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Abstract Methods This study assessed data from two cohorts of patients with alpha‐synucleinopathies (University of Brescia and University of Rome Tor‐Vergata cohorts). Consecutive participants with video‐polysomnography‐confirmed iRBD, Parkinson's disease (PD), dementia with Lewy bodies (DLB) and controls underwent neurological, clinical and 123I‐FP‐CIT SPECT imaging assessments. Individuals with iRBD were longitudinally monitored to collect clinical phenoconversion to PD or DLB. The main outcome was to identify whole brain 123 I‐FP‐CIT SPECT measures reflecting monoaminergic deficits in each clinical group as compared to controls. Results The cohort (n = 184) included 45 patients with iRBD, 47 PD, 42 DLB and 50 age‐matched controls. Individuals with iRBD were categorized as RBD‐DAT− (n = 32) and RBD‐DAT+ (n = 13), according to nigrostriatal assessment used in clinical practice. Compared to controls, RBD‐DAT− showed an early involvement of the left insula, which increased in RBD‐DAT+, and was present in patients with Parkinson's disease and dementia with Lewy bodies. Longitudinal cox regression analyses revealed a higher risk of phenoconversion in individuals with iRBD and insular monoaminergic deficits [HR = 3.387; CI 95%: 1.18–10.27]. Interpretation In this study, altered insular monoaminergic binding in iRBD was associated with phenoconversion to DLB or PD. These findings may provide a helpful stratification approach for future pharmacological or non‐pharmacological interventions.

Abstract The proper functioning of the heart relies on the intricate interplay between the central nervous system and the local neuronal networks within the heart itself. While the central innervation of the heart has been extensively studied, the organization and functionality of the intracardiac nervous system (IcNS) remain largely unexplored. Here, we present a comprehensive taxonomy of the IcNS, utilizing single-cell RNA sequencing, anatomical studies, and electrophysiological techniques. Our findings reveal a diverse array of neuronal types within the IcNS, exceeding previous expectations. We identify a subset of neurons exhibiting characteristics akin to pacemaker/rhythmogenic neurons similar to those found in Central Pattern Generator networks of the central nervous system. Our results underscore the heterogeneity within the IcNS and its key role in regulating the heart’s rhythmic functionality. The classification and characterization of the IcNS presented here serve as a valuable resource for further exploration into the mechanisms underlying heart functionality and the pathophysiology of associated cardiac disorders.

Aims: Highly cross-linked polyethylene (HXLPE) greatly reduces wear in total hip arthroplasty, compared to conventional polyethylene (CPE). Cross-linking is commonly achieved by irradiation. This study aimed to compare the degree of cross-linking and in vitro wear rates across a cohort of retrieved and unused polyethylene cups/liners from various brands. Methods: Polyethylene acetabular cups/liners were collected at one centre from 1 April 2021 to 30 April 2022. The trans-vinylene index (TVI) and oxidation index (OI) were determined by Fourier-transform infrared spectrometry. Wear was measured using a pin-on-disk test. Results: A total of 47 specimens from ten brands were included. The TVI was independent of time in vivo. A linear correlation (R2 = 0.995) was observed between the old and current TVI standards, except for vitamin E-containing polyethylene. The absorbed irradiation dose calculated from the TVI corresponded to product specifications for all but two products. For one electron beam-irradiated HXLPE, a mean dose of 241% (SD 18%) of specifications was determined. For another, gamma-irradiated HXLPE, a mean 41% (SD 13%) of specifications was determined. Lower wear was observed for higher TVI. Conclusion: The TVI is a reliable measure of the absorbed irradiation dose and does not alter over time in vivo. The products of various brands differ by manufacturing details and consequently cross-linking characteristics. Absorption and penetration of electron radiation and gamma radiation differ, potentially leading to higher degrees of cross-linking for electron radiation. There is a non-linear, inverse correlation between TVI and in vitro wear. The wear resistance of the HXLPE with low TVI was reduced and more comparable to CPE. Cite this article: Bone Joint Res 2024;13(11):682–693.

Abstract Multiple myeloma (MM) is a plasma cell (PC) disorder characterized by skeletal involvement at the time of diagnosis. Recently, cell-free DNA (cfDNA) has been proven to recapitulate the heterogeneity of bone marrow (BM) disease. Our aim was to evaluate the prognostic role of cfDNA at diagnosis according to disease distribution, and to investigate the role of the MM microenvironment inflammatory state in supplying the release of cfDNA. A total of 162 newly diagnosed MM patients were screened using 18F-FDG PET/CT and assessed by ultra low-pass whole genome sequencing (ULP-WGS). High cfDNA tumor fraction (ctDNA) levels were correlated with different tumor mass markers, and patients with high ctDNA levels at diagnosis were more likely to present with metabolically active paraskeletal (PS) and extramedullary (EM) lesions. Moreover, we demonstrated that microenvironment cancer-associated fibroblast (CAFs)-mediated inflammation might correlate with high ctDNA levels. Indeed, a high cfDNA TF level at diagnosis predicted a poorer prognosis, independent of R-ISS III and 1q amplification; the inclusion of >12% ctDNA in the current R-ISS risk score enables a better identification of high-risk patients. ctDNA can be a reliable and less invasive marker for disease characterization, and can refine patient risk.

Abstract Lynch syndrome is rarely associated with rectal cancer (RC) and thus, metachronous RC has been scarcely investigated. This study aimed to analyze the mucosal immune microenvironment in sporadic and metachronous RC. We analyzed the mucosal immune microenvironment in the 25 metachronous RCs present in the IMMUNOREACT 1 and 2 multicentre observational studies (624 patients). A panel of immune markers was retrospectively investigated at immunohistochemistry: CD3, CD4, CD8, CD8b, Tbet, FoxP3, PD-L1, MSH6, and PMS2 and CD80. Single-cell suspensions were subjected to flow-cytometry to determine the proportion of epithelial cells (pan-cytokeratin) acting as antigen-presenting cells (expressing CD80, CD86, HLA-ABC) and the proportion of activated CD8 + T cells (CD8 + positive for CD28, CD38), inhibitory T cells (CD3 + CTLA-4+) of activated CD4 + T helper cells (CD4 + CD25+) and activated T regulatory cells (CD4 + CD25 + FoxP3+). No mismatch repair gene deficiencies were observed in the patients. The previous history of colorectal adenoma was significantly more frequent in metachronous RC. In healthy epithelial cells, HLA-ABC expression was significantly higher in patients with metachronous RC. In therapy-naïve metachronous RC patients, a significantly lower level of circulating lymphocytes and CD3 + T-cell infiltration in the healthy mucosa surrounding the RC was observed compared to patients with non-metachronous cancer. Our study supports the hypothesis that metachronous RC can occur in a cancerization field in patients with weak systemic and local immune systems. The peculiar site of RC makes the mismatch-repair genes deficiency in metachronous cancer onset less relevant.

