The relationship between epicardial adipose tissue (EAT) and atrial fibrillation (AF) has gained interest in recent years. Previous literature on the topic presents great heterogeneity, focusing especially on computed tomog-raphy imaging. Aim of the present study is to determine whether an increased volume of left atrial (LA) EAT evaluated at routine pre-procedural cardiac magnetic resonance imaging (MRI) relates to AF recurrences after catheter ablation. 50 patients undergoing AF cryoballoon ablation and pre-procedural cardiac MRI allowing quantification of LA EAT were enrolled. In one patient segmentation of LA EAT could not be achieved. After a median follow-up of 16.0 months, AF recurrences occurred in 17 patients (34%). Absolute volume of EAT was not different in patients with and without AF recurrences (10.35 ml vs. 10.29 ml; p-value=0.963), whereas volume of EAT indexed on the LA (EATi) was lower, albeit non statistically significant, in patients free from arrhythmias (12.77% vs. 14.06%; p-value=0.467). Receiver operating characteristic curve testing the ability of EATi to predict AF recurrence after catheter ablation showed sub-optimal performance (AUC: 0.588). The finest identified cut-off of EATi was 10.65%, achieving a sensitivity of 0.5, a specificity of 0.82, a positive predictive value of 0.59 and a negative predictive value of 0.76. Patients with values of EATi lower than 10.65% showed greater survival free from arrhythmias than patients with values above this cut-off (84% vs. 48%; p-value=0.04). In conclusion, indexed LA EAT volume evaluated at cardiac MRI independently relates to arrhythmia recurrence after AF cryoballoon ablation.

Background: In 2014 the World Health Organization (WHO) warned of an emerging world-wide crisis of antibiotic resistant microorganisms. In response, government and professional organizations recommended that health care systems adopt antimicrobial stewardship programs (ASPs). In the United States, the Centers for Medicare Services (CMS) mandated antimicrobial stewardship in the hospital inpatient setting. Effective January 1, 2020, the Joint Commission required ambulatory centers that prescribe antibiotics, such as wound centers, to institute an ASP. Chronic wounds often remain open for months, during which time patients may receive multiple courses of antibiotics and numerous antimicrobial topical treatments. The wound clinician plays an integral role in reducing antimicrobial resistance in the outpatient setting: antibiotics prescribed for skin and soft tissue infections are among the most common in an outpatient setting. One of the most challenging aspects of antimicrobial stewardship in treating chronic wounds is the inaccuracy of bacterial and infection diagnosis. Methods: Joint Commission lists five elements of performance (EP): (1) Identifying an antimicrobial stewardship leader, (2) establishing an annual antimicrobial stewardship goal, (3) implementing evidence-based practice guidelines related to the antimicrobial stewardship goal, (4) providing clinical staff with educational resources related to the antimicrobial stewardship goal, and (5) collecting, analyzing, and reporting data related to the antimicrobial stewardship goal. This article focuses on choosing and implementing an evidence-based ASP goal for 2020. Discussion: Clinical trials have demonstrated the ability of fluorescence imaging (MLiX) to detect clinically significant levels of bacteria in chronic wounds. Combined with clinical examination of signs and symptoms of infection, the MLiX procedure improves the clinician’s ability to diagnose infection and can guide antimicrobial use. In order to satisfy the elements of performance, the MLiX procedure was incorporated into the annual ASP goal for several wound care centers. Clinicians were educated on the fluorescence imaging device and guidelines were instituted. Collection of antimicrobial utilization data is underway.

Fatty Acid Amide Hydrolase (FAAH) is one of the enzymes responsible of endocannabinoids metabolism. The inhibition of FAAH is a useful and indirect strategy to raise endogenous cannabinoid concentrations, which would be useful for the treatment of various pathological processes in which cannabinoid concentrations are lowered. In the present work, we present an extensive 3D-QSAR/CoMSIA study on a series of 90 irreversible inhibitors of FAAH of pyrimidinyl-piperazine-carboxamide structure. The final model obtained was extensively validated (q2 = 0.734; r2test = 0.966; r2m = 0.723), and based on the information derived from the contour maps we reported a series of 10 new compounds designed as powerful FAAH inhibitors (pIC50 of the best-proposed compounds = 12.196; 12.416).

Deck inclination and vertical displacements are among the most important technical parameters to evaluate the health status of a bridge and to verify its bearing capacity. Several methods, both conventional and innovative, are used for structural rotations and displacement monitoring; no one of these does allow, at the same time, precision, automation, static and dynamic monitoring without using high cost instrumentation. The proposed system uses a common laser pointer and image processing. The elastic line inclination is measured by analyzing the single frames of a HD video of the laser beam imprint projected on a flat target. For the image processing, a code was developed in Matlab® that provides instantaneous rotation and displacement of a bridge, charged by a mobile load. An important feature is the synchronization of the load positioning, obtained by a GNSS receiver or by a video. After the calibration procedures, a test was carried out during the movements of a heavy truck maneuvering on a bridge. Data acquisition synchronization allowed to relate the position of the truck on the deck to inclination and displacements. The inclination of elastic line was obtained with a precision of 0.01 mrad. The results demonstrate the suitability of the method for dynamic load tests, control and monitoring of bridges.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is a rare and aggressive hematologic cancer originating from the malignant transformation of plasmacytoid dendritic cell precursors. This malignancy progresses rapidly, with frequent relapses and a poor overall survival rate, underscoring the urgent need for effective treatments. However, diagnosing and treating BPDCN have historically been challenging due to its rarity and the lack of standardized approaches. Recognizing BPDCN as a distinct disease entity is recent, and standardized treatment protocols are yet to be established. Traditionally, conventional chemotherapy and stem cell transplantation have been the primary methods for treating BPDCN patients. Advances in immunophenotyping and molecular profiling have identified potential therapeutic targets, leading to a shift towards CD123-targeted immunotherapies in both clinical and research settings. Ongoing developments with SL-401, IMGN632, CD123 Chimeric Antigen Receptors (CAR) T-cells, and Bispecific Antibodies (BsAb) show promising advancements. However, the therapeutic effectiveness of CD123-targeting treatments needs improvement through innovative approaches and combining treatments with other anti-leukemic drugs. Exploring combinations, such as CD123-targeted immunotherapies with azacitidine and venetoclax, is suggested to enhance antineoplastic responses and improve survival rates in BPDCN patients. In conclusion, this multifaceted approach offers hope for more effective and tailored therapeutic interventions against this challenging hematologic malignancy

Carbonate rocks occupy about 6490 km2 in Albania (23% of the country) and the total exploitable karst water resources are estimated in 2.84*109 m3/year (about 65% of the total exploitable groundwater resources in the country, and about 70% of those used for water supply). In addition, karst massifs are very rich in thermal waters, related to the ascending fluids which are essential for the development of hypogenic karstification in the outer Albanides. This type of karst facilitates the circulation regime of deep fluids, which are revealed at the surface through both numerous phenomena of hypogene karst and hot springs. The relatively small Kruja Tectonic Zone is characterized by the presence of SE-NW oriented carbonate structures, rich in thermal sources, and contains more than the 80% of Albania thermal springs. One of its most interesting carbonate structures, for the presence of both cold and thermal waters, is the small karst structure of Makaresh, with a surface of 22 km2. The purpose of this article is to describe the characteristics and factors that affect the quantitative and qualitative formation of cold and thermal groundwater in this massif. Based on the physico-chemical characteristics, groundwaters of the study area are classified in cold and thermal waters. The former are mainly of HCO3-Ca or HCO3-Ca-Mg type (Electrical Conductivity 580-650 μS/cm, Temperature 13.9-16.6° C). Thermal waters are mainly of the Cl-Na-Ca type (EC 7200-7800 μS/cm, T 18.5-22.5° C); further, they are characterized by high hydrogen sulphide concentration, up to about 350 mg/l. The presence of two groundwater types in the Makaresh massif is connected to the presence of two groundwater circulation systems. The main factors of the groundwater physic-chemical quality are the solution of rocks and minerals therein contained, the presence of hypogenic speleogenesis, and the mixing of the groundwater of the two systems. The hydrogeological studies proved that karst rocks contain considerable fresh water resources; the capacity of water wells used for the drinking water supply reaches up to about 50 l/s. Thermal waters are not currently exploited due to their temperature, but they are potentially suitable for thermal uses, by drilling boreholes at depth of about 1000 m.

The goal of the study was to assess the farmers’ acceptance of three sustainable production strategies, namely ‘Agro-forestry’, ‘Alternative protein source’ and ‘Prolonged maternal feeding’. Data on the acceptance of these strategies were collected by a survey of dairy farmers in six EU countries (AT, BE, DK, FI, IT, UK). An extended version of the Technology Acceptance Model (TAM) was applied by means of Structural Equation Modelling to testing various hypotheses on attitudes and intentions of dairy farmers towards these novel production strategies, as well as the influence of organic practices and collaborative behaviours along the supply chain. We found that the most preferred strategy - across all countries - was soy substitution by alternative protein sources. We also found that the intention to adopt a sustainable production strategy may derive from the influence of opinions (and behaviours) of relevant others, showing the role of interactions among farmers and other stakeholders in the adoption of innovations. Finally, the perceived usefulness of all investigated strategies is higher for organic farmers, while collaborative patterns reduce the impact of subjective norm on usefulness and overall acceptance. Our findings should encourage policy makers to consider the important role of supply chain management practices, including collaboration, to enhance the sustainability of dairy farming systems.

In the present work we have studied the short-term edaphic recovery of a burned pine forest of Pinus pinaster Aiton in Cerro del Castillo (Sierra de Guadarrama, Central Spain) in which a hydrological-forestry restoration was being carried out after the fire occurred in July 2022. For this purpose, variations in physicochemical properties (conductivity, relative humidity, organic matter and pH) and collembolan communities were analyzed by comparing the soils of a natural pine forest and a burned pine forest during the 24 weeks after the fire in 3 different samplings. With the data obtained, a series of diversity indices were calculated and statistical analyses such as ANOVA, hierarchical classification and principal component analysis were developed, with the aim of understanding in greater depth the recovery of collembolan populations, the changes in these physicochemical variables and the relationships between both parameters. This study shows how the fire reduced the amount of organic matter and water, and increased soil pH and conductivity, affecting edaphic fauna populations. In the short term, there was an increase in relative humidity and a decrease in electrical conductivity. The edaphic fauna communities of the burned pine forest increased their diversity and equity without reaching the values of the natural pine forest. At the specific level, however, the springtail populations matched the richness and even reached a very slightly higher Shanon-Wiener diversity index than that the natural pine forest populations in just 24 weeks. Finally, it was observed that the samples from the burned pine forest with recovered collembolan populations had the closest physicochemical parameters to those of the natural pine forest.

Acute myeloid leukemia (AML) is the second common hematologic malignancy in children. The incidence of childhood AML is much lower than acute lymphoblastic leukemia (ALL), which makes the childhood AML a rare disease in children. The role of genetic abnormalities in AML classification, management and prognosis prediction is much more important than before. The WHO classification of myeloid neoplasms and the European LeukemiaNet (ELN) classification were both revised in 2022. The application of the new information in childhood AML will be upcoming in the next few years. The frequency of each genetic abnormality in adult and childhood AML is different, therefore, in this review we emphasize in well-known genetic subtypes in childhood AML, including Core-binding factor AML (CBF AML), KMT2Ar (KMT2A/11q23 rearrangement) AML, normal karyotypes AML with somatic mutations, unbalanced cytogenetic abnormalities AML, NUP98 11p15/NUP09 rearrangement AML and acute promyelocytic leukemia (APL). Current risk group classification, management algorithm in childhood AML and novel treatment modalities, such as targeted therapy, immune therapy, chimeric antigen receptor (CAR) T-cell therapy are reviewed. Finally, the indications of hematopoietic stem cell transplantation (HSCT) in AML are discussed.

Live streaming conferences increase the participation of a diverse audience, help defray travel costs and overcome problems related to travel restrictions. In this article, we lay out tips for implementing live-streaming in scientific meetings. We also cover legal, ethical, and technical aspects implicated with live-streaming scientific talks. To write this article, we leveraged knowledge from our experience in organizing the symposium “Deciphering the Denisovans,” presented at the 88th Annual Meeting of the American Association of Physical Anthropology (AAPA) in Cleveland, OH, in 2019, as well as literature on the topic.

Lung cancer is the leading cause of cancer death worldwide, with non-small cell lung cancer (NSCLC) making up 80% of cases. Some genetic factors leading to NSCLC development include genetic mutations and PD-L1 expression. PD-L1 proteins are targeted in an NSCLC treatment called targeted gene therapy. However, this treatment is effective in a low percentage of patients. This study aimed to create machine learning models to use features like the number of mutations and the level of PD-L1 proteins in cancer cells, along with others, to predict whether a patient will receive clinical benefit from gene therapy treatment. This was done by downloading and merging datasets from cbioportal.org to create a sample size for the model. Features with high correlations to clinical benefit were identified. Three machine-learning models were created using these features to predict clinical benefits in patients, and each model’s accuracy was evaluated. All three models were accurate between 55-85%, with two of the models averaging an accuracy around 75%. Doctors can use these models to more accurately predict whether gene therapy treatment is likely to work in a patient before prescribing it to them.

