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Abstract We present the calculation of the short-distance power corrections to the CP-violation parameter ε K coming from dimension-8 operators in the ∆S = 2 effective Hamiltonian. A first estimate of this contribution, obtained for large-N c and in the chiral limit, was provided in ref. [1]. Here we evaluate and include the O m K 2 / m c 2 $$ \mathcal{O}\left({m}_K^2/{m}_c^2\right) $$ and O Λ QCD 2 / m c 2 $$ \mathcal{O}\left({\Lambda}_{\mathrm{QCD}}^2/{m}_c^2\right) $$ contributions that, a priori, could induce O $$ \mathcal{O} $$ (1) corrections to previous estimates, as m K is numerically of order ΛQCD. Our computation shows that there are several dimension-8 operators besides the one considered before. Their effect on ε K , however, accidentally cancels out to a large extent, leaving the final correction at the level of 1%.

The lack of information on structural basis where proteins are involved, as well as the biomineralization processes of different systems such as bones, diatom frustules, and eggshells, have intrigued scientists from different fields for decades. This scientific curiosity has led to the use of methodologies that help understand the mechanism involved in the formation of these complex structures. Therefore, this work focuses on the use of eggshell membranes from different species of ratites (emu and ostrich) and reptiles (two species of crocodiles) as a model to differentiate biocalcification and biosilicification by introducing calcium phosphate or silica inside the membrane fiber mantles. We performed this to obtain information about the process of eggshell formation as well as the changes that occur in the membrane during crystal formation. In order to identify and understand the early processes leading to the formation of the microstructures present in the eggshell, we decided to carry out the synthesis of silica-carbonate of calcium, barium, and strontium called biomorph in the presence of intramineral proteins. This was carried out to evaluate the influence of these proteins on the formation of specific structures. We found that the proteins on untreated membranes, present a structural growth similar to those observed in the inner part of the eggshell, while in treated membranes, the structures formed present a high similarity with those observed in the outer and intermediate part of the eggshell. Finally, a topographic and molecular analysis of the biomorphs and membranes was performed by scanning electron microscopy (SEM), Raman and Fourier-transform Infrared (FTIR) spectroscopies.

Background: An increasing amount of evidence suggests that migraine is a response to cerebral energy deficiencies or oxidative stress levels that exceed antioxidant capacity. Current pharmacological options are inadequate in treating patients with chronic migraine, and a growing interest focuses on nutritional approaches as non-pharmacological treatments. The ketogenic diet, mimicking fasting that leads to an elevation of ketone bodies, is a therapeutic intervention targeting cerebral metabolism that has recently shown great promise in the prevention of migraines. Moreover, Mediterranean elements like vegetables, nuts, herbs, spices, and olive oil that are sources of anti-inflammatory elements (omega-3 fatty acids, polyphenols, vitamins, essential minerals, and probiotics) may create a positive brain environment by reducing imbalance in the gut microbiome., Methods: On the basis of these indications, a combined Mediterranean-ketogenic diet was administered to chronic migraine patients for 4 (T1) and 8 weeks (T2), and anthropometric estimations were collected at T1 and T2 while biochemical parameters at only T2., Results: A significant reduction (p < 0.01) in migraine frequency and intensity was detected as early as 4 weeks of dietary intervention, which was associated with a reduced fat mass (p < 0.001) as well as Homa index (p < 0.05) and insulin levels (p < 0.01) after 8 weeks., Conclusion: Overall, Mediterranean-ketogenic diet may be considered an effective non-pharmacological intervention for migraine, with positive outcomes on body composition., (Published by Elsevier Ltd.)

