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Background/Objectives: Retinal ganglion cell (RGC) protection represents an unmet need in glaucoma. This study assessed the neuroprotective, antioxidant, and anti-inflammatory effect of a new nutraceutical formulation named Epicolin, based on citicoline, homotaurine, epigallocatechin-3-gallate, forskolin, and vitamins, through in vitro and in vivo studies. Methods: The neuroprotective effect of Epicolin or its single components, and Epicolin compared to an untreated control and two marketed formulations [Formulation G (FG) and N (FN)], was evaluated in neuroblastoma cells (SH-SY5Y) challenged with staurosporine. The antioxidant potential and the scavenging activity of Epicolin compared to the untreated control, and FG and FN, was evaluated in SH-SY5Y cells and through oxygen radical absorbance capacity acellular assay, respectively. Moreover, the protective effect against hypoxic damage was evaluated in Muller cells (MIO-M1) subjected to hypoxia. The efficacy of Epicolin was also evaluated in DBA/2J glaucomatous mice through the use of a pattern electroretinogram (PERG), immunostaining, and real-time PCR. Results: Among the nutraceutical formulations tested, only Epicolin showed a significant neuroprotective effect on SH-SY5Y attributable to the synergistic action of its single ingredients. As for antioxidant and scavenging activity, Epicolin showed a higher efficacy compared to FG and FN. Furthermore, Epicolin showed the same protective effect on MIO-M1 cells reducing HIF-1α expression. Finally, Epicolin treatment on DBA/2J mice protected the RGCs from loss of function, as demonstrated by PERG analysis, and attenuated their death by enhancing brain-derived neurotrophic factor (BDNF) and reducing interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) expression. Conclusions: Epicolin, due to its neuroprotective, antioxidant, and anti-inflammatory properties, represents a promising potential treatment for glaucoma. [ABSTRACT FROM AUTHOR]

The development and calibration of a measurement system designed for assessing the performance of the avalanche photodiodes (APDs) used in the Compton scattering polarimeter of the CUSP project is discussed in this work. The designed system is able to characterize the APD gain G A P D and energy resolution across a wide range of temperatures T (from −20 °C to +60 °C) and bias voltages V b i a s (from 260 V to 410 V). The primary goal was to experimentally determine the G A P D dependence on the T and V b i a s in order to establish a strategy for stabilizing G A P D by compensating for T fluctuations, acting on V b i a s . The results demonstrate the system capability to accurately characterize APD behavior and develop feedback mechanisms to ensure its stable operation. This work provides a robust framework for calibrating APDs for space environments. It is essential for the successful implementation of spaceborne polarimeters such as the Compton scattering polarimeter foreseen aboard the CUbeSat Solar Polarimeter (CUSP) mission under development to perform solar flare X-ray polarimetry. [ABSTRACT FROM AUTHOR]

Biological materials always exhibit heterogeneous physical properties, both mechanical and chemical, which give them a rich phenomenology that poses significant challenges in the developing of effective models. The Flory–Rehner theory revolutionized our understanding of the dynamics of the liquid-polymers coupling in soft swollen gels, recognizing polymers as elastic networks stretched by the presence of liquid. Despite its foundational role, applying this theory to bodies with non uniform physical properties requires further improvements. This article proposes a unified approach to address mechano-diffusion challenges in multi-domain bodies, that is in material bodies made of regions having different chemo-mechanical properties, and focuses on the dehydration and remodeling of biological-like materials. Drawing inspiration from natural systems, we integrate principles from nonlinear mechanics and swelling theories; in particular, what is specifically new is the idea of applying the notion of the multiplicative decomposition of the strain–developed for plasticity–to model the swelling properties of a body made of two or more materials. The article gives a systematic presentation of the subject, and guides readers through key concepts and practical insights, aiming to provide a robust framework for modeling chemo-mechanical interactions. Moreover, it paves the way for the modeling of heterogenous bodies having spatially-varying properties. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To (1) investigate whether different labels for neck pain after a motor vehicle crash (MVC) influenced recovery expectations and management beliefs, (2) explore reasons for low recovery expectations and greater likelihood for lodging a claim, and (3) explore the moderating effect of neck pain history and sociodemographic characteristics. DESIGN: Online randomized experiment with nested qualitative content analysis. METHODS: We randomized 2229 participants from the general population (mean age: 46.7 ± 17.5 years; 72.4% females; 66% with previous or current neck pain; 10% with an MVC experience) to read 1 of 5 scenarios describing a patient with neck pain after an MVC, each was labeled as whiplash injury, whiplash-associated disorder, posttraumatic neck pain, neck pain, or neck strain. The primary outcome was recovery expectations, rated on a 0- to 10-point scale. RESULTS: Participants allocated to whiplash-associated disorder or neck pain had lower recovery expectations than those allocated to neck strain (adjusted mean difference [95% confidence interval]: -0.5 [-0.9 to -0.1] for both comparisons). Whiplash-associated disorder led to more recovery uncertainty, while neck pain led to greater doubt about the health care provider. Most secondary outcomes showed significant but small differences. Participants allocated to neck strain were less inclined to claim than those allocated to whiplash-associated disorder or whiplash injury due to less perceived need for financial support. Neck pain history moderated labeling effects on recovery expectations; household income moderated the claim intention. CONCLUSIONS: Labels for neck pain after an MVC influenced recovery expectations and management preferences. The clinical relevance of the small effects was unclear. [ABSTRACT FROM AUTHOR]