Individuals with low health literacy (HL) are known to have poorer health outcomes and to have higher mortality rates compared to individuals with higher HL: hence, the improvement of HL is a key outcome in modern healthcare systems. Healthcare providers are therefore asked to support patients’ literacy skills by encouraging the implementation of autonomy-supportive patient centered communication (PCC), which in turn requires the enhancement of patient engagement. Our main hypothesis is that the well-known relationship between autonomy-supportive PCC and HL is mediated by patient engagement which is known to play a role in HL promotion and that is related to PCC as well. The purpose of this study was to formulate a hypothetical structural equation model (SEM) linking PCC to patient engagement and HL. A cross-sectional survey design was employed involving 1007 Italian chronic patients. The hypothetical model was tested using SEM to verify the hypothesized mediation of patient engagement between PCC and HL. Results show that the theoretical model has a good fit indexes and that patient engagement fully mediates the relationship between PCC and HL. This finding suggests healthcare systems to implement a new paradigm where patients are supported to play an autonomous role in their own healthcare.

Air pollution is a critical issue impacting urban environments, leading to severe health problems and environmental degradation. This comprehensive review examines the potential of green systems—specifically green walls, active green walls, and urban greenery systems—to mitigate atmospheric pollutants such as particulate matter (PM), volatile organic compounds (VOCs), and carbon dioxide (CO2). By systematically analyzing 44 recent studies, the review highlights the pollutant capture efficiency of various green technologies and plant species in both indoor and outdoor settings. Active green walls, particularly those utilizing plant species such as Chlorophytum comosum and Sansevieria trifasciata, were found to be highly effective, with VOC reduction efficiencies up to 96.34%, PM reductions by 65.42%, and CO2 reduction rates reaching 4.8% under optimal conditions. The review identifies key strengths in current research, including diverse experimental setups and the use of sophisticated measurement techniques, but also notes significant limitations such as variability in experimental conditions and a lack of long-term performance data. The study underscores the importance of proper maintenance to sustain green systems' efficacy and highlights the potential issue of pollutant resuspension, which remains under-researched. Practical implications for urban planning are discussed, advocating for the integration of effective green systems into urban infrastructure to enhance air quality and public health. Recommendations for future research include the need for standardized metrics, long-term studies, economic feasibility analyses, and real-world validation of simulation models to better understand and optimize green systems for urban air pollution mitigation.

The R23Cu7Mg4 (R = Ca, Eu) intermetallics, studied by single crystal X-ray diffraction, were found to be isostructural with the Yb23Cu7Mg4 prototype (hP68, k4h2fca, space group P63/mmc), forming a small group inside the bigger 23:7:4 family, otherwise adopting the hP68-Pr23Ir7Mg4 crystal structure. The observed structural peculiarity is connected with the divalent character of the R component and with a noticeable volume contraction, resulting in a clear clustering of title compounds inside the whole 23:7:4 family. The occurrence of fragments typical of similar compounds, particularly Cu-centered trigonal prisms and Mg-centered core-shell polyicosahedral clusters with R at vertices, induced the search of significant structural relationships. In this work, a description of the hexagonal crystal structure of the studied compounds is proposed as a linear intergrowth along the c-direction of the two types of slabs R10CuMg3 (parent type: hP28-kh2ca, SG 194) and R13Cu6Mg (parent type: hR60-b6a2, SG 160). The ratio of these slabs in the studied structure is 2:2 per unit cell, corresponding to the simple equation 2XR10CuMg3 + 2XR13Cu6Mg = 2XR23Cu7Mg4. This description assimilates the studied compounds to the (Ca,Eu,Yb)4CuMg ones, where the same slabs (of p3m1 layer symmetry) are stacked in a different way/ratio, and constitutes a further step towards a structural generalization of R-rich ternary intermetallics.

The recent legalization of Cannabis sativa L. in many regions has revealed a need for effective propagation and biotechnologies for the species. Micropropagation affords researchers and producers methods to rapidly propagate insect/disease/virus free clonal plants, store germplasm, and forms the basis for other biotechnologies. Despite this need, research in the area is limited due to the long history or prohibitions and restrictions. Existing literature has multiple limitation: many publications use hemp as a proxy for drug-type Cannabis when it is well established that there is significant genotype specificity, studies using drug-type cultivars are predominantly op-timized using a single cultivar, most protocols have not been replicated by independent groups, and some attempts demonstrate a lack of reproducibility across genotypes. Due to culture decline and other problems the multiplication phase of micropropagation (stage 2) has not been fully developed in many reports. This review will provide a brief background on the history and botany of Cannabis as well as a comprehensive and critical summary of Cannabis tissue culture. Special attention will be paid to current challenges faced by researchers, the limitations of existing Cannabis micropropagation studies, and recent developments and future directions of Cannabis tissue culture technologies.

Dendritic cell (DC) cancer vaccines are a promising therapeutic approach, leveraging the immune system to fight tumors. These vaccines utilize DCs' ability to present tumor-associated antigens to T cells, triggering a robust immune response. DC vaccine development has progressed through three generations. The first generation involved priming DCs with tumor-associated antigens or messenger RNA outside the body, showing limited clinical success. The second generation improved efficacy by using cytokine mixtures and specialized DC subsets to enhance immunogenicity. The third generation uses blood-derived DCs to elicit a stronger immune response. Clinical trials indicate that cancer vaccines have lower toxicity than traditional cytotoxic treatments. However, achieving significant clinical responses with DC immunotherapy remains challenging. Combining DC vaccines with immune checkpoint inhibitors (ICIs) such as anti-cytotoxic T-lymphocyte Antigen 4 and anti-programmed Death-1 antibodies has shown promise by enhancing T cell responses and improving clinical outcomes. These combinations can transform non-inflamed tumors into inflamed ones, boosting ICIs' efficacy. Current research is exploring new checkpoint targets like LAG-3, TIM-3, and TIGIT, considering their potential with DC vaccines. Additionally, engineering T cells with chimeric antigen receptors or T cell receptors could further augment the anti-tumor response. This comprehensive strategy aims to enhance cancer immunotherapy, focusing on increased efficacy and improved patient survival rates.

Microbiome research has gained considerable interest due to the emerging evidence of its impact on human and animal health. Similar to higher organisms, the gut-associated microbiota of mosquitoes affect host fitness and other phenotypes. It is now well established that microbes can alter pathogen transmission in mosquitoes, either positively or negatively, and avenues are being explored to exploit microbes for vector control. However, less attention has been paid to how microbiota affect phenotypes that impact vectorial capacity. Several mosquito and pathogen components, such as vector density, biting rate, survival, vector competence and pathogen extrinsic incubation period all influence pathogen transmission. Interestingly, the mosquito gut-associated microbes can impact each of these components, and therefore ultimately modulate vectorial capacity. Promisingly, this expands the options available to exploit microbes for vector control by also targeting parameters that affect vectorial capacity. However, there are still many knowledge gaps in the biology of the mosquito – microbe symbiosis that need to be addressed in order to understand these interactions more thoroughly and exploit them efficiently. Here, we review current evidence of the impacts of the microbiome on aspects of vectorial capacity highlighting opportunities for novel vector control strategies and areas where further studies are required.

In the context of sustainable development, integrating the work aspect into health promotion systems is essential, ensuring that employees maintain a healthy balance between their professional and personal lives, which respects and amplifies the potential of every individual. Lately, there has been a noticeable shift of medical professionals from the public to the private sector. This trend paints a bleak picture, highlighting the vulnerabilities of a system teetering on the brink of failure, with significant impacts on patient care. Among the myriad reasons behind this shift, burnout stands out prominently. Medical professionals face increasing pressures due to understaffing, limited organizational support, and insufficient resources, leading to feelings of cynicism, exhaustion, and detachment from their roles. Utilizing the Maslach et al. questionnaire, we assessed the risk of burnout among physicians in public hospitals to identify and underscore preventive measures and improvements, correlating our findings with key aspects of organizational empowerment. Our research indicates that enhancing interpersonal relationships and resources—both within teams and between the organization and its physicians—is crucial for the revival of the healthcare system. This approach aims at improving the delivery of healthcare services and offering appropriate recognition to healthcare professionals, aligning with the principles of sustainable employment.

In this systematic review, the PRISMA method was applied to examine publications from the last two decades that have investigated the noxious gaseous emissions from dairy barns. The aim was to analyse the outcomes from literature studies estimating the quantities of polluting gases produced in dairy barns, with specific focus on ammonia (NH₃) emissions. The review also explores proposed methods to reduce the associated effects through mitigation strategies. Estimation of NH₃ emissions is significantly influenced by the complex interactions among several factors, including animal management practices, such as controlling animal behavioral activities; manure management, like utilising practices for floor manure removal; the type of structure housing the animals, whether it is naturally or mechanically ventilated; and environmental conditions, such as the effects of temperature, wind speed, relative humidity, and ventilation rate on NH₃ release in the barn. These influential components have been considered by researchers, identifying targeted mitigation strategies. Despite growing attention to the issue, gaps in the scientific literature were identified and discussed, particularly regarding the analysis of mitigation strategies and their long-term impacts (i.e., environmental, economic and productivity-wise).

We confidently approach current issues in Green Finance (GF) from the perspective of an international organization, where the first author has previous experience as a support assistant. In fact, the economy of the EU (European Union) is deeply involved in the changing needs related to the dramatic consequences of climate change and environmental degradation, which has placed the needs of a more sustainable economy at the top of the international agenda. The environmental, social and governance (ESG) aspects are marginally addressed to arouse a major interest in questions raised by green financial products which require long-term profit expectations, and which above all contain a margin of risk that is difficult to calculate in the landscape of traditional financial instruments. Through a careful approach akin to artificial intelligence research methods, we attempt to “materialize” at least the most visible clues of this fashionable economic shift through what we call SMC (sustainable material culture) objects. The presented SMC objects serve as tangible representations of sustainable practices and can promote awareness and action incorporating into everyday life and business practices a powerful reminder and catalyst for a shift towards more sustainable investment and consumption patterns.

A great improvement in food safety and quality controls worldwide has been achieved through the development of biosensing platforms. Foodborne pathogens continue to cause serious outbreaks due to the ingestion of contaminated food. The development of new, sensitive, portable, high-throughput, and automated platforms is a primary objective to allow detection of pathogens and their toxins in foods. Listeria monocytogenes is one common foodborne pathogen. Major outbreaks of listeriosis have been caused by a variety of foods, including milk, soft cheeses, meat, fermented sausages, poultry, seafood and vegetable products. Due to its high sensitivity and easy setup, electrochemical impedance spectroscopy (EIS) has been extensively applied for biosensor fabrication and in particular in the field of microbiology as a mean to detect and quantify foodborne bacteria. Here we describe a miniaturized, portable EIS platform consisting of a microfluidic device with EIS sensors for the detection of L. monocytogenes in milk samples, connected to a portable impedance analyzer for on-field application in clinical and food diagnostics but also for biosecurity purposes. To achieve this goal microelectrodes were functionalized with antibodies specific for L. monocytogenes. The binding and detection of L. monocytogenes was achieved in the range 2.2 x 103 cfu/ml to 1 x 102 with a Limit of Detection (LoD) of 5.5 cfu/ml.

Lumpy skin disease (LSD) vaccination and epidemiological distribution remain unknown in some parts of Ethiopia including the Sidama regional state. With this, an assessment of LSD vaccine-related problems and serological study was performed in selected districts of Sidama regional state representing three agroecological zones from September 2021 to June 2022. A cross-sectional study of qualitative and quantitative studies was used. The result showed a few portion of respondents know about LSD (29.2%), and vaccinate their cattle (23.3%). 20.8% of the respondents stated LSD occurrence in their vaccinated cattle while focus group discussion with the professionals stated the possible reasons related to electric power disruption that impacted LSD vaccine cold-chain. The other study was on sero-epedimiology of LSD which showed an overall animal and herd level sero-prevalence of 40.8% and 81%, respectively. Higher and lower sero-prevalence was observed in lowland (48%) and highland (28%) areas, respectively. Furthermore, risk factor analysis showed the existence of a significant association between management systems, breed, and body condition score (BCS) of cattle. In conclusion, both qualitative and quantitative study results showed the need for intervention in terms of community-based awareness creation about LSD clinical signs, vaccination advantages, and options for electric power supply together with the frequently updated information on LSD prevalence.

This literature review was aimed to identifying the opportunistic bacterial pathogens that can be transmitted by contaminated food and represent a current threat for patients particularly suscep-tible to infections because of underlying conditions or predisposing factors. The analysis was focused on recent case or outbreak reports, and systematic reviews published in years 2019 - 2023 and resulted in sorting 24 bacterial groups comprising genera or species able to cause a variety of systemic or invasive infections if ingested with food or drinking water. These included both bacteria known to cause mild infections in immunocompetent persons and bacteria considered innocuous that are used in food fermentation or as probiotics. No recent cases from dietary routes were reported for bacteria of critical importance as nosocomial pathogens and widely occurring in food products, primarily, Acinetobacter baumanii and Klebsiella pneumoniae. However, the very first sources of their introduction in the clinical environment still need to be estab-lished. In many instances, risky dietary habits such as eating raw fish, seafood, raw meat, unpasteurized milk and derived products or the lack of control on fermentation processes led to the reported illnesses, pointing out to the necessity to improve the hygiene of production and consumer’s awareness of risks.

