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Introduction: In patients with Hereditary Angioedema (HAE) related to primary C1 inhibitor deficiency (C1INH), the defective clearance of immune complexes and apoptotic materials along with impairment of normal humoral response potentially leads to autoimmunity. Few studies report evidence on autoimmune diseases in C1INH-HAE, but no large population studies focus on rare connective tissue diseases (RCTDs). We aim at evaluating for the first time prevalence and distribution of RCTDs - Systemic Lupus Erytematosus (SLE), primary Sjogren Syndrome (SjS), primary antiphospholipid syndrome (APS), Systemic Sclerosis (SSc), and mixed connective tissue diseases (MCTD) in a large Italian cohort of C1INH-HAE patients. Methods: A multicenter observational study includes C1INH-HAE patients from ITACA Centers throughout Italy (time frame Sept 2023-March 2024). Inclusion criteria are i. a defined diagnosis of type I or type II C1INH-HAE; ii. age =15 years (puberty already occurred); iii. enrollment in the ITACA Registry. The diagnosis of SLE, primary SjS, primary APS, SSc, and MCTD are made in accordance with international classification criteria. Results: Data are collected from a total of 855 C1INH-HAE patients referring to 15 ITACA Centers. Patients with concomitant RCTDs were 18/855 (2.1%) with F:M ratio 3.5 and a prevalent type I C1INH-HAE diagnosis (87.2%). A diagnosis of SLE results in 44.5% of cases (n=8) while the remaining diagnoses are primary SjS (22.2%, n=4), primary APS (16.6%, n=3), SSc (11.2%, n=2), and a single case of MCTD (5.5%). The female gender is prevalent in all the RCTDs. Patients on long term prophylaxis (LTP) are significantly prevalent in RCTDs group than in the whole C1INH-HAE population (p<0.01). Conclusions: A relevant prevalence of RCTDs is documented in C1INH-HAE patients, mainly SLE. Patients with RCTDs are on LTP in a significant proportion supporting the idea of a bidirectional link between C1INH-HAE and autoimmunity. [ABSTRACT FROM AUTHOR]

Background: Birt-Hogg-Dubé (BHD) syndrome is a genetic condition caused by pathogenic variants in the FLCN gene resulting in benign skin lesions, spontaneous pneumothorax, and increased risk for a variety of renal tumors. Skin manifestations of BHD include trichodiscoma (TD) and fibrofolliculoma (FF), which may represent the same pathologic entity. These lesions can identify BHD patients, who upon positive genetic testing can be considered for life-long surveillance for renal neoplasms. Objective: To characterize patients diagnosed with TD and FF including rates and outcomes of genetics referral. Methods: Retrospective chart reviews of patients with confirmed or possible diagnosis of TD or FF at the University of Michigan from September 2002 through October 2020 to assess pathologic findings, personal and family history of BHD manifestations, referral for genetic evaluation, and genetic testing results. Results: 64 patients had a pathologic diagnosis of TD or FF, 16 of whom (25%) were referred to cancer genetics. Fourteen patients completed genetic evaluation, 9 of whom were diagnosed with BHD (64%), with 6 unique pathogenic variants in FLCN. Conclusion: Providers should consider referral for genetic evaluation for patients with biopsy-proven TD or FF, as early diagnosis of BHD provides the opportunity for early detection and treatment of other BHD-associated conditions. Capsule Summary: • Birt-Hogg-Dube syndrome includes renal cancer, pneumothorax, and trichodiscomas and fibrofolliculomas and is caused by pathogenic variants in FLCN. • Patients with trichodiscoma or fibrofolliculoma should be considered for referral to cancer genetics to allow identification of pathogenic FLCN variants and thus family cascade testing and surveillance for renal tumors. [ABSTRACT FROM AUTHOR]

Data from the National Survey of Children's Health 2016–2020 was used to examine the association between physical activity and anxiety and depression among autistic youth, non-autistic youth with ADHD, and non-autistic non-ADHD youth. There was a significant negative association between physical activity and anxiety among all groups. Reduction in anxiety or depression associated with greater physical activity was at least as large or larger among autistic or nonautistic youth with ADHD than among non-autistic non-ADHD youth. Unfortunately, even autistic youth who were physically active 4 to 7 days a week showed very high rates of anxiety (54.5%) and depression (23.1%). Very high levels of dual diagnosis of anxiety and depression in autistic youth and youth with ADHD also emerged. Findings highlight a need to determine the cause-and-effect relationships among physical activity, anxiety, and depression across groups and to prioritize mental health screenings and support for autistic youth and youth with ADHD. [ABSTRACT FROM AUTHOR]

Neonatal hyperbilirubinemia (NH) is a common condition in newborns, with elevated bilirubin levels potentially causing neurological damage or death. Accurate and timely measurements of total serum bilirubin are essential to prevent these outcomes. Direct spectrophotometry, a reliable method for measuring bilirubin, is particularly useful in constrained settings due to its potential for portable low-cost instrumentation. However, this method is susceptible to interference from hemoglobin, often present due to hemolysis. Typically, this interference is reduced using complex optical filters, reagents, multiple wavelengths, or combinations thereof, which increase costs and complexity while reducing usability. This study presents a hemoglobin compensation algorithm applied to a simple, portable, two-wavelength (465 and 590 nm) reflectance photometer designed to receive 30 µL of plasma or whole blood samples and perform the measurement without any reagents. Testing across five bilirubin and hemoglobin levels (4.96 to 28 mg/dL and 0.06 to 0.99 g/dL, respectively) demonstrated that the algorithm effectively reduces hemoglobin interference and overestimation errors. The overall root mean square error was reduced from 4.86 to 1.45 mg/dL, while the measurement bias decreased from −4.46 to −0.10 mg/dL. This substantial reduction in overestimation errors supports future clinical trials with neonatal blood samples. [ABSTRACT FROM AUTHOR]