To date, strategies aiming to modulate cell to extracellular matrix (ECM) interactions during organoid derivation remain largely unexplored. Here renal decellularized ECM (dECM) hydrogels are fabricated from porcine and human renal cortex as biomaterials to enrich cell-to-ECM crosstalk during the onset of kidney organoid differentiation from human pluripotent stem cells (hPSCs). Renal dECM-derived hydrogels are used in combination with hPSC-derived renal progenitor cells to define new approaches for 2D and 3D kidney organoid differentiation, demonstrating that in the presence of these biomaterials the resulting kidney organoids exhibit renal differentiation features and the formation of an endogenous vascular component. Based on these observations, a new method to produce kidney organoids with vascular-like structures is achieved through the assembly of hPSC-derived endothelial-like organoids with kidney organoids in 3D. Major readouts of kidney differentiation and renal cell morphology are assessed exploiting these culture platforms as new models of nephrogenesis. Overall, this work shows that exploiting cell-to-ECM interactions during the onset of kidney differentiation from hPSCs facilitates and optimizes current approaches for kidney organoid derivation thereby increasing the utility of these unique cell culture platforms for personalized medicine., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Background: Virtual reality (VR) emerges as a promising non-pharmacological intervention for managing symptoms and providing distraction during chemotherapy. This study aims to assess VR's effectiveness on cancer-related symptoms, vital signs, and the patients' perception of chemotherapy in lung cancer patients. Methods : A quasi-experimental study was conducted on 100 patients. Participants were allocated into an intervention group (n = 55), which experienced immersive VR, and a comparison group (n = 45), which received usual care. Data were collected through questionnaires and checklists, including feedback on the VR experience, pain, vital signs, and common cancer symptoms, assessed through the Edmonton Symptom Assessment Scale. Results : VR had a significant impact on reducing the perception of chemotherapy length. Patients reported high levels of satisfaction and tolerability. No adverse events were observed. VR did not have significant influence on pain intensity or vital signs. The only exceptions were oxygen saturation, where a significant difference ( p = 0.02) was reported, and the perception of chemotherapy duration. Conclusions : As a non-pharmacological intervention, VR proves to be beneficial in minimizing the perceived length of chemotherapy sessions for lung cancer patients, enhancing their overall treatment experience. The intervention was found to be a safe, feasible, and well-accepted distraction technique. Future research should explore VR's potential effects on a wider range of symptoms and evaluate its impact on long-term outcomes.