Abstract Post-neoadjuvant therapy (post-NAT) and post-surgical circulating tumor DNA (ctDNA) risk stratification may enhance the management of patients with locally advanced rectal cancer (LARC). In this study, we assessed the prognostic value of ctDNA-based MRD detection in LARC patients using a personalized, tumor-informed ctDNA assay. Plasma samples from LARC patients (N = 30) were analyzed retrospectively using the Signatera™ assay. The neoadjuvant rectal (NAR) score was calculated and compared to ctDNA status to predict recurrence risk and survival outcomes. ctDNA-positive patients post-NAT and post-surgery had worse Disease Free Survival (DFS) (HR: 7.82; p = 0.001, HR: 19.65; p = 0.001) when compared to ctDNA-negative patients. In the post-NAT setting, patients who responded to NAT had superior DFS compared to patients who did not clear their ctDNA or showed no radiological response (HR: 24.7, p = 0.001 and HR: 5.1, p = 0.054, respectively). When ctDNA status is used alongside the NAR score in the post-NAT setting, patients who were ctDNA-positive with an intermediate or high NAR score showed significantly worse DFS (HR: 47.5, p

Abstract Background Contraception knowledge and attitudes are largely formed from conversations within one’s social network. More recently, this network has expanded to include social media. As the fastest growing social media platform, we aimed to assess popular contraception videos on TikTok for content understandability, actionability and accuracy. Methods This is a secondary analysis of the most viewed, contraception-specific TikTok videos that were previously coded as containing educational messaging in a content-analysis study. We assessed videos for understandability (ability to explain a key message) and actionability (identify what they can do to act on that message) using the Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT-A/V) instrument and for Currency, Relevance, Authority, Accuracy, and Purpose (CRAAP) using a modified instrument within the health information education literature. Results The 174 videos with educational content scored as understandable but not actionable in PEMAT-A/V assessment, with videos created by healthcare providers (HCPs) performing better than those by non-HCPs in six of eleven domains of understandability. Videos overall scored well in relevance and purpose within the CRAAP assessment. Videos created by HCP’s (n = 99) scored higher than those by non-HCPs (n = 75) in relevance (score = 3.9 versus 3.3), authority (score = 4.8 versus 1.7), accuracy (score = 6.0 versus 3.5), and purpose (score = 7.1 versus 5.7) [all p

Abstract Background Health care staff should be given the opportunity to participate in research, but recruiting clinicians via their employing organisation is not always straightforward or quick in the UK. Unlike many countries outside the UK, very low-risk survey, interview or focus group studies can be subject to some of the same governance approval procedures as interventional studies. An exemplar study carried out by the NIHR funded Palliative Care Research Partnership North West Coast is used to highlight the challenges still faced by researchers and health care organisations when setting up a low-risk staff study across multiple NHS and non-NHS sites. Methods A study database was created and information was collected on the first point of contact with the clinical site, Health Research Authority (HRA) and local organisational approval times, time from trust or hospice agreement to the first survey participant recruited and overall site survey recruitment numbers. Descriptive statistics (median, range) were used to analyse these data. Results Across participating NHS trusts, it took a median of 147.5 days (range 99–195) from initial contact with the local collaborator to recruitment of the first survey participant and hospice sites mirrored these lengthy timescales (median 142 days, range 110–202). The lengthiest delays in the HRA approval process were the period between asking NHS trusts to assess whether they had capacity and capability to support the research and them granting local agreement. Local approval times varied between trusts and settings which may indicate organisations are applying national complex guidance differently. Conclusions There is the potential for HRA processes to use more NHS resources than the research study itself when recruiting to a low-risk staff study across multiple organisations. There is a need to reduce unnecessary administrative burden and bureaucracy to give clinicians and research staff more opportunities to participate in research, and to free up NHS R&D departments, research nurses and clinicians to focus on more demanding and patient focused research studies. Hospices need standardised guidance on how to assess the risk of being involved in low-risk research without adopting the unnecessarily complex systems that are currently used within the NHS.

Abstract Background Studies on the in-depth documentation of wild greens use in the Mediterranean Diet (MD) are vital to understanding patterns of cross-geographical change in wild food ingredients in the Mediterranean context, their appreciated taste, and possible evolution. Our present study aims to document the leafy, wild-sourced plant portion of the MD in the unique and isolated matrifocal community of Olympos, North Karpathos Isle, Greece. Methods An ethnobotanical field study focussing on traditionally wild-sourced edible greens (chórta) was conducted during the spring of 2023 via 42 semi-structured interviews with local people. Results Our study documented 69 wild green taxa, along with their culinary uses and linguistic labels. Half of the gathered wild greens have a bitter taste (i.e. members of Asteraceae and Brassicaceae), while 70% of the top-quoted greens are bitter. These greens were mostly consumed cooked. Nearly half of the quoted taxa had been previously recorded as used in the food system of central Crete. In contrast, one-fourth of the folk phytonyms recorded in Olympos do not match the ones found in Crete and the rest of Greece, which may be linked to the Doric culture that the community remained attached to because of its isolation. However, the plant-human interaction kernel is similar to that of surrounding areas. Moreover, the community of Olympos seems to rely less on aromatic wild greens (compared with Crete). Conclusion Cross-cultural foraging comparison is crucial for better understanding the circulation, exchange, and evolution of local plant knowledge under the MD umbrella. Our study assesses, in particular, how noteworthy phytolinguistic differences indicating different ancient trajectories of cultural encounters/exchanges may not necessarily be reflected in differences in terms of plant reports. As often postulated in linguistic ethnobiology, ancient linguistic labels sometimes remain as “empty shells”. Given the fragile environment and the increasing over-tourism during the summer months the study site is experiencing, the presented data could contribute to a more substantial shift towards sustainable eco-tourism initiatives involving the foraging and cooking of wild greens.

Abstract Seed quality is the set of physical, genetic, and physiological characteristics, reflecting the overall germination potential. Maintaining an optimal seed quality is essential for agriculture and seed banks to preserve genetic diversity. Compared to conventional methods (e.g., germination tests), non-invasive approaches allow a more sustainable and rapid evaluation of seed quality but this is limited by high costs. The measurement of ultra-weak photon emission (UPE) and delayed fluorescence (DL), defined as biological phenomena potentially related to the physiological status of living systems, may represent a suitable approach to estimate seed quality. To test this hypothesis, seeds of five agriculturally relevant legume species (Phaseolus vulgaris L., Lathyrus sativus L., Cicer arietinum L., Pisum sativum L., and Vicia faba L.), stored at different conditions (room temperature or -18 °C) for several years, were analysed using a LIANA© prototype to collect data regarding DL and UPE occurring after UV excitation. The obtained data were integrated with germination parameters which underline species-specific behaviours in response to storage conditions. The prediction models show variable efficiency in classifying seeds based on germination which underline species-dependent links between photon emission and seed quality. Therefore, these measurements represent novel, non-invasive, and rapid approaches to evaluate seed quality.

Abstract Quantum states beyond thermodynamic equilibrium represent fascinating and cutting-edge research. However, the behavior of dynamical quantum phase transitions in complex open quantum systems remains poorly understood. Here, using state-of-the-art numerical approaches, we show that by quenching the qubits-oscillator coupling in a dissipative two-qubit Rabi model, the system undergoes dynamical quantum phase transitions. These transitions are characterized by kinks in the Loschmidt echo rate function at parameter values close to a thermodynamic quantum phase transition and are associated with distinct entanglement features. The two classes of critical phenomena depend on qubit interactions and entanglement, revealing different behaviors of the critical exponent of the first kink of the Loschmidt echo for interacting versus non-interacting qubits. This research enhances our understanding of non-equilibrium quantum systems and offers potential applications in quantum sensing and metrology, as it examines how dynamical transitions can enhance the sensitivity of the Loschmidt echo to the quench parameters.