Herpes zoster ophthalmicus results from the reactivation of the latent varicella zoster virus, affecting the first branch of the trigeminal nerve. In 20–70% of cases, Zoster Ophthalmicus can lead to ocular involvement, affecting various orbital structures. Orbital myositis is a rare but severe complication of herpes zoster ophthalmicus. We present a case of a 52-year-old man with no significant medical history who developed zoster-associated right ocular myositis and dacryocystitis. He was treated with intravenous acyclovir and oral steroids. A review of the literature identified 29 patients across 19 studies. The median age was 61 years, with a slight female predominance. In 55% of cases, the patients had no notable medical history. The most common presentation of myositis involved all oculomotor muscles. There were 22 cases who were treated with intravenous antiviral therapy and 19 received steroids. A full resolution of symptoms was achieved in 51.7% of patients. Zoster-related orbital myositis is a rare complication that should be considered even in immunocompetent individuals. It may occur either before or after the appearance of a vesicular rash. Magnetic resonance imaging is the preferred radiological exam for assessing orbital involvement. Intravenous antiviral therapy should be started within 72 h of symptom onset, and its combination with systemic corticosteroids appears to be an effective treatment for zoster-related ocular myositis. [ABSTRACT FROM AUTHOR]

Curcumin (Cur), the primary curcuminoid found in Curcuma longa L., has garnered significant attention for its potential anti-inflammatory and antibacterial properties. However, its hydrophobic nature significantly limits its bioavailability. Additionally, adipose-derived stem cells (ADSCs) possess immunomodulatory properties, making them useful for treating inflammatory and autoimmune conditions. This study aims to verify the efficacy of poly(ε-caprolactone) nanocapsules (NCs) in improving Cur's bioavailability, antibacterial, and immunomodulatory activities. The Cur-loaded nanocapsules (Cur-NCs) were characterized for their physicochemical properties (particle size, polydispersity index, Zeta potential, and encapsulation efficiency) and stability over time. A digestion test simulated the behavior of Cur-NCs in the gastrointestinal tract. Micellar phase analyses evaluated the Cur-NCs' bioaccessibility. The antibacterial activity of free Cur, NCs, and Cur-NCs against various Gram-positive and Gram-negative strains was determined using the microdilution method. ADSC viability, treated with Cur-NCs and Cur-NCs in the presence or absence of lipopolysaccharide, was analyzed using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assay. Additionally, ADSC survival was assessed through the Muse apoptotic assay. The expression of both pro-inflammatory (interleukin-1β and tumor necrosis factor-α) and anti-inflammatory (IL-10 and transforming growth factor-β) cytokines on ADSCs was evaluated by real-time polymerase chain reaction. The results demonstrated high stability post-gastric digestion of Cur-NCs and elevated bioaccessibility of Cur post-intestinal digestion. Moreover, Cur-NCs exhibited antibacterial activity against Escherichia coli without affecting Lactobacillus growth. No significant changes in the viability and survival of ADSCs were observed under the experimental conditions. Finally, Cur-NCs modulated the expression of both pro- and anti-inflammatory cytokines in ADSCs exposed to inflammatory stimuli. Collectively, these findings highlight the potential of Cur-NCs to enhance Cur's bioavailability and therapeutic efficacy, particularly in cell-based treatments for inflammatory diseases and intestinal dysbiosis. [ABSTRACT FROM AUTHOR]

There is an expanding body of evidence showing that synthetic peptides in combination with radioactive isotopes can be utilized for medical purposes. This area is of particular interest in oncology where applications in diagnosis and therapy are at different stages of development. We review the contributions in this area by the group originally founded by Carlo Pedone in Naples many years ago. We highlight the work of this group in the context of other developments in this area, focusing on three biologically relevant receptor systems: somatostatin, gastrin‐releasing peptide, and cholecystokinin‐2/gastrin receptors. We focus on key milestones, state of the art, and challenges in this area of research as well as the current and future outlook for expanding clinical applications. [ABSTRACT FROM AUTHOR]

Brain–computer interfaces (BCIs) are promising tools for motor neurorehabilitation. Achieving a balance between classification accuracy and system responsiveness is crucial for real-time applications. This study aimed to assess how the duration of time windows affects performance, specifically classification accuracy and the false positive rate, to optimize the temporal parameters of MI-BCI systems. We investigated the impact of time window duration on classification accuracy and false positive rate, employing Linear Discriminant Analysis (LDA), Multilayer Perceptron (MLP), and Support Vector Machine (SVM) on data acquired from six post-stroke patients and on the external BCI IVa dataset. EEG signals were recorded and processed using the Common Spatial Patterns (CSP) algorithm for feature extraction. Our results indicate that longer time windows generally enhance classification accuracy and reduce false positives across all classifiers, with LDA performing the best. However, to maintain the real-time responsiveness, crucial for practical applications, a balance must be struck. The results suggest an optimal time window of 1–2 s, offering a trade-off between classification performance and excessive delay to guarantee the system responsiveness. These findings underscore the importance of temporal optimization in MI-BCI systems to improve usability in real rehabilitation scenarios. [ABSTRACT FROM AUTHOR]

The capability of amyloid‐like peptide fibers to emit intrinsic‐fluorescence enables the study of their formation, stability and hardening through time‐resolved fluorescence analysis, without the need for additional intercalating dyes. This approach allows the monitoring of amyloid‐like peptides aggregation kinetics using minimal sample volumes, and the simultaneous testing of numerous experimental conditions and analytes, offering rapid and reproducible results. The analytical procedure applied to the aromatic hexapeptide F6, alone or derivatized with PEG (polyethylene glycol) moiety of different lengths, suggests that aggregation into large anisotropic structures negatively correlates with initial monomer concentration and relies on the presence of charged N‐ and C‐termini. PEGylation reduces the extent of aggregates hardening, possibly by retaining water, and overall impacts the final structural properties of the aggregates. [ABSTRACT FROM AUTHOR]

