after PAB, comparing the patch (n = 7) and sham (n = 10) groups.ResultsNine weeks after PAB, the RV wall was thickened, the RV cavity was enlarged with a reduced left ventricular cavity, and RV wall interstitial fibrosis was increased. However, these effects were diminished in the patch group. Left ventricular ejection fraction in the patch group was higher than in the sham group (p < 0.001), right end-systolic pressure was lower (p = 0.045), and tricuspid annular plane systolic excursion improved in the patch group (p = 0.007). In addition, von Willebrand factor expression was significantly greater in the patch group (p = 0.007).ConclusionsThe placement of a degradable, biohybrid patch onto the RV in a right ventricular failure model with fixed afterload improved myocardial output, moderated pressure stress, and was associated with reduced right ventricular fibrosis.

The association between inflammation with depression and suicide has prompted many investigations of the potential contributors to inflammatory pathology in these psychiatric illnesses. However, a distillation of diverse clinical findings into an integrated framework of the possible involvement of major physiological processes in the elicitation of pathological inflammation in depression and suicide has not yet been explored. Therefore, this review aims to provide a concise synthesis of notable clinical correlates of inflammatory pathology in subjects with various depressive and suicidal clinical subtypes into a mechanistic framework, which includes aberrant immune activation, deregulated neuroendocrine signaling, and impaired host-microbe interaction. These issues are of significant research interest as their possible interplays might be involved in the development of distinct subtypes of depression and suicide. We conclude the review with discussion of a pathway-focused therapeutic approach to address inflammatory pathology in these psychiatric illnesses within the realm of personalized care for affected patients.

Summary: Background: We report extended follow-up of TROG99.03, a randomised phase III trial in early-stage follicular lymphoma (ESFL) including new information on the role of adjuvant rituximab and translational studies. Methods: Patients with ESFL were randomised to involved field radiotherapy (IFRT) or IFRT plus 6-cycles cyclophosphamide/vincristine/prednisolone (IFRT + CVP). From 2006 rituximab was added to IFRT + CVP (IFRT + R-CVP). Clinical and multi-omic parameters were evaluated. Findings were validated in two independent ESFL cohorts (99 and 60 patients respectively). Findings: Between 2000 and 2012, 150 (75 per arm) patients were recruited. 48% were positron emission tomography (PET)-staged. By protocol, at median follow-up 11.3-years, progression-free survival (PFS) remained superior for IFRT+(R)CVP vs. IFRT (hazard ratio [HR] = 0.60, 95% CI = 0.37–0.98, p = 0.043; 10-year PFS 62% vs. 43%) respectively. Although no significant difference in overall survival was observed (HR = 0.44, 95% CI = 0.16–1.18, p = 0.11, 10-year OS 95% vs. 84%), patients receiving IFRT+(R)CVP experienced fewer composite (histological transformation and death) events (p = 0.045). PFS of IFRT + R-CVP-treated patients compared with all other treatments lacking rituximab (IFRT alone plus IFRT + CVP) was superior (HR = 0.36, 95% CI = 0.13–0.82, p = 0.013). Amongst PET-staged patients, PFS differences between IFRT + R-CVP vs. IFRT were maintained (HR = 0.38, 95% CI = 0.16–0.89, p = 0.027) indicating benefit distinct from stage migration. FL-related mutations and BCL2-translocations were not associated with PFS. However, by multivariate analysis elevated CD8A gene expression in diagnostic biopsy tissue was independently associated with improved PFS (HR = 0.45, 95% CI = 0.26–0.79, p = 0.037), a finding confirmed in both ESFL validation cohorts. CD8A gene expression was raised (p = 0.02) and CD8+ T-cell density higher within follicles in ESFL vs. advanced-stage FL (p = 0.047). Human leucocyte antigen class I specific neoantigens were detected in 43% of patients, suggesting neoantigen-specific CD8+ T-cells have a role in confining the spread of the disease. Interpretation: Adjuvant R-CVP and elevated intratumoural CD8 expression were independently associated with sustained disease control after radiotherapy in ESFL. Funding: Cancer Council Victora; National Health and Medical Research Council; Leukaemia Foundation; Mater Foundation.