The Italian Peninsula, a natural pier across the Mediterranean Sea, witnessed intricate population events since the very beginning of human occupation in Europe. In the last few years, an increasing number of modern and ancient genomes from the area has been published by the international research community. This genomic perspective started unveiling the relevance of Italy to understand the post-Last Glacial Maximum (LGM) re-peopling of Europe, the earlier phase of the Neolithic westward migrations, and its linking role between Eastern and Western Mediterranean areas after the Iron Age. However many open questions are still waiting for more data to be addressed in full. With this review, we summarize the current knowledge emerging from the available ancient Italian individuals and, by re-analysing them all at once, we try to shed light on the avenues future research in the area should cover. In particular, open questions concern i) the fate of pre-Villabruna Europeans and to what extent their genomic components were absorbed by the post-LGM hunter-gatherers; ii) the role of Sicily and Sardinia before LGM; iii) to what degree the documented genetic structure within the Early Neolithic settlers can be described as two separate migrations; iv) what are the population events behind the marked presence of an Iranian Neolithic-like component in Bronze Age and Iron Age Italian and Southern European samples.

The implementation of sentinel lymph node (SLN) biopsy is changing the scenario in the surgical treatment of early-stage cervical cancer and the oncologic safety of replacing bilateral pelvic lymphadenectomy with SLN biopsy is currently under investigation. One of the undisputed values of SLN biopsy is its diagnostic accuracy in detecting low-volume metastases (LVM) via pathologic ultrastaging. In early-stage cervical cancer, the reported incidence of LVM ranges from 4 to 20%. The prognostic impact and the role of adjuvant treatment in patients with LVM is still unclear. Some non-prespecified analyses in prospective studies showed no impact on the oncologic outcomes compared to node-negative disease. However, the heterogeneity of the studies, the differences in the disease stage and the use of adjuvant treatment, and the concomitant pelvic lymphadenectomy (PLND) make any conclusion on this topic hard. Current guidelines suggest considering micrometastasis (MIC) as a node-positive disease, while isolated tumor cells (ITC) as a node-negative disease, with a low level of evidence. This review aims to highlight the unanswered questions about the definition, identification, prognostic and therapeutic role of LVM and underline the present and future challenges we are facing. We hope this review will guide further research, giving robust evidence on LVM and their impact on clinical practice.

This review summarizes the most recent developments of research on protozoan parasite infections ac-quired through food and drinking water and is aimed at gathering updated knowledge on the risk factors, illnesses caused, and measures for prevention. Reports included dated from 2019 to the present and regarded recent outbreaks and cases of severe infec-tions, prevalence in different population segments and food handlers, and occurrence in food and drinking water. Cryptosporidium spp., Entamoeba histolytica, Giardia intestinalis, Trypanosoma cruzi and Toxoplasma gondii were the microorganisms most frequently involved in large outbreaks and/or severe infections, while Cyclospora cayetanensis was most frequently involved in single case reports. Cystoisospora belli was implied in severe infections in immunocompromised patients, while Blastocystis homi-nis, Sarcocystis spp., Dientamoeba fragilis, Endolimax nana and Pentatrichomonas hominis appeared to be less relevant for number of symptomatic infections and pathogenic potential. A progressive improvement in surveillance of protozoan infections and infection sources was highlighted, especially in developed countries. The apparent increase in cases was concomitant with the implementa-tion of reporting systems and the application of molecular diagnostic methods that represent valuable in-struments for establishing epidemiological links and preventing or limiting outbreaks. The pathogenic role and sources of infection should be better elucidated for some species.

(1) Background: Immunosuppressed patients, especially those receiving B-cells depleting therapies (BCDT), are at major risk to develop reduced vaccine seroconversion and contract severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection. The aim of our study is to assess safety and efficacy of the pre-exposure prophylactic combination of Tixagevimab and Cilgavimab (TGM-CGM) in a cohort of rheumatic patients diagnosed with Autoimmune Rheumatic Diseases; (2) Methods: We performed a prospective study using the clinical medical charts of 25 patients treated with Rituximab and received a single injection of TGM/CGM. The cohort was followed for 6 months from the injection and compared to a control group of 25 immunosuppressed patients who did not receive TGM-CGM. We assessed the incidence and the severity of Covid-19 in both groups, as well as early and late adverse events; (3) Results: Despite the small sample, we noticed a downward trend in the incidence and severity of symptomatic infection in the group treated with TGM/CGM. In the experimental cohort, one patient was completely asymptomatic, four patients were oligosymptomatic infection, and just one had mild-moderate infection versus 4 oligosymptomatic and 5 mild-moderate infection in the control group. We observed also a reduction in time to nasopharyngeal swab negativization. No adverse events were reported in our data. We collected the dosage of anti-Receptor-Binding Domain (RBD) SARS-CoV2 spike protein for 21 patients, revealing adequate seroconversion in 12 patients out of 21; (4) Conclusions: Even though the study was conducted during the Omicron wave, notably known to be less responsive to monoclonal antibodies, we proved that TGM-CGM could be a risk-free additional tool to prevent SARS-Cov2 infection in rheumatic immunosuppressed patients.

Screening and early diagnosis of diseases are crucial for a patient's treatment to be successful and to improve their survival rate, especially in cancer. The development of non-invasive analytical methods able to detect biomarkers of pathologies is a critical point to define a successful treat-ment and a good outcome. This study extensively reviews electrochemical methods used for the development of biosensors in liquid biopsy, owing to their ability to provide rapid response, pre-cise detection, and low detection limits. We also discuss new developments in electrochemical biosensors, which can improve the specificity and sensitivity of standard analytical procedures. Electrochemical biosensors demonstrate remarkable sensitivity in detecting minute quantities of analytes, encompassing proteins, nucleic acids, and circulating tumor cells, even within challeng-ing matrices such as urine, serum, blood, and various other body fluids. Among the various de-tection techniques used for the detection of cancer biomarkers, even in the picogram range, volt-ammetric sensors are deeply discussed in this review because of their advantages and technical characteristics. This widespread utilization stems from their ability to facilitate quantitative de-tection of ions and molecules with exceptional precision. The comparison of each electrochemical technique is discussed to provide the selection of appropriate analytical methods.

With an increasing aging population worldwide, the concept of multimorbidity has attracted growing interest over recent years, especially in frailty, which leads to progressive multisystem decline and increased adverse clinical outcomes. The relative contribution of multiple disorders to overall frailty index in older populations has not been established so far. This study aimed to assess the association between the Vulnerable Elders Survey-13 (VES-13) score, which is acknowledged to be one of the most widely used measures of frailty, and the most common ac-companying diseases among hospitalized adults aged 60 years old and more. 2860 participants with an average age of 83 years were included in this study. Multiple logistic regression with adjustment for age and nutritional status was used to assess the independent impact of every particular disease on vulnerability. Diabetes mellitus type 2, coronary artery disease, atrial fibrillation, heart failure, chronic kidney disease, osteoarthritis, fractures, eyes disorders, depression, dementia, pres-sure ulcers, and urinary incontinence were associated with higher scores of VES-13. Hospital admission of older subjects with those conditions should primarily draw attention to the risk of functional decline and while qualifying older patients for further treatment, particularly in surgery and oncology. At the same time, lipid disorders, gastrointestinal diseases, higher body mass index and albumins level were related to lower risk of being vulnerable, what may be attributed to younger age and better nu-tritional status of those patients.

The early detection of cutaneous melanoma, a potentially lethal cancer with rising incidence, is key to increase survival and therapeutic adjustment. Especially in stages II-IV biomarkers are urgently needed for adjuvant therapy purposes after resection and for treatment of metastatic patients. We here investigated if fatty acid (FA) and protein composition of small extracellular vesicles (sEV) deriving from plasma of 0-I, II, and III-IV stage melanoma patients (n=38) could reflect disease stage and thus function as biomarker. The subpopulation of sEV expressing CD81 (CD81sEV) was isolated by an ad hoc immune affinity technique from microvesicle-depleted plasma. Biological macromolecules were investigated by gas chromatography and mass spectrometry in CD81sEV. A higher content of FA and a decrease in Saturation Index (C18:0/C18:1), already detectable in early stages, distinguished patients’ from healthy donor CD81sEV. Proteomics (identifier PXD024434) detected an exclusive and significant increase of CD14, PON1, PON3 and APOA5 in stage II and a significant decrease of Rap1b in stage III-IV CD81sEV. The FA and proteomic stage dependent CD81sEV signature strengthens the potential of circulating sEV studies in providing discriminatory information for early diagnosis, prediction of metastatic behavior and follow up of melanoma patients.

Whey is the main by-product of the dairy industry and contains sugars (lactose) and proteins (especially serum proteins and, at lesser extent, residual caseins), which can be valorized by the fermentative action of yeasts. In the present study, we characterized the spoilage yeast fraction inhabiting natural whey starter (NWS), the undefined starter culture of thermophilic lactic acid bacteria used in Parmigiano Reggiano (PR) cheesemaking, and evaluated thermotolerance, mating type, and the aptitude to produce ethanol and bioactive peptides from whey lactose and proteins, respectively, in a selected pool of strains. We found that PR NWS yeast population consists of other species (Saccharomyces cerevisiae, Wickerhamiella pararugosa, and Torulaspora delbrueckii) in addition to the well-documented Kluyveromyces marxianus, with multiple biotypes scored within each species. Haploid and diploid K. marxianus strains were identified through MAT genotyping, while thermotolerance assay allowed the selection of strains suitable to grow up to 48 °C. In whey fermentation assay, one thermotolerant strain was suitable to release ethanol with yield of 86.5%, while another candidate was able to produce the highest amounts of both ethanol and bioactive peptides with potentially anti-hypertensive function. The present work demonstrated that PR NWS is a reservoir of ethanol and bioactive peptides producer yeasts, which can be exploited to valorize whey, in agreement with the principles of circularity and sustainability.

Objective: to retrospectively evaluate the incidence rate (IR) of echocardiographic signs suspected for pulmonary hypertension (PH) in Systemic sclerosis (SSc) patients after the introduction of a combination therapy with bosentan and sildenafil for treatment or prevention of digital ulcers. Methods: patients attending the Scleroderma Unit of the Universital Hospital of Careggi from July 2010 to July 2023 were enrolled. Patients older than 18 years old, with an history of digital ulcers, treated with bosentan and sildenafil in combination for at least 12 months were included. Patients with a diagnosis of PH preceding the introduction of the therapy were excluded. Demographical data, disease duration, laboratoristic and instrumental data (pulmonary function tests, echocardiographic estimation of pulmonary artery pressure (PAPs) and ultrasonographic value of renal resistive index) were collected. The IR of echocardiographic signs suspected for pulmonary hypertension and their 95% confidence interval were calculated in events/1000 patients-years.Results: forty-seven patients were enrolled; mean disease duration was 12,14 years (SD 5,87). Mean duration of the combination treatment was 78.33 (SD 41.37) months and total at-risk time was 3525 months. Two patients (4,2%) presented echocardiographic signs of PH (sPAP 50 mmHg and 40 mmHg); the IR was calculated to be 6.8/1000 patients-years (95% CI 6,02-7,7). In one of the 2 patients RHC excluded PAH, while the other patient refused to undergo to RHC and PAH could not be confirmed/excluded. A stability of PFTs and echocardiografic PAPs was observed during the observation time. Conclusions: the results of this retrospective study suggest that combination therapy with endothelin receptor antagonist and Phosphodiesterase-5 (PDE5) inhibitors could help in preventing PAH in SSc; prospective case-control studies on larger population are needed to improve knowledge in this field.

Background: Increased DNA damage and the propension to cancer development, depend on the modulation of the mechanisms to control and maintain genomic integrity. Poly(ADP-Ribose)Polymerase activation and automodification are early responses to genotoxic stress. Upon binding to DNA strand breaks, the enzyme, a molecular DNA nick sensor, is hyperactivated: this is the first step in a series of events leading to either DNA repair or apoptosis. Enzyme hyperactivation and automodification can be easily measured and are widely used to look at DNA damage extent in the cell. We investigated whether these two markers (increased catalytic activity and auto modification), could help to monitor DNA damage in lymphocytes of flower growers from Southern Italy, occupationally exposed to pesticides. Methods: Peripheral lymphocyte lysates were analysed for Poly(ADP-Ribose) Polymerase activity, and by SDS-PAGE and anti-Poly(ADP-Ribose)Polymerase 1-antibody to measure automodified anti-Poly(ADP-Ribose) Polymerase levels by densitometry. Results: Poly(ADP-Ribose)Polymerase activity levels were consistent with those of enzyme auto-modification. Growers daily exposed to pesticides, showed both biomarkers very high, either in the presence or in the absence of pathologies. Conclusions: PARP activity and auto-modification in peripheral blood lymphocytes are possible,non-invasive, and routinar tools to monitor the healthy conditions of floricoltorists.

