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The hepatitis C virus (HCV) is responsible for approximately 50 million infections worldwide. Effective drug treatments while available face access barriers, and vaccine development is hampered by viral hypervariability and immune evasion mechanisms. The CD4+ and CD8+ T-cell responses targeting HCV non-structural (NS) proteins have shown a role in the viral clearance. In this paper, we reviewed the studies exploring the relationship between HCV structural and NS proteins and their effects in contributing to the elicitation of an effective T-cell immune response. The use of different vaccine platforms, such as viral vectors and virus-like particles, underscores their versability and efficacy for vaccine development. Diverse HCV antigens demonstrated immunogenicity, eliciting a robust immune response, positioning them as promising vaccine candidates for protein/peptide-, DNA-, or RNA-based vaccines. Moreover, adjuvant selection plays a pivotal role in modulating the immune response. This review emphasizes the importance of HCV proteins and vaccination strategies in vaccine development. In particular, the NS proteins are the main focus, given their pivotal role in T-cell-mediated immunity and their sequence conservation, making them valuable vaccine targets.

Visceral leishmaniasis (VL) results from protozoa Leishmania infantum and L. donovani infection. This study investigated whether host factors would explain the relapses. First, susceptibility to amphotericin B of L. infantum isolates was evaluated in vitro. Then, clinical data and the lipid profile of patients with relapsing and non-relapsing VL were assessed. Susceptibility to amphotericin B was similar between the isolates. CD4+ lymphocytes were reduced in both groups of patients in the first episode and with relapsing VL. Still, the strongest blood cell indicator associated with relapses was low total lymphocyte counts. Total plasma cholesterol, high-density lipoprotein, low-density lipoprotein, and, uniquely, triglycerides of the six individuals in the first episode and twenty-three with relapsing VL were lower in relapsing patients than those in the first episode. Deceased patients had extremely low low-density lipoprotein. After CD4+ decreases, lymphocyte CD8+ reduction is the final stage of immunological failure. The lower lipid concentrations appear to be secondary to the depletion of fat stores by inflammation-induced cachexia and fat exhaustion provoked by the co-occurrence of both diseases, which can finally lead to death.

This paper presents a review on the formability evaluation of AHSS, enhancing necking-based failure criteria limitations. Complementary fracture/damage constitutive modeling approaches specifically tailored to formability evaluation, validated through numerical and experimental methods, are also subjects of research. AHSS are widely processed through sheet metal forming processes. Although an excellent choice when lightweight, high-strength, and ductility are critical factors, their multi-phase microstructure accentuates forming challenges. To accurately model forming behavior, necking-based failure criteria as well as direct fracture models require improvements. As a necking-based failure model, the conventional forming limit diagram/curve (FLD/FLC) presents limitations in estimating direct fracture (surface cracks, edge cracks, shear cracks), as well as deformation histories under non-linear strain paths. Thus, significant research efforts are being made towards the development of advanced fracture constitutive models capable of predicting fracture scenarios without necking, which are more frequently observed in the realm of AHSS. Scientific community research is divided into several directions aiming at improving the forming and fracture behavior accuracy of parts subjected to sheet metal forming operations. In this review paper, a comprehensive overview of ductile fracture modeling is presented. Firstly, the limitations of FLD/FLC in modeling fracture behavior in sheet metal forming operations are studied, followed by recent trends in constitutive material modeling. Afterwards, advancements in material characterization methods to cover a broad range of stress states are discussed. Finally, damage and fracture models predicting failure in AHSS are investigated. This review paper supplies relevant information on the current issues the sheet metal forming community is challenged with due to the trend towards AHSS employment in the automotive industry.

The principle of reflection of ultrasonic waves at lubricated interfaces has been widely studied in recent years using different models. In this work, two different models (the spring model and the resonance model) were used to verify the influence of the acoustic properties of four different lubricating oils. A simple three-layer configuration was used, where carefully prepared, well-controlled gaps between stainless steel plates were established to accommodate a drop of oil. Optical measurements showed that the gaps formed were: gap 1 = 11 µm, gap 2 = 85 µm, gap 3 = 100 µm, and gap 4 = 170 µm. The smaller gap (11 µm) was found to be in the limit measurement range using the spring model for the sensor used in this work (14 MHz), whereas the resonance method was used for the thicker gaps. For the resonance model, the use of the phase spectra helped the identification of the resonance frequencies. The results showed good agreement between the measured thicknesses and the nominal gap values. There was little effect of the acoustic properties of the oils on the measured values, with the largest discrepancies found for the oil with the highest speed of sound (PAO4). This new way to characterize oil properties in a thin gap, where the material and geometry of the contact are fully characterized, enables us to compare different measurement methods and understand their sensitivity when testing similar materials of the same class of lubricants, as small deviations are crucial in real-life applications.

