Being motivated has positive influences on task performance. However, motivation could result from various motives that affect different parts of the brain. Analyzing the motivation effect from all affected areas requires a high number of EEG electrodes, resulting in high cost, inflexibility, and burden to users. In various real-world applications, only the motivation effect is required for performance evaluation regardless of the motive. Analyzing the relationships between the motivation-affected brain areas associated with the task’s performance could limit the required electrodes. This study introduced a method to identify the cognitive motivation effect with a reduced number of EEG electrodes. The temporal association rule mining (TARM) concept was used to analyze the relationships between attention and memorization brain areas under the effect of motivation from the cognitive motivation task. For accuracy improvement, the artificial bee colony (ABC) algorithm was applied with the central limit theorem (CLT) concept to optimize the TARM parameters. From the results, our method can identify the motivation effect with only FCz and P3 electrodes, with 74.5% classification accuracy on average with individual tests. Full article

Cytochrome P450 CYP121A1 is a well-known drug target against Mycobacterium tuberculosis, the human pathogen that causes the deadly disease tuberculosis (TB). CYP121A1 is a unique P450 enzyme because it uses classical and non-classical P450 catalytic processes and has distinct structural features among P450s. However, a detailed investigation of CYP121A1 protein structures in terms of active site cavity dynamics and key amino acids interacting with bound ligands has yet to be undertaken. To address this research knowledge gap, 53 CYP121A1 crystal structures were investigated in this study. Critical amino acids required for CYP121A1’s overall activity were identified and highlighted this enzyme’s rigid architecture and substrate selectivity. The CYP121A1-fluconazole crystal structure revealed a novel azole drug–P450 binding mode in which azole heme coordination was facilitated by a water molecule. Fragment-based inhibitor approaches revealed that CYP121A1 can be inhibited by molecules that block the substrate channel or by directly interacting with the P450 heme. This study serves as a reference for the precise understanding of CYP121A1 interactions with different ligands and the structure–function analysis of P450 enzymes in general. Our findings provide critical information for the synthesis of more specific CYP121A1 inhibitors and their development as novel anti-TB drugs. Full article

Flavobacterium psychrophilum is currently one of the most important pathogens in aquaculture worldwide, causing high losses to farmed salmonids particularly during early growth stages with significant economic impact. Despite previous attempts, no effective vaccine has been developed, and protection against introduction into farms is difficult due to the ubiquitous occurrence of the pathogen. A better understanding of the mechanism of disease development is essential for targeted therapeutic and preventive measures in farms. Unfortunately, the pathogenesis of diseases caused by F. psychrophilum has not been elucidated yet. Previously, several putative virulence factors have been identified. Some appear to be essential for disease development, while others are probably dispensable. The importance of some factors has not yet been explored. This review focuses on the supposed virulence factors of F. psychrophilum and the current knowledge about their importance in the pathogenesis of the disease. Full article

The electronic structure of 7/9-AGNR superlattices with up to eight unit cells has been studied by means of state-of-the-art Density Functional Theory (DFT) and also by two model Hamiltonians, the first one including only local interactions (Hubbard model, Hu) while the second one is extended to allow long-range Coulomb interactions (Pariser, Parr and Pople model, PPP). Both are solved within mean field approximation. At this approximation level, our calculations show that 7/9 interfaces are better described by spin non-polarized solutions than by spin-polarized wavefunctions. Consequently, both Hu and PPP Hamiltonians lead to electronic structures characterized by a gap at the Fermi level that diminishes as the size of the system increases. DFT results show similar trends although a detailed analysis of the density of states around the Fermi level shows quantitative differences with both Hu and PPP models. Before improving model Hamiltonians, we interpret the electronic structure obtained by DFT in terms of bands of topological states: topological states localized at the system edges and extended bulk topological states that interact between them due to the long-range Coulomb terms of Hamiltonian. After careful analysis of the interaction among topological states, we find that the discrepancy between ab initio and model Hamiltonians can be resolved considering a screened long-range interaction that is implemented by adding an exponential cutoff to the interaction term of the PPP model. In this way, an adjusted cutoff distance $\lambda =2$ allows a good recovery of DFT results. In view of this, we conclude that the correct description of the density of states around the Fermi level (Dirac point) needs the inclusion of long-range interactions well beyond the Hubbard model but not completely unscreened as is the case for the PPP model. Full article