Background: Post-traumatic stress disorder (PTSD) is a common debilitating psychiatric condition for which pharmacological therapy is not always solvable. Various treatments have been suggested for these patients. Deep brain stimulation (DBS) is currently under investigation for patients affected by PTSD. 2) Methods: We review the neurocircuitry and up to date clinical concepts that may be of relevance for the implementation of DBS in posttraumatic stress disorder (PTSD). 3) Results: The role of DBS in treatment-refractory PTSD patients has been investigated relying on both preclinical and clinical studies. 4) Conclusions: DBS for PTSD is in its preliminary phases and likely to provide hope to patients with medical refractory PTSD following the results of randomized controlled studies.

The European Food Safety Authority (EFSA) has identified some risk factors for the occurrence of side effects linked to energy drinks (EDs) consumption by young people. Tachycardia, sleeplessness, caffeine addiction may be caused by excessive consumption of EDs during parties, sport matches, ect. EDs consumption has been evaluated in a sample of students in Italy together with some aspects of their lifestyle. The survey was performed in two high schools from September 2014 to June 2015. 583 students between 14 to 18 years were recruited and a standard questionnaire (EFSA checklist) was used to collect information on responders characteristics, beverages consumption, EDs with alcohol, and EDs and sports. 350 out of 583 responders (60%) consumed EDs and 146 out of 583 responders (25%) reported an occasional alcohol consumption. Despite 82 out of 146 alcoholic drinkers (56%) were EDs-alcohol consumers, only 70 out of 583 adolescents (12%) reported habitual EDs consumption. Moreover, 38 out of 379 (10%) of all physically active adolescents reported frequent EDs consumption before sportive trainings. Study results highlight the need for primary prevention measures in communication campaigns and training delivered by school to limit potential health threats related to excess of EDs consumption.

Chronic kidney disease (CKD) is actually considered a public health priority according to the increasing number of patients affected by this condition: this casuistry is not only related to specific glomerular, tubular or autoimmune diseases or a consequence of acute kidney injury (AKI) episodes leading to organ failure, but it is tied to the progression of life expectancy and the impact of comorbidities such as cardiovascular disease, diabetes and cancer. CKD and its comorbidities promote low grade inflammatory status with an impact on patients’ clinical conditions, reducing their possibility for kidney transplantation or graft survival and their survival when receiving renal replacement therapies such as hemodialysis (HD) or peritoneal dialysis (PD). CKD is often referred to as an ageing accelerator: innate immune system dysregulation, in the uraemic proinflammatory milieu, is involved in this accelerated senescence phenomena and pentraxins, particularly Pentraxin-3 (PTX-3), are of particular interest in the development of kidney disease. A complete understanding of the mechanism of CKD progression, innate immune system involvement and a proper definition of PTX-3 role in kidney disease, could redefine the approach for diagnosis and a more centered patients’ management to slow down CKD progression over time and reduce its clinical and social impact.

Telomeres are structures at the ends of eukaryotic chromosomes that help maintain genomic stability. During aging, telomere length gradually shortens, producing short telomeres, which are considered markers of premature cellular senescence. This is believed to contribute to age-related diseases, including Alzheimer's disease (AD) and based on this, several studies have hypothesized that telomere shortening may characterize AD. Current research, however, has been inconclusive regarding the direction of the association between leukocyte telomere length (LTL) and disease risk. We assessed the association between LTL and AD in a retrospective case-control study of a sample of 255 unrelated patients with late-onset AD (LOAD), including 120 sporadic cases and 135 with positive family history for LOAD, and a group of 279 cognitively healthy unrelated controls, which were all from Calabria, a region from south Italy. Following regression analysis, telomeres were found to be significantly shorter in LOAD cases than in controls (p<0.001 for both sporadic and familial cases). Interestingly, LTL were associated to disease risk independently of the presence of conventional risk factors (e.g., age, sex, MMSE scores, presence of the APOE-ε4 allele). Altogether, our findings lend support to the notion that LTL shortening may be an indicator of the patho-genesis of LOAD.

Background: high-altitude work exposes individuals to reduced oxygen levels, imposing physi-ological adaptations. These conditions can induce alterations in the cardiovascular system, po-tentially exacerbating pre-existing health issues and impacting overall well-being of workers in such environments. This study has investigated the cardiovascular challenges for the high-altitude worker on Etna volcano. Methods: Through an observational study, ten healthy, non-smoking male participants underwent cardiovascular and pulmonary function tests at alti-tudes below 500m and above 3000m, simulating work conditions on the volcano. Results: signif-icant findings include elevated systemic blood pressure and heart rate, indicating an increased cardiovascular workload necessary for adaptation to hypoxia. Conclusions: the study highlights the importance of acclimatization to high altitude for minimizing cardiovascular risks among workers. It calls for the development of safety protocols, underlining the critical role of preven-tative measures and specific safety protocols for high-altitude workers.

The persistence of symptoms following COVID-19 infection represents a significant challenge in healthcare management. During the outbreak, tele-rehabilitation emerged as a new tool to support healthcare structures in providing rehabilitation services. This study assessed the effectiveness and the feasibility of a 3-week home-based motor and respiratory rehabilitation program for long COVID-19 individuals after traditional rehabilitation. Twenty-three patients completed the program and underwent functional tests at different time points (i.e. baseline, after hospital discharge, and after tele-rehabilitation). Motor function was evaluated using the instrumented Six-Minutes Walking Test (i6MWT), with monitored heart rate and oxygen saturation. Conversely, respiratory function was measured via forced vital capacity (FVC) and maximal voluntary ventilation (MVV) tests. Significant improvements (p &lt; 0.05) in motor and respiratory function were observed throughout the intervention, including an 18.3% increase in walked distance from the baseline. The findings suggest that a home-based tele-rehabilitation can enhance motor and respiratory function in post-COVID patients. Despite limitations such as sample size and lack of control group, the positive outcomes seem to support the feasibility of the proposed tele-rehabilitation program in managing long COVID symptoms and promoting functional recovery. Further research is needed to validate these findings and explore tele-rehabilitation’s potential in broader patient populations.

Studying models of healthy aging and exceptional longevity is crucial to understand a possible longevity signature as most of them show resistance to age-related diseases. In particular, semi- and supercentenarians are a highly selected group, having survived significant adversities, including the Spanish Flu and COVID-19 pandemics, indicating distinctive immune system characteristics. This paper analyse the inflammatory scores (INFLA-score, Systemic Inflammation Response Index (SIRI)) and Aging-Related Immune Phenotype (ARIP) indicators calculated from the dataset of the DESIGN project, including 249 participants aged 19-111 years, trying to understand the immune-inflammatory (IMFLAM) role to achieve longevity. Statistical analyses, including linear regression and one-way ANOVA, were performed to explore the correlations between these parameters and age. Both INFLA-score and SIRI showed a significant increase with age. However, no statistical difference is observed when analysing the values for semi- and supercentenarians with those for other age groups, whose values are similar to that of adults and less than younger centenariansRegarding ARIP values, it is noteworthy that when comparing the CD8 Naive/Effector scores between groups, no significant differences were observed between the semi- and supercentenarian group and the other groups. These results support the idea that the control of IMFLAM response can promote extreme longevity.

The 2021/2022 influenza season was not characterised by a well-defined incidence peak. A high value of incidence was recorded in week 13, but it was still lower than in other influenza seasons. This abnormal circulation was probably due to relaxation of the COVID-19 pandemic restriction measures, which greatly reduced the circulation of respiratory-transmitted viruses, including human respiratory syncytial virus (HRSV). The symptoms of SARS-CoV-2 and influenza are quite similar, sharing the human-to-human transmission route via respiratory droplets. The aim of this study was to estimate the rate of coinfection with influenza viruses and/or HRSV in SARS-CoV-2-positive subjects (N=940) in a population of central Italy during the 2021/2022 season. A total of 54 cases of coinfection were detected during the study period, 51 cases (5.4%) of SARS-CoV-2 and influenza virus and three cases (0.3%) of SARS-CoV-2 and HRSV coinfection. These results highlight the importance of continuous monitoring of the circulation of influenza virus and other respiratory viruses in the context of the COVID-19 pandemic.

Immunoglobulin G (IgG), a type of antibody, represents approximately 75% of serum antibodies in humans, and is the most common type of antibody found in blood circulation Consequently, the development of simple, fast and reliable systems for IgG detection are of considerable interest which can be achieved using electrochemical sandwich-type immunosensors. In this study we have developed an immunosensor sub-strate using an inexpensive and very simple fabrication method based on ZnO nanorods obtained through the electrodeposition of ZnO. The ZnO nanorods were treated by electrodepositing a layer of reduced gra-phene oxide to ensure an easy immobilization of the antibodies. On this substrate, the sandwich configura-tion of the immunosensor was built through different incubation steps, that were all optimized. The im-munosensor is electrochemically active thanks to the presence of gold nanoparticles tagging the secondary antibody, therefore it has been used to measure the current density of the hydrogen development reaction which is indirectly linked to the concentration of H-IgG antigens. In this way the calibration curve was constructed obtaining a linear range of 1-100 ng / ml with a detection limit of few ng / mL and good sensi-tivity.

The aim of the present study was to evaluate the effects on the presence and distribution of oxyntopeptic cells (OPs) and enteroendocrine cells (EECs) expressing GHR, NPY and SOM in the gastric mucosa of European seabass and seabream of dietary levels of bioactive peptides (BPs) obtained from salmon processing by-products (in silico approach). In this study, 27 seabass and 27 seabreams were divided into three experimental groups: a control group (CTR) fed a control diet and two groups fed different levels of BP to replace fishmeal: 5% BP (BP5%) and 10% BP (BP10%). The stomach of each fish was sampled and processed for immunohistochemistry. Some SOM, NPY and GHR-IR cells exhibited alternating “open type” and “closed type” EECs morphologies. In seabream gastric mucosa, the BP10% group (16.8 ± 7.5) showed a significant change in NPY-IR cell number compared to CTR (CTR 8.5 ± 4.8) and BP5% (BP10% vs. CTR P ≤ 0.01; BP10% vs. BP5% P ≤ 0.05). In seabream, SOM-IR cells in the BP 10% diet (16.8 ± 3.5) differed from those in CTR (12.5 ± 5) (CTR vs. BP 10% P ≤ 0.05) and BP 5% (12.9 ± 2.5) (BP 5% vs. BP 10% P ≤ 0.01). In seabass, EEC SOM-IR cells increased at 10 % BP (5.3 ± 0.7) compared to 5 % BP (4.4 ± 0.8) (5 % BP vs. 10 % BP P ≤ 0.05). The results obtained suggest that salmon BPs have a promising impact as circulating ingredients for seabass and seabream.

Intense alterations of mineral and bone metabolism are prevalent in chronic kidney disease (CKD) and represent an important cause of morbidity and decreased quality of life. These disor-ders have traditionally been defined as renal osteodystrophy and classified based on bone biop-sy, but due to a lack of bone biopsy data and validated radiological methods to evaluate bone morphology in children, it has been difficult to adequately evaluate renal osteodystrophy in pe-diatric CKD. This has led to suboptimal management of bone disorders in children. CKD-mineral and bone disorder (CKD-MBD) is a new term used to describe a systemic disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is a triad of biochemical imbalances of cal-cium, phosphate, parathyroid hormone and vitamin D, bone abnormalities and soft tissue calci-fication. This literature review aims to explore the pathogenesis, diagnostic approach, and treat-ment of CKD-MBD in children and the specific consequences of renal osteodystrophy on growing skeleton, with a specific focus on the biological basis of this peculiar condition.

Pregestational and gestational diabetes mellitus are relevant complications of pregnancy and antidiabetic drugs are prescribed to obtain glycemic control and improve perinatal outcomes. The objective of this study was to highlight the prescription pattern of antidiabetics before, during and after pregnancy in Italy and to evaluate its appropriateness. A multi-database cross sectional population study using a Common Data Model was performed. In a cohort of about 450,000 women, the prescribing profile of antidiabetics seemed to be in line with the Italian standards for the treatment of GDM which currently do not recommend the use of oral antidiabetics and non-insulin injection, even if a small share of new users (up to 3.8% in the third trimester) used oral antidiabetics. A substantial variability in the prescription pattern was observed among the Italian regions considered: the highest increase was registered in Tuscany (4.2%), Umbria (3.5%) and Emilia-Romagna (2.6%) while the lowest in Lombardy (1.5%), Veneto (1.7%) and Apulia (1.7%). Analysing the prevalence of use of antidiabetics between foreign women we observed that the consumption during pregnancy was higher than Italians (second trimester: 1,8% vs 0,9%, third trimester: 3,6% vs 1,8%).