Objectives: The research aimed to test the job demands-resources (JD-R) model on a sample of Italian oncology workers, and the role of perceived organizational support (POS) as a moderator of the effects of JD on outcomes (job satisfaction and burnout [BO]). Methods: Based on the JD-R model, a correlational study was designed to investigate the relationships between JD, POS as a job resource, self-esteem (as a personal resource), and job outcomes (BO and job satisfaction); the research involved a sample of oncology nurses (N = 235) from an Italian public hospital, who completed a questionnaire during working hours. Relationships between variables were investigated with multiple regressions and moderation analysis. Results: Results confirmed that JD predict both BO and job satisfaction; POS is a weak predictor of job outcomes, but its mediator role in the JD-outcomes relationship was confirmed: the more the nurses perceive a supportive organization, the weaker the positive relationship between JD and BO. Significance of results: Findings are consistent with other contributions that highlighted that organizational job resources may attenuate the adverse effect of JD on positive and negative outcomes: POS may play a central role in employee well-being and health, acting as a possible moderator, and somehow defusing the positive association between JD and outcomes. [ABSTRACT FROM AUTHOR]

The field of ophthalmic surgery demands accurate identification of specialized surgical instruments. Manual recognition can be time-consuming and prone to errors. In recent years neural networks have emerged as promising techniques for automating the classification process. However, the deployment of these advanced algorithms requires the collection of large amounts of data and a painstaking process of tagging selected elements. This paper presents a novel investigation into the application of neural networks for the detection and classification of surgical instruments in ophthalmic surgery. The main focus of the research is the application of active learning techniques, in which the model is trained by selecting the most informative instances to expand the training set. Various active learning methods are compared, with a focus on their effectiveness in reducing the need for significant data annotation -- a major concern in the field of surgery. The use of convolutional neural networks (CNNs) and recurrent neural networks (RNNs) to achieve high performance in the task of surgical tool detection is outlined. The combination of artificial intelligence (AI), machine learning, and Active Learning approaches, specifically in the field of ophthalmic surgery, opens new perspectives for improved diagnosis and surgical planning, ultimately leading to an improvement in patient safety and treatment outcomes. [ABSTRACT FROM AUTHOR]

The use of native and malted triticale (MT) flour in dry pasta has been limited despite the potential of triticale in cereal-based food production. In this study, triticale-based dry spaghetti with increasing levels of substitution (0, 25, 50, and 75 g/100 g w/w) of MT flour were formulated and analyzed. Samples were analyzed for technological and nutritional traits, including the in vitro starch and protein digestions. The gradual substitution of native triticale flour with MT increased (p < 0.05) the total dietary fiber content, whereas total starch decreased (p < 0.05). Adding MT flour increased the cooking loss and the stickiness of cooked pasta (p < 0.05). Using MT flour modulated the in vitro starch digestion, lowering the slowly digestible and resistant starch contents. The in vitro protein digestibility was positively affected using MT at the highest substitution level. Overall, MT could be used to formulate dry pasta products being the substitution to native triticale up to 50 g/100 g, a good compromise between nutritional quality and technological characteristics. [ABSTRACT FROM AUTHOR]

Background: The function of polymorphonuclear neutrophils (PMNs) decreases with age, which results in infectious and inflammatory complications in older individuals. The underlying causes are not fully understood. ATP release and autocrine stimulation of purinergic receptors help PMNs combat microbial invaders. Excessive extracellular ATP interferes with these mechanisms and promotes inflammatory PMN responses. Here, we studied whether dysregulated purinergic signaling in PMNs contributes to their dysfunction in older individuals. Results: Bacterial infection of C57BL/6 mice resulted in exaggerated PMN activation that was significantly greater in old mice (64 weeks) than in young animals (10 weeks). In contrast to young animals, old mice were unable to prevent the systemic spread of bacteria, resulting in lethal sepsis and significantly greater mortality in old mice than in their younger counterparts. We found that the ATP levels in the plasma of mice increased with age and that, along with the extracellular accumulation of ATP, the PMNs of old mice became increasingly primed. Stimulation of the formyl peptide receptors of those primed PMNs triggered inflammatory responses that were significantly more pronounced in old mice than in young animals. However, bacterial phagocytosis and killing by PMNs of old mice were significantly lower than that of young mice. These age-dependent PMN dysfunctions correlated with a decrease in the enzymatic activity of plasma ATPases that convert extracellular ATP to adenosine. ATPases depend on divalent metal ions, including Ca2+, Mg2+, and Zn2+, and we found that depletion of these ions blocked the hydrolysis of ATP and the formation of adenosine in human blood, resulting in ATP accumulation and dysregulation of PMN functions equivalent to those observed in response to aging. Conclusions: Our findings suggest that impaired hydrolysis of plasma ATP dysregulates PMN function in older individuals. We conclude that strategies aimed at restoring plasma ATPase activity may offer novel therapeutic opportunities to reduce immune dysfunction, inflammation, and infectious complications in older patients. [ABSTRACT FROM AUTHOR]