A population of sea urchins, Paracentrotus lividus, from the central west coast of Portugal was studied to characterise their reproductive biology and possible relationships with environmental factors. An annual gametogenic cycle was found, with a broad spawning season, from May to November, according to a relatively synchronous gamete maturation process. Depending on the environmental factors (temperature, photoperiod), two separate periods could be distinguished, with more individuals maturing and spawning at the same time. When this happened, the first event evolved when temperature rose to a critical point, and the second occurred afterwards, when temperature decreased significantly. Notwithstanding, it was found that individuals matured later than previously described for other populations (e.g., north of Portugal), mostly in late spring, with a higher gonadosomatic index in May. A new classification scale was proposed for identifying the stages of P. lividus gametogenic cycle, based on new findings. It contributed to its simplification and easier comprehension. This study provides useful information for a differentiated sustainable management of P. lividus, according to local conditions. Establishing a closed harvesting season might be considered, based on the differences observed between Portuguese populations and other European ones.

Kala-azar, also known as visceral leishmaniasis (VL), is a disease caused by Leishmania infantum and L. donovani. Patients experience symptoms such as fever, weight loss, paleness, and enlarged liver and spleen. The disease also affects immunosuppressed individuals and has an overall mortality rate of up to 10%. This overview explores the literature on the pathogenesis of preclinical and clinical stages, including studies in vitro and in animal models, as well as complications and death. Asymptomatic infection can result in long-lasting immunity. VL develops in a minority of infected individuals when parasites overcome host defenses and multiply in tissues such as the spleen, liver, and bone marrow. Hepatosplenomegaly occurs due to hyperplasia, resulting from parasite proliferation. A systemic inflammation mediated by cytokines develops, triggering acute phase reactants from the liver. These cytokines can reach the brain, causing fever, cachexia and vomiting. Similar to sepsis, disseminated intravascular coagulation (DIC) occurs due to tissue factor overexpression. Anemia, hypergammaglobulinemia, and edema result from the acute phase response. A regulatory response and lymphocyte depletion increase the risk of bacterial superinfections, which, combined with DIC, are thought to cause death. Our understanding of VL’s pathogenesis is limited, and further research is needed to elucidate the preclinical events and clinical manifestations in humans.

Infection with Leishmania amazonensis and L. mexicana may lead to diffuse cutaneous leishmaniasis. The cure is exceptional, especially for the strange case of this lady. Case report: The patient acquired the disease in childhood and remained with lesions for over 30 years, albeit several treatments. She worsened after a pregnancy, developing disseminated lesions. Miltefosine with amphotericin B and pentamidine resulted in remission. Lesions reappeared after one year, accompanied by intra-nasal infiltration of the disease. The nasal spraying of a single ampoule of pentavalent antimoniate resulted in the sustained disappearance of the nasal symptoms and all the cutaneous lesions. After over eight years, she remains disease-free, albeit under renal replacement therapy. The high nasal mucosal antimonial concentration may explain the long-lasting cure via new MHC class I epitope-specific CD8+ cell clones against L. amazonensis present in the nasal mucosa.