Background: Functional recovery remains a core clinical objective for patients with bipolar disorder (BD). Sociodemographic, clinical, and neurocognitive variables are associated with long‐term functional impairment, yet the impact of sex differences is unclear. Functional remediation (FR) is a validated intervention aimed at achieving functional recovery in BD. The present study assessed the effect of sex differences of FR on psychosocial functioning at post‐treatment (6‐months) and 12‐month follow‐up (FUP). To the best of our knowledge, this is the first study to explore the role of sex as a factor in the efficacy of FR. Methods: 157 participants with BD were randomly assigned to either FR (N = 77) or treatment as usual group (80). Clinical, sociodemographic, neuropsychological, and functional data were obtained using a comprehensive assessment battery. Sex differences were explored via a general linear model (GLM) for repeated measures to compare the effect of sex on the intervention over time (6 months and FUP). Results: Results demonstrated that FR benefits both sexes, males (p = 0.001; d' = 0.88) and females (p = 0.04; d' = 0.57), at 6 months suggesting a generalized functional improvement. Conversely, at 12‐month FUP sex differences were observed only in males (p = 0.005; d' = 0.68). Conclusions: FR is a beneficial intervention for males and females after treatment, suggesting that there are no relevant distinct needs. Females may benefit from ongoing psychosocial functioning booster sessions after the intervention to maintain original improvements. Future research exploring sex differences could help to identify strategies to offer personalized FR intervention approaches in individuals with BD. [ABSTRACT FROM AUTHOR]

One of the goals of modern orcharding is to produce a high volume of fruits with uniform size, organoleptic parameters, and health characteristics. The aim of this work was to study various shoot types and their prevailing positions along the cane and to identify how shoot type can influence the quality of fruit from the Actinidia tree. The experiment was conducted over a two-year period in a commercial orchard of Actinidia chinensis, cv. Gold 3. The shoots along the cane were classified as follows: spur shoots (SPs), terminated shoots (TEs), non-terminated shoots (NTs), and cut non-terminated shoots (CNTs). The data were statistically processed using ANOVA and Principal Component Analysis (ACP). Four different categories of fruit were obtained from the four shoot types, and their various attributes were compared. The prevailing category (comprising 55% of the studied fruits) was TEs, which are characterised by a higher soluble solid content, sweetness, and excellent health characteristics, as well as the reduced hardness of their pulp, which would support the hypothesis that harvesting could be brought forward. The second most common category (comprising 19% of total fruit) with the lowest soluble solid content, but a high antioxidant capacity, was that which was detached from the CNTs, while 13% of the fruit was produced from NTs, which had the lowest health value but good sweetness perception. Finally, the category with the lowest fruit percentage over the total fruit harvested (10%) was SPs, which are characterised by their smaller size. It has yet to be determined what the performance of each category will be post-harvest; whether it is possible to assign the quality categories while harvesting the fruit or to differentiate the harvest time accordingly remains subject to debate. [ABSTRACT FROM AUTHOR]

The self-assembly of peptides and peptide analogues may be exploited to develop platforms for different biomedical applications, among which CEST-MRI (chemical exchange saturation transfer magnetic resonance imaging) represents one of the most attractive techniques to be explored as a novel metal-free contrast approach in imaging acquisitions. A lysine-containing peptide sequence (LIVAGK-NH2, named K2) was thus modified by insertion, at the N-terminus, of a peptide nucleic acid (PNA) base, leading to a primary amine suitable for the signal generation. a-K2, c-K2, g-K2 and t-K2 peptides were synthesized and characterized. The c-K2 sequence displayed gelling properties and the Watson and Crick pairing, arising from its combination with g-K2, allowed a significant increase in the mechanical responsivity of the hydrogel. These matrices were able to generate a CEST signal around 2.5 ppm from water and, after assessing their cytocompatibility on GL261 (murine glioma), TS/a (murine breast carcinoma), and 3T3-NIH (murine fibroblasts) cell lines, their capability to work as implants for in vivo detection, was proved by intratumor injection in Balb/c mice inoculated with TS/a murine breast cancer cells. [ABSTRACT FROM AUTHOR]

Advantages like biocompatibility, biodegradability and tunability allowed the exploitation of peptides and peptidomimetics as versatile therapeutic or diagnostic agents. Because of their selectivity towards transmembrane receptors or cell membranes, peptides have also been identified as suitable molecules able to deliver in vivo macromolecules, proteins or nucleic acids. However, after the identification of the homodimer diphenylalanine (FF) as an aggregative motif inside the Aβ1–42 polypeptide, short and ultrashort peptides have been studied as building blocks for the fabrication of supramolecular, ordered nanostructures for applications in biotechnological, biomedical and industrial fields. In this perspective, many hybrid molecules that combine FF with other chemical entities have been synthesized and characterized. Two novel hybrid derivatives (tFaF and cFgF), in which the FF homodimer is alternated with the peptide‐nucleic acid (PNA) heterodimer "g‐c" (guanine‐cytosine) or "a‐t" (adenine‐thymine) and their dimeric forms (tFaF)2 and (cFgF)2 were synthesized. The structural characterization performed by circular dichroism (CD), Fourier transform infrared (FTIR) and fluorescence spectroscopies highlighted the capability of all the FF‐PNA derivatives to self‐assemble into β‐sheet structures. As a consequence of this supramolecular organization, the resulting aggregates also exhibit optoelectronic properties already reported for other similar nanostructures. This photoemissive behavior is promising for their potential applications in bioimaging. [ABSTRACT FROM AUTHOR]

Introduction: Perchlorates are ionic inhibitors antagonizing iodine transport into thyrocytes, hampering thyroid hormone synthesis. Nevertheless, perchlorates are not considered as first-line treatment in hyperthyroidism and thyrotoxicosis as compared to other pharmacological and non-pharmacological interventions. Aim: Reassessing the therapeutic role of perchlorates in hyperthyroidism and thyrotoxicosis throughout a systematic review of the Literature. Methods: Guidelines were searched and examined to summarize current recommendations on the use of perchlorates in the management of hyperthyroidism. Randomized and non-randomized clinical trials were also searched and reviewed to summarize the efficacy/effectiveness and safety of perchlorates in hyperthyroidisms and thyrotoxicosis. Results: The management of specific forms of hyperthyroidism was considered, including Graves' disease (GD) in non-pregnant adults, hyperthyroidisms in pregnancy, iodine media contrast-induced hyperthyroidism, amiodarone-induced hyperthyroidisms, and thyroid storm. Most of the reported studies had remarkable limitations in terms of study design (non-controlled trials, lack of blinding), low number of participants, and the lack of clinically relevant endpoints, such as cardiovascular events, cardiovascular mortality, and teratogenicity. Overall, perchlorates could be considered a second-line treatment after thionamides, radioiodine, and total thyroidectomy in both GD and hyperthyroidisms in pregnancy. The therapeutic potential of perchlorates alone or in combination with other agents could be considered a second-line treatment of iodine-related hyperthyroidisms and thyroid storm. Conclusion: Despite the low level of evidence, perchlorates could be considered in such specific forms of thyroid disorders, including iodine-induced hyperthyroidism and thyroid storm. [ABSTRACT FROM AUTHOR]