The studies on the bioinvasion phenomenon focus mainly on the biological and ecological traits of a species, while scattered literature is addressed to a correct systematic assessment and an updated geographical distribution on the whole. It is noteworthy that non-indigenous species should be monitored on both sides of their range, i.e., towards the front of dispersal and beyond the original range. The backside range boundaries are not often monitored or well delimited; thus, the novel global distribution of an invasive taxon is not often accurately delimitated. A model species for highlighting criticisms about the scarce knowledge on the novel range was chosen. Brachidontes pharaonis is a mussel that has successfully colonised the Mediterranean Sea, following an immigration pathway through the Suez Canal from the Red Sea, presumably from a wider Indo-Pacific area. In this case, the Indo-Pacific boundaries have been overlooked and are still misunderstood due to diverse causes, principally as the synonymy with the congeneric B. variabilis has created confusion in the taxonomic identification. The present review demonstrates that the borders of the B. pharaonis range are still unclear and that the species should be analysed in a wider geographical area. Records of B. pharaonis from Southeast Asia should be treated with caution as this area is out of its range. The Indian and Pacific Oceans host the taxon B. variabilis, composed of two potential cryptic species. Data from the literature highlight the importance of the integrative taxonomic approach to solving various issues concerning the species group complex, morphological variations and cosmopolitan claims of species. [ABSTRACT FROM AUTHOR]

Vitamin D (Vit D) is a fat-soluble molecule acting like a hormone, and it is involved in several biological mechanisms such as gene expression, calcium homeostasis, bone metabolism, immune modulation, viral protection, and neuromuscular functions. Vit D deficiency can lead to chronic hypocalcemia, hyperparathyroidism, and many other pathological conditions; in this context, low and very low levels of 25-hydroxy-vitamin D (25-OH-D) were found to be associated with an increased risk of COVID-19 infection and the likelihood of many severe diseases. For all these reasons, it is important to quantify and monitor 25-OH-D levels to ensure that the serum/blood concentrations are not clinically suboptimal. Serum concentration of 25-OH-D is currently the main indicator of Vit D status, and it is currently performed by different assays, but the most common quantitation techniques involve immunometric methods or chromatography. Nevertheless, other quantitation techniques and instruments are now emerging, such as AFIAS-1® and AFIAS-10® (Boditech and Menarini) based on the immunofluorescence analyzer, that guarantee an automated system with cartridges able to give quick and reliable results as a point-of-care test (POCT). This work aims to compare AFIAS-1® and AFIAS-10® (Boditech and Menarini) Vit D quantitation with Ultra High-Performance Liquid Chromatography coupled with tandem mass spectrometry that currently represents the gold standard technique for Vit D quantitation. The analyses were performed in parallel on 56 samples and in different conditions (from fresh and frozen plasma) to assess the reliability of the results. Any statistically significant differences in methods, the fixed error, and the error proportional to concentration were reported. Results obtained in all conditions showed a good correlation between both AFIAS® instruments and LC-MS/MS, and we can affirm that AFIAS-1® and AFIAS-10® are reliable instruments for measuring 25-OH-D with accuracy and in a fast manner. [ABSTRACT FROM AUTHOR]

Background: Mastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25–60% of patients reporting pain 3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP. Methods: Ketamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale. Discussion: This project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic. Trial registration: ClinicalTrials.gov NCT05037123. Registered on September 8, 2021. [ABSTRACT FROM AUTHOR]

Background: Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in the TSC1 and TSC2 genes, causing overactivation of the mechanistic (previously referred to as mammalian) target of rapamycin (mTOR) signaling pathway in fetal life. The mTOR pathway plays a crucial role in several brain processes leading to TSC-related epilepsy, intellectual disability, and autism spectrum disorder (ASD). Pre-natal or early post-natal diagnosis of TSC is now possible in a growing number of pre-symptomatic infants. Data sources: We searched PubMed for peer-reviewed publications published between January 2010 and April 2023 with the terms "tuberous sclerosis", "autism", or "autism spectrum disorder"," animal models", "preclinical studies", "neurobiology", and "treatment". Results: Prospective studies have highlighted that developmental trajectories in TSC infants who were later diagnosed with ASD already show motor, visual and social communication skills in the first year of life delays. Reliable genetic, cellular, electroencephalography and magnetic resonance imaging biomarkers can identify pre-symptomatic TSC infants at high risk for having autism and epilepsy. Conclusions: Preventing epilepsy or improving therapy for seizures associated with prompt and tailored treatment strategies for autism in a sensitive developmental time window could have the potential to mitigate autistic symptoms in infants with TSC. [ABSTRACT FROM AUTHOR]