Objective: High-grade aneuploidies of X and Y sex chromosomes (HGAs) are exceedingly rare and complex conditions. We aimed to investigate the effect of supernumerary X chromosomes (extra-Xs) on the clinical, hormonal, metabolic, and echocardiographic features of patients with HGAs., Design and Methods: In a cross-sectional study, we compared 23 subjects with HGAs and 46 age-matched subjects with 47,XXY Klinefelter syndrome (KS), according to the number of extra-Xs: two (47,XXY and 48,XXYY), three (48,XXXY and 49,XXXYY), or four supernumerary Xs (49,XXXXY). A second cohort consisting of 46 pubertal stage-matched KS subjects was employed for validation. Clinical, hormonal, metabolic and ultrasonographic parameters were collected and analyzed., Results: The increase in the number of extra-Xs was associated with a progressive adverse effect on height, pubertal development, testicular volume and function, adrenal steroidogenesis, and thyroid function. A progressive linear increase in ACTH and a decrease in cortisol/ACTH ratios were found. Weight and body mass index, Sertoli cell function, lipid profile, and glucose tolerance post-oral glucose tolerance test were all worse in the HGA cohort compared to KS. Cardiac evaluation revealed a linear association with reduced left and right end-diastolic diameters and reduced ejection fraction., Conclusion: The increase in the number of extra-Xs is associated with a "dose-dependent" progressive impairment in steroid producing glands, thyroid function, cardiac structure, and performance., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: The aim of this study was to describe how specific mental health-trained social workers can assist in the evaluations and follow-up of patients presenting with mental health concerns in the pediatric emergency department (ED)., Methods: Work was performed at a quaternary children's hospital ED with 95,000 annual ED visits across 2 locations. Patients requiring mental health services identified based on presenting complaint or from universal suicide screen were included. Emergency department team first evaluates the patients for medical screening and then consults a team of social workers specialized in acute mental health screening (AMHS). The team evaluates and provides recommendation for disposition and assists in plan completion. For patients not admitted, AMHS team makes 24- and 48-hour calls to ensure safety. We collected and analyzed the data on all eligible patients from September 2015 through June 2019 for (1) demographic information, (2) trends in number of consults to AMHS, (3) disposition plans and trends by year, and (4) frequency of follow-up phone calls., Results: A total of 5950 patient visits were reviewed, for 4454 distinct patients. Most patients were 12 to 17 years of age, female, and White, with Medicaid being the predominant insurance. The most common chief complaint was suicidal ideation/plan/attempt. Self-referrals were the majority of assessments, and 59% of patients were already receiving mental health services. Median team response time was 19 minutes. There was an upward trend in consults. Psychiatric hospitalization was the most common disposition; more than 95% of the other visits had timely follow-up phone calls., Conclusion: Despite an increasing number of patients presenting to the ED with mental health crisis, safe and efficient management is possible with ED staff-social worker partnership. This approach can ensure that eligible patients receive consistent and evidence-based evaluations and can allow ED clinicians to respond to medical emergencies that require their attention., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The role of osteocalcin (OCN) in pubertal development, male hypogonadism, and the effect of testosterone (Te) replacement therapy (TRT) remains unclear. We aimed to investigate the total OCN (tOCN) concentrations in male patients with Klinefelter syndrome (KS), a model of adult hypergonadotropic hypogonadism., Methods: This retrospective longitudinal study investigated 254 male patients with KS (47,XXY) between 2007 and 2021 at an academic referral center, categorized as (1) prepubertal, (2) pubertal, and (3) adults. All prepubertal patients were Te-naïve. Adult patients were subcategorized as (1) eugonadal, (2) hypogonadal, and (3) receiving TRT. We also analyzed 18 adult patients with available tOCN levels before and 3 months after TRT commencement., Results: The tOCN levels varied throughout the lifespan according to pubertal status, were highest in eugonadal and significantly lower in TRT subjects, correlated with both LH (p = 0.017) and FSH levels (p = 0.004) in adults, and significantly declined after 3 months of TRT (p = 0.006) in the adult KS cohort. HPG-axis hormones levels demonstrated no correlation in prepubertal boys. Adjustment for age and body mass index confirmed previous results and revealed significant inverse correlations with total Te (p = 0.004), calculated free Te (p = 0.016), the Te/LH (p = 0.010), and calculated free Te/LH ratios (p = 0.031)., Conclusion: In KS, a model of male hypergonadotropic hypogonadism, tOCN levels were not associated with gonadal function during normal prepuberty and pubertal development but were associated with worse testicular function and a higher degree of HPG stimulation in adults. TRT acutely reduced tOCN levels in adults., (© 2024. The Author(s).)