Shoulder muscles are active during front-crawl swimming to provide propulsion and stabilize the glenohumeral and scapulothoracic joints. Researchers have proposed that fatigue might contribute to altered activation of these muscles and represent a risk factor for injuries. Tensiomyography (TMG) might function as a noninvasive tool to detect changes in contractile measures of the skeletal muscles due to exercise-induced neuromuscular fatigue, though it has not yet been used in the shoulder muscles of swimmers. To assess the effects of a fatiguing swimming protocol on shoulder muscle TMG measures and isometric strength in competitive swimmers. Cross-sectional study. Swimming pool facility. A total of 14 young front-crawl competitive swimmers (11 males and 3 females; age = 21 ± 3 years [range, 17–26 years], height = 1.78 ± 0.06 m, mass = 73.1 ± 9.2 kg). Participants completed TMG and isometric strength assessments before and after 30-minute, high-intensity swim training. The TMG assessment was performed on 7 muscles of the shoulder according to front-crawl biomechanics and the applicability of the technique to obtain data, such as time to contraction and muscle-belly radial displacement. Isometric strength was assessed using a digital handheld dynamometer during shoulder flexion, extension, external rotation, and internal rotation. Fatigue induced a smaller radial displacement, mostly observable in latissimus dorsi (−1.0 mm; 95% CI = −1.7, −0.3 mm; P =.007) and pectoralis major muscles (−1.4 mm; 95% CI = −2.4, −0.4 mm; P =.007). Only shoulder extension showed an isometric strength reduction after the fatiguing protocol (−0.03 N/kg; 95% CI = −0.05, −0.01 N/kg; F1,13 = 4.936; P =.045; ηp2 = 0.275). This study provides preliminary evidence for the usefulness of TMG to detect fatigue-induced changes in contractile properties of the shoulder muscles in swimmers, in particular the latissimus dorsi and pectoralis major. [ABSTRACT FROM AUTHOR]

Hydrogen combustion engine vehicles have the potential to rapidly enter the market and reduce greenhouse gas emissions (GHG) compared to conventional engines. The ability to provide a rapid market deployment is linked to the fact that the industry would take advantage of the existing internal combustion engine production chain. The aim of this paper is twofold. First, it aims to develop a methodology for applying life-cycle assessment (LCA) to internal combustion engines to estimate their life-cycle GHG emissions. Also, it aims to investigate the decarbonization potential of hydrogen engines produced by exploiting existing diesel engine technology and assuming diverse hydrogen production routes. The boundary of the LCA is cradle-to-grave, and the assessment is entirely based on primary data. The products under study are two monofuel engines: a hydrogen engine and a diesel engine. The hydrogen engine has been redesigned using the diesel engine as a base. The engines being studied are versatile and can be used for a wide range of uses such as automotive, cogeneration, maritime, off-road, and railway; however, this study focuses on their application in pickup trucks. As part of the redesign process, certain subsystems (e.g., combustion, injection, ignition, exhaust gas recirculation, and exhaust gas aftertreatment) have been modified to make the engine run on hydrogen. Results revealed that employing a hydrogen engine using green hydrogen (i.e., generated from water electrolysis using wind-based electricity) might reduce GHG emission by over 90% compared to the diesel engine This study showed that the benefits of the new hydrogen engine solution outweigh the increase of emissions related to the redesign process, making it a potentially beneficial solution also for reconditioning current and used internal combustion engines. [ABSTRACT FROM AUTHOR]

Background: Physical activity could increase the production of oxidative stress biomarkers, affecting the metabolism and excretion of antiretroviral drugs and, consequently, the clinical outcome. Nowadays, people living with HIV (PLWH) are mostly switching from triple to dual therapy, but no data are available in terms of physical functioning and oxidative stress. The aim of this study was to evaluate if some antioxidant biomarkers and physical functioning tests could be different according to triple or dual antiretroviral therapy. Methods: PLWH were evaluated at baseline (BL), while treated with three drugs, and six months after the switch to dual therapy. Physical functioning was quantified using validated tools. Mitochondrial and cytosol antioxidant molecules were evaluated through liquid chromatography. Results: Twenty-five patients were analyzed. A statistically significant difference between triple and dual therapy was found for mitochondrial glutathione, but not for physical tests. Evaluating differences between physically active and inactive individuals, the following statistically significant differences were suggested, considering triple therapy (mitochondrial n-formyl-methionine p = 0.022, triglycerides p = 0.023) and double therapy (mitochondrial glycine p = 0.035, cytosol glutamic acid p = 0.007, cytosol s-adenosylmethionine p = 0.021). Conclusions: For the first time, this study suggests possible differences in terms of antioxidant molecules and physical functioning in PLWH switching from triple to dual therapy. [ABSTRACT FROM AUTHOR]

Dexamethasone (DEX) is a synthetic analogue of cortisol commonly used for the treatment of different pathological conditions, comprising cancer, ocular disorders, and COVID-19 infection. Its clinical use is hampered by the low solubility and severe side effects due to its systemic administration. The capability of peptide-based nanosystems, like hydrogels (HGs) and nanogels (NGs), to serve as vehicles for the passive targeting of active pharmaceutical ingredients and the selective internalization into leukemic cells has here been demonstrated. Peptide based HGs loaded with DEX were formulated via the "solvent-switch" method, using Fmoc-FF homopeptide as building block. Due to the tight interaction of the drug with the peptidic matrix, a significant stiffening of the gel (G′ = 67.9 kPa) was observed. The corresponding injectable NGs, obtained from the sub-micronization of the HG, in the presence of two stabilizing agents (SPAN®60 and TWEEN®60, 48/52 w/w), were found to be stable up to 90 days, with a mean diameter of 105 nm. NGs do not exhibit hemolytic effects on human serum, moreover they are selectively internalized by RS4;11 leukemic cells over healthy PBMCs, paving the way for the generation of new diagnostic strategies targeting onco-hematological diseases. [ABSTRACT FROM AUTHOR]