Sarcoidosis is a multisystemic disease of unknown etiology characterized by the formation of granulomas in various organs, especially lung and mediastinal hilar lymph nodes. The clinical course and manifestations are unpredictable: spontaneous remission can occur in approximately two thirds of patients; up to 20% of patients have chronic course of the lung disease (called Ad-vanced Pulmonary Sarcoidosis) resulting in progressive loss of lung function, sometimes life-threatening that can lead to respiratory failure and death. The immunopathology mechanism leading from granuloma formation to the fibrosis in APS still remains elusive. Recent studies have provided new insights into the genetics factors and immune components involved in the clinical manifestation of the disease. In this review we aim to summarize the clinical-prognostic charac-teristics and molecular pathways which are believed to be associated with the development of APS

Patient engagement is receiving a growing attention in the healthcare context. However, although worldwide healthcare stakeholders agree that patient engagement is a priority for quality and effective care, no shared recommendations on how to promote patient engagement are currently available. Based on these premises, a Consensus Conference (CC) was promoted to address four main issues: What is the definition of Patient Engagement? How measuring Patient Engagement? What are the most recommended methodologies and the tools to promote Patient Engagement? What is the role of new technologies in promoting of Patient Engagement? The consensus was obtained through an iterative process that began with a systematic synthesis of the available literature in each domain followed by plenary expert discussions. This CC - including the systematic analysis of internationals scientific evidences (2749 sources across the major international scientific databases) together with experiences of a multi-disciplinary consortium of investigators and key stakeholders - attempted to provide the first evidence-based Expert Consensus Statement for the promotion of Patient Engagement in chronic care. These recommendations should be envisaged as inspirational principles to promote a real eco-system of engagement and might orient health services research and interventions.

Antimicrobial resistance has been stated to be a global health problem. In Chile, the use of antibiotics should be declared by medical prescription, however, it is unknown what happens to the drugs once the treatment ends. One possibility is that these end up being disposed of in the trash or down the drain. In both scenarios, antibiotics could accumulate in the environment, stimulating the emergence of antimicrobial resistance mechanisms and their transfer between microorganisms. Unfortunately, sometimes wastewater ends up in bodies of water, due to the dragging of elements by rain, or by the presence of illegal water discharges. In this work, we use shotgun metagenomics to elucidate the functional and microbial composition of biohazard elements in the bay of Puerto Varas City, Chile. As expected, we found a high diversity in microbial communities, with bacterial elements described as human or animal pathogens. Also, we detect a diverse repertory of virulence and antibiotic-resistant genes (ARGs), related with macrolides, beta-lactams, and tetracyclines resistance, which are consistent with the families of antibiotics most used in Chile. Similar ARGs were identified in DNA mobile elements. In addition, we tested the AMR ability in 20 bacterial strains recovered from the Llanquihue lake. This is the first report of the presence of genomic elements that could constitute a health problem for the people who live around the Llanquihue Lake of Chile, considering the importance of the interconnection between environmental, animal, and human health, a concept known as One Health.

Metabolic-associated fatty liver disease (MASLD) is not only associated with traditional cardiovascular risk factors such as T2DM and obesity, but it is also an independent risk factor for the development of cardiovascular disease. MASLD has been shown to be independently related to endothelial dysfunction and atherosclerosis. MASLD is characterized by a chronic proinflammatory response that, in turn, may induce a prothrombotic state. Several mechanisms such as endothelial and platelet dysfunction, changes in the coagulation cascade, decreased fibrinolytic activity can contribute to induce the prothrombotic state. Platelets are players and addresses of metabolic dysregulation; obesity and insulin resistance are related to platelet hyperactivation. Furthermore, platelets can exert a direct effect on liver cells, particularly through the release of mediators from granules. Growing data in literature support the use of antiplatelet agent as a treatment for MASLD. The use of antiplatelets drugs seems to have potential clinical implication for the prevention of HCC patients with MASLD, since platelets contribute to fibrosis progression and cancer development. This review aims to summarize the main data on the role of platelets in the pathogenesis of MAFLD and its main complications such as cardiovascular events and the development of liver fibrosis. Furthermore, we will examine the role of antiplatelet therapy not only in the prevention and treatment of cardiovascular events but also as a possible anti-fibrotic and anti-tumor agent.

Literature data on Legionella spp. presence in houses water networks have been increasing during the last years, but epidemiological reports assert a high incidence of Legionnaires’ disease infection in Italy. Updating our previously published data, we report a five-year survey on Legionella spp. colonization in 235 buildings with an independent hot water production (IB); 82 buildings with a central hot water production (CB); and 58 buildings with a solar thermal system for hot water production (TB). In all the 375 buildings Legionella spp. was researched in hot and cold water samples and microbiological potability standards of cold water were evaluated. Legionella spp. was detected in 27% of the water networks, mostly in CB and TB. We detected correlations between the presence of bacteria and some physical-chemical parameters (low chlorine level and optimal temperature for Legionella spp. growth). Cold water resulted free from microbiological hazards, except for coliform bacteria isolated in three separate cases, and Legionella spp., detected when cold water temperature was about 20°C. After a five-year survey we confirm the presence of a Legionnaires’ disease risk and the need of training programs for all the workers involved in residential water systems management.

Severe Acute Respiratory Disease Syndrome Coronavirus 2 has caused a global pandemic. Monoclonal antibodies, antiviral therapy (Remdesivir) and immunomodulatory agents represent one of the most promising therapies to prevent disease progression and reduce the relative risk of severe COVID-19. The aim of this study was to evaluate the impact on the disease progression of the main pharmacological options approved for the patients admitted in hospital with acute COVID-19 infection, according to their vaccination status.. We conducted a study including adult patients with confirmed COVID-19 admitted to the Infectious Diseases Unit of Alessandria’s Hospital in Italy, from October 2021 to March 2022. 102 patients were included in the analysis. The mean age was 69.2 ±15.4 years, 66.7% were males. According to the internal hospital’s guidelines, 47.06% patients with mild to moderate disease were treated with mAbs, 45.10% were treated with Remdesivir, of which 10.78% received combination therapy with mAbs. The most frequently complications were pneumonia (18.63%), respiratory failure (15.68%) and acute respiratory distress syndrome (13.72%). The mean length of hospitalization was 13.42 (±10.90) days and the mortality rate was 11.76%. The treatment with mAbs and immunomodulatory therapy for mild to moderate COVID-19 infection seem to be effective to improve the outcome reducing disease progression and mortality. C-reactive protein (CRP) and ferritin could be considered a good inflammatory marker of disease progression.

Background: Breast cancer remains a significant health concern among women globally. Despite advancements in awareness and diagnostic techniques, it persists as a leading cause of death, with profound impacts on affected individuals' quality of life. Primary and secondary prevention, including regular screenings and practices like Breast Self-Examination (BSE), are pivotal in ensuring early diagnosis. The NHS in Italy offers screenings for women aged 50-69 every two years, managed by the Local Health Authority. However, the participation rates, especially among the Chinese female population residing in Italy, are not well-understood. Methods: Using a snowball method, we electronically disseminated a survey to investigate how Chinese women living in Italy engage with available NHS screening programs. The survey also explores their practice of BSE, the use and impact of technological tools on prevention, and aims to understand their depth of knowledge and misconceptions about breast cancer. Results: The data revealed a significant gap in breast cancer screening adherence and knowledge among Chinese women in Italy, with a notable discrepancy between the general population and those who have previously encountered cancer. Conclusions: The results highlight the urgent need for interventions that are culturally sensitive, stressing that these actions are not only desirable but essential.

Coronavirus disease 19 (COVID-19) continues to spread worldwide as a severe pandemic. The Omicron BA.2 became the predominant variant and the protagonist of the ongoing surge. As the virus continues to mutate, using of approved drugs or developing new therapeutic or prophylactic therapies against COVID-19 could be more complex. Sotrovimab is a monoclonal antibody (mAb) targeting the conserved epitope on the spike protein receptor; the most recent studies observed that it has substantially decreased in vitro activity against the Omicron BA.2 subvariant, but real-life data are still scarce. We describe the outcome of a case series of outpatients with BA.1 or BA.2 infection treated with sotrovimab. We conducted a retrospective observational study including all non-hospitalized adult patients treated with sotrovimab, for which a Sanger sequencing of SARS-CoV-2 was performed within a regional genomic surveillance program. Eleven (50%) patients with BA.1 infection and eleven (50%) with BA.2 infection were considered. Most patients were immunocompromised. During the follow-up period, no patient died and only one with BA.1 infection was hospitalized for severe COVID-19 pneumonia onset. One month after treatment, 90.9% of patients were completely asymptomatic in each group. We demonstrated that patients carrying the BA.2 variant treated with sotrovimab did not evolve to severe COVID-19, showing a similar outcome to BA.1 infected patients. Further studies are needed to prove that vaccination or the presumably high doses of mAbs used can protect this group of patients at high risk of progression.

Background: Colorectal adenoma undergoes neoplastic progression via the normal epithelium-adenoma-adenocarcinoma sequence as reported in the Vogelgram. The risk of developing cancer is strongly associated with the number and size of adenoma and with the subtype. Currently, adenomatous polyps can be distinguished on the basis of histology: the prevalence are tubular, 5-15% are villous and tubular/villous. Considering the increased risk for malignant transformation described for tubular/villous adenomas, patients diagnosed with adenomatous polyposis are at increased risk of developing CRC. The Wnt/β-catenin pathway plays a key role in the onset of colorectal adenoma, in particular intestinal cells first acquire loss-of-function mutations in APC gene that induce the formation of adenomas. Methods: Wnt/β-catenin pathway APC, Wnt3a, Wnt5a, LEF1, BCL9 genes and protein expression analyses were conducted by qRT-PCR and western blot in 68 colonic samples (polyps and adjacent mucosa) from 41 patients, of which 17 affected by FAP. Ten normal colonic mucosal samples were collected from 10 healthy donors. Results: In this study both APC gene and protein resulted less expressed in colon tumor compared to the adjacent colonic mucosa. Conversely, activated β-catenin was more expressed in polyps than in the adjacent mucosa. All results confirmed literature data on carcinomas. A statistically significant correlation between Wnt3a and BCL9 both in polyps and in the adjacent mucosa underlies that the canonical Wnt pathway is activated in early colon carcinogenesis and that the adjacent mucosa is already altered. Conclusion: This is the first study analyzing the difference in expression of Wnt/β-catenin pathway in human colorectal adenomas. Understanding the progression from adenomas to colorectal carcinomas is essential for the development of new therapeutic strategies and improving clinical outcomes.

Background: Spinal schwannomas and meningiomas are the most common spinal cord benign tumors in adults and total excision is the goal of the treatment. The traditional surgical approach is performed by total laminectomy, but recently unilateral hemilaminectomy has been recognized as a valuable surgical alternative. We report the clinical results of patients affected by spinal schwannoma and meningioma in whom total laminectomy or unilateral hemilaminectomy were performed. Material and Methods: A retrospective study of patients who underwent resection of spinal meningioma or schwannoma by laminectomy or unilateral hemilaminectomy approaches in our Institute from January 2013 to January 2023 was made. The baseline data of these patients, operative approach and postoperative outcome were compared. Results: The study was performed on 41 patients with mean age of 62.5 ±14.6 years. Our series included 24 (59%) cases of schwannomas and 17 (41%) cases of meningiomas, with a prevalent location in the thoracic spine. The average schwannomas volume was 3,6 ±2,7 cm3, whereas the average meningiomas volume was 1.1 ±0.5 cm3. Total excision was achieved in all cases. Operative time of schwannomas was longer (p=0.001) respect to meningiomas with higher intra-operative blood loss (p=0.000). Total laminectomy approach was performed in 24 out of 41 patients (59%) and unilateral hemilaminectomy approach in 17 out of 41 (41%) patients. Unilateral hemilaminectomy was associated with shorter postoperative bed rest (p=0.003), shorter hospitalization (p=0.028) and lower postoperative pain (p=0.02) respect to total laminectomy. Conclusions: Both spinal schwannomas and spinal meningiomas in various size can be safely and effectively treated with unilateral hemilaminectomy approach. This approach grants more advantages compared with standard total laminectomy, including shorter postoperative bed rest, shorter hospitalization and reduced postoperative pain.

Mitochondrial dysfunction is relevant mechanism in cardiac aging. Here, we investigated the effects of late-life enalapril administration at non-antihypertensive dose on mitochondrial genomic stability, oxidative damage, and mitochondrial quality control (MQC) signaling in the heart of aged rats. The protein expression of selected mediators (i.e., mitochondrial antioxidant enzymes, energy metabolism, mitochondrial biogenesis, dynamics, and autophagy) was measured in old rats randomly assigned to receive enalapril (n=8) or placebo (n=8) from 24 to 27 months of age. We also assessed mitochondrial DNA (mtDNA) content, citrate synthase activity, oxidative lesions to protein and mtDNA (i.e., carbonyls and abundance of mtDNA4834 deletion), and mitochondrial transcription factor A (TFAM) binding to specific mtDNA regions. Enalapril attenuated cardiac hypertrophy and oxidative stress-derived damage (mtDNA oxidation, mtDNA4834 deletion, and protein carbonylation), while increasing mitochondrial antioxidant defenses. TFAM binding to mtDNA regions involved in replication and deletion generation was increased following enalapril administration. Increased mitochondrial mass as well as mitochondriogenesis and autophagy signaling was found in enalapril-treated rats. Late-life enalapril administration mitigates age-dependent cardiac hypertrophy and oxidative damage, while increasing mitochondrial mass and modulating MQC signaling. Further analyses are needed to conclusively establish whether enalapril may offer cardioprotection during aging.