European semi-natural dry grasslands are among the most endangered terrestrial ecosystems, being recognised as habitats of community interest by the EU Habitats Directive. The occurrence and preservation of these habitats depend on a combination of anthropogenic and natural factors, although little is known regarding the role of past land-use changes. Here, we investigated the role of time since cultivation abandonment as a major driver of grassland successional dynamics in the Mediterranean agro-pastoral system of Alta Murgia, southern Italy. By integrating cartographic information on the past agricultural land-use with the main abiotic constraints (patch area, slope and aspect), we used generalised additive mixed models to test for the probability of occurrence of current grassland habitat types along time since cultivation abandonment (10 to 200 years). Our results disclosed the successional sequence of grassland plant communities since crop abandonment in the study area, highlighting that the distribution of semi-natural grassland communities largely depends on land use history besides current environmental patterns. Among the habitat types protected under the EU Habitats Directive, we highlighted that xero-thermic communities may represent an intermediate step of grassland succession after cultivation abandonment, while more mesic perennial communities indicate a late successional stage. These successional dynamics are further modulated by mesoclimatic conditions associated with slope and aspect, especially in case of long-standing pastures that were not historically affected by agricultural transformations. Our findings can contribute to a deeper understanding of dynamics relevant to spontaneous vegetation recovery in open environments, which is a prerequisite for setting up effective grassland conservation and restoration actions. Furthermore, our results underline the value of integrating historical maps and current information for the assessment of habitat conservation status., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Klinefelter syndrome is the most common chromosomal disorder in males and the most common cause of hypergonadotropic hypogonadism. We describe the natural history of testicular dysfunction in patients with Klinefelter syndrome through the integration of clinical, hormonal, and quantitative ultrasound data in a life-course perspective., Design: Prospective semilongitudinal study., Methods: We included 155 subjects with 47,XXY karyotype (age range: 7 months-55 years) naïve to testosterone replacement therapy. Subjects were divided according to pubertal stage and age group (transition age and adults). Serial clinical, hormonal, and testicular ultrasound (US) assessments were performed., Results: Testicular development progresses until Tanner stage 4, with subsequent regression, whereas Sertoli and germ cell impairment is not hormonally detected before Tanner stages 3-4, as reflected by normal inhibin B values until stage 4 and the fall in the inhibin B/follicle-stimulating hormone ratio thereafter. The testosterone/luteinizing hormone ratio peaks during Tanner stages 2-3 and declines from Tanner stage 4 onward, preceding the development of overt hypogonadism. US echotexture progressively worsens until transition age, reflecting ongoing gonadal compromise, whereas quantitative US echotexture measures and the presence of both hypoechoic lesions and microlithiasis independently and significantly predict a lower circulating testosterone level., Conclusions: The findings from this large prospective study contribute to our understanding of the natural history of testicular dysfunction in Klinefelter syndrome, underlining the importance of quantitative testicular US in infancy and childhood, as well as during pubertal development and transition age, for the optimal care of Klinefelter syndrome patients., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society.)

We tackle the problem of coupling a spatiotemporal model for simulating the spread and control of an invasive alien species with data coming from image processing and expert knowledge. In this study, we implement a spatially explicit optimal control model based on a reaction-diffusion equation which includes an Holling II type functional response term for modeling the density control rate. The model takes into account the budget constraint related to the control program and searches for the optimal effort allocation for the minimization of the invasive alien species density. Remote sensing and expert knowledge have been assimilated in the model to estimate the initial species distribution and its habitat suitability, empirically extracted by a land cover map of the study area. The approach has been applied to the plant species Ailanthus altissima (Mill.) Swingle within the Alta Murgia National Park. This area is one of the Natura 2000 sites under the study of the ongoing National Biodiversity Future Center (NBFC) funded by the Italian National Recovery and Resilience Plan (NRRP), and pilot site of the finished H2020 project ECOPOTENTIAL, which aimed at the integration of modeling tools and Earth Observations for a sustainable management of protected areas. Both the initial density map and the land cover map have been generated by using very high resolution satellite images and validated by means of ground truth data provided by the EU Life Alta Murgia Project (LIFE12 BIO/IT/000213), a project aimed at the eradication of A. altissima in the Alta Murgia National Park., (© 2023. Springer Nature Limited.)

Functional hypogonadotropic hypogonadism (FHH) is an increasingly frequent condition, whose pathological mechanisms are not yet fully clarified. The concept of FHH has now completely replaced that of late onset hypogonadism, that only concerned the ageing man. FHH is the result of an impairment of the hypothalamic-pituitary gonadal axis (HPG-A) function, resulting in decreased testosterone concentrations associated with low or inappropriately normal gonadotropin levels and infertility; it can be diagnosed once organic causes of hypogonadism are excluded. The growing occurrence of FHH derives from its association with widespread conditions, such as obesity and diabetes mellitus, but also to the increasing ease and frequency of use of several drugs, such as opioids, glucocorticoids, and sex steroids. Moreover, given the tendency of many subjects to excessive physical activity and drastic reduction in caloric intake, FHH may also be secondary to low energy availability. Finally, the association with HIV infection should not be overlooked. Therefore, there is an important variability in the diseases that can lead to FHH. Despite the heterogeneity of the underlying pathologies, the mechanisms leading to FHH would seem quite similar, with the initial event represented by the impairment at the HPG-A level. Nevertheless, many different biological pathways are involved in the pathogenesis of FHH, therefore the aim of the current paper is to provide an overview of the main relevant mechanisms, through a detailed analysis of the literature, focusing specifically on pathogenesis and clinical, diagnostic and therapeutic aspects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Spaziani, Carlomagno, Tarantino, Angelini, Vincenzi and Gianfrilli.)