Large language models (LLMs) can potentially transform healthcare, particularly in providing the right information to the right provider at the right time in the hospital workflow. This study investigates the integration of LLMs into healthcare, specifically focusing on improving clinical decision support systems (CDSSs) through accurate interpretation of medical guidelines for chronic Hepatitis C Virus infection management. Utilizing OpenAI's GPT-4 Turbo model, we developed a customized LLM framework that incorporates retrieval augmented generation (RAG) and prompt engineering. Our framework involved guideline conversion into the best-structured format that can be efficiently processed by LLMs to provide the most accurate output. An ablation study was conducted to evaluate the impact of different formatting and learning strategies on the LLM's answer generation accuracy. The baseline GPT-4 Turbo model's performance was compared against five experimental setups with increasing levels of complexity: inclusion of in-context guidelines, guideline reformatting, and implementation of few-shot learning. Our primary outcome was the qualitative assessment of accuracy based on expert review, while secondary outcomes included the quantitative measurement of similarity of LLM-generated responses to expert-provided answers using text-similarity scores. The results showed a significant improvement in accuracy from 43 to 99% (p < 0.001), when guidelines were provided as context in a coherent corpus of text and non-text sources were converted into text. In addition, few-shot learning did not seem to improve overall accuracy. The study highlights that structured guideline reformatting and advanced prompt engineering (data quality vs. data quantity) can enhance the efficacy of LLM integrations to CDSSs for guideline delivery. [ABSTRACT FROM AUTHOR]

Idiopathic Interstitial Pneumonias (IIPs) are a heterogeneous group of the broader category of Interstitial Lung Diseases (ILDs), pathologically characterized by the distortion of lung parenchyma by interstitial inflammation and/or fibrosis. The American Thoracic Society (ATS)/European Respiratory Society (ERS) international multidisciplinary consensus classification of the IIPs was published in 2002 and then updated in 2013, with the authors emphasizing the need for a multidisciplinary approach to the diagnosis of IIPs. The histological evaluation of IIPs is challenging, and different types of IIPs are classically associated with specific histopathological patterns. However, morphological overlaps can be observed, and the same histopathological features can be seen in totally different clinical settings. Therefore, the pathologist's aim is to recognize the pathologic–morphologic pattern of disease in this clinical setting, and only after multi-disciplinary evaluation, if there is concordance between clinical and radiological findings, a definitive diagnosis of specific IIP can be established, allowing the optimal clinical–therapeutic management of the patient. [ABSTRACT FROM AUTHOR]

Metastasis arises from disseminated tumour cells (DTCs) that are characterized by intrinsic phenotypic plasticity and the capability of seeding to secondary organs. DTCs can remain latent for years before giving rise to symptomatic overt metastasis. In this context, DTCs fluctuate between a quiescent and proliferative state in response to systemic and microenvironmental signals including immune-mediated surveillance. Despite its relevance, how intrinsic mechanisms sustain DTCs plasticity has not been addressed. By interrogating the epigenetic state of metastatic cells, we find that tumour progression is coupled with the activation of oncogenic enhancers that are organized in variable interconnected chromatin domains. This spatial chromatin context leads to the activation of a robust transcriptional response upon repeated exposure to retinoic acid (RA). We show that this adaptive mechanism sustains the quiescence of DTCs through the activation of the master regulator SOX9. Finally, we determine that RA-stimulated transcriptional memory increases the fitness of metastatic cells by supporting the escape of quiescent DTCs from NK-mediated immune surveillance. Overall, these findings highlight the contribution of oncogenic enhancers in establishing transcriptional memories as an adaptive mechanism to reinforce cancer dormancy and immune escape, thus amenable for therapeutic intervention. Metastasis arises from disseminated tumour cells (DTCs) while the underlying mechanism of DTCs plasticity remains underexplored. Here, the authors show that spatially organized oncogenic enhancers on chromatin sustain the establishment of retinoic acid (RA)-stimulated transcriptional memory through activation of SOX9, supporting the escape of quiescent DTCs from NK-mediated immune surveillance. [ABSTRACT FROM AUTHOR]

Background: The ability to merge the two retinal images to perceive depth (stereopsis) plays an important role in human vision. Its proper development requires binocular alignment and good visual acuity in both eyes during childhood. Because treatments are more effective when applied early, early diagnosis is important. Unfortunately, assessing stereo deficiencies in infants and young children remains challenging. Recently, it has been shown that ocular-following responses (OFRs; reflexive, short-latency eye movements induced by the sudden motion of a large textured pattern) are sensitive to changes in interocular correlation, making them potentially useful for stereo deficiency assessments. To test this hypothesis, we measured OFRs elicited by dichoptic stimulation in children with normal and compromised stereopsis (due to amblyopia). Methods: Two groups of six children (age- and sex-matched: 3M/3F aged 7–12 yo), one with compromised stereopsis and one with normal stereopsis, were included. OFRs were recorded using a custom high-resolution video eye-tracking system. The relative differences between eye displacement induced by correlated stimuli (up-correlated–down-correlated) and anticorrelated (up-anticorrelated–down-anticorrelated) were compared. Results: We found significant differences between OFRs induced by two dichoptic conditions (correlated and anticorrelated stimuli) in most children with normal stereopsis, whereas no differences were observed in children with compromised stereopsis, indicating a lack of disparity detectors. Conclusions: OFRs might thus be exploited as a diagnostic tool for the objective identification of stereo deficiencies in children. This might lead to improved early diagnosis and treatment outcomes for conditions like amblyopia and strabismus. [ABSTRACT FROM AUTHOR]