Cyber competitions are usually team activities, where team performance not only depends on the members’ abilities but also on team collaboration. This seems intuitive, especially given that team formation is a well-studied discipline in competitive sports and project management, but unfortunately, team performance and team formation strategies are rarely studied in the context of cybersecurity and cyber competitions. Since cyber competitions are becoming more prevalent and organized, this gap becomes an opportunity to formalize the study of team performance in the context of cyber competitions. This work follows a cross-validating two-approach methodology. The first is the computational modeling of cyber competitions using Agent-Based Modeling. Team members are modeled, in NetLogo, as collaborating agents competing over a network in a red team/blue team match. Members’ abilities, team interaction and network properties are parametrized (inputs), and the match score is reported as output. The second approach is grounded in the literature of team performance (not in the context of cyber competitions), where a theoretical framework is built in accordance with the literature. The results of the first approach are used to build a causal inference model using Structural Equation Modeling. Upon comparing the causal inference model to the theoretical model, they showed high resemblance, and this cross-validated both approaches. Two main findings are deduced: first, the body of literature studying teams remains valid and applicable in the context of cyber competitions. Second, coaches and researchers can test new team strategies computationally and achieve precise performance predictions. The targeted gap used methodology and findings which are novel to the study of cyber competitions. Full article

Mechanical insufflation-exsufflation (MI-E) is essential for secretion clearance, especially in neuromuscular disorders. For the best outcomes, initiation of MI-E should be started at the correct time with regular evaluation to the response to treatment. Typically, cough peak flow has been used to evaluate cough effectiveness with and without MI-E. This review highlights the limitations of this and discussed other tools to evaluate MI-E efficacy in this rapidly developing field. Such tools include the interpretation of parameters (like pressure, flow and volumes) that derive from the MI-E device and external methods to evaluate upper airway closure. In this review we pinpoint the differences between different devices in the market and discuss new tools to better titrate MI-E and detect pathological responses of the upper airway. We discuss the importance of point of care ultrasound (POCUS), transnasal fiberoptic laryngoscopy and wave form analysis in this setting. To improve clinical practice newer generation MI-E devices should allow real-time evaluation of waveforms and standardize some of the derived parameters. Full article

The use of temporary resin for provisional restorations is a fundamental step to maintain the position of prepared teeth, to protect the pulpal vitality and the periodontal health as well as the occlusion. The present study aimed at evaluating the biological effects of two resins used in dentistry for temporary restorations, Coldpac (Yates Motloid) and ProTemp 4™ (3M ESPE ™), and their eluates, in an in vitro model of human gingival fibroblasts (hGFs). The activation of the inflammatory pathway NFκB p65/NLRP3/IL-1β induced by the self-curing resin disks was evaluated by real-time PCR, Western blotting and immunofluorescence analysis. The hGFs adhesion on resin disks was investigated by means of inverted light microscopy and scanning electron microscopy (SEM). Our results suggest that hGF cells cultured in adhesion and with eluate derived from ProTemp 4™ (3M ESPE ™) resin evidenced a downregulation in the expression of the inflammatory mediators such as NFκB p65, NLRP3 and IL-1β compared to the cells cultured with Coldpac (Yates Motloid) after 24 h and 1 week of culture. Furthermore, the cells cultured with ProTemp 4™ (3M ESPE ™) after 24 h and 1 week of culture reported a higher cell viability compared to the cells cultured with Coldpac (Yates Motloid), established by MTS cell analysis. Similar results were obtained when hGFs were placed in culture with the eluate derived from ProTemp 4™ (3M ESPE ™) resin which showed a higher cell viability compared to the cells cultured with eluate derived from Coldpac (Yates Motloid). These results highlighted the lower pro-inflammatory action and improved cell biocompatibility of ProTemp 4™ (3M ESPE ™), suggesting a better performance in terms of cells–material interaction. Full article