The NETTER-1 study has proven peptide receptor radionuclide therapy (PRRT) to be one of the most effective therapeutic options for metastatic neuroendocrine tumors (NETs), improving progression-free survival and overall survival. However, PRRT response assessment is challenging and no consensus on methods and timing has yet been reached among experts in the field. This issue is owing to the suboptimal sensitivity and specificity of clinical biomarkers, limitations of morphological response criteria in slowly growing tumors and necrotic changes after therapy, a lack of standardized parameters and timing of functional imaging, and the heterogeneity of PRRT protocols in the literature. The aim of this article is to review the most relevant current approaches for PRRT efficacy prediction and response assessment criteria in order to provide an overview of suitable tools for safe and efficacious PRRT.

Bacteriotherapy is emerging as a strategic and effective approach to treat infections by providing putatively harmless bacteria (i.e., probiotics) as antagonists to pathogens. A proper delivery of probiotics or their metabolites (i.e., post-biotics) can avail itself of biomaterial encapsulation by innovative manufacturing technologies. This review paper aims at providing the most recent biomaterial-assisted strategies proposed to treat infections or disbiosis using bacteriotherapy. We revised the encapsulation processes across multiscale biomaterial approaches, which could be ideal to target different tissues and suit diverse therapeutic opportunities. Hydrogels, and in particular polysaccharides, are the focus of this review, as they have been reported to better sustain vitality of the live cells incorporated. Specifically, the approaches for fabricating hydrogel-based devices with increasing dimensionality (D), namely, 0D (i.e., particles), 1D (i.e., fibers), 2D (i.e., fiber meshes), and 3D (i.e., scaffolds) endowed with probiotics, were detailed by describing their advantages and challenges, along with a future overlook in the field. Electrospinning, electrospray and 3D bioprinting were investigated as new biofabrication methods for probiotic encapsulation within multidimensional matrices. Finally, examples of biomaterial-based systems for cell and post-biotic release were reported.

In recent decades, the interest in PFAS has grown exponentially around the world, due to the toxic effects induced by these chemical compounds in humans, as well as in other animals and in plants. However, current knowledge related to the antistress responses that organisms can express when exposed to these substances is still insufficient and therefore it requires further investigation. The present study focuses on antioxidant responses in Squalius cephalus and Padogobius bonelli, exposed to significant levels of PFAS in an area of the Veneto region subjected to a recent relevant pollution case. These two ubiquitous freshwater species were sampled in three rivers characterized by different concentrations of PFAS. Several biomarkers of oxidative stress have been evaluated and the results suggest that PFAS chronic exposure induces some physiological responses in the target species, at both cellular and tissue scales. The risk of oxidative stress seems to be kept under control by the antioxidant system by means of gene activation at the mitochondrial level. Moreover, the histological analysis suggests an interesting protective mechanism against damage to the protein component based on lipid vacuolization.

Historically, admission of hematological patients in the ICU shortly after the start of a critical illness is associated with better survival rates. Early intensive interventions administered by MET could have a role in the management of hematological critically ill patients, eventually reducing ICU admission rate. In this retrospective and monocentric study, we evaluate the safety and effectiveness of intensive treatments administered by the MET in a medical ward frame. The administered interventions were mainly helmet CPAP and pharmacological cardiovascular support. Frequent reassessment by the MET at least every 8 to 12 hours was guaranteed. We analyze data from 133 hematological patients that required MET intervention. In hospital mortality was 38%; mortality doesn’t increase in patients not immediately transferred to the ICU. Only 3 patients died without a former admission in ICU; in these cases, mortality was not related to the acute illness. Moreover, 37% of patients overcame the critical episode in the hematological ward. Higher SOFA and MEWS scores were associated with a worst survival rate, while neutropenia and pharmacological immunosuppression were not. The MET approach seems to be safe and effective. SOFA and MEWS confirmed to be effective tools for prognostication.

The “red code” (RD) represents the highest levels of emergency in the emergency department (ED). The study retrospectively analyzed RDs in the Regina Margherita Children’s Hospital ED, a regional referral center in north Italy, between 1 July 2020 and 30 June 2023. The aim was to describe RD characteristics and to identify significant correlations between presenting complaints and clinical management. The study includes 934 RDs (0.9% of overall ED admissions); 64% were assigned based on the Pediatric Assessment Triangle alteration. Most patients, 86.5%, followed the medical pathway, while 13.5% were surgical cases. Admission complaints were respiratory (46.9%), neuropsychiatric (26.7%), traumatic (11.8%), cardiologic (9.3%), metabolic (3.8%), and surgical (1.5%). Seventy-six per cent of patients received vascular access, and intraosseous access was obtained in 2.2% of them. In one-third of RDs, an urgent critical care evaluation was necessary, and 19% of cases required admission to the intensive care unit. The overall mortality rate was 3.4% (0.4% in ED setting). The study identified six distinct diagnostic pathways, each associated with specific characteristics in clinical presentation, management, therapeutic interventions, and outcomes: this underscored the significance of a systematic approach in improving outcomes in pediatric RD management.

Food-borne transmission is a recognized route for many viruses associated with gastrointestinal, hepatic or neurological diseases. Therefore, it is essential to identify new bioactive compounds with broad-spectrum antiviral activity is needed to exploit innovative solutions against these hazards. Lately, antimicrobial peptides (AMPs) have been recognized as promising antiviral agents. Indeed, while the antibacterial and antifungal effects of these molecules have been widely reported, their use as potential antiviral agents has not yet been fully investigated. Herein, the antiviral activity of previously identified or newly designed AMPs, was evaluated against the non-enveloped RNA viruses, Hepatitis A virus (HAV), and Murine Norovirus (MNV), a surrogate for human Norovirus. Moreover, specific assays were performed to recognize at which stage of the viral infection cycle the peptides could function. Results showed that almost all peptides displayed virucidal effects with about 90% of infectivity reduction on HAV or MNV. However, the decapeptide RiLK1 demonstrated, together with its antibacterial and antifungal properties, a notable reduction in viral infection for both HAV and MNV, possibly through direct interaction with viral particles or inhibition of the viral bonding to the cell receptors. Hence, RiLK1 could represent a versatile ‘antimicrobial agent effective against various foodborne pathogens including viruses, bacteria, and fungi.

Background: Olecranon fractures are common injuries of the upper limb in adults. Simple dis-placed trasverse fractures are generally surgically treated with tension-band wiring (TBW) or plate fixation (PF). The purpose of this retrospective study is to compare the clinical-functional outcome, complications and reoperation rates between TBW and PF for Mayo IIA fractures. Methods: 72 patients treated with PF or TBW at our institution, completed our survey and clinical evaluation and their demographic and clinical data were recorded and analysed. The clini-cal-functional outcomes were evaluated assessing ROMs and three validated scoring systems: the Disabilities of the Arm, Shoulder, and Hand (DASH), the Mayo Elbow Performance Score (MEPS) and the Patient American Shoulder and Elbow Surgeons Standardized Elbow Assess-ment score (pASES-e). Results: 38 patients (53%) underwent TBW and 34 (47%) PF. The mean DASH, MEPS and pASES-e scores were respectively 14.5±17.2, 80.5±14.7 and 83.6±12.4 in the TBW group and 21±21.7, 75.6±15.3 and 75.1±19.2 in the PF group (p=0.16, p=0.17 and p=0.03). The mean duration of surgery and hospitalisation period were longer in the PF group (p=0.002, p=0.37) whereas the complication and reoperation rates were higher after TBW (p=0.15, p=0.24). Conclusion: According to the literature, both TBW and PF resulted comparable valid surgical op-tions for the treatment of simple isolated displaced olecranon fractures, revealing that they both provide good/excellent outcomes with no significant differences.

We here report the de novo transcriptome assembly and functional annotation of Eusirus cf. giganteus clade g3, providing the first database of expressed sequences from this giant Antarctic amphipod. RNA-sequencing, carried out on the whole-body of a single juvenile individual likely undergoing molting, revealed the dominant expression of hemocyanins. The mRNAs encoding these oxygen-binding proteins cumulatively accounted for about 40% of the total transcriptional effort, highlighting the key biological importance of high hemocyanin production in this Antarctic amphipod species. We speculate that this observation may mirror a strategy previously described in Antarctic cephalopods, which compensate the decreased ability to release oxygen to peripheral tissues at sub-zero temperatures by massively increasing total blood hemocyanin content compared with temperate species. These preliminary results will undoubtedly require confirmation through proteomic and biochemical analyses aimed at characterizing the oxygen-binding properties of E. cf. giganteus clade g3 hemocyanins, and at investigating whether other Antarctic arthropod species exploit similar adaptations to cope with the challenges posed by the extreme conditions of the polar environment.

Pancreatic cancer (PC) has a poor prognosis and displays resistance to immunotherapy. A better understanding of tumor-derived extracellular vesicles (EVs) effects on immune responses might contribute to improved immunotherapy. EVs derived from Capan-2 and BxPC-3 PC cells isolated by ultracentrifugation were characterized by atomic force microscopy, western blot (WB), nanoparticle tracking analysis and label-free proteomics. Fresh PBMCs from healthy donors were treated with PC- or control-derived heterologous EVs followed by flow cytometry analysis of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated, or -untreated PBMCs was performed and IFN-γ concentration was measured by ELISA. Notably, most of the proteins identified in Capan-2 and BxPC-3 EVs by proteomic analysis were connected in a single functional network (p=1x10-16) and were involved in “Immune System” (FDR: 1.10x10-24 and 3.69x10-19, respectively). Interestingly, treatment of healthy donor-derived PBMCs with Capan-2 EVs, but not with BxPC-3 EVs or heterologous control EVs induced early activation of CD8+ and CD4+ lymphocytes. Proteomics of lymphocytes sorted from EV-treated PBMCs was consistent with their activation by Capan-2 EVs, indicating IFN-γ among major upstream regulators, as confirmed by ELISA. Proteomic and functional analyses indicate that PC-EVs have pleiotropic effects, and some may activate early immune response, which might be relevant for the development of highly needed immunotherapeutic strategies in this immune-cold tumor.

How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models. Here, we studied isocitrate dehydrogenases (IDH) genes mutations in the human model of HSPC and provide a review of the literature on this topic. IDH1/2 mutations occur in ~20% of AML, are recognized among the mutations earliest acquired during leukemogenesis, and are target of specific inhibitors (ivosidenib and enasidenib, respectively). In order to investigate the direct effects of these mutations on the HSPC we expressed by lentiviral transduction either IDH1-R132H or IDH2-R140Q mutants into human CD34+ healthy donor cells and analyzed the colony-forming unit (CFU) ability. CFU ability was dramatically compromised with a complete trilineage block of differentiation. Strikingly, the block was reversed by the specific inhibitors, confirming it was a specific effect induced by the mutants. In line with this observation, the CD34+ leukemic precursors isolated from a patient with IDH2-mutated AML at baseline and during enasidenib treatment showed over time a progressive and marked improvement of their fitness in terms of CFU ability and propensity to differentiate, attaining clonal trilinear reconstitution of hematopoiesis and complete hematological remission.

In this paper, we present demographic, clinical, anamnestic, cognitive, and functional data, as well as haematological, haematochemical, immunological and genetic parameters of an exceptional individual: Antonino Turturici, a semi-supercentenarian who held the title of the oldest living Italian centenarian from December 28, 2020, to September 23, 2021. The purpose of this study is to offer fresh insights into extreme phenotypes, with a particular focus on immune-inflammatory parameters. To the best of our knowledge, this study represents the first phenotypic investigation of a semi-supercentenarian, illustrating both indicators of age-related immune phenotype (ARIP) recognized as significant gauges of biological ageing and INFLA-score, a metric designed to assess the cumulative impact of inflammatory markers. The aim of this study was, indeed, to advance our understanding of the role of immune-inflammatory responses in achieving extreme longevity. The results bolster the idea that the immune system can play a role in promoting extreme longevity. However, this does not exclude the involvement of other body systems or organs in achieving extreme longevity.