Despite the promising outcomes achieved over time in Asset Management, data accessibility, correlation, analysis, and visualization still represent challenges. The integration, readability, and interpretation of heterogeneous information by different stakeholders is a further concern, especially at the urban scale, where spatial data integration is required to correlate virtual information with the real world. The Geographic Information System (GIS) allows these connections, representing and digitizing extensive areas with significant benefits for asset analysis, management, and decision-making processes. Such benefits are central for managing large and widespread university campuses as they are comparable to small cities, covering a wide urban region and including resources highly integrated into the urban context. The paper presents how GIS integrated into Business Intelligence (BI) tools can support university Asset Management System (AMS) creation for the optimal use of resources, illustrating the University of Turin case study. The results discussion considers the relationship between the different elements of the assets and their synergy with the city. It focuses on four themes, dealing with the asset identification of buildings and resources, especially the educational ones, asset spatiotemporal evolution, and buildings' distances for proximity analysis. The benefits achievable through the AMS, related challenges, and possible future developments are highlighted. [ABSTRACT FROM AUTHOR]

Compared to conventional fossil-fueled vehicles, electric vehicles offer several environmental benefits. However, even electric vehicles are not completely environmentally friendly because many of their parts are not recycled today. These parts, especially the magnets that power them, end up in landfills at the end of the vehicle's life cycle. This study aims to evaluate the environmental impacts of recycled (NdDy)FeB permanent magnets obtained by means of a novel hydrogen-decrepitation-based, magnet-to-magnet recycling technique. The Life Cycle Assessment methodology was used to compare, on a like-to-like basis, recycled and virgin permanent magnets. The core data provided by an industry partner served as the foundation for modelling the recycling process. Three different functional units were investigated based on three parameters, namely the magnet mass, magnetization coercivity, and energy product. Results revealed that the recycled magnet outperformed the virgin magnet in most impact categories. In terms of carbon footprint, recycling permanent magnets through hydrogen decrepitation would allow for an 18─33% reduction with respect to their production from virgin materials, depending on the assumed functional unit. [ABSTRACT FROM AUTHOR]

Data from the National Survey of Children's Health 2016–2019 was used to examine the co-occurrence of autism and ADHD and the impact on anxiety and depression among adolescents age 12–17. Rates of anxiety and depression were up to ten-fold the prevalence of adolescents not diagnosed with autism or ADHD. Over half of autistic females (57%) and nearly half of autistic males (49%) are also diagnosed with ADHD. Autistic females with ADHD had the highest co-occurrence of anxiety at 72% followed by autistic males with ADHD at 69%. The prevalence of depression was highest among autistic adolescents with ADHD yet was consistent across genders (male/female) at 38–39%. Adolescents diagnosed with autism and/or ADHD are at heightened risk for anxiety and depression. [ABSTRACT FROM AUTHOR]

Background: Distal pancreatectomy (DP) represents the best therapeutic option for patients with body-tail pancreatic neoplasms (PNs). The enhanced recovery after surgery protocol is widely used for treating patients with PN to speed up postoperative recovery. This study aims to describe our institute's experience in the application of fast recovery protocol in a cohort of patients treated with DP, identifying predictors facilitating a decrease in the length of hospital stay. Patient and Methods: Were retrospectively enrolled 60 consecutive cases of DP performed from January 2016 to June 2022 in patients treated with enhanced recovery protocol, 25% of them were treated with spleen preserving procedure. Single-variable logistic regression models were used to evaluate the potential association between patient characteristics and the probability of postoperative complications. Standard linear regression models were used for length of stay, number of postoperative days (PODs) from surgery to full bowel function recovery, and PODs to the interruption of intravenous analgesia administration. Results: Thirty-four (57%) patients underwent open surgery and 26 (43%) laparoscopic surgery. Patients who underwent laparoscopic surgery and spleen-preserving procedures experienced a lower complication rate (P = .037), shorter length of stay, and time of analgesic requirements. With single-variable logistic regression models patients treated with laparoscopic surgery had statistically significant higher recovery times in terms of nasogastric tube removal (P = .004) and early enteral nutrition (P = .001). Conclusion: Continual refinement with enhanced recovery protocol for treating PN patients based on perioperative counseling and surgical decision-making is crucial to reduce patient morbidity and time for recovery. [ABSTRACT FROM AUTHOR]

Background: Intraoperative blood loss has an unfavorable impact on the outcome of patients undergoing liver surgery. Today, the use of devices capable of minimizing this risk with high technical performance becomes mandatory. Into this scenario fits the CUSA® Clarity Ultrasonic Surgical Aspirator System. This prospective survey involving five liver surgery centers had the objective of investigating whether this innovative ultrasonic surgical aspirator is safe and effective in the transection of the liver parenchyma. Materials and Methods: This clinical study was a prospective, multicenter, single-arm Post-Market Clinical Follow-up study investigating 100 subjects who underwent liver surgery using the CUSA Clarity Ultrasonic Surgical Aspirator System at five centers during a period of 1 year and 8 months. After collecting all the patient's clinical information and instrument usage details, surgeons completed a brief survey giving their opinions on the performance of CUSA. Therefore, safety and efficacy outcomes were evaluated. Results: Surgeons had a 95% success rate in complete removal of the mass with an average overall operative time of 4 hours and 34 minutes. Overall, there were no complications or device deficiencies. Conclusion: The CUSA Clarity Ultrasonic Surgical Aspirator System performs well during liver surgery with a low complication rate. ClinicalTrials.gov Identifier: NCT04298268. [ABSTRACT FROM AUTHOR]

Fmoc-diphenylalanine (Fmoc-FF) is a low-molecular-weight peptide hydrogelator. This simple all-aromatic peptide can generate self-supporting hydrogel materials, which have been proposed as novel materials for diagnostic and pharmaceutical applications. Our knowledge of the molecular determinants of Fmoc-FF aggregation is used as a guide to design new peptide-based gelators, with features for the development of improved tools. Here, we enlarge the plethora of Fmoc-FF-based hydrogelated matrices by studying the properties of the Fmoc-FFK tripeptide, alone or in combination with Fmoc-FF. For multicomponent matrices, the relative weight ratios between Fmoc-FFK and Fmoc-FF (specifically, 1/1, 1/5, 1/10, and 1/20 w/w) are evaluated. All the systems and their multiscale organization are studied using different experimental techniques, including rheology, circular dichroism, Fourier transform infrared spectroscopy, and scanning electron microscopy (SEM). Preliminary profiles of biocompatibility for the studied systems are also described by testing them in vitro on HaCaT and 3T3-L1 cell lines. Additionally, the lysine (K) residue at the C-terminus of the Fmoc-FF moiety introduces into the supramolecular material chemical functions (amino groups) which may be useful for modification/derivatization with bioactive molecules of interest, including diagnostic probes, chelating agents, active pharmaceutical ingredients, or peptide nucleic acids. [ABSTRACT FROM AUTHOR]