Fatty acid synthesis has been extensively investigated as a therapeutic target in cancers, including colorectal cancer (CRC). Fatty acid synthase (FASN), a key enzyme of de novo lipid synthesis, is significantly upregulated in CRC, and therapeutic approaches of targeting this enzyme are currently being tested in multiple clinical trials. However, the mechanisms behind the pro-oncogenic action of FASN are still not completely understood. Here, for the first time, we show that overexpression of FASN increases the expression of glutamine–fructose-6-phosphate transaminase 1 (GFPT1) and O-linked N-acetylglucosamine transferase (OGT), enzymes involved in hexosamine metabolism, and the level of O-GlcNAcylation in vitro and in vivo. Consistently, expression of FASN significantly correlates with expression of GFPT1 and OGT in human CRC tissues. shRNA-mediated downregulation of GFPT1 and OGT inhibits cellular proliferation and the level of protein O-GlcNAcylation in vitro, and knockdown of GFPT1 leads to a significant decrease in tumor growth and metastasis in vivo. Pharmacological inhibition of GFPT1 and OGT leads to significant inhibition of cellular proliferation and colony formation in CRC cells. In summary, our results show that overexpression of FASN increases the expression of GFPT1 and OGT as well as the level of protein O-GlcNAcylation to promote progression of CRC; targeting the hexosamine biosynthesis pathway could be a therapeutic approach for this disease. Full article

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and foetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, which play a critical role in maintaining immune homeostasis, are crucial in pregnancy to prevent immune-mediated rejection of the foetus. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring foetal acceptance. In contrast, HDP is associated with Treg dysfunction, which is marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, in which Tregs fail to adequately modulate the maternal immune response against foetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs, the review explores the complexities of translating in vitro and animal model findings into effective clinical therapies. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy. Full article

Pancreaticolithiasis represents a rare phenomenon, being superimposed most of the time on a form of chronic pancreatitis of multifactorial etiology. Pancreaticolithiasis is a late complication of the phenomenon of chronic pancreatitis. The reverberant inflammatory process, followed by the fibrotic degeneration of the pancreatic parenchyma, and pancreatic fluid stasis at the ductal level are factors that contribute to the phenomenon of calcium precipitation. This article describes the case of a patient with a diagnosis of pancreaticolithiasis (Wirsung duct lithiasis), a phenomenon superimposed on chronic pancreatitis of ethanolic cause (Rosemont classification). It was decided to perform surgery via the classical approach with the perfection of corporeo-caudal pancreatectomy and preservation of the splenic vessels (Kimura procedure) with pancreatico-jejunal anastomosis on the Roux-en-Y loop. The aim of this study is to identify the best method of treatment for pancreaticolithiasis. To enhance the case and provide a basis for standardization, a literature review was carried out, which included a total of six articles. The results of this study highlight that, currently, the management of symptomatic pancreaticolithiasis encompasses medical therapy (enzyme replacement therapy), interventional therapy (ESWL (extracorporeal shock wave lithotripsy) ± ERCP (endoscopic retrograde cholangiopancreatography), ERCP + sphincterotomy + stent insertion, and POP (oral pancreatoscopy)), and surgical treatment. In conclusion, based on the analysis conducted in this study, the size of the calculi present determines which is the suitable therapeutic care. Unlike stones over 0.5 cm, when surgery is explicitly advised for therapeutic purposes in the absence of endoscopic techniques, stones under 0.5 cm should be treated using endoscopic procedures. Full article

Introduction: The current state of pathology practice and the variability in diagnosing pT4a colon cancer have been underexplored in existing studies. Our objective was to establish a specific cutoff point to distinguish between the pathological stages of pT3 and pT4a in colon cancer. Methods: We conducted a cross-sectional study involving pT3 and pT4 (pN0-2, cM0) colon cancers, measuring the distance to the serosa. Patients were categorized and analyzed based on this distance and the peritoneal reaction, with the aim being to ascertain their prognostic implications. Results: A total of 384 patients were analyzed. Patients with a distance between the invading front of cancer and the serosa ≥ 1 mm without a peritoneal reaction exhibited a median survival of 118 months, contrasting the amount of 70 months for those with <1 mm plus peritoneal reaction. Only lengths <1 mm with peritoneal reaction showed a significant correlation with mortality (p < 0.001). Conclusion: Our study revealed that patients in whom neoplastic cells were less than 1 mm from the serosal surface, accompanied by a peritoneal reaction (hemorrhage, inflammation, neovascularization, fibrin), had significantly lower survival rates compared to those with more than 1 mm distance and without peritoneal response (70 vs. 118 months, p < 0.001). Hence, such cases should be considered within the pT4a stage. Full article