Abstract In most studied eukaryotes, chromosomes are monocentric, with centromere activity confined to a single region. However, the rush family (Juncaceae) includes species with both monocentric (Juncus) and holocentric (Luzula) chromosomes, where centromere activity is distributed along the entire chromosome length. Here, we combine chromosome-scale genome assembly, epigenetic analysis, immuno-FISH and super-resolution microscopy to study the transition to holocentricity in Luzula sylvatica. We report repeat-based holocentromeres with an irregular distribution of features along the chromosomes. Luzula sylvatica holocentromeres are predominantly associated with two satellite DNA repeats (Lusy1 and Lusy2), while CENH3 also binds satellite-free gene-poor regions. Comparative repeat analysis suggests that Lusy1 plays a crucial role in centromere function across most Luzula species. Furthermore, synteny analysis between L. sylvatica (n = 6) and Juncus effusus (n = 21) suggests that holocentric chromosomes in Luzula could have arisen from chromosome fusions of ancestral monocentric chromosomes, accompanied by the expansion of CENH3-associated satellite repeats.

Abstract This paper examines the challenges and drivers shaping EU agriculture in the medium term, focusing on its capacity to meet societal demands and remain resilient. Key drivers include climate change, global population growth, and geopolitical shifts, while innovation fosters adaptation. The EU’s regulatory responses and the evolution of the Common Agricultural Policy (CAP) will determine how agriculture reconciles environmental sustainability with farmers’ concerns about fair competition, influencing global outcomes.

Diffuse large B‐cell lymphoma (DLBCL) is the most prevalent subtype of non‐Hodgkin lymphoma (NHL) in domestic dogs, with many similarities to its human counterpart. The progression of the disease is rapid, and treatment must be initiated early to achieve cancer remission and extend life. This study examined the relationship between progression‐free survival (PFS) and microRNA (miRNA) expression in dogs with DLBCL. miRNAs are small non‐coding RNA molecules that typically regulate gene expression post‐transcriptionally. They are involved in several pathophysiological processes, including the growth and progression of cancer. Based on the analysis of small RNA sequencing (sRNA‐seq) data, we validated a group of miRNAs in lymph nodes from 44 DLBCL‐affected dogs with known outcomes. We used quantitative PCR to quantify their expression and report a specific subset of miRNAs is associated with decreased PFS in dogs with DLBCL. The miR‐192‐5p and miR‐16‐5p expression were significantly downregulated in dogs with increased PFS. These results indicate that miRNA profiling may potentially identify dogs with DLBCL that will experience poor outcomes following treatment. Identifying specific miRNAs that correlate with the progression of canine DLBCL could aid the development of individualized treatment regimens for dogs.

Background and objective: High-resolution micro-ultrasound (microUS) is an advanced imaging tool. Our objective was to determine whether systematic microUS use for transrectal biopsy (TRBx) improves the detection rate for clinically significant prostate cancer (csPCa) in comparison to transperineal biopsy (TPBx) performed with magnetic resonance imaging (MRI)/conventional transrectal ultrasound (TRUS) fusion software. Methods: We retrospectively analyzed data for men who underwent prostate biopsies, including those on active surveillance (AS). TRBx was performed under microUS guidance, while MRI/TRUS fusion was consistently used to guide TPBx. Patients were matched according to propensity score matching (PSM). The primary endpoint was comparison of the csPCa detection rate with the two approaches. Secondary endpoints included predictors of csPCa (International Society of Urological Pathology grade group ≥2, assessed via multivariable logistic regression) and complication rates. Key findings and limitations: Overall, 1423 patients were enrolled. After applying PSM we identified an analytical cohort of 1094 men, 582 in the TRBx group and 512 in the TPBx group. There was no significant difference in the csPCa detection rate between the TRBx (45%) and TPBx (51%) groups (p = 0.07). Complications occurred in nine of 1094 patients (1%). On adjusted multivariable analysis, TPBx had a similar csPCa detection rate to TRBx (adjusted odds ratio [aOR] 1.26;p = 0.09). Predictors of csPCa detection were a positive family history (aOR 1.68; 95% confidence interval [CI] 1.20–2.35; p = 0.002); age (aOR 1.04, 95% CI 1.02–1.06; p

We report a 55-year-old men patient with a primitive central nervous system non-Hodgkin lymphoma B cell (LNH PNSLC), treated with chemotherapy rituximab, methotrexate, and ibrutinib (first treatment) who developed a refractory ventricular arrhythmic storm two hours after the ibrutinib intake. Indeed, ibrutinib could be associated with severe and occasionally fatal cardiac events. The swift emergence of a ventricular electrical storm with cardiac arrest demanded the prompt initiation of veno-arterial extracorporeal membrane oxygenation to effectively navigate this critically ill patient toward recovery. This intervention was deemed imperative, given the absence of any available antidote for the effects of ibrutinib. Veno-arterial extracorporeal membrane oxygenation proved successful in rescuing this patient, resulting in a complete neurological recovery. Consequently, he was able to resume his chemotherapy treatment.

Abstract Anthropogenic emissions alter atmospheric composition and therefore the climate, with implications for air pollution- and climate-related human health. Mortality attributable to air pollution and non-optimal temperature is a major concern, expected to shift under future climate change and socioeconomic scenarios. In this work, results from numerical simulations are used to assess future changes in mortality attributable to long-term exposure to both non-optimal temperature and air pollution simultaneously. Here we show that under a realistic scenario, end-of-century mortality could quadruple from present-day values to around 30 (95% confidence level:12-53) million people/year. While pollution-related mortality is projected to increase five-fold, temperature-related mortality will experience a seven-fold rise, making it a more important health risk factor than air pollution for at least 20% of the world’s population. These findings highlight the urgent need to implement stronger climate policies to prevent future loss of life, outweighing the benefits of air quality improvements alone.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) poses a significant challenge due to late-stage diagnoses resulting from nonspecific early symptoms and the absence of early diagnostic biomarkers. MicroRNAs (miRNAs) play a crucial role in regulating diverse biological processes, and their abnormal expression is observed in various diseases, including cancer. Cancer stem cells (CSCs) are thought to act as a driving force in PDAC spread and recurrence. In pursuing the goal of unravelling the complexities of PDAC and its underlying molecular mechanisms, our study aimed to identify PDAC-associated miRNAs and relate them to disease progression, focusing on their involvement in various PDAC stages in patients and in reliable in vitro models, including pancreatic CSC (PaCSC) models. Methods The miRNA profiling datasets of serum and solid biopsies of PDAC patients deposited in GEO DataSets were analyzed by REML-based meta-analysis. The panel was then investigated by Real Time PCR in serum and solid biopsies of 37 PDAC patients enrolled in the study, as well as on BxPC-3 and AsPC-1 PDAC cell lines. We extended our focus towards a possible role of PDAC-associated miRNAs in the CSC phenotype, by inducing CSC-enriched pancreatospheres from BxPC-3 and AsPC-1 PDAC cell lines and performed differential miRNA expression analysis between PaCSCs and monolayer-grown PDAC cell lines. Results Meta-analysis showed differentially expressed miRNAs in blood samples and cancerous tissues of PDAC patients, allowing the identification of a panel of 9 PDAC-associated miRNAs. The results emerging from our patients fully confirmed the meta-analysis for the majority of miRNAs under investigation. In vitro tasks confirmed the aberrant expression of the panel of PDAC-associated miRNAs, with a dramatic dysregulation in PaCSC models. Notably, PaCSCs have shown significant overexpression of miR-4486, miR-216a-5p, and miR-216b-5p compared to PDAC cell lines, suggesting the recruitment of such miRNAs in stemness-related molecular mechanisms. Globally, our results showed a dual behaviour of miR-216a-5p and miR-216b-5p in PDAC while miR-4486, miR-361-3p, miR-125a-5p, miR-320d expression changes during the disease suggest they could promote PDAC initiation and progression. Conclusions This study contributed to an enhanced comprehension of the role of miRNAs in the development and progression of PDAC, shedding new light on the miRNA landscape in PDAC and its intricate interplay with CSCs, and providing specific insights useful in the development of miRNA-based diagnostic biomarkers and therapeutic targets.