The self-assembly of complex structures from a set of non-identical building blocks is a hallmark of soft matter and biological systems, including protein complexes, colloidal clusters, and DNA-based assemblies. Predicting the dependence of the equilibrium assembly yield on the concentrations and interaction energies of building blocks is highly challenging, owing to the difficulty of computing the entropic contributions to the free energy of the many structures that compete with the ground state configuration. While these calculations yield well known results for spherically symmetric building blocks, they do not hold when the building blocks have internal rotational degrees of freedom. Here we present an approach for solving this problem that works with arbitrary building blocks, including proteins with known structure and complex colloidal building blocks. Our algorithm combines classical statistical mechanics with recently developed computational tools for automatic differentiation. Automatic differentiation allows efficient evaluation of equilibrium averages over configurations that would otherwise be intractable. We demonstrate the validity of our framework by comparison to molecular dynamics simulations of simple examples, and apply it to calculate the yield curves for known protein complexes and for the assembly of colloidal shells. Predicting the effective assembly of a set of proteins into a desired structure has traditionally been a challenging task. Here, authors demonstrate that advancements in automatic differentiation make it possible to address this problem using classical statistical mechanics. [ABSTRACT FROM AUTHOR]

In active matter, particles typically experience mediated interactions, which are not constrained by Newton's third law and are therefore generically non-reciprocal. Non-reciprocity leads to a rich set of emerging behaviors that are hard to account for starting from the microscopic scale, due to the absence of a generic theoretical framework out of equilibrium. Here we consider bacterial mixtures that interact via mediated, non-reciprocal interactions (NRI) like quorum-sensing and chemotaxis. By explicitly relating microscopic and macroscopic dynamics, we show that, under conditions that we derive explicitly, non-reciprocity may fade upon coarse-graining, leading to large-scale equilibrium descriptions. In turn, this allows us to account quantitatively, and without fitting parameters, for the rich behaviors observed in microscopic simulations including phase separation, demixing, and multi-phase coexistence. We also derive the condition under which non-reciprocity survives coarse-graining, leading to a wealth of dynamical patterns. Again, our analytical approach allows us to predict the phase diagram of the system starting from its microscopic description. All in all, our work demonstrates that the fate of non-reciprocity across scales is a subtle and important question. Non-reciprocal interactions (NRI) are ubiquitous in active systems, but, in the presence of NRI, it is difficult to predict which microscopic systems correspond to a given macroscopic description. Dinelli et al. relate microscopic and macroscopic dynamics of active mixtures and show that non-reciprocity strongly depends on the scale of description. [ABSTRACT FROM AUTHOR]

Background: Current clinical phenotyping of musculoskeletal pain provides very limited evidence‐ based support to personalized medicine. This paper discusses the potential of somatosensory phenotyping to contribute to personalized medicine for prognosis and prediction of treatment effects. Methods: Highlight of definitions and regulatory requirements for phenotypes and biomarkers. Appraisal of the literature on somatosensory phenotyping in musculoskeletal pain. Results: Somatosensory phenotyping can identify clinical conditions and manifestations that may affect treatment decisions. However, studies have shown inconsistent associations of phenotyping measures with clinical outcomes, and the strength of association is mostly weak. Most somatosensory measures have been developed for research, are too demanding to find large acceptance in clinical settings, and have uncertain clinical usefulness. Conclusions: Current somatosensory measures will unlikely be validated as strong prognostic or predictive biomarkers. However, they still have the potential to support personalized medicine. Including somatosensory measures in biomarker signatures, that is, a set of measures that are collectively associated with outcomes, is potentially more useful than aiming to the identification of single biomarkers. Furthermore, somatosensory phenotyping may be introduced as part of patient's evaluation to contribute to better‐informed and personalized treatment decisions. To this purpose, a change in the way research currently approaches somatosensory phenotyping is warranted. A pathway is proposed that involves: (1) the identification of clinically applicable measures that are specific to clinical conditions; (2) the association of somatosensory phenotypes with outcomes; (3) multi‐site replication; and (4) the determination of clinical benefits in randomized controlled trials. Significance: Somatosensory phenotyping has the potential to support personalized medicine. However, current measures do not seem to meet the criteria for being strong prognostic or predictive biomarkers, most of them are too demanding to find large acceptance in clinical settings, and their clinical usefulness has not been proven. The value of somatosensory phenotyping can be more realistically determined by re‐orienting research to the development of simplified testing protocols, applicable to large‐scale clinical practice, and tested for clinical usefulness in randomized controlled trials. [ABSTRACT FROM AUTHOR]