Introduction: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) mortality remains high despite revascularization and the use of the intra-aortic balloon pump (IABP). Advanced mechanical circulatory support (MCS) devices, such as catheter-based ventricular assist devices (cVAD), may impact mortality. We aim to identify predictors of mortality in AMI-CS implanted with IABP and the proportion eligible for advanced MCS in an Asian population. Methods: We retrospectively analyzed a cohort of Society for Cardiovascular Angiography and Intervention (SCAI) stage C and above AMI-CS patients with IABP implanted from 2017–2019. We excluded patients who had IABP implanted for indications other than AMI-CS. Primary outcome was 30-day mortality. Binary logistic regression was used to calculate adjusted odds ratios (aOR) for patient characteristics. Results: Over the 3-year period, 242 patients (mean age 64.1 ± 12.4 years, 88% males) with AMI-CS had IABP implanted. 30-day mortality was 55%. On univariate analysis, cardiac arrest (p < 0.001), inotrope/vasopressor use prior to IABP (p = 0.004) was more common in non-survivors. Non-survivors were less likely to be smokers (p = 0.001), had lower ejection fraction, higher creatinine/ lactate and lower pH (all p < 0.001). On multi-variate analysis, predictors of mortality were cardiac arrest prior to IABP (aOR 4.00, CI 2.28–7.03), inotrope/vasopressor prior to IABP (aOR 2.41, CI 1.18–4.96), lower arterial pH (aOR 0.02, CI 0.00–0.31), higher lactate (aOR 2.42, CI 1.00–1.19), and lower hemoglobin (aOR 0.83, CI 0.71–0.98). Using institutional MCS criteria, 106 patients (44%) would have qualified for advanced MCS. Conclusions: Early mortality in AMI-CS remains high despite IABP. Many patients would have qualified for higher degrees of MCS. Full article

More than half of patients hospitalized with liver cirrhosis are dealing with an episode of acute kidney injury; the most severe pattern is hepatorenal syndrome due to its negative prognosis. The main physiopathology mechanisms involve renal vasoconstriction and systemic inflammation. During the last decade, the definition of hepatorenal syndrome changed, but the validated criteria of diagnosis are still based on the serum creatinine level, which is a biomarker with multiple limitations. This is the reason why novel serum and urinary biomarkers have been intensively studied in recent years. Meanwhile, the imaging studies that use shear wave elastography are using renal stiffness as a surrogate for an early diagnosis. In this article, we focus on the physiopathology definition and highlight the novel tools used in the diagnosis of hepatorenal syndrome. Full article

Background: Among elderly inpatients, malnutrition is one of the most important predictive factors affecting length of stay (LOS), mortality, and risk of re-hospitalization. Methods: We conducted an observational, retrospective study on a cohort of 2206 acutely inpatients. Serum albumin and lymphocytes were evaluated. Instant Nutritional Assessment (INA) and the Prognostic Nutritional Index (PNI) were calculated to predict in-hospital mortality, LOS, and risk of rehospitalization. Results: An inverse relationship between LOS, serum albumin, and PNI were found. Deceased patients had lower albumin levels, lower PNI values, and third- and fourth-degree INA scores. An accurate predictor of mortality was PNI (AUC = 0.785) after ROC curve analysis; both lower PNI values (HR = 3.56) and third- and fourth-degree INA scores (HR = 3.12) could be independent risk factors for mortality during hospitalization after Cox regression analysis. Moreover, among 309 subjects with a lower PNI value or third- and fourth-class INA, hospitalization was re-hospitalization. Conclusions: PNI and INA are two simple and quick-to-calculate tools that can help in classifying the condition of hospitalized elderly patients also based on their nutritional status, or in assessing their mortality risk. A poor nutritional status at the time of discharge may represent an important risk factor for rehospitalization in the following thirty days. This study confirms the importance of evaluating nutritional status at the time of hospitalization, especially in older patients. This study also confirms the importance for adequate training of doctors and nurses regarding the importance of maintaining a good nutritional status as an integral part of the therapeutic process of hospitalization in acute departments. Full article