Abstract Background Physical activity is thought to be a key component in reducing postoperative complications following major abdominal surgery. The available literature on exercise interventions following radical cystectomy in patients with bladder cancer is scarce but suggests that physical activity and exercise might improve physical function and health-related quality of life, thus calling for further investigation. The CanMoRe-trial is a single-blinded randomised controlled trial (Clinicals Trials NCT03998579 25/06/2019), aimed at evaluating the impact of an exercise intervention in primary care following robot-assisted radical cystectomy. This study seeks to explore patients’ experiences of the exercise intervention in the CanMoRe-trial to gain a better understanding of facilitating aspects and potential barriers. Methods A qualitative study was conducted involving 20 patients from the intervention group of the CanMoRe-trial who were interviewed individually between October 2020 and March 2023 using a semi-structured interview guide. The interviews were recorded and transcribed verbatim and reflexive thematic analysis was used to analyse the data. Results Four main themes were identified: Having to adapt to new circumstances, describing the challenges regarding physical activity patients face after discharge. Optimising conditions for rehabilitation, describing how practical conditions affect patients’ ability to exercise. Motivated to get back to normal, describing patients´ desire to get back to normal life and factors influencing motivation. Importance of a supportive environment, describing the impact of social support, support from physiotherapists, and how the environment where exercise takes place impacts patients’ ability to exercise. Conclusion This study found that patients participating in the CanMoRe-trial are positive towards physical exercise in PC following radical RARC. They are motivated to get back to normal life but face major challenges when arriving home following surgery, which affect their ability to perform physical activity and engage in exercise. Conditions need to be optimised to support patients’ ability to engage in exercise by providing an accessible PC location to perform exercise in. A supportive environment is also needed, including guidance from healthcare professionals regarding which type of exercise, intensity and amount of exercise that should be performed, enabling patients gradually to develop self-efficacy regarding exercise and focusing on goals related to patients’ normal lives before surgery.

Abstract Simple physico-chemical techniques can be used to evaluate the composition, structure, and characteristics of plant seeds to determine their viability, quality, and possible uses in agriculture. Advanced analytical techniques, including thermo gravimetric analysis (TGA), electron paramagnetic resonance (EPR), and high-pressure liquid chromatography (HPLC), provide completely new insights and more precise information. They can be integrated to build up seed quality profiles, with great advantage to assess water content, organic compounds, and inorganic metals without the need to carry out many extraction procedures, as requested by more conventional methods. In this study, seed lots from three different plant species such as Triticum turgidum L. subsp. durum (wheat), Trigonella foenum graecum L. (trigonella or fenugreek), and Atriplex halimus L. (saltbush or sea orach) have been used to test the potential of TGA, EPR, and HPLC to discriminate between seed-specific features. A key finding of this study is that HPLC is essential in Principal Component Analysis (PCA) because various seeds (from the same species or other species) may contain compounds with varying polarity groups. The reported data confirm the efficacy of this approach. These data, fully available for other users, are coherently constructed and provide a proof of concept for future seed quality control studies.

Abstract Background COVID-19 pandemic caused by the Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) represents the biggest global health emergency in recent decades. The host immune response to SARS-CoV-2 seems to play a key role in disease pathogenesis and clinical manifestations, with Natural Killer (NK) lymphocytes being among the targets of virus-induced regulation. Methods This study performed a single-cell multi-omics analysis of transcripts and proteins of NK lymphocytes in COVID-19 patients, for the characterization of the innate immunological response to infection. NK cells were isolated from peripheral blood samples collected from adult subjects divided into 3 study groups: (1) non-infected subjects (Naïve group, n = 3), (2) post COVID-19 convalescent subjects (Healed group, n = 3) and (3) patients that were vaccinated against SARS-CoV-2 (Vaccine group, n = 3). Cells were then analysed by the BD Rhapsody System for the single-cell multi-omics investigation of transcriptome and membrane proteins. Results The bioinformatic analysis identified 5 cell clusters which differentially expressed gene/protein markers, defining NK cell subsets as “Active NK cells” and “Mature NK cells”. Calculating the relative proportion of each cluster within patient groups, more than 40% of the Naïve group cell population was found to belong to Mature NKs, whereas more than 75% of the Vaccine group cell population belonged to the cluster of Active NKs. Regarding the Healed group, it seemed to show intermediate phenotype between Active and Mature NK cells. Differential expression of specific genes, proteins and signaling pathways was detected comparing the profile of the 3 experimental groups, revealing a more activated NK cell phenotype in vaccinated patients versus recovered individuals. Conclusions The present study detected differential expression of NK cell markers in relation to SARS-CoV-2 infection and vaccine administration, suggesting the possibility to identify key molecular targets for clinical-diagnostic use of the individual response to viral infection and/or re-infection.

Abstract Purpose The purpose of this study is to investigate the impact of Mayo Adhesive Probability (MAP) score and body mass index (BMI) on renal function decline after robotic assisted partial nephrectomy (RAPN). Methods We queried our prospective database for patients who underwent RAPN between January 2018 and December 2023. Outcomes were development of de novo CKD‐S3 (estimated glomerular filtration rate [eGFR]

Abstract As seismic events continue to pose significant threats to urban infrastructure, leveraging smartphones equipped with accelerometers for real-time monitoring has gained prominence. To ascertain the reliability and sensitivity of smartphone-based measurements, an in-depth characterization of their response is essential. This article presents a thorough characterization of the performance of typical accelerometers installed on three distinct smartphone models. For this, a novel experimental apparatus has been developed to conduct a comparative study involving three different smartphones against a reference accelerometer. We determine each accelerometer’s transfer functions for Fourier frequencies 0.1–40 Hz, evidencing main differences and demonstrating a higher sensitivity than expected. Possible implementation in future distributed networks of heterogeneous and synchronized sensors, capable of independently generating and validating timely alerts in particular seismic events, are also discussed.

Abstract Although vaccination is considered the most effective weapon against influenza, coverage rates, national vaccination policies, and funding vary largely around the globe. Despite their huge potential for achieving herd immunity, child-focused national vaccination strategies that favor pain-free nasal vaccines are uncommon. CENTRAL, Embase, and MEDLINE were last searched on November 13, 2023. Active-controlled randomized controlled trials comparing the live-attenuated intranasal vaccine with the inactivated intramuscular influenza vaccine in children were included. Event rates of laboratory-confirmed influenza virus infection, all-cause mortality, hospitalization, serious adverse events, adverse events, and financial outcomes were extracted based on the PRISMA 2020 Guideline. PROSPERO: CRD42021285412. Pooled odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the random-effects model when at least three comparable outcomes were available. We found no significant difference between quadrivalent live-attenuated intranasal and trivalent inactivated intramuscular (OR = 1.48; 95% CI 0.49–4.45) or between trivalent live-attenuated intranasal and inactivated intramuscular vaccines (OR = 0.77, CI = 0.44–1.34) regarding their efficacy. However, the subgroup analysis of large, multi-center trials indicated that the trivalent live attenuated intranasal influenza vaccine was superior to the trivalent inactivated intramuscular influenza vaccine (12,154 people, OR = 0.50, CI = 0.28–0.88). Only 23 “vaccine-related serious adverse events” were recorded among 17 833 individuals, with no significant difference between methods. The widespread initiation of pediatric national flu vaccination programs prioritizing the live-attenuated intranasal influenza vaccine would be beneficial. Multi-continent, high-quality studies that include children younger than two years old and those living in subtropical and tropical regions are needed to further enhance our understanding.