Muscle pain can be associated with hyperalgesia that may spread outside the area of primary injury due to both peripheral and central sensitization. However, the influence of endogenous pain inhibition is yet unknown. This study investigated how endogenous pain inhibition might influence spreading hyperalgesia in experimental muscle pain. Conditioned pain modulation (CPM) was assessed in 30 male volunteers by cold pressor test at the non-dominant hand as conditioning and pressure pain thresholds (PPT) at the dominant 2nd toe as test stimuli. Subjects were classified as having inhibitory or facilitating CPM based on published reference values. Subsequently, muscle pain and hyperalgesia were induced by capsaicin injection into the non-dominant supraspinatus muscle. Before and 5, 10, 15, 20, 30, 40, 50 and 60 min later, PPTs were recorded at the supraspinatus, infraspinatus and deltoid muscle, ring finger and toe. Compared to baseline, PPTs decreased at the supraspinatus, infraspinatus and deltoid muscle (p≤0.03), and increased at the finger and toe (p<0.001). In facilitating CPM (n=10), hyperalgesia occurred at 5, 10, 15, 20 and 40 min (p≤0.026). In inhibitory CPM (n=20), hyperalgesia only occurred after 10 and 15 min (p≤0.03). At the infraspinatus muscle, groups differed after 5 and 40 min (p≤0.008). The results suggest that facilitating CPM is associated with more spreading hyperalgesia than inhibitory CPM. This implies that poor endogenous pain modulation may predispose to muscle pain and spreading hyperalgesia after injury, and suggest that strategies to enhance endogenous pain modulation may provide clinical benefits. [ABSTRACT FROM AUTHOR]

Epileptogenesis in infants with tuberous sclerosis complex (TSC) is a gradual and dynamic process, leading to early onset and difficult-to-treat seizures. Several cellular, molecular and pathophysiologic mechanisms, including mammalian target of rapamycin (mTOR) dysregulation, GABAergic dysfunction and abnormal connectivity, may play a role in this epileptogenic process and may also contribute to the associated developmental encephalopathy. Disease-specific antiseizure medications or drugs targeting the mTOR pathway have proved to be effective in TSC-associated epilepsy. Pre-symptomatic administration of vigabatrin, a GABAergic drug, delays seizure onset and reduces the risk of a subsequent epileptic encephalopathy, such as infantile spasms syndrome or Lennox–Gastaut syndrome. Everolimus, a rapamycin-derived mTOR inhibitor, reduces seizure frequency, especially in younger patients. This evidence suggests that everolimus should be considered early in the course of epilepsy. Future trials are needed to optimize the use of everolimus and determine whether earlier correction of mTOR dysregulation can prevent progression to developmental and epileptic encephalopathies or mitigate their severity in infants with TSC. Clinical trials of several other potential antiseizure drugs (cannabidiol and ganaxolone) that target contributing mechanisms are also underway. This review provides an overview of the different biological mechanisms occurring in parallel and interacting throughout the life course, even beyond the epileptogenic process, in individuals with TSC. These complexities highlight the challenges faced in preventing and treating TSC-related developmental and epileptic encephalopathy. [ABSTRACT FROM AUTHOR]

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Background: TP53 gene plays a major role in the negative control of cell proliferation and in the regulation of signaling cascades. TP53 mutation may have a relevant role in the malignant transformation of thyroid cells as well as thyroid tumor progression. TP53 mutation has been detected only in few well differentiated thyroid carcinomas and is absent in benign conditions. Methods: A total of 162 prospective thyroid cytology and corresponding histological samples diagnosed from atypia of indeterminate significance (AUS) to malignant, were studied via immunocytochemistry for p53. Hence, 50 benign lesions (B) were used as negative control. Molecular analysis for p53 only was performed. Results: The cytology resulted in 50 B, 48 AUS, 40 follicular neoplasms (FNs), 23 suspicious for malignancy (SFM), and 1 malignant (M) case. The authors reported 102 negative and 60 positive p53 cases. The 60 positive cases included 27 cases with weak and/or focal cytoplasmic positivity (+1) and 33 with cases moderate (2+) to strong (3+) cytoplasmic and/or nuclear expression. Overall, 71 cases had histology (2 B, 11 AUS, 37 FN, 20 SFM, and 1 M) including 61.7% benign and 38.2% malignant diagnoses. Only 16 of 71 (5 FN, 10 SFM, and 1 M) were p53‐positive. Furthermore, 100% AUS and 86.5% FN cases were p53‐negative, none of which had malignant histology. All p53‐positive cases were associated with a larger nodule size, tall‐cell variant subtype, multifocality, extra thyroidal infiltration, and nodal metastases. Noninvasive follicular thyroid neoplasm with papillary like nuclear features were negative for p53. Few discrepancies in p53 intensity were observed on histology; there were no differences with the molecular testing. Conclusions: p53 might be useful in discriminating thyroid follicular lesions. p53 is likely to be a useful diagnostic marker in recognizing indeterminate lesions that are well‐differentiated thyroid cancers. p53 might be useful in discriminating thyroid follicular lesions. p53 is likely to be a useful diagnostic marker in recognizing indeterminate lesions that are well‐differentiated thyroid cancers. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a 64-year-old female patient who experienced a delayed-type hypersensitivity reaction after taking a tablet of fosfomycin trometamol for a urinary tract infection. The patient had previously experienced a similar reaction after receiving an iodinated contrast agent. Skin tests and a lymphocyte transformation test confirmed a sensitization to trometamol. Trometamol is commonly used as a buffer in various medications and cosmetic products. This case highlights the importance of considering excipients, such as trometamol, in allergy workups and the potential consequences for patients who may encounter this ingredient in multiple medications and treatments. [Extracted from the article]