Purpose of the article: Interleukin-23 inhibitors, such as tildrakizumab, have emerged as safe and effective options for the management of psoriasis. Yet their efficacy in elderly patients (aged 65 years or more), particularly in those with difficult-to-treat areas involvement, remains insufficiently explored. We conducted this real-life retrospective multicentric observational study to assess the effectiveness of tildrakizumab in elderly patients with moderate-to-severe psoriasis, with involvement of difficult-to-treat areas.Materials and methods: We enrolled forty-nine patients aged 65 years old or more (mean age 73.1 ± 6.0), all treated with tildrakizumab for at least 28 weeks. The effectiveness of tildrakizumab was assessed by Static Physician’s Global Assessment of Genitalia (sPGA-G), fingernail-PGA (f-PGA), palmoplantar PGA (pp-PGA), scalp-specific PGA (sc-PGA), and Psoriasis Area and Severity Index (PASI) scores.Results: Significant improvements in PASI scores were observed within 28 weeks of treatment, with 77.5%, 60%, and 45.2% of patients achieving PASI75, PASI90, and PASI100, respectively. The mean PASI decreased significantly from baseline (13.6 ± 9.9) to 1.3 ± 1.7 at week 28. More than 90% of patients had clear sPGA-G and pp-PGA scores and over 70% had clear f-PGA and sc-PGA scores after 28 weeks.Conclusions: Our findings suggest that tildrakizumab could be a valuable option for the treatment of elderly patients, including those with difficult-to-treat areas involvement.

The mucus serves as a protective barrier in the gastrointestinal tract against microbial attacks. While its role extends beyond merely being a physical barrier, the extent of its active bactericidal properties remains unclear, and the mechanisms regulating these properties are not yet understood. We propose that inflammation induces epithelial cells to secrete antimicrobial peptides, transforming mucus into an active bactericidal agent. To investigate the properties of mucus, we previously developed mucosoid culture models that mimic the healthy human stomach epithelium. Similar to organoids, mucosoids are stem cell-driven cultures; however, the cells are cultivated on transwells at air–liquid interface. The epithelial cells of mucosoids form a polarized monolayer, allowing differentiation into all stomach lineages, including mucus-secreting cells. This setup facilitates the secretion and accumulation of mucus on the apical side of the mucosoids, enabling analysis of its bactericidal effects and protein composition, including antimicrobial peptides. Our findings show that TNFα, IL1β, and IFNγ induce the secretion of antimicrobials such as lactotransferrin, lipocalin2, complement component 3, and CXCL9 into the mucus. This antimicrobial-enriched mucus can partially eliminate Helicobacter pylori, a key stomach pathogen. The bactericidal activity depends on the concentration of each antimicrobial and their gene expression is higher in patients with inflammation and H.pylori-associated chronic gastritis. However, we also find that H. pylori infection can reduce the expression of antimicrobial encoding genes promoted by inflammation. These findings suggest that controlling antimicrobial secretion in the mucus is a critical component of epithelial immunity. However, pathogens like H. pylori can overcome these defenses and survive in the mucosa.