Aim and Objective: The purpose of this study was to generate a conceptual definition and theory of grief for nurses working on the frontlines during the COVID‐19 pandemic using grounded theory methodology. Background: The COVID‐19 pandemic has had a negative impact on nurses working on the frontlines. The increasing flow of diagnosed COVID‐19 cases, diverse unknowns and demands in the treatment of patients with COVID‐19, and depression related to countless deaths can trigger grief experiences. Design: A mixed methods approach, including the qualitative method of grounded theory and a quantitative 30‐question survey, was used in this study. Methods: Eight focus group sessions were conducted with registered nurses working on the frontlines during the pandemic. Sessions were audio recorded and analysed using constant comparative data analysis. Following the interviews, a survey including demographics and self‐report inventories was completed by participants. The COREQ checklist was used to assess study quality. Results: Major concepts that emerged include 'facing a new reality', 'frustrations', 'stress' and 'coping'. Core concepts were combined into a conceptual definition of grief and a grounded theory of the experience of nurses working on the frontlines during the pandemic. Cross comparisons of qualitative and quantitative findings were made and compared with the literature. Conclusions: This study provides a better understanding of the grief experience of nurses working on the frontlines during the COVID‐19 pandemic. It is necessary to recognise professional grief and develop intervention strategies that lead to grief reconciliation. Relevance to Clinical Practice: Findings provide useful insights for healthcare administrators to provide support and develop interventions to reduce frustrations and stress of frontline registered nurses. Patient or Public Contribution: This study design involved registered nurses participating in focus group sessions. Participants detailed their experience working on the frontlines of the COVID‐19 pandemic with patients, family and hospital administration. [ABSTRACT FROM AUTHOR]

This study involves student responses to open-ended questions regarding the credibility of a New York Times news article after viewing library instructional materials. The authors present the use of content analysis as a means of assessing students' source evaluations. The analysis revealed that all students were able to correctly list three factors that contribute to a source's credibility, and nearly all students (96.5%) were able to define bias. Interestingly, 42.6% of students evaluated the New York Times article as not credible, for a variety of categorical reasons. These findings led to actionable changes to library instruction content. [ABSTRACT FROM AUTHOR]

PURPOSE: A subset of renal cell carcinoma (RCC) cases occur because of a hereditary predisposition. However, the prevalence and profiling of germline alterations in RCC have not been fully characterized. Additionally, clinicopathologic factors associated with pathogenic or likely pathogenic (P/LP) germline variants in patients with RCC remain poorly understood. METHODS: A retrospective analysis of patients with RCC who underwent genetic evaluation was performed. The frequency of P/LP germline variants and genes was evaluated in this cohort. The association between genetic testing outcomes and clinicopathologic features was also assessed. RESULTS: A total of 321 patients with RCC who had germline testing were identified. Within this cohort, 42 patients (13.1%) had P/LP variants. Genes with the most frequent germline mutations were FLCN (n = 10, 3.1%), SDHB (n = 4, 1.2%), VHL (n = 4, 1.2%), MLH1 (n = 3, 0.9%), and CHEK2 (n = 4, 1.2%). Among patients with P/LP variants, 19 (45.2%) had a potentially targetable mutation. The presence of bilateral or multifocal tumors was associated with P/LP variants (P =.0012 and P =.0098, respectively). Patients who had targeted gene testing had higher rates of P/LP variants compared with multigene panel testing (P =.015). Age and family history of cancers (RCC and non-RCC) did not have any statistically significant association with germline testing outcomes. CONCLUSION: Among patients with RCC, unselected for a known familial predisposition, 13.4% had P/LP variants. Almost half of patients with P/LP variants had a potentially targetable mutation. Targeted gene panel testing is a feasible option for patients, particularly if syndromic features are present. Age and family history were not associated with P/LP variants. Future studies are needed to optimize current genetic evaluation criteria to expand the detection of patients with RCC who may have germline mutations. This study showed that 13% of patients with kidney cancers had a germline variant, nearly half of whom had a potentially targetable mutation. Broader genetic evaluation criteria may be needed given the therapeutic implications. [ABSTRACT FROM AUTHOR]

State‐of‐the‐art perovskite‐based electrocatalysts for zinc−air batteries (ZABs) may include one or more Critical Raw Materials (CRMs) like Co, Ru, and rare earth elements, for oxygen reduction/evolution reactions. Under the warnings described by the CRMs Act in Europe, future research in this field must limit the use of these elements, find more sustainable formulations, and better design/integration strategies to trade off costs, supply, and performances. In this benchmarking study, three main perovskites, i. e., LaNiO3‐δ (LNO), LaMnO3+δ (LMO), and LaMn0.5Ni0.5O3 (LMNO), are studied as quasi‐CRM‐free benchmarks and integrated with a novel gel electrolyte from a natural biopolymer in primary and secondary ZABs. By comparing literature performances based on the number of total/active site CRMs for the first time, these reference perovskites showed Zn utilizations >90 % in primary ZABs, with LMO and LMNO approaching 94 % at 2 mA/cm2, the highest result in the field. In secondary ZABs, LMO demonstrated limited cyclability (62 cycles), while LMNO had a moderate number of cycles (117 cycles) and the highest round‐trip efficiency (54.3 %), while LNO presented the lowest charge potential (2.04 V) and longer cyclability (455 cycles). This work demonstrates encouraging performance with fewer CRMs and proper integration in more sustainable ZABs, opening the way to future CRM‐free perovskites. [ABSTRACT FROM AUTHOR]