Severe pain is a widespread health problem in need of novel treatment approaches. In the current study we used real water to give virtual objects (i.e., animated virtual water) more realistic physical properties (wet liquid qualities). Healthy volunteers aged 18–34 participated in a within-subject randomized study comparing participants' worst pain during brief thermal stimuli with (1) No Immersive Virtual Reality (VR), versus (2) during VR + no tactile feedback versus (3) VR + real water (with tactile feedback from co-located real objects). Tactile feedback significantly decreased pain intensity (VR analgesia, p < 0.01), compared to VR with no tactile feedback, and compared to No VR (baseline). Tactile feedback made the virtual water feel significantly more real, increased participant's sense of presence, and both VR conditions were distracting (significantly reduced accuracy on an attention demanding task). As a non-pharmacologic analgesic, mixed reality reduced pain by 35% in the current study, comparable to the analgesia from a moderate dose of hydromorphone in previous published experimental studies. Tactile feedback also significantly increased avatar embodiment, the participants illusion of ownership of the virtual hands, which has potential to improve the effectiveness of avatar therapy for chronic pain in future studies. Mixed reality should be tested as treatment in pain patients. [ABSTRACT FROM AUTHOR]

A cylindrical hydrogel tube, completely submerged in water, hydrates by swelling and filling its internal cavity. When it comes back into contact with air, it dehydrates: the tube thus expels the solvent through the walls, shrinking. This dehydration process causes a depression in the tube cavity, which can lead to circumferential buckling. Here we study the occurrence of such buckling using a continuous model that combines nonlinear elasticity with Flory–Rehner theory, to take into account both the large deformations and the active behaviour of the hydrogel. In quasi-static approximation, we use the incremental deformation formalism, extended to the chemo-mechanical equations, to determine the threshold value of the enclosed volume at which buckling is triggered. This critical value is found to depend on the shell thickness, chemical potential and constitutive features. The results obtained are in good agreement with the results of the finite element simulations of the complete dynamic problem. [ABSTRACT FROM AUTHOR]

Intraocular lenses (IOLs) are commonly implanted after surgical removal of a cataractous lens. A variety of IOL materials are currently available, including collamer, hydrophobic acrylic, hydrophilic acrylic, PHEMA copolymer, polymethylmethacrylate (PMMA), and silicone. High-quality polymers with distinct physical and optical properties for IOL manufacturing and in line with the highest quality standards on the market have evolved to encompass medical needs. Each of them and their packaging show unique advantages and disadvantages. Here, we highlight the evolution of polymeric materials and mainly the current state of the art of the unique properties of some polymeric systems used for IOL design, identifying current limitations for future improvements. We investigate the characteristics of the next generation of IOL materials, which must satisfy biocompatibility requirements and have tuneable refractive index to create patient-specific eye power, preventing formation of posterior capsular opacification. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is a heterogeneous condition, characterized by complex genetic architectures and intertwined genetic/environmental interactions. Novel analysis approaches to disentangle its pathophysiology by computing large amounts of data are needed. We present an advanced machine learning technique, based on a clustering analysis on genotypical/phenotypical embedding spaces, to identify biological processes that might act as pathophysiological substrates for ASD. This technique was applied to the VariCarta database, which contained 187,794 variant events retrieved from 15,189 individuals with ASD. Nine clusters of ASD-related genes were identified. The 3 largest clusters included 68.6% of all individuals, consisting of 1455 (38.0%), 841 (21.9%), and 336 (8.7%) persons, respectively. Enrichment analysis was applied to isolate clinically relevant ASD-associated biological processes. Two of the identified clusters were characterized by individuals with an increased presence of variants linked to biological processes and cellular components, such as axon growth and guidance, synaptic membrane components, or transmission. The study also suggested other clusters with possible genotype–phenotype associations. Innovative methodologies, including machine learning, can improve our understanding of the underlying biological processes and gene variant networks that undergo the etiology and pathogenic mechanisms of ASD. Future work to ascertain the reproducibility of the presented methodology is warranted. [ABSTRACT FROM AUTHOR]