Detection of minimal residual disease (MRD) is a major independent prognostic marker in the clinical management of pediatric and adult B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL), and risk stratification nowadays heavily relies on MRD diagnostics. MRD can be detected using flow cytometry based on aberrant expression of markers (antigens) during malignant B-cell maturation. Recent advances highlight the significance of novel markers (e.g., CD58, CD81, CD304, CD73, CD66c, and CD123), improving MRD identification. Second and next-generation flow cytometry, such as the EuroFlow consortium’s eight-color protocol, can achieve sensitivities down to 10⁻⁵ (comparable with the PCR-based method) if sufficient cells are acquired. The introduction of targeted therapies (especially those targeting CD19, such as blinatumomab or CAR-T19) introduces several challenges for flow cytometric MRD analysis, such as the occurrence of CD19-negative relapses. Therefore, innovative flow cytometry panels, including alternative B-cell markers (e.g., CD22 and CD24), have been designed. (Semi-)automated MRD assessment, employing machine learning algorithms and clustering tools, shows promise but does not yet allow robust and sensitive automated analysis of MRD. Future directions involve integrating artificial intelligence, further automation, and exploring multicolor spectral flow cytometry to standardize MRD assessment and enhance diagnostic and prognostic robustness of MRD diagnostics in BCP-ALL. Full article

Perovskite solar cells (PSCs) have attracted much attention due to their low cost, high efficiency, and solution processability. With the development of various materials in perovskite solar cells, self-assembled monolayers (SAMs) have rapidly become an important factor in improving power conversion efficiency (PCE) due to their unique physical and chemical properties and better energy level matching. In this topical review, we introduced important categories of self-assembled molecules, energy level modulation strategies, and various characteristics of self-assembled molecules. In addition, we focused on reviewing the application of self-assembled molecules in solar cells, and explained the changes that self-assembled molecules bring to PSCs by introducing the mechanism and effect of self-assembled molecules. Finally, we also elaborated on the challenges currently faced by self-assembled molecules and provided prospects for their applications in other optoelectronic devices. Full article

The consumer decision-making process for buying food products is based on various factors. One of these is the perceived value that the consumer acquires upon seeing a certification label, such as “Protected Designation of Origin” (PDO) and “Protected Geographical Indication” (PGI), which is an indicator of product quality and the degree of sustainability of the supply chain. The aim of the study is to identify the main factors influencing the behaviour and purchasing intentions of Italian consumers through the divulgation of a survey and the application of a statistical approach. The results were elaborated upon using a conceptual model, estimated following the partial least squares approach to structural equation modelling. As a result, the perception of quality influences purchasing decisions and food patterns, as labels play an increasing role in contemporary society, thus making quality standards relevant for the buying outcome. This research contributes to supporting studies on the importance of certifications of origin, as well as highlighting that food safety is a major determinant in the purchasing of certified food products. Full article

The objective of this study was to investigate age-related changes in cashmere production and the population of active secondary hair follicles in cashmere goats across different age groups as well as to explore the association between secondary hair follicle activity and oxidative stress. A total of 104 adult Inner Mongolian ewe goats, aged between 2 and 7 years old, were randomly selected as experimental subjects. Skin samples were collected in August 2020 and cashmere samples were collected in April 2021. The cashmere fiber yield, staple length, and diameter showed age-related variations in cashmere goats aged 2 to 7 years (p < 0.05). Cashmere production was higher in goats aged 2–4 years compared to those aged 5–7 years (p < 0.05). There were no significant differences in the population of primary and secondary hair follicles among goats aged 2 to 7 years. However, the population of active secondary hair follicles varied significantly with age, with the younger group (aged 2–4 years) having a higher population than those aged 5–7 years (p < 0.05). A moderate negative correlation was observed between cashmere fiber diameter and the population of active secondary hair follicles (p < 0.05). Age-related variations in skin antioxidant capacity and oxidative damage were observed among cashmere goats aged 2 to 7 years old (p < 0.05). Goats aged 2 to 4 years exhibited higher antioxidant capacity and lower oxidative damage (p < 0.05). Interestingly, the skin’s antioxidant capacity and oxidative damage exhibited significant positive and negative correlations with the population of active secondary hair follicles (p < 0.05). This study presents a novel approach to enhance the activity of secondary hair follicles and improve cashmere production performance through the regulation of oxidative stress. Full article

A composite structure containing a metallic skeleton and polyurea elastomer interpenetrating phase was fabricated, and its anti-penetration performance for low-velocity large mass fragments was experimentally studied. The protection capacity of three polyurea was compared based on the penetration resistance force measurement. Results show that the polyurea coating layer at the backside improves the performance of the polyurea-filled spherical cell porous aluminum (SCPA) plate due to its backside support effect and phase transition effect, which are accompanied by a large amount of energy absorption. The frontal-side-coated polyurea layer failed to shear and provided a very limited strengthening effect on the penetration resistance of the interpenetrating phase composite panel. The filling polyurea in SCPA increased the damage area and formed a compression cone for the backside coating layer, leading to a significant stress diffusion effect. The anti-penetration performance was synergistically improved by the plug block effect of the interpenetrating phase composite and the backside support effect of the PU coating layer. Compared with SCPA, the initial impact failure strength and the average resistance force of the composite plate were improved by 120–200% and 108–274%, respectively. Full article