Introducción: Las anomalías dentarias resultan de alteraciones en la odontogénesis, generando variaciones en tamaño, forma, estructura o número de los dientes, siendo más prevalentes en la dentición permanente. Objetivo: Describir las alteraciones de forma, número y erupción observadas clínicamente en niños y adolescentes de la población indígena Pemón-Arekuna de Kavanayén, Edo. Bolívar - Venezuela. Material y métodos: Se realizó una investigación de tipo descriptivo, de campo, diseño transversal. Los datos se recolectaron en levantamiento epidemiológico, durante jornada médico-odontológica de Fundación Proyecto Mayū en Kavanayén, Edo. Bolívar - Venezuela en Abril 2023. Se evaluaron clínicamente a 179 pacientes, 102 niñas y 77 niños, con edades comprendidas entre 7 meses y 17 años, registrando las anomalías de forma, número y erupción detectadas. Resultados: Se identificaron alteraciones de forma, número y erupción en 8 pacientes, resultando una prevalencia del 4,47%. Para las alteraciones de forma la prevalencia fue 1,12%. Igualmente, la prevalencia de alteraciones de número fue 1,12% para los supernumerarios y 1,12% para las agenesias, pues cada alteración afectó a 2 pacientes. Por otro lado, la prevalencia de alteraciones en la erupción fue de 3,35%, estando presentes en 6 de los pacientes. Conclusiones: Las alteraciones de forma, número y erupción dental evaluadas clínicamente presentaron moderada prevalencia en la población indígena Pemón-Arekuna de Kavanayén. El presente estudio no contó con información radiográfica, por lo que los resultados subrayan la importancia de futuras investigaciones para clarificar y enriquecer la comprensión de estas anomalías dentales en contextos específicos.

Graphene-based hybrid filler polymer composites represent a significant advancement in materials science and engineering due to graphene’s remarkable mechanical, thermal, and electrical properties. This comprehensive review systematically evaluates both traditional (e.g., mechanical and solution mixing) and modern fabrication techniques (e.g., in situ polymerization, chemical modification, electrospinning, and layer-by-layer assembly) employed in the synthesis of these composites, comparing their effectiveness in enhancing material properties such as strength, thermal stability, and conductivity. Emphasizing the synergistic interactions between graphene and other fillers within polymer matrices, the paper discusses mechanisms that lead to superior composite performance. A thorough survey of the literature highlights successful examples where these composites have demonstrated significant advancements in mechanical, thermal, and electrical properties. Three detailed tables summarize findings from published studies, illustrating the enhanced properties and achievements at various filler concentrations across different preparation methods. The review concludes by outlining future research directions aimed at optimizing graphene hybrid filler polymer composites for broader scientific and industrial utilization. By consolidating current knowledge and providing a practical resource, this review aims to guide researchers and practitioners in harnessing the full potential of these advanced materials.

BackgroundParaneoplastic pemphigus (PNP), also called paraneoplastic autoimmune multiorgan syndrome (PAMS), is a rare autoimmune disease with mucocutaneous and multi-organ involvement. PNP/PAMS is typically associated with lymphoproliferative or haematological malignancies, and less frequently with solid malignancies. The mortality rate of PNP/PAMS is elevated owing to the increased risk of severe infections and disease-associated complications, such as bronchiolitis obliterans.ObjectivesThese guidelines summarize evidence-based and expert-based recommendations (S2k level) for the clinical characterization, diagnosis and management of PNP/PAMS. They have been initiated by the Task Force Autoimmune Blistering Diseases of the European Academy of Dermatology and Venereology with the contribution of physicians from all relevant disciplines. The degree of consent among all task force members was included.ResultsChronic severe mucositis and polymorphic skin lesions are clue clinical characteristics of PNP/PAMS. A complete assessment of the patient with suspected PNP/PAMS, requiring histopathological study and immunopathological investigations, including direct and indirect immunofluorescence, ELISA and, where available, immunoblotting/immunoprecipitation, is recommended to achieve a diagnosis of PNP/PAMS. Detection of anti-envoplakin antibodies and/or circulating antibodies binding to the rat bladder epithelium at indirect immunofluorescence is the most specific tool for the diagnosis of PNP/PAMS in a patient with compatible clinical and anamnestic features. Treatment of PNP/PAMS is highly challenging. Systemic steroids up to 1.5 mg/kg/day are recommended as first-line option. Rituximab is also recommended in patients with PNP/PAMS secondary to lymphoproliferative conditions but might also be considered in cases of PNP/PAMS associated with solid tumours. A multidisciplinary approach involving pneumologists, ophthalmologists and onco-haematologists is recommended for optimal management of the patients.ConclusionsThese are the first European guidelines for the diagnosis and management of PNP/PAMS. Diagnostic criteria and therapeutic recommendations will require further validation by prospective studies.