Abstract Abnormal cytoplasmic localization and accumulation of pathological transactive response DNA binding protein of 43 kDa (TDP-43) underlies several devastating diseases such as amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP-43 pathology (FTLD-TDP). A key element is the correlation between disease progression and spatio-temporal propagation of TDP-43-mediated pathology in the central nervous system. Several lines of evidence support the concept of templated aggregation and cell to cell spreading of pathological TDP-43. To further investigate this mechanism in vivo, we explored the efficacy of capturing and masking the seeding-competent region of extracellular TDP-43 species. For this, we generated a novel monoclonal antibody (mAb), ACI-6677, that targets the pathogenic protease-resistant amyloid core of TDP-43. ACI-6677 has a picomolar binding affinity for TDP-43 and is capable of binding to all C-terminal TDP-43 fragments. In vitro, ACI-6677 inhibited TDP-43 aggregation and boosted removal of pathological TDP-43 aggregates by phagocytosis. When injecting FTLD-TDP brain extracts unilaterally in the CamKIIa-hTDP-43NLSm mouse model, ACI-6677 significantly limited the induction of phosphorylated TDP-43 (pTDP-43) inclusions. Strikingly, on the contralateral side, the mAb significantly prevented pTDP-43 inclusion appearance exemplifying blocking of the spreading process. Taken together, these data demonstrate for the first time that an immunotherapy targeting the protease-resistant amyloid core of TDP-43 has the potential to restrict spreading, substantially slowing or stopping progression of disease.

Abstract Focal liver lesions are frequently encountered during imaging studies, and hemangiomas represent the most common solid liver lesion. Liver hemangiomas usually show characteristic imaging features that enable characterization without the need for biopsy or follow-up. On the other hand, there are many benign and malignant liver lesions that may show one or more imaging features resembling hemangiomas that radiologists must be aware of. In this article we will review the typical imaging features of liver hemangiomas and will show a series of potential liver hemangiomas’ mimickers, giving radiologists some hints for improving differential diagnoses. Critical relevance statement The knowledge of imaging features of potential liver hemangiomas mimickers is fundamental to avoid misinterpretation. Key Points Liver hemangiomas typically show imaging features that enable avoiding a biopsy. Many benign and malignant liver lesions show imaging features resembling hemangiomas. Radiologists must know the potentially misleading imaging features of hemangiomas’ mimickers. Graphical Abstract

Aquaculture and waste valorization have the potential to show solid achievements toward food security and improvements in the circularity of resources, which are crucial aspects of achieving a sustainable lifestyle in agreeance with Agenda 2030 goals. This study aims to optimize and simplify the decision-making processes for the valorization of marine wastes (natural and from aquaculture) as secondary raw materials to produce high-value-added market goods. However, significant concentrations of pollutants may be present within wastes, compromising overall quality, and social dynamics can hinder their usage further. Goro’s lagoon was chosen as a case study, where the relations between the ecosystem services, a thriving bivalve economy, and social dynamics are deeply rooted and intertwined. Therefore, in the manuscript cost–benefit and foresight analyses are conducted to determine the best usage for algal biomass considering pollution, social acceptance, and profitability. These analyses are virtually conducted on bio-refineries that could be operating in the case study’s area: briefly, for a thirty-year running bio-plant, the CBA indicates the two best alternatives with an income of 5 billion euros (NPV, with a 5% discount rate) for a biofuel-only production facility, and a half for a multiproduct one, leading to the conclusion that the first is the best alternative. The foresight, instead, suggests a more cautious approach by considering external factors such as the environment and local inhabitants. Hence, the main innovation of this work consists of the decision-maker’s holistic enlightenment toward the complexities and the hidden threats bound to this kind of closed-loop efficiency-boosting process, which eventually leads to optimized decision-making processes.

Abstract Glioblastoma (GBM), one of the deadliest brain tumors, accounts for approximately 50% of all primary malignant CNS tumors, therefore novel, highly effective remedies are urgently needed. Boron neutron capture therapy, which has recently repositioned as a promising strategy to treat high-grade gliomas, requires a conspicuous accumulation of boron atoms in the cancer cells. With the aim of selectively deliver sodium borocaptate (BSH, a 12 B atoms-including molecule already employed in the clinics) to GBM cells, we developed novel cell membrane-derived vesicles (CMVs), overcoming the limits of natural extracellular vesicles as drug carriers, while maintaining their inherent homing abilities that make them preferable to fully synthetic nanocarriers. Purified cell membrane fragments, isolated from patient-derived GBM stem-like cell cultures, were used to prepare nanosized CMVs, which retained some membrane proteins specific of the GBM parent cells and were devoid of potentially detrimental genetic material. In vitro tests evidenced the targeting ability of this novel nanosystem and ruled out any cytotoxicity. The CMVs were successfully loaded with BSH, by following two different procedures, i.e. sonication and electroporation, demonstrating their potential applicability in GBM therapy.

ABSTRACT Increasing lignocellulosic feedstock for advanced biofuels can tackle the decarbonization of the transport sector. Dedicated biomass produced alongside food systems with low indirect land use change (iLUC) impact can broaden the feedstock availability, thus streamlining the supply chains. The objective of this study was the design and evaluation of advanced ethanol value chains for the Emilia‐Romagna region based on low iLUC feedstock. Two dedicated lignocellulosic crops (biomass sorghum and sunn hemp) were evaluated in double cropping systems alongside food crop residues (corn stover and wheat straw) as sources to simulate the value chains. A parcel‐level regional analysis was carried out, then the LocaGIStics2.0 model was used for the spatial design and review of the biomass delivery chain options regarding cost and greenhouse gas (GHG) emissions of the different feedstock mixes. Literature data on bioethanol production from similar feedstocks were used to estimate yields, process costs, and GHG emissions of a biorefinery process based on these biomasses. Within the chain options, GHG emissions were overly sensitive to cultivation input, mostly N‐fertilization. This considered, GHG emissions resulted similar across different feedstock with straw/stover (averaging 13 g CO2eq MJ−1 fuel), sunn hemp (14 g CO2eq MJ−1 fuel), and biomass sorghum (16 g CO2eq MJ−1 fuel). On the other hand, the bioethanol produced from biomass sorghum (608 € Mg−1 of bioethanol) was cheaper compared with straw (632 € Mg−1), sunn hemp (672 € Mg−1), and stover (710 € Mg−1). The bioethanol cost ranged from 0.0017 to 0.020 € MJ−1 fuel depending on the feedstock, with operations and maintenance impacting up to 90% of the final cost. In summary, a single bioethanol plant with an annual capacity of 250,000 Mg of biomass could replace from 5% to 7% of the Emilia‐Romagna's ethanol fuel consumption, depending on the applied sourcing scenario.