“Climate, Psychology and Change” offers a profound exploration of the psychological ramifications of the climate and ecological emergency (CEE), proposing a paradigm shift in psychotherapy to better support individuals and communities grappling with environmental distress. The book critiques the prevailing hyper-individualized and neoliberal societal framework, advocating for a decolonized, systemic psychotherapeutic approach that emphasizes interconnectedness across species and that challenges human exceptionalism. It outlines four psychological phases that individuals may experience in their environmental consciousness journey, epiphany, immersion, crisis, and resolution, highlighting their non-linear and systemic nature. This work underscores the importance of understanding distress within its broader social and ecological contexts and addresses the profound inequalities and injustices exacerbated by the CEE. With contributions from diverse psychological and non-traditional backgrounds, it introduces concepts like ‘ubuntu’, advocating for community-focused resilience practices. The book calls for a re-evaluation of psychotherapeutic practices to include communal and nature-connected approaches, offering innovative solutions like climate cafes and social dreaming. It presents a critical yet hopeful vision for the role of psychotherapy in navigating the challenges of the CEE, urging a rethinking of our relationship with the planet and each other, making it an essential read for those seeking to align psychotherapeutic practice with the realities of our changing world. Full article

Numerous therapeutic and diagnostic approaches used within a clinical setting depend on the administration of compounds via systemic delivery. Biomaterials at the nanometer scale, as dendrimers, act as delivery systems by improving cargo bioavailability, circulation time, and the targeting of specific tissues. Although evaluating the efficacy of pharmacological agents based on nanobiomaterials is crucial, conducting toxicological assessments of biomaterials is essential for advancing clinical translation. Here, a zebrafish larvae model was explored to assess the biocompatibility of poly(amido amine) (PAMAM), one of the most exploited dendrimers for drug delivery. We report the impact of a systemic injection of polyethylene glycol (PEG)-modified G4 PAMAM conjugated with rhodamine (Rho) as a mimetic drug (PEG–PAMAM–Rho) on survival, animal development, inflammation, and neurotoxicity. A concentration- and time-dependent effect was observed on mortality, developmental morphology, and innate immune system activation (macrophages). Significant effects in toxicological indicators were reported in the highest tested concentration (50 mg/mL PEG–PAMAM–Rho) as early as 48 h post-injection. Additionally, a lower concentration of PEG–PAMAM–Rho (5 mg/mL) was found to be safe and subsequently tested for neurotoxicity through behavioral assays. In accordance, no significative signs of toxicity were detected. In conclusion, the dose response of the animal was assessed, and the safe dosage for future use in theragnostics was defined. Additionally, new methodologies were established that can be adapted to further studies in toxicology using other nanosystems for systemic delivery. Full article

Emerging tick-borne viruses such as Powassan virus (POWV), Bourbon virus (BRBV), and Heartland virus (HRTV), whilst rare, can cause severe health problems in humans. While limited clinical cases have been reported thus far in Virginia, the presence of tick-borne viruses poses a serious health threat, and the extent of their prevalence in Virginia is unknown. Here, we sought evidence of POWV, BRBV, and HRTV exposure in Virginia via a serological assessment of wildlife and livestock. Wildlife in Virginia were found to be seropositive against POWV (18%), BRBV (8%), and HRTV (5%), with western and northern regions of the state having a higher prevalence. Multiple wildlife species were shown to have been exposed to each virus examined. To a lesser extent, cattle also showed exposure to tick-borne viruses, with seroprevalences of 1%, 1.2%, and 8% detected in cattle against POWV, BRBV, and HRTV, respectively. Cross-reactivity against other known circulating mosquito-borne flaviviruses was ruled out. In conclusion, there is widespread exposure to tick-borne viruses in western and northern Virginia, with exposure to a diverse range of both domestic and wild animal populations. Our study provides the first confirmation that HRTV is circulating in the Commonwealth. These findings strengthen the existing evidence of emerging tick-borne viruses in Virginia and highlight the need for public health vigilance to avoid tick bites. Full article