Recombinant follicle-stimulating hormone (FSH) is commonly used for the treatment of female infertility and is increasingly being used in males as well, as recommended by notable guidelines. FSH is composed of an α subunit, shared with other hormones, and a β subunit, which confers specificity of biological action by interacting with its surface receptor (FSHR), predominantly located in granulosa and Sertoli cells. However, FSHRs also exist in extra-gonadal tissues, indicating potential effects beyond male fertility. Emerging evidence suggests that FSH may have extra-gonadal effects, including on bone metabolism, where it appears to stimulate bone resorption by binding to specific receptors on osteoclasts. Additionally, higher FSH levels have been associated with worse metabolic and cardiovascular outcomes, suggesting a possible impact on the cardiovascular system. FSH has also been implicated in immune response modulation, as FSHRs are expressed on immune cells and may influence inflammatory response. Furthermore, there is growing interest in the role of FSH in prostate cancer progression. This paper aims to provide a comprehensive analysis of the literature on the extra-gonadal effects of FSH in men, with a focus on the often-conflicting results reported in this field. Despite the contradictory findings, the potential for future development in this area is substantial, and further research is needed to elucidate the mechanisms underlying these effects and their clinical implications.

Xylella fastidiosa subsp. pauca (Xfp), has attacked the olive trees in Southern Italy with severe impacts on the olive agro-ecosystem. To reduce both the Xfp cell concentration and the disease symptom, a bio-fertilizer restoration technique has been used. Our study applied multi-resolution satellite data to evaluate the effectiveness of such technique at both field and tree scale. For field scale, a time series of High Resolution (HR) Sentinel-2 images, acquired in the months of July and August from 2015 to 2020, was employed. First, four spectral indices from treated and untreated fields were compared. Then, their trends were correlated to meteo-events. For tree-scale, Very High Resolution (VHR) Pléiades images were selected at the closest dates of the Sentinel-2 data to investigate the response to treatments of each different cultivar. All indices from HR and VHR images were higher in treated fields than in those untreated. The analysis of VHR indices revealed that Oliarola Salentina can respond better to treatments than Leccino and Cellina cultivars. All findings were in agreement with in-field PCR results. Hence, HR data could be used to evaluate plant conditions at field level after treatments, while VHR imagery could be used to optimize treatment doses per cultivar., (© 2023. The Author(s).)

This protocol presents the use of SARS-CoV-2 isolates to infect human kidney organoids, enabling exploration of the impact of SARS-CoV-2 infection in a human multicellular in vitro system. We detail steps to generate kidney organoids from human pluripotent stem cells (hPSCs) and emulate a diabetic milieu via organoids exposure to diabetogenic-like cell culture conditions. We further describe preparation and titration steps of SARS-CoV-2 virus stocks, their subsequent use to infect the kidney organoids, and assessment of the infection via immunofluorescence. For complete details on the use and execution of this protocol, please refer to Garreta et al. (2022). 1 ., Competing Interests: Declaration of interests A patent has been submitted to use human organoids to study SARS-CoV-2 infections and possibly develop new therapies. J.M.P. is a shareholder of Apeiron Biologics, which is developing ACE2 decoys for COVID-19 therapy., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism., Competing Interests: Declaration of interests A patent has been submitted to use human organoids to study SARS-CoV-2 infections and possibly develop new therapies. J.M.P. is a shareholder of Apeiron Biologics, which is developing ACE2 decoys for COVID-19 therapy., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)