ABSTRACTInfectious diseases pose a significant burden on the general population, particularly older adults who are more susceptible to severe complications. Immunization plays a crucial role in preventing infections and securing a healthier aging, but actual vaccination rates among older adults and frail individuals (OAFs) remains far from recommended targets. This study aims to collect and share good practices implemented in several Italian local health districts during the SARS-CoV-2 pandemic to ease routine immunization for OAFs. A 28-items questionnaire has been developed to collect information on organization aspect of immunization services and local good practices implemented before and during the SARS-CoV-2 pandemic. Twelve Public Health managers representative of 9 Italian Regions were further interviewed between January and March 2021. Despite literature suggests several effective interventions to increase vaccine demand, improve vaccine access, and enhance healthcare providers’ performance, our survey highlighted substantial heterogeneity in their implementation at local level. Seven good local practices have been identified and described: mass vaccination centers; vaccination mobile units; drive-through vaccination; co-administration; tailored pathways; cooperation among providers involved in vaccination; digitization. Our survey pointed out valuable strategies for enhancing routine immunization for OAFs. Providers should combine effective interventions adequate to their specific context and share good practices.

ABSTRACTThis 1:30,000 scale geological map describes Oxia Planum, Mars, the landing site for the ExoMars Rosalind Franklin rover mission. The map represents our current understanding of bedrock units and their relationships prior to Rosalind Franklin’s exploration of this location. The map details 15 bedrock units organised into 6 groups and 7 textural and surficial units. The bedrock units were identified using visible and near-infrared remote sensing datasets. The objectives of this map are (i) to identify where the most astrobiologically relevant rocks are likely to be found, (ii) to show where hypotheses about their geological context (within Oxia Planum and in the wider geological history of Mars) can be tested, (iii) to inform both the long-term (hundreds of metres to ∼1 km) and the short-term (tens of metres) activity planning for rover exploration, and (iv) to allow the samples analysed by the rover to be interpreted within their regional geological context.

BackgroundAntibody-mediated rejection is a significant cause of kidney transplant failure. Recent studies have shown that the MHC class I MICA gene influences the transplantation outcome. However, the role of the primary MICA receptor, NKG2D, has yet to be explored.AimWe aimed to investigate the correlation between recipient/donor MICA allele matching and NKG2D genotype with the risk of antibody-mediated rejection and their potential clinical effects and implications for organ maintenance therapy.MethodsOf the 524 patients who underwent transplantation, 387 were eligible for the study. Complete MICA allele and two functional polymorphisms of NKG2D (rs1049174C>G and rs2255336G>A) were analyzed in 148 transplanted patients and 146 controls.ResultsIncreased recipient/donor MICA allele mismatches correlate with an elevated risk of antibody-mediated rejection (X2 = 6.95; Log-rank=0.031). Notably, the rs1049174[GG] genotype contributes to a significantly increased risk of antibody-mediated rejection (X2 = 13.44; Log-rank=0.001 and X2 = 0.34; Log-rank=0.84). The combined effect of two MICA allele mismatches and rs1049174[GG] genotype shows the highest risk (X2 = 23.21; Log-rank

Chest trauma is the leading cause of death in people under 40. It is estimated to cause around 140,000 deaths each year. The key aims are to reduce mortality and the impact of associated complications to expedite recovery and to restore patient’s conditions. The recognition of lesions through appropriate imaging and early treatment already in the emergency department are fundamental. The majority can be managed in a non-surgical way, but especially after traumatic cardiac arrest, a surgical approach is required. One of the most important surgical procedures is the Emergency Department Thoracotomy (EDT). The aim of this review is to provide a comprehensive synthesis about the management of thoracic trauma, the surgical procedures, accepted indications, and technical details adopted during the most important surgical procedures for different thoracic trauma injuries. Literature from 1990 to 2023 was retrieved from multiple databases and reviewed. It is also important to emphasize the medico-legal implications of this type of trauma, both from the point of view of collaboration with the judicial authority and in the prevention of any litigation.

Embodiment (the sensation that arises when the properties of an external instrument are processed as if they are the attributes of one's own biological body) and (tele)presence (the sensation of being fully engaged and immersed in a location other than the physical space occupied by one's body) sustain the perception of the physical self and potentially improve performance in teleoperations (a system that enables human intelligence to control robots and requires implementing an effective human-machine interface). Embodiment and presence may be interdependent and influenced by right temporo-parietal junction (rTPJ) activity. We investigated the interplay between embodiment, (tele)presence, and performance in teleoperation, focusing on the role of the rTPJ. Participants underwent a virtual reality task with transcranial direct current stimulation (tDCS) twice, receiving either active or sham stimulation. Behavioral measures (driving inaccuracy, elapsed time in the lap, time spent in attentional lapses, short-term self-similarity, and long-term self-similarity), perceived workload (mental demand, physical demand, temporal demand, own performance, effort, and frustration), embodiment's components (ownership, agency, tactile sensations, location, and external appearance), and presence's components (realism, possibility to act, quality of interface, possibility to examine, self-evaluation of performance, haptic, and sounds) were assessed. The results showed that rTPJ stimulation decreased perceived ownership but enhanced presence with changes in the complexity of visuomotor adjustments (long and short-term self-similarity indices). Structural equation modeling revealed that embodiment increased visuomotor inaccuracy (a composite variable of overall performance, including deviations from the optimal trajectory and the time taken to complete the task), presence reduced workload, and workload increased inaccuracy. These results suggested a dissociation between embodiment and presence, with embodiment hindering performance. Prioritizing virtual integration may lower human performance, while reduced workload from presence could aid engagement. These findings emphasize the intricate interplay between rTPJ, subjective experiences, and performance in teleoperation.

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

Abstract Background Medical staff are regularly confronted with workplace violence (WPV), which poses a threat to the safety of both staff and patients. Structured de-escalation training (DET) for Emergency Department (ED) staff has been shown to positively affect the reporting of WPV incidents and possibly reduce its impact. This study aimed to describe the development of incidence rates, causes, means, targets, locations, responses, and the time of WPV events. Additionally, it explored the effect of the staff trained in DET on the objective and subjective severity of the respective WPV events. Methods In a retrospective, single-center cohort study, we analyzed ten years of WPV events using the data of Staff Observation Aggression Scale-Revised (SOAS-R) score (ranging from 0 to 22) in a tertiary ED from 2014 to 2023. The events were documented by ED staff and stored in the electronic health record (EHR). Results Between 2014 and 2023, 160 staff members recorded 859 incidents, noting an average perceived severity of 5.78 (SD = 2.65) and SOAS-R score of 11.18 (SD = 4.21). Trends showed a non-significant rise in incident rates per 10,000 patients over time. The WPV events were most frequently reported by nursing staff, and the cause of the aggression was most often not discernible (n = 353, 54.56%). In total, n = 273 (31.78%) of the WPV events were categorized as severe, and the most frequent target of the aggressive behavior was the staff. WPV events occurred most frequently in the traumatology section and the detoxification rooms. While the majority of events could be addressed with verbal interventions, more forceful interventions were performed significantly more often for higher severity WPV events. More WPV events occurred during off-hours and were of a significantly higher objective and subjective severity. Overall, the presence of staff with completed DET led to significantly higher SOAS-R scores and higher perceived severity. Conclusion The findings underline the relevance of WPV events in the high-risk environment of an ED. The analyzed data suggest that DET significantly fostered the awareness of WPV. While most events can be addressed with verbal interventions, WPV remains a concern that needs to be addressed through organizational measures and further research.