Background Social decision-making (SDM) is often studied through gaming paradigms, in which participants allocate resources among themselves and others based on predefined rules. In an adapted version of the ultimatum game (UG), SDM behavior was modulated in response to the degree of fairness of monetary offers and the social context of opponents, designed to generate either prosocial or punishing behaviors.

Psoriasis is a chronic inflammatory disease that can affect any part of the body but, when it appears in certain areas, like the face, it can have a very significant psychological impact. Biologics, in particular IL-17 and IL-23 drug inhibitors, have shown relevant clinical efficacy in the management of psoriatic lesions in difficult-to-treat areas. In post hoc analysis of phase III trials in plaque psoriasis, bimekizumab has shown safety and complete clearance of high-impact areas. However, these studies did not focus on the effect of bimekizumab on facial lesions. Therefore, this case series represents the first clinical real-life experience of rapid and successful management of facial psoriasis with bimekizumab in six patients.

Leber hereditary optic neuropathy (LHON) is an important example of mitochondrial blindness with the m.11778G>A mutation in the MT-ND4 gene being the most common disease-causing mtDNA variant worldwide. The REFLECT phase 3 pivotal study is a randomized, double-masked, placebo-controlled trial investigating the efficacy and safety of bilateral intravitreal injection of lenadogene nolparvovec in patients with a confirmed m.11778G>A mutation, using a recombinant adeno-associated virus vector 2, serotype 2 (rAAV2/2-ND4). The first-affected eye received gene therapy; the fellow (affected/not-yet-affected) eye was randomly injected with gene therapy or placebo. The primary end point was the difference in change from baseline of best-corrected visual acuity (BCVA) in second-affected/not-yet-affected eyes treated with lenadogene nolparvovec versus placebo at 1.5 years post-treatment, expressed in logarithm of the minimal angle of resolution (LogMAR). Forty-eight patients were treated bilaterally and 50 unilaterally. At 1.5 years, the change from baseline in BCVA was not statistically different between second-affected/not-yet-affected eyes receiving lenadogene nolparvovec and placebo (primary end point). A statistically significant improvement in BCVA was reported from baseline to 1.5 years in lenadogene nolparvovec-treated eyes: -0.23 LogMAR for the first-affected eyes of bilaterally treated patients (P < 0.01); and -0.15 LogMAR for second-affected/not-yet-affected eyes of bilaterally treated patients and the first-affected eyes of unilaterally treated patients (P < 0.05). The mean improvement in BCVA from nadir to 1.5 years was -0.38 (0.052) LogMAR and -0.33 (0.052) LogMAR in first-affected and second-affected/not-yet-affected eyes treated with lenadogene nolparvovec, respectively (bilateral treatment group). A mean improvement of -0.33 (0.051) LogMAR and -0.26 (0.051) LogMAR was observed in first-affected lenadogene nolparvovec-treated eyes and second-affected/not-yet-affected placebo-treated eyes, respectively (unilateral treatment group). The proportion of patients with one or both eyes on-chart at 1.5 years was 85.4% and 72.0% for bilaterally and unilaterally treated patients, respectively. The gene therapy was well tolerated, with no systemic issues. Intraocular inflammation, which was mostly mild and well controlled with topical corticosteroids, occurred in 70.7% of lenadogene nolparvovec-treated eyes versus 10.2% of placebo-treated eyes. Among eyes treated with lenadogene nolparvovec, there was no difference in the incidence of intraocular inflammation between bilaterally and unilaterally treated patients. Overall, the REFLECT trial demonstrated an improvement of BCVA in LHON eyes carrying the m.11778G>A mtDNA mutation treated with lenadogene nolparvovec or placebo to a degree not reported in natural history studies and supports an improved benefit/risk profile for bilateral injections of lenadogene nolparvovec relative to unilateral injections.