Inertial sensors (IMUs) have been recently widely used in exercise and rehabilitation science as they can provide reliable quantitative measures of range of motion (RoM). Moreover, the pressure pain threshold (PPT) evaluation provides an objective measure of pain sensation in different body areas. The aim of this study was to evaluate the efficacy of physiotherapy treatment in people with adhesive capsulitis in terms of RoM and pain improvement measured by IMUs and the PPT. A combined prospective cohort/cross-sectional study was conducted. Nineteen individuals with adhesive capsulitis (10/19 females, 54 ± 8 years) and nineteen healthy controls (10/19 females, 51 ± 6 years) were evaluated for active glenohumeral joint RoM and PPT on shoulder body areas. Then, individuals with adhesive capsulitis were invited to 20 sessions of a physiotherapy protocol, and the assessments were repeated within 1 week from the last session. The range of motion in the flexion (p = 0.001) and abduction (p < 0.001) of the shoulder increased significantly after the physiotherapy protocol. Similarly, the PPT was found to increase significantly in all the assessed shoulder body areas, leading to no significant differences compared to the healthy controls. IMU and PPT assessments could be used to evaluate the efficacy of physical therapy in people with adhesive capsulitis. [ABSTRACT FROM AUTHOR]

Background: Diffuse large B-cell lymphoma (DLBCL) is a hematological malignancy representing one-third of non-Hodgkin’s lymphoma cases. Notwithstanding immunotherapy in combination with chemotherapy (RCHOP) is an effective therapeutic approach for DLBCL, a subset of patients encounters treatment resistance, leading to low survival rates. Thus, there is an urgent need to identify predictive biomarkers for DLBCL including the elderly population, which represents the fastest-growing segment of the population in Western countries. Methods: Gene expression profiles of n=414 DLBCL biopsies were retrieved from the public dataset GSE10846. Differentially expressed genes (DEGs) (fold change >1.4, p-value <0.05, n=387) have been clustered in responder and non-responder patient cohorts. An enrichment analysis has been performed on the top 30 up-regulated genes of responder and non-responder patients to identify the signatures involved in gene ontology (MSigDB). The more significantly upregulated DEGs have been validated in our independent collection of formalin-fixed paraffin-embedded (FFPE) biopsy samples of elderly DLBCL patients, treated with R-CHOP as first-line therapy. Results: From the analysis of two independent cohorts of DLBCL patients emerged a gene signature able to predict the response to R-CHOP therapy. In detail, expression levels of EBF1, MYO6, CALR are associated with a significant worse overall survival. Conclusions: These results pave the way for a novel characterization of DLBCL biomarkers, aiding the stratification of responder versus non-responder patients. [ABSTRACT FROM AUTHOR]

Multicomponent hydrogels (HGs) based on ultrashort aromatic peptides have been exploited as biocompatible matrices for tissue engineering applications, the delivery of therapeutic and diagnostic agents, and the development of biosensors. Due to its capability to gel under physiological conditions of pH and ionic strength, the low molecular-weight Fmoc-FF (Nα-fluorenylmethoxycarbonyl-diphenylalanine) homodimer is one of the most studied hydrogelators. The introduction into the Fmoc-FF hydrogel of additional molecules like protein, organic compounds, or other peptide sequences often allows the generation of novel hydrogels with improved mechanical and functional properties. In this perspective, here we studied a library of novel multicomponent Fmoc-FF based hydrogels doped with different amounts of the tripeptide Fmoc-FFX (in which X= Cys, Ser, or Thr). The insertion of these tripeptides allows to obtain hydrogels functionalized with thiol or alcohol groups that can be used for their chemical post-derivatization with bioactive molecules of interest like diagnostic or biosensing agents. These novel multicomponent hydrogels share a similar peptide organization in their supramolecular matrix. The hydrogels' biocompatibility, and their propensity to support adhesion, proliferation, and even cell differentiation, assessed in vitro on fibroblast cell lines, allows us to conclude that the hybrid hydrogels are not toxic and can potentially act as a scaffold and support for cell culture growth. [ABSTRACT FROM AUTHOR]

Enhancing the reversible Li growth efficiency in "Li-free" solid-state batteries is key for the deployment of this technology. Here, we demonstrate a nanoscale material design path that enables the reversible cycling of a lithium-free solid-state battery, using Li7La3Zr2O12 (LLZO) electrolyte. By means of nanometric Ag–Cu bilayers, directly sputtered onto the LLZO, we can effectively control Li deposition. The robust thin film bilayer, which is compatible with LLZO, enables stable cycling, accommodating the volume changes without the need for extra external pressure. [ABSTRACT FROM AUTHOR]

The detectors for the three first generation extremely large telescope (ELT) instruments MICADO (Multi‐AO Imaging Camera for Deep Observations), HARMONI (A High Angular Resolution Monolithic Optical and Near‐infrared Integral Field Spectrograph), and METIS (A Mid‐infrared ELT Imager and Spectrograph) cover from the optical to longwave infrared wavelengths. MICADO and HARMONI detector focal planes require 17 ×$$ \times $$ H4RG (Hawaii‐4RG) near‐infrared whilst the METIS focal planes consist of 5 ×$$ \times $$ SWIR (shortwave infrared) detectors and one longwave infrared detector. Procurement of the optical and SWIR detectors has been completed, whilst the H4RGs and long wavelength detectors are still in progress. A custom cryogenic facility for infrared array testing (FIAT) has been designed and developed at European Southern Observatory (ESO) over the last few years in order to characterize the infrared detectors for ELT and future Very Large Telescope instruments. FIAT is currently being commissioned in our labs with an H4RG engineering detector. FIAT will be used to characterize the science H4RG‐15 detectors for MICADO and HARMONI, the two first‐light instruments of the ELT while the existing Mosaic Test Facility (MTF) will be used for characterizing the SWIR detectors for METIS. This paper presents an overview of the detector systems for the three instruments, their engineering challenges, and the requirements for the detectors' performance and their characterization program. The paper will also describe a test setup for H4RG detectors including a new preamplifier design with options to operate the detector in different modes and it will also report on the test results from the engineering H4RG detector, as part of the commissioning of FIAT and discuss detector performance and related detector issues. [ABSTRACT FROM AUTHOR]