Abstract Many insects utilise optical information in linearly polarised light for navigation, with the degree of linear polarisation (DoLP) determining whether the ‘visibility’ of such optical information is available to them. However, changes in degree of linear polarisation in response to increased atmospheric levels of fine particulate matter (PM2.5) are poorly understood. We present analyses based on both ground-based monitoring and particulate matter modelling, establishing a quantitative relationship between PM2.5 mass concentration and the DoLP. We apply this relationship to a global PM2.5 projection for 2050 and estimate the increase in number and spatial extent of low visibility days for honeybees. We find an increase by up to 20% in the geographical extent of low visibility days in 2050, with an augmented frequency of low visibility days across an area exceeding 0.75 million km2 in India and 2 million km2 in China. More frequent and widespread low visibility conditions can reduce the ability of insects to navigate, especially in hotspot regions.

Abstract Background The German multicenter research consortium BipoLife aims to investigate the mechanisms underlying bipolar disorders. It focuses in particular on people at high risk of developing the disorder and young patients in the early stages of the disease. Functional and structural magnetic resonance imaging (MRI) data was collected in all participating centers. The collection of neuroimaging data in a longitudinal, multicenter study requires the implementation of a comprehensive quality assurance (QA) protocol. Here, we outline this protocol and illustrate its application within the BipoLife consortium. Methods The QA protocol consisted of (1) a training of participating research staff, (2) regular phantom measurements to evaluate the MR scanner performance and its temporal stability across the course of the study, and (3) the assessment of the quality of human MRI data by evaluating a variety of image metrics (e.g., signal-to-noise ratio, ghosting level). In this article, we will provide an overview on these QA procedures and show exemplarily the influence of its application on the results of standard neuroimaging analysis pipelines. Discussion The QA protocol helped to characterize the various MR scanners, to record their performance over the course of the study and to detect possible malfunctions at an early stage. It also assessed the quality of the human MRI data systematically to characterize its influence on various analyses. Furthermore, by setting up and publishing this protocol, we define standards that must be considered when analyzing data from the BipoLife consortium. It further promotes a systematic evaluation of data quality and a definition of subject inclusion criteria. In the long term, it will help to increase the chance of achieving clinically relevant results.

Abstract Background Evidence shows that motivational practices focused on utility, importance, and autonomy shape university students’ motivational orientation toward learning. On the other hand, the relationship between these variables and motivational orientation toward learning is not linear and requires models that describe their behavior over time. Method In this study, mathematical modeling based on system dynamics methodology is used to simulate in health students the temporal dynamics of the motivational orientation toward learning based on the behavior of these variables in different scenarios. Results The results indicate that a) Mastery is sensitive to changes in frequency when importance and autonomy practices are performed; b) the development of Mastery is critical in the first three semesters of academic life, but its loss is hardly recoverable even when practices are incorporated in subsequent semesters; c) Utility-focused motivational practices have no significant effect on the development of learning-oriented motivation. Conclusion These findings have significant practical implications for higher education. Understanding the critical role of Mastery in the early stages of academic life and the limited potential for recovery if lost can help raise awareness of the importance of early implementation of motivational practices focused on relevance and autonomy.

A typical halogen-free flame-retardant (HFFR) formulation for electric cables may contain polymers, various additives, and fire-retardant fillers. In this study, composites are prepared by mixing natural magnesium hydroxide (n-MDH) with linear low-density polyethylene (LLDPE) and a few types of ethylene–octene copolymers (C8-POE). Depending on the content of LLDPE and C8-POE, we obtained composites with different crystallinities that affected the final mechanical properties. The nucleation effect of the n-MDH and the variations in crystallinity caused by the blending of C8-POE/LLDPE/n-MDH were investigated. Notably, in the C8-POE/LLDPE blend, we found a decrease in the crystallization temperature of LLPDE compared to pure LLDPE and an increase in the crystallization temperature of C8-POE compared to pure C8-POE. On the contrary, the addition of n-MDH led to an increase in the crystallization temperature of LLDPE. As expected, the increase in the crystallinity of the polyolefin matrix of composites led to higher elastic modulus, higher tensile strength, and lower elongation at break. It has been observed that crystallinity also influences fire performance. Overall, these results show how to obtain the required mechanical features for halogen-free flame-retardant compounds for electric cable applications, depending on the quantities of the two miscible components in the final blend.

The Sorrento Peninsula is characterized by a significant occurrence of examples of vernacular architecture, which exhibit distinctive morphological and constructive features. These have been the subject of numerous studies. However, some buildings have undergone a process of transformation over time, the details of which have yet to be investigated. Architectures that initially held a rural character were enlarged and ennobled, thereby becoming what could be termed as “villas of delights”. However, these clearly manifest their origin based on the permanence of some vernacular features. This paper focuses on the analysis of a case study, Villa Murat, which is exemplary in illustrating this process. This thorough interdisciplinary research combines historical investigation, based mainly on archival documents, with a direct examination of the Villa. This has enabled the retracing of the building’s evolution and of the events that occurred in it. An integrated survey, which employed photogrammetry and laser scanning, enabled the assessment of the current state of conservation. The ultimate objective of this research is to propose conservative interventions which, in conjunction with the suggested new intended use, could ensure the preservation of the Villa.

The ERC Advanced Grant AN-ICON, coordinated by Andrea Pinotti and hosted by the Department of Philosophy Piero Martinetti of the University of Milan, is cross-disciplinary project that brings together aesthetics, media theory, archaeology and various disciplines to address the complexities of contemporary mediascape, particularly in the realm of Extended Reality (XR). Within XR, which encompasses Virtual Reality (VR), Augmented Reality (AR) and Mixed Reality (MR), ‘an-icons’ emerge as self-negating images that blur iconic boundaries and promote environmental presence. This paper provides an insight into AN-ICON’s diverse investigations dedicated to immersive technologies. It explores the cultural lineage of VR, AR and XR, their intersections with design and urban spaces, and the emerging prospects for digital memory studies. It also highlights the therapeutic, educational and prosocial potential of these media, informed by their historical and mediarchaeological backgrounds.

Introduction: Monogenic obesity is caused by a unique genetic dysfunction, often appears in childhood, and can be accompanied by neuroendocrine, skeletal, developmental, and behavioral disorders, among other manifestations. Some variants in the SH2B1 gene have been suggested as strong candidates for the development of autosomal dominant obesity. Case Presentation: We describe here the clinical response after 1 year of setmelanotide treatment in a 22-year-old patient with an SH2B1 variant. After 3 months of treatment, our patient lost 5.4% of body weight. This period was followed by a 3-month period of noncompliance, in which the patient gained 4% body weight. After reinstating daily drug administration, the patient showed a 19.5% reduction in body weight and a clear improvement in all hunger scales after 1 year of treatment. Conclusion: These results indicate that the changes seen are drug dependent and provide positive evidence for the administration of setmelanotide in adult patients with heterozygous variants in the SH2B1 gene.