Featured Application: We present an HPLC method development and validation for the quantitation of boswellic acids in Boswellia resin samples and construction of a multivariate model for the clustering of different sample species. The resin of Boswellia plant species has been used since ancient times for its several bio-active curative effects. In modern times, extracts of this resin are still widely commercialized on the food supplements and nutraceuticals market. Nowadays the legislation on botanical extracts and the increasing demand for their safety and traceability are setting new standards for their chemical characterization. In this work we present an easy, feasible and rugged HPLC-UV-based approach for the quantitation of boswellic acids in food-supplement-grade resin extracts of Boswellia plant species. This method can be used for quality control purposes as well as for studying their differences in regional origin, years of harvesting and species-related differences. The method employs a C18 (3 × 150 mm, 3 µm) analytical HPLC column, and the separation is carried out through a gradient of acetonitrile/water with 0.1% formic acid. The method was validated following the ICH guidelines and used to quantitate different samples of commercial resin of Boswellia carteri and serrata together with other samples from unknown species. The six known boswellic acids were identified and quantified in all the analyzed samples. The results were used to build a multivariate model to graphically appreciate their difference through their clustering. The model was then augmented by adding further quantitation data for boswellic acids belonging to different species of Boswellia obtained by another scientific publications to increase the number of studied samples. [ABSTRACT FROM AUTHOR]

In this paper, we present the generalities of the Compton interaction process; we analyse the different paradigms of Inverse Compton Sources, implemented or in commissioning phase at various facilities, or proposed as future projects. We present an overview of the state of the art, with a discussion of the most demanding challenges. [ABSTRACT FROM AUTHOR]

Background and objective: There is no report of the rate of opioid prescription at the time of hospital discharge, which may be associated with various patient and procedure-related factors. This study examined the prevalence and factors associated with prescribing opioids for head/neck pain after elective craniotomy for tumor resection/vascular repair. Methods: We performed a retrospective cohort study on adults undergoing elective craniotomy for tumor resection/vascular repair at a large quaternary-care hospital. We used univariable and multivariable analysis to examine the prevalence and factors (pre-operative, intraoperative, and postoperative) associated with prescribing opioids at the time of hospital discharge. We also examined the factors associated with discharge oral morphine equivalent use. Results: The study sample comprised 273 patients with a median age of 54 years [IQR 41,65], 173 females (63%), 174 (63.7%) tumor resections, and 99 (36.2%) vascular repairs. The majority (n = 264, 96.7%) received opioids postoperatively. The opiate prescription rates were 72% (n = 196/273) at hospital discharge, 23% (19/83) at neurosurgical clinical visits within 30 days of the procedure, and 2.4% (2/83) after 30 days from the procedure. The median oral morphine equivalent (OME) at discharge use was 300 [IQR 175,600]. Patients were discharged with a median supply of 5 days [IQR 3,7]. On multivariable analysis, opioid prescription at hospital discharge was associated with pre-existent chronic pain (adjusted odds ratio, aOR 1.87 [1.06,3.29], p = 0.03) and time from surgery to hospital discharge (compared to patients discharged within days 1–4 postoperatively, patients discharged between days 5–12 (aOR 0.3, 95% CI [0.15; 0.59], p = 0.0005), discharged at 12 days and later (aOR 0.17, 95% CI [0.07; 0.39], p < 0.001)). There was a linear relationship between the first 24 h OME (p < 0.001), daily OME (p < 0.001), hospital OME (p < 0.001), and discharge OME. Conclusions: This single-center study finds that at the time of hospital discharge, opioids are prescribed for head/neck pain in as many as seven out of ten patients after elective craniotomy. A history of chronic pain and time from surgery to discharge may be associated with opiate prescriptions. Discharge OME may be associated with first 24-h, daily OME, and hospital OME use. Findings need further evaluation in a large multicenter sample. The findings are important to consider as there is growing interest in an early discharge after elective craniotomy. [ABSTRACT FROM AUTHOR]

We realize steady curved shapes from homogeneous hydrogel flat structures which are in contact with two environments at different chemical conditions. We numerically investigate the behaviour of beam-like and plate-like structures during the transient state, which realize osmotic pumps. Through numerical experiments, we determine the relationship between the difference in the chemical potentials at the top and bottom of a beam and the curvature of the bent beam as well as the Gaussian curvature of a spherical cap morphed from a flat plate. We also propose an approximate modeling of both the beam and the plate, to evaluate explicitly that relationship and show the good agreement between those formulas and the outcomes of the numerical simulations. [ABSTRACT FROM AUTHOR]