The antibiotic tetracycline demeclocycline (DMC) was recently reported to rescue α-synuclein (α-Syn) fibril-induced pathology. However, the antimicrobial activity of DMC precludes its po-tential use in long-term neuroprotective treatments. Here, we synthesized a DMC derivative with residual antibiotic activity and improved neuroprotective effects. The molecule, called de-rivative demeclocycline (DDMC), was obtained by the removal of both dimethylamino substitu-ents at position 4 and the reduction of the hydroxyl group at position 12a on ring A of DMC. The modifications strongly diminished its antibiotic activity against Gram-positive and Gram-negative bacteria. Moreover, this compound preserved the low toxicity of DMC in dopaminergic cell lines while improving its ability to interfere with α-Syn amyloid-like aggregation, showing the highest effectiveness of all tetracyclines tested. Likewise, DDMC demonstrated the ability to reduce seeding induced by the exogenous addition of α-Syn preformed fibrils (α-SynPFF ) in ex vitro models and in SH-SY5Y-α-Syn-tRFP cells. In addition, in the presence of DDMC, α-SynPFF were less inflammogenic, as they dampened the release of tumor necrosis factor α (TNF-α) and glutamate by microglial cells compared to control fibrils. Our results suggest that DDMC may be a promising drug candidate for hit-to-lead development and preclinical studies in PD and other synucleinopathies.

After the influenza H1N1 pandemic of 2009, the seasonal A/Brisbane/59/2007 strain was replaced by the A/California/07/2009 strain for the influenza virus vaccine composition. After several seasons with no indications on the occurrence of antigenic drift, A/Michigan/45/2015 was chosen as the H1N1 vaccine strain for season 2017/2018. Since the immune response to influenza is shaped by the history of exposure to antigenically similar strains, the potential cross-protection between seasonal human influenza vaccine strains and the emerging pandemic strains was investigated. Human serum samples were tested by haemagglutination inhibition and single radial haemolysis assays against A/Brisbane/59/2007, A/California/07/2009, and A/Michigan/45/2015 strains. Strong cross-reactions between A/California/07/2009 and A/Michigan/45/2015 strains were observed in 2009/2010, most likely induced by the start of the 2009 pandemic, and the subsequent post-pandemic seasons from 2010/2011 onwards when A/California/07/2009 becomes the predominant strain. In 2014/2015 season, population immunity against A/California/07/2009 and A/Michigan/45/2015 strains increased again, associated with strong cross-reactions. While haemagglutination inhibition assay has a higher sensitivity for detection of new seasonal drift, the single radial haemolysis assay is an excellent tool to determine the presence of pre-existing immunity, allowing a potential prediction on the booster potential of influenza vaccines against newly emerging drifted strains.

Background: This systematic review aims to investigate whether percutaneous transhepatic gallbladder drainage (PTGDB), as definitive treatment, is superior to emergency cholecystectomy (EC) in high-risk patients with acute cholecystitis (AC). Material and methods: A systematic literature search was performed until December 2022 using Scopus, Medline/PubMed and Web of Science databases in order to compare PTGDB as definitive treatment vs EC in AC. Results: Seventeen studies (1 Randomized Control Trials and 16 observational studies) have been included with a total of 783,672 patients (32,634 treated with PTGDB vs 4,663 who underwent laparoscopic cholecystectomy, 343 who underwent open cholecystectomy and 746,032 who underwent cholecystectomy, but without laparoscopic or open approach being specified). The quality assessment (ROBINS-I) of the not randomized studies showed a serious risk, differently the evaluation of the randomized study (RoB 2) showed a low risk of bias. Analysis of the results shows that PTGDB, despite being minimally invasive, do not have different incidence of complications than EC (RR 0.77 95% CI [0.44 to 1.34]; I2 = 99%; P=0.36). A lower postoperative mortality was reported in patients who underwent EC (2.37%) than in PTGDB group (13.78 %) (RR 4.21; 95% CI [2.69 to 6.58]; P < 0.00001), furthermore the risk of hospital readmission for biliary complications (RR 2.19 95% CI [1.72 to 2.79]; I2 = 48 %; P<0.00001) and hospital stay (MD 4.29 95% CI [2.40 to 6.19]; P<0.00001) were lower in EC group. Conclusions: No advantage in using PTGDB as a definitive treatment over EC in the management of critically ill patients with AC has been demonstrated; the results of our systematic review and meta-analysis suggest using EC as the treatment of first choice, even for very high-surgical-risk patient in which PTGDB should be reserved. The major limitation of this systematic review and meta-analysis is associated to a low quality of evidence for the serious bias in the not randomized studies. For this reason, new high powered and well-designed clinical trials are needed to recommend PTGDB as definitive treatment in patients unfit for surgery or those who refuse to undergo surgery.

Ketogenic dietary therapies (KDTs) are an effective and safe non-pharmacological treatment for drug-resistant epilepsy, but adherence can be challenging for both patients and caregivers. In Europe, there are no adequate tools to measure it other than monitoring ketosis. This study aimed to adapt and validate the Brazilian adherence questionnaire, Keto-check, into the Italian version: iKetoCheck. Using the Delphi technique, 12 judges validated the contents through agreement rate and the Content Validity Index (CVI). The iKetocheck was self-completed electronically by drug-resistant epilepsy or GLUT1 deficiency patients within an interval of 15 days to measure its reproducibility. Test-retest reliability was evaluated using Pearson correlation and relative significance test. Exploratory and confirmatory factorial analyses were made using Factor software. The final tool, iKetoCheck, consists of 10 questions with 5-point Likert scale answers. It evaluates various aspects such as informing caregivers about the diet, organization of meals, measurement of ketosis, weighing food consumed, diet negligence, use of carbohydrate-free medications, attending follow-up visits, reading food labels, consulting an expert for dietary concerns, and cooking at home. The factorial analysis resulted in three factors: "attention," "organization," and "precision," with satisfactory results for indices in exploratory and confirmatory analyses. Although higher mean values of ketonemia measurement were observed in patients with a higher adherence score, these values were not statistically significant (p=0.284). In conclusion, iKetoCheck is a valid tool for evaluating KDTs' adherence in Italian drug-resistant epilepsy or GLUT1 deficiency patients. It can provide valuable information to improve patient management and optimize the effectiveness of KDTs.

Bacterial adhesion to the surface of the adhesive material is an important step in the formation of plaque and enamel demineralization. In order to correlate the material composition to the specific surface roughness of the resin and to the probable more favourable adhesion of bacteria, scanning electron microscopy, combined with focus ion bean micromachining, together with stylus profilometry analysis have been in vitro performed to reveal the structural nature of three orthodontic adhesive resins used for bracket bonding and, above all, to understand how compositional factors can influence specific pivotal properties such as material’s surface roughness and robustness. In particular, we speculated about the morphological features that determine an increase in the bacterial adhesion and we proposed focused ion beam technique as a valuable tool to compare the internal structures of the polymers and to determine the peculiar mechanical properties of the examined adhesive resins.

Background: Chronic pelvic pain is a debilitating condition affecting quality of life. Endometriosis is one of the leading causes of CPP, but recent studies highlighted the role of interstitial cystitis/bladder pain syndrome (IC/PBS) in causing CPP. Only some studies addressed the coexistence between these two conditions, which seems more frequent than what is supposed, leading to diagnostic delays and unnecessary surgeries. This systematic review aimed to evaluate the estimate of the coexistence of endometriosis and IC/PBS. Methods: We performed a systematic review of the literature indexed on PubMed, Scopus, ISI Web of Science, and Cochrane using a combination of keywords and text words represented by “painful bladder syndrome”, “endometriosis”, “interstitial cystitis”, “bladder pain syndrome”. We performed a meta-analysis of the results. Results: Meta-analysis shows that the coexistence of endometriosis and IC/PBS in women with CPP ranges between 15,5-78,3%, which is higher than the prevalence of IC/PBS in the general population. Conclusions: Women with CPP need a multidisciplinary approach and a referral to centers with specific expertise. In cases of endometriosis unresponsive to treatment, other reasons for CPP need to be ruled out, above all in women not responsive to treatment.

Background: Systemic autoimmune rheumatic diseases (SARDs), including Systemic Lupus Erythematosus (SLE) and Rheumatoid Arthritis (RA), are characterized by chronic inflammation and autoimmunity. Identifying reliable biomarkers is crucial for enhancing diagnosis, monitoring disease progression, and evaluating therapeutic responses. This study explores the potential of serum Syndecan-1 (SDC-1) as a biomarker for these conditions and concurrently examines its relationship with free light chain (FLC) expression levels in the same patients. Methods: A retrospective analysis was performed on serum samples from 120 patients (60 RA, 60 SLE), alongside 50 healthy donors (HD). Serum levels of κ and λ FLCs were determined by turbidimetric assay, while SDC-1 levels were measured using ELISA. Statistical analyses, including the Kruskal-Wallis test, Wilcoxon-Mann-Whitney U test, multivariable linear regression and Spearman’s correlation, were employed to compare biomarker levels across groups and to explore correlations among them. Results: Significantly increased levels of SDC-1, κ-FLC, and λ-FLC were observed in patients diagnosed with RA and SLE compared to HD (p < 0.001), while no significant differences in the κ/λ ratio were noted among the groups (p = 0.4). A statistically significant difference in subject age was also identified. However, multivariate regression analysis indicated that RA and SLE statuses are significantly associated with the levels of these markers, with minimal confounding by age. A significant correlation was observed separately in all groups between the FLC markers. Conversely, no correlation was detected between SDC-1 and FLCs, nor between these markers and age. Conclusion: Elevated serum levels of FLCs and SDC-1 in RA and SLE patients compared to healthy controls underscore their potential as biomarkers for SARDs. The findings also suggest sustained plasma cells activation, supporting the SDC-1 role in the pathogenesis of these conditions.

Science is addressing global societal challenges and, due to limitations in research financing, scientists are turning to public at large to jointly tackle specific environmental issues. Citizens are therefore increasingly involved in monitoring programs, appointed as citizen scientists with potential to delivering key data at near no cost to address environmental challenges, so fostering scientific knowledge and advise policy- and decision-makers. One of the first and most successful example of marine citizen science in the Mediterranean is represented by the integrative and collaborative implementation of several jellyfish spotting campaigns in Italy, Spain, Malta, Tunisia started in 2009. Altogether, in terms of time coverage, geographic extent, and number of citizen records, these represent the most effective marine citizen science campaign so far implemented in the Mediterranean Sea. Here we analyzed a collective database merging records over the above four Countries, featuring more than 100,000 records containing almost 25,000 observations of jellyfish specimens, collected over a period of 3 to 7 years (from 2009 to 2015) by citizen scientists participating in any of the national citizen science programs included in this analysis. Such a wide citizen science exercise demonstrates to be one of the so far available most valuable and cost-effective tools to understanding ecological drivers of jellyfish proliferations over the Western and Central Mediterranean basins, and a powerful contribute to develop tailored adaptation and management strategies, mitigate jellyfish impacts on human activities in coastal zones, and support implementation of marine spatial planning, Blue Growth and conservation strategies.

Abstract: Background: epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early-onset, and unfavorable developmental outcome. We describe a cohort of pediatric patients with EE who underwent intravenous methylprednisolone (IVMP) pulse therapy to examine its efficacy/tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were: ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction >50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of Life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: Twenty-one patients were included. The responding rate was 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Genetic etiology and encephalopathy related to status epilepticus during NREM sleep (ESES) were predictive of efficacy (p=0.0475). The fourth month of therapy was the minimum time point to establish the effectiveness of the treatment. All patients showed improvements in QoL, EEG tracing and postural-motor development. No relevant adverse events were observed. Conclusions: Our study confirms the efficacy and tolerability of pulse IVMP treatment in pediatric patients with EE, especially with genetic etiology and ESES. The fourth month of therapy was the minimum time point to establish its effectiveness. QoL, EEG and postural-motor development also showed improvement.

The process of identifying and approving a new drug is a time-consuming and expensive procedure. One of the biggest issues to overcome is the risk of hepatotoxicity, which is one of the main reasons for drug withdrawal from the market. While animal models are the gold standard in preclinical drug testing, the translation of results into therapeutic intervention is often ambiguous due to interspecies differences in hepatic metabolism. The discovery of human induced Pluripotent Stem Cells (hiPSCs) and their derivatives has opened new possibilities for drug testing. We used mesenchymal stem cells and hepatocytes both derived from hiPSC, together with endothelial cells, to miniaturize the process of generating hepatic organoids. These organoids were then cultivated in vitro using both static and dynamic cultures. Additionally, we tested spheroids composed solely by induced hepatocytes. By miniaturizing the system, we demonstrated the possibility of maintaining the organoids, but not the spheroids, in culture for up to 15 days. This timeframe may be sufficient to carry out a hypothetical pharmacological test or screening. In conclusion, we propose that the hiPSC-derived liver organoids model could complement or, in the near future, replace the pharmacological and toxicological tests conducted on animals.