Abstract Background Occupational therapists are increasingly asked to demonstrate the effectiveness, appropriateness, and efficiency of their interventions to funding bodies. However, the extent to which this is practiced and the health policy context within which such a practice is situated differs internationally. The aim of this scoping review was to establish which quality indicators are used internationally for this purpose. Methods We conducted a scoping review, limiting our search to Europe and the English-speaking world. To search for suitable literature, we used specialized databases from medicine, health sciences, and related fields, including CINAHL Complete and MEDLINE, as well as free internet search via Google. Furthermore, we contacted national occupational therapy associations from several countries asking for access to documents found within this search that were only accessible to association members. Results The screening process identified 32 studies and documents from six national contexts. We identified and described process-level indicators, functional outcome indicators, one outcome indicator based on individual goal attainment (the Goal Attainment Scale, or GAS), and PRO-Ergo, a patient-reported experience measure (PREM). There was little information on the use of quality indicators to demonstrate the effectiveness, appropriateness, and efficiency of occupational therapy services to funding bodies in Europe and the English-speaking world that was openly available. The identified process indicators were in most cases not specific to occupational therapy interventions. Functional outcome indicators were highly specific to certain client groups or health conditions and partially appropriate for use in occupational therapy. The GAS was found to be a highly customizable measure which allowed an evaluation on body structure and function levels as well as activity and participation levels. PRO-Ergo was focused on the clients’ subjective view and their experience with occupational therapy interventions. Conclusions All identified quality indicators have advantages and disadvantages. Process-level indicators specific to occupational therapy could be a chance to foster the use of best practice methods. GAS and PRO-Ergo seem to be the most versatile assessment, allowing an evaluation on the level of activity and participation. Functional outcome indicators that cover a broad area of client problems may be useful additional quality indicators for some areas of practice.

Abstract During summer, ammonia emissions in Southeast Asia influence air pollution and cloud formation. Convective transport by the South Asian monsoon carries these pollutant air masses into the upper troposphere and lower stratosphere (UTLS), where they accumulate under anticyclonic flow conditions. This air mass accumulation is thought to contribute to particle formation and the development of the Asian Tropopause Aerosol Layer (ATAL). Despite the known influence of ammonia and particulate ammonium on air pollution, a comprehensive understanding of the ATAL is lacking. In this modelling study, the influence of ammonia on particle formation is assessed with emphasis on the ATAL. We use the EMAC chemistry-climate model, incorporating new particle formation parameterisations derived from experiments at the CERN CLOUD chamber. Our diurnal cycle analysis confirms that new particle formation mainly occurs during daylight, with a 10-fold enhancement in rate. This increase is prominent in the South Asian monsoon UTLS, where deep convection introduces high ammonia levels from the boundary layer, compared to a baseline scenario without ammonia. Our model simulations reveal that this ammonia-driven particle formation and growth contributes to an increase of up to 80% in cloud condensation nuclei (CCN) concentrations at cloud-forming heights in the South Asian monsoon region. We find that ammonia profoundly influences the aerosol mass and composition in the ATAL through particle growth, as indicated by an order of magnitude increase in nitrate levels linked to ammonia emissions. However, the effect of ammonia-driven new particle formation on aerosol mass in the ATAL is relatively small. Ammonia emissions enhance the regional aerosol optical depth (AOD) for shortwave solar radiation by up to 70%. We conclude that ammonia has a pronounced effect on the ATAL development, composition, the regional AOD, and CCN concentrations.

Abstract Background Diets with high inclusion of corn co-products such as corn fermented protein (CFP) may contain excess Leu, which has a negative impact on feed intake and growth performance of pigs due to increased catabolism of Val and Ile and reduced availability of Trp in the brain for serotonin synthesis. However, we hypothesized that the negative effect of using CFP in diets for weanling pigs may be overcome if diets are fortified with crystalline sources of Val, Trp, and (or) Ile. Methods Three hundred and twenty weanling pigs were randomly allotted to one of 10 dietary treatments in a completely randomized design, with 4 pigs per pen and 8 replicate pens per treatment. A corn-soybean meal diet and 2 basal diets based on corn and 10% CFP or corn and 20% CFP were formulated. Seven additional diets were formulated by fortifying the basal diet with 20% CFP with Ile, Trp, Val, Ile and Val, Ile and Trp, Trp and Val, or Ile, Trp and Val. A two-phase feeding program was used, with d 1 to 14 being phase 1 and d 15 to 28 being phase 2. Fecal scores were recorded every other day. Blood samples were collected on d 14 and 28 from one pig per pen. On d 14, fecal samples were collected from one pig per pen in 3 of the 10 treatments to determine volatile fatty acids, ammonium concentration, and microbial protein. These pigs were also euthanized and ileal tissue was collected. Results There were no effects of dietary treatments on any of the parameters evaluated in phase 1. Inclusion of 10% or 20% CFP in diets reduced (P

Abstract We have studied the spin polarization of $$\Lambda $$ Λ hyperons in heavy ion collisions at center-of-mass energies $$\sqrt{s_\textrm{NN}}= 200$$ s NN = 200 GeV and $$\sqrt{s_\textrm{NN}}= 5.02$$ s NN = 5.02 TeV carried out at RHIC and LHC colliders. We have calculated the mean spin vector at local thermodynamic equilibrium, including all known first-order terms in the gradients of the thermo-hydrodynamic fields, assuming that the hadronization hypersurface has a uniform temperature. We have also included the feed-down contributions to the polarization of $$\Lambda $$ Λ stemming from the decays of polarized $$\Sigma ^*$$ Σ ∗ and $$\Sigma ^0$$ Σ 0 hyperons. The obtained results are in good agreement with the data. In general, the component of the spin vector along the global angular momentum, orthogonal to the reaction plane, shows strong sensitivity to the initial longitudinal flow velocity. Furthermore, the longitudinal component of the spin vector turns out to be very sensitive to the bulk viscosity of the plasma at the highest LHC energy. Therefore, the azimuthal dependence of spin polarization can effectively constrain the initial hydrodynamic conditions and the transport coefficients of the quark gluon plasma.

Abstract Traditional security detection methods face challenges in identifying zero-day attacks in critical infrastructures (CIs) integrated with the industrial internet of things (IIoT). These attacks exploit unknown vulnerabilities and are difficult to detect due to their connection to physical systems. The integration of legacy ICS networks with modern computing and networking technologies has significantly expanded the attack surface, making these systems more susceptible to cyber-attacks. Despite existing security measures, attackers continually find ways to breach these operating networks. Anomaly detection systems are critical in protecting these CIs from current cyber threats. This study investigates the effectiveness of unsupervised anomaly detection models in detecting operational anomalies that could lead to cyber-attacks, thereby disrupting and negatively impacting quality of life. We preprocess the data with a focus on cybersecurity and chose the SWAT dataset because it accurately represents the types of attack vectors that critical infrastructures commonly encounter. We evaluated the performance of isolation forest (IF), local outlier factor (LOF), one-class SVM (OCSVM), and Autoencoder algorithms—trained exclusively on normal data—in enhancing cybersecurity within IIoT environments. Our comprehensive analysis includes an assessment of each model’s detection capabilities. The findings highlight the VAE-LSTM model’s potential to identify cyber-attacks within seconds in a high-frequency dataset, suggesting near real-time detection capability. The final model combines the reconstruction ability of the variational autoencoder (VAE) with regularization using the Kullback–Leibler divergence, reflecting the non-Gaussian nature of industrial system data. Our model successfully detected 23 out of 26 attack scenarios in the SWAT dataset, demonstrating its effectiveness in improving the security of IIoT-based CIs.