Adaptive optics (AO) is employed for the continuous measurement and correction of ocular aberrations. Human eye refractive errors (lower-order aberrations such as myopia and astigmatism) are corrected with contact lenses and excimer laser surgery. Under twilight vision conditions, when the pupil of the human eye dilates to 5–7 mm in diameter, higher-order aberrations affect the visual acuity. The combined use of wavefront (WF) technology and AO systems allows the pre-operative evaluation of refractive surgical procedures to compensate for the higher-order optical aberrations of the human eye, guiding the surgeon in choosing the procedure parameters. Here, we report a brief history of AO, starting from the description of the Shack–Hartmann method, which allowed the first in vivo measurement of the eye's wave aberration, the wavefront sensing technologies (WSTs), and their principles. Then, the limitations of the ocular wavefront ascribed to the IOL polymeric materials and design, as well as future perspectives on improving patient vision quality and meeting clinical requests, are described. [ABSTRACT FROM AUTHOR]

Calorimeters, as other detectors, have to face the increasing performance demands of the new energy frontier experiments. For a future Muon Collider the main challenge is given by the Beam Induced Background that may pose limitations to the physics performance. However, it is possible to reduce the BIB impact by exploiting some of its characteristics by ensuring high granularity, excellent timing, longitudinal segmentation and good energy resolution. The proposed design, the Crilin calorimeter, is an alternative semi-homogeneous ECAL barrel for the Muon Collider based on Lead Fluoride Crystals (PbF 2 ) with a surface-mount UV-extended Silicon Photomultipliers (SiPMs) readout with an optimized design for a future Muon Collider. [ABSTRACT FROM AUTHOR]

Recently there has been a growing interest in non-pharmacological treatments for ADHD. We evaluated the efficacy of a specific Omega-3/6 dietary supplement (two capsules containing 279 mg eicosapentaenoic acid [EPA], 87 mg Docosahexaenoic Acid [DHA], 30 mg gamma linolenic acid [GLA] each) in ameliorating inattentive symptoms in inattentive-ADHD children (6–12 years) with a baseline ADHD-RS-Inattention score ≥ 12. Secondary objectives included changes in global functioning, severity of illness, depression, and anxiety symptoms, learning disorders and in the fatty acids blood levels. The study was a randomised, double-blind, placebo-controlled efficacy and safety trial with a 6-month double-blind evaluation of Omega-3/6 vs placebo (Phase-I) and a further 6-month-open-label treatment with Omega-3/6 on all patients (Phase-II). In total 160 subjects were enrolled. No superiority of Omega-3/6 supplement to placebo was observed on the primary outcome (ADHD-RS-inattention score) after the first 6-months, with 46.3% of responders in the Omega-3/6 group and 45.6% in the placebo group; a slight (not statistically significant) reduction in Omega-6/3 ratio blood levels was measured in the active treatment group. Twelve months after enrolment, percentages of responders were similar between groups. A mild statistical, although not clinically significant, improvement was observed on the ADHD-RS-total score in the Omega-3/6 group but not on the ADHD-RS-Inattention score; a slight (not-statistically significant) reduction in Omega-6/3 ratio was observed in the group taking active treatment only during Phase II. In conclusion, no clinical beneficial effects of Omega-3/6 were detected on inattentive symptoms, suggesting a limited role of Omega-3/6 dietary products in children with mild ADHD-I. Trial registration: At the time of the Ethical submission, according to the clinical trial Italian law, registration was not mandatory for food additive as Omega 3/6 were then classified. The trial was approved by the Ethical Committee of the Cagliari University Hospital (resolution n. 662; September 22nd, 2011). [ABSTRACT FROM AUTHOR]

A 65-year-old woman presented with painful nodules on her back after returning to Switzerland from Congo. The nodules were furunculoid in nature and had central ulceration. Dermoscopically, erythematous lesions with a central larval breathing hole, resembling a periscope, were observed. The larvae were identified as Cordylobia anthropophaga. Furuncular myiasis is rare in Switzerland and is often seen in patients returning from regions where these flies are prevalent. The authors suggest using the "periscope sign" as a dermatoscopic finding to aid in the diagnosis of this condition. [Extracted from the article]

This article discusses a case of delayed-type hypersensitivity reaction to a jellyfish. The patient, a 44-year-old man, developed itchy skin lesions on his forearm and other areas of his body after being stung by a jellyfish while swimming in the Mediterranean Sea. Despite taking antihistamines and applying steroids, the symptoms did not improve. A histologic examination revealed characteristic features of a hypersensitivity reaction. The patient was treated with topical therapy and showed rapid improvement. The article emphasizes the importance of considering travel history and potential triggers when diagnosing unusual skin findings. [Extracted from the article]