Milk serves as a crucial source of natural bioactive compounds essential for human nutrition and health. The gastrointestinal digestion of milk proteins releases various biologically active peptides that positively impact human health and enhance physiological performance. With the growing production of cheese, Greek yogurt, and other dairy products, the volume of unutilized acid whey is significantly increasing. Acid whey, containing almost all whey proteins and approximately one-quarter of casein, presents a valuable raw material for generating peptides with potential health benefits. These peptides exhibit properties such as antioxidant, antimicrobial, anti-inflammatory, anticarcinogenic, antihypertensive, antithrombotic, opioid, mineral-binding, and growth-stimulating activities, contributing to improved human immunity and the treatment of chronic diseases. Enzymatic hydrolysis of milk proteins has been developed as a method to produce these peptides, facilitating their use in food fortification. To incorporate whey into functional beverages, it undergoes fermentation by lactic acid bacteria with proteolytic activity. To specifically enrich these beverages with peptides exhibiting targeted bioactivities, it is essential to select lactic acid bacteria strains possessing the requisite protease profiles. Additionally, the sensory properties of the final product can be enhanced using starter cultures with diverse metabolic capabilities, even in the absence of added flavoring agents. Given the imperative to develop waste-free technologies and enhance the profitability of the dairy industry, there is a growing need to efficiently utilize and transform acid whey into a broad spectrum of valuable products and food additives. This approach is justified not only by the nutritional benefits of the bioactive components in whey but also by the commercial potential of safe and health-enhancing products.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

In order to shorten the detection time and improve the average precision on embedded devices, A lightweight and high accuracy model is proposed for passion fruit in complex environments (backlight, occlusion, overlap, sunny, cloudy, rainy). Firstly, replacing the backbone network of YOLOv5 with a lightweight GhostNet model reduces the number of parameters and computation while improving detection speed. Secondly, a new feature branch is added to the GhostNet network, and the feature fusion layer in the neck network is reconstructed to effectively combine the lower-level and higher-level features, which not only improves the accuracy of the model but also maintains its lightweight. Finally, the knowledge distillation methods are used to transfer the knowledge from the more capable teacher model to the less capable student model, which significantly improving the detection accuracy. The improved model is denoted as G-YOLO-NK. The average accuracy of the G-YOLO-NK network is 96.00%, which is 1.00% higher than the original YOLOv5s model. Furthermore, the improved model size is 7.14MB, reduced to half of the original model, and the real-time detection frame rate is 11.25 FPS on the Jetson Nano. Compared to the state-of-the-art model, the proposed model outperforms them in terms of average precision and detection performance. The present work provides an effective model for real-time detection of passion fruits in complex orchard scenes, which can provide valuable technical support for the development of orchard picking robots and greatly improve the intelligence level of orchards.

The Simultaneous Localization And Mapping (SLAM) scanner is an easy and portable Light Detection And Ranging (LiDAR) data acquisition device. Its main output is a 3D point cloud covering the scanned scene. Regarding the importance of accuracy in the survey domain, this paper aims to assess the accuracy of two SLAM scanners: the NavVis VLX and the BLK2GO Scanner. This assessment is conducted for both outdoor and indoor environments. In this context, two types of reference data are used: the Total Station (TS) and the static scanner Z+F Imager 5016. To carry out the assessment, four comparisons are tested: cloud to cloud, cloud to mesh, mesh to mesh, and edge detection board assessment. However, the results of the assessments confirm that the accuracy of indoor SLAM scanner measurements (5 mm) is greater than that of outdoor ones (between 10 mm and 60 mm). Moreover, the comparison of cloud to cloud provides the best accuracy regarding direct accuracy measurement without manipulations. Finally, based on the high accuracy, scanning speed, flexibility, and the accuracy differences between tested cases, it is confirmed that SLAM scanners are effective tools for data acquisition.

The impact of interaction SS with MJO on rainfall along Java Island to East Nusa Tenggara has been studied using daily rainfall observation data from 2140 weather observation stations, which are also equipped with GSMaP, OLR, and ERA5 data. There were 61 SS events found, 17 during active MJO and 44 in inactive MJO. Rainfall increases more in the western study area when the active MJO and more in the eastern study area when the inactive MJO is due to SS. SS reduces rainfall in the Jakarta region, regardless of the activity or inactivity of the MJO. SS causes extreme rainfall to only occur in a small part of certain areas, so it tends to significantly reduce the possibility of extreme rainfall. In the southern part of the IMC, SS predominates over MJO in supporting increased water vapor transport. Large-scale synoptic circulations like the monsoon, SS, and MJO can interact with local land-sea wind circulation to produce spatiotemporal variability in rainfall on Java Island. Rainfall mostly increases in the afternoon and decreases in the morning when SS occurs, whether there is MJO or not. Convective instability analysis indicates that SS increases precipitation, most likely by lowering CIN and raising VIMFC.

Acoustic Radiation Forced Impulse (ARFI) is an ultrasound integrated method, measuring stiff-ness by point shear wave elastography. To evaluate the diagnostic performance of ARFI of the liver and of the spleen, combined with spleen dimension and platelet count, in predicting clinical events in cirrhosis, a prospective and cross-sectional study was conducted between February 2017 and February 2021. The following ratio scores with ARFI measurements were performed: ALSDP (ARFI Liver-Spleen Diameter-to-Platelets ratio score), ASSDP (ARFI Spleen-Spleen Diam-eter-to-Platelets ratio score), ASSAP (ARFI Spleen-Spleen Area-to-Platelets ratio score), ALSAP (ARFI Liver-Spleen Area-to-Platelets ratio score). In 100 enrolled subjects, spleen ARFI, ASSDP, ASSAP, were significantly associated with high-risk oesophageal varices (HRVs) in the prospec-tive short- and long-term follow-up and in the cross-sectional study (p 0.7). ARFI-ratio scores can predict, in cirrhotic patients, the risk of developing HVRs in short and long-term period.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Superior fiber quality is one of the most important objectives in cotton breeding. To detect the genetic basis underlying fiber quality, an F2 population containing 413 plants was constructed by crossing Jifeng 914 and Jifeng 173, both of which have superior fiber quality, with Jifeng 173 being better. Five fiber quality traits were investigated in the F2, F2:3, F2:4, and F2:5 populations. Quantitative trait loci (QTL) mapping was conducted based on a high-density genetic map containing 11,488 single nucleotide polymorphisms (SNPs) and spanning 4,202.12 cM in length. Transgressive segregation patterns and complex correlations in the five tested traits were observed. A total of 108 QTLs were found, including 27 for fiber length (FL), 16 for fiber strength (FS), 24 for micronaire (MC), 17 for fiber uniformity (FU), and 24 for fiber elongation rate (FE). Chromosome A7 contained 12 QTL, ranking the first. No QTL was found on chromosome D1 and D11. Each QTL contributed 1.98%–21.45% to the phenotypic variation (PV), including 13 major effect QTLs that contributed more than 10% toward PV. Two QTLs could be repeatedly detected in three populations, including qFL-D3-2 in F2, F2:4, and F2:5 with 9.18%–21.45% of PV, qFS-A11-1 in F2:3, F2:4 and F2:5 with 6.05%–10.41% of PV. Another seven stable QTLs could be detected in two populations, including four major effect QTLs: qFL-A12-3, qFS-D10-2, qMC-D6-2, and qMC-D8-1. Fourteen QTL-overlapping regions were found, which might explain the complex correlations among the five phenotypic traits. Four regions on chromosome A11, D3, D6, and D10 covered by both stable and major effect QTLs are promising for further fine mapping. The genomic regions of the two QTLs detected in three populations and the four major effect QTLs contain 810 genes. Gene functional analysis revealed that the annotated genes are mainly involved in protein binding and metabolic pathways. Fifteen candidate genes in the qFL-D3-2 region are highly expressed in fiber or ovules during fiber initiation, elongation, secondary cell wall thickening, or maturation stages. qRT-PCR revealed that Ghir_D03G005440.1 and Ghir_D03G011310.1 may play a role in promoting fiber initiation, Ghir_D03G006470.1 may be beneficial for promoting fiber elongation. This study provides more information for revealing the molecular genetic basis underlying cotton fiber quality.

Currently there are fewer depth models applied to pepper picking detection, while the existing generalized neural networks have problems such as large model parameters, long training time, and low model accuracy.In order to solve the above problems, this paper proposes a Yolo-chili target detection algorithm for chili pepper detection. First, the classical target detection algorithm yolov5 is used as a benchmark model, and an adaptive spatial feature pyramid structure combining the attention mechanism and the idea of multi-scale prediction is introduced to improve the model's detection effect on occluded peppers and small target peppers. Secondly, a three-channel attention mechanism module is introduced to improve the algorithm's long-distance recognition ability and reduce the interference of redundant testers. Finally, the quantized pruning method is used to reduce the model parameters and realize the lightweight processing of the model. Applying the method to the homemade chili pepper dataset, the AP value of chili pepper reaches 93.11%; the accuracy rate is 93.51% and the recall rate is 92.55%.The experimental results show that yolo-chili is able to achieve accurate and real-time pepper detection under complex orchards.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

Aiming at the problems of inaccurate segmentation of long object and information loss of small object in real-time semantic segmentation algorithm, this paper proposes a lightweight multi-branch real-time semantic segmentation network based on BiseNetV2. The new auxiliary branch makes full use of spatial details and context information to cover the long object in the field of view. Meanwhile, in order to ensure the inference speed of the model, the asymmetric convolution is used in each stage of the auxiliary branch to design a structure with low computational complexity. In the multi-branch fusion stage, the alignment and fusion module is designed to provide guidance information for deep and shallow feature mapping, so as to make up for the problem of feature misalignment in the fusion of information at different scales, and thus reduce the loss of small target information. In order to further improve the model’s awareness of key information, a global context module is designed to capture the most important features in the input data. The proposed network uses NVIDIA GeForce RTX 3080 Laptop GPU experiment, on the road street view data set Cityscapes and CamVid average occurring simultaneously ratio reached 77.1% and 78.4% respectively, with running speed of 127 frames/s respectively and 112 frames/s. The experimental results show that the proposed algorithm can achieve real-time segmentation and improve the accuracy significantly, showing good semantic segmentation performance

In this paper we study a class of impulsive delayed neural networks with parameter uncertainties and reaction-diffusion terms. Using the properties of M-matrices and some inequality techniques, some sufficient conditions are derived to guarantee the global exponential stability of the given system. The results obtained are presented by simple algebraic inequalities, which are certainly more concise than previous methods. Finally, the validity and usefulness of our results are illustrated by arithmetic examples.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Pyrops candelaria is one of the common pests of fruit trees, but the research on the pathogenic microorganisms it may carry is very limited. Therefore, it is essential to reveal the pathogenic microbes it carries and their potential hazards. This study found a new virus from the transcriptome of P. candelaria, which was first reported in P. candelaria and named as PyCaV (Pyrops candelaria associated virus). RACE and bioinformatics assay revealed that the full-length of PyCaV is 10855 bp with the polyA tail, containing a single open reading frame (ORF) encoding a polyprotein consisting of 3171 amino acid (aa). The virus has a typical Iflavirus structure, including two rhv domains, a RNA helicase domain (HEL), a 3C cysteine protease domain (Pro), and a RNA-dependent RNA polymerase domain (RdRp). Further phylogenetic analysis revealed that this virus belongs to family Iflaviridae and sequence alignements analysis suggedted PyCaV is new member in unassigned genus of family Iflaviridae. Further in-depth analysis of virus-infection-part showed that PyCaV is distributing in the whole longan lanternfly, including its head, chest, and abdomen, but more PyCaV was identified in the chest. The distribution of PyCaV in different parts of P. candelaria was further explored, which showed that more PyCaV were detected in its piercing-sucking mouthparts and chest viscera. Statistical analysis showed that the PyCaV infection was affected by time and locations.

With the burgeoning growth of online retail, the issue of counterfeit products has become a significant threat to both consumer trust and brand integrity, posing challenges to sustainable market practices. Online retail platforms are promoted to redesign their channel structures and enhance brand traceability to tackle counterfeits using blockchain technology. To investigate the interactions between blockchain technology and the channel structures of online retail platforms, we design a game theory model incorporating a manufacturer with(out) blockchain participation selling products via an online retail platform that operates an agency channel and/or a reselling channel. We show that the critical trade-off of blockchain participation comprises the brand assurance effect of the blockchain, the channel competition intensification effect, and the blockchain adoption cost. The platform is capable of strategically designing the channel structure to encourage (while discouraging) blockchain participation by the manufacturer. Our analysis highlights the complementarity between blockchain participation and the channel structure. Furthermore, the effect of the consumer’s belief in the reselling channel, the commission fee in the agency channel, and the substitutability between channels are investigated in depth. The research provides valuable insights for online retail platforms and policymakers seeking to foster a sustainable and trustworthy e-commerce ecosystem.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

The paper describes the new method for image compression based on coordinated group signal transformation. The algorithm is a type of difference coding. Coordinated processing significantly simplifies the difference signal conversion scheme using a single group codec for all signals. The described method considers color channels as correlated signals of a multi-channel communication system. The specifics of the processed data required modification of the coordinated group processing algorithm. First, we changed how to calculate the difference signals to prevent data loss. Secondly, the group codec was supplemented with a neural network to improve the quality of reconstructed images. We considered the following types of neural networks: fully connected, recurrent, convolution, and convolution in the Fourier space. Based on the simulation results, it is best to use fully connected neural networks if the goal is to minimize processing delay time. These networks have a response time of 13 ms. On the other hand, if the priority is to improve quality in cases where delays are not critical, then convolution neural networks in the Fourier space should be used. These networks have a response time of 140 ms and are of significant interest.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.