Umbilical hernias in calves occur with relative frequency. Most abdominal surgeries can be performed in cattle using standing sedation and local blocks. Romifidine is widely used in calves, alone or in combination with opioids. Tramadol administered as an intravenous slow injection provided better analgesia than an IV bolus in cows. The aim of the present study was to compare the response to surgical stimulus, and sedative effects of tramadol administered intravenously either as a bolus or a slow injection in romifidinesedated calves. Twenty Frisian calves undergoing umbilical hernia repair received romifidine (0.08 mg/kg IM; time 0) followed by tramadol (1 mg/kg IV) 5 min later either as a bolus (n = 10, B group) or a slow injection over 10 min (n = 10, SI group). Surgical area was infiltrated with lidocaine (4 mg/kg). Heart rate (HR), respiratory rate (RR), systolic, dyastolic and mean arterial pressure (SAP, DAP, MAP), sedation scores and response to surgical stimulus were recorded for up to 55 min. After the calves recovered a standing position, postoperative pain scores were assessed for up to 50 min. Sedation scores were significantly higher in the SI group than in the B group at 55 min (p < 0.05). HR, RR, SAP and response to surgical stimulus were significantly higher in the B group than in the SI group (p < 0.05). No significant differences were recorded in postoperative pain scores between groups (p > 0.05). Romifidine IM followed by intravenous tramadol, as a bolus or slow injection and local infiltration with lidocaine provided adequate sedation and analgesia in calves undergoing umbilical hernia repair.

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for approximately 6.8 million deaths worldwide, threatening more than 753 million individuals. People with severe coronavirus disease-2019 (COVID-19) infection often exhibit an immunosuppression condition, resulting in greater chances of developing co-infections with bacteria and fungi, including opportunistic yeasts belonging to the Saccharomyces and Candida genera. In the present work, we have reported the case of a 75-year-old woman admitted at a Brazilian university hospital with an arterial ulcer in the left foot, which was being prepared for surgical amputation. The patient presented other underlying diseases and presented positive tests for COVID-19 prior to hospitalization. She received antimicrobial treatment, but her general condition worsened quickly, leading to death by septic shock after 4 days of hospitalization. Blood samples collected on the day she died were positive for yeast-like organisms, which were later identified as Saccharomyces cerevisiae by both biochemical and molecular methods. The fungal strain exhibited low minimal inhibitory concentration values for the antifungal agents tested (amphotericin B, 5-flucytosine, caspofungin, fluconazole and voriconazole), and it was able to produce important virulence factors, such as extracellular bioactive molecules (e.g., aspartic peptidase, phospholipase, esterase, phytase, catalase, hemolysin and siderophore) and biofilm. Despite the activity against planktonic cells, the antifungals were not able to impact the mature biofilm parameters (biomass and viability). Additionally, the S. cerevisiae strain caused the death of Tenebrio molitor larvae, depending on the fungal inoculum, and larvae immunosuppression with corticosteroids increased the larvae mortality rate. In conclusion, the present study highlighted the emergence of S. cerevisiae as an opportunistic fungal pathogen in immunosuppressed patients presenting several severe comorbidities, including COVID-19 infection.

Coffee is considered one of the most important commercial commodities globally, and in 2020, it moved to a global market of USD 102.02 billion. However, the attack of pests in coffee production can cause significant economic losses. Leucoptera coffeella is a critical pest in coffee-producing countries, with productivity losses reaching 87%. The knowledge of the spatial distribution patterns of L. coffeella is essential to developing an efficient sampling and control plan. Moreover, it allows us to target for control specific locations/seasons where L. coffeella occurrence is at its highest density before reaching the economic injury level. Therefore, our objective in this study was to determine the spatial distribution of L. coffeella in coffee crops through geostatistical analysis. Data on the population density of L. coffeella were collected over four years on a farm with 18 center pivots located in the Brazilian Cerrado. The presence of L. coffeella was recorded in all 18 pivots during the entire time of the study (2016 to 2020). The highest densities were from July to November. These high densities of L. coffeella positively correlated with maximum air temperatures and wind speed. It was also verified to negatively correlate with minimum air temperatures and rainfall. The surrounding vegetation does not affect the pest densities. The pest hotspots appeared in different pivots and different locations inside pivots. Furthermore, L. coffeella showed an aggregated distribution pattern. For three years, the colonization started at the edge of the crop. The sampling should be performed equidistant as the pest is distributed equally in all directions. The information found in this study provides valuable information to initiate timely management and control methods in coffee crops with a high incidence of L. coffeella, thus reducing production costs and the harmful effects of pesticide use.

We evaluated the efficacy and residual toxicity of nine commercial insecticides on Plutella xylostella and their selectivity to the predator ant Solenopsis saevissima under laboratory and field conditions. First, to test the insecticides’ effectiveness and selectivity, we conducted concentration-response bioassays on both species and the mortalities were recorded 48 h after exposure. Next, rapeseed plants were sprayed following label rate recommendations in the field. Finally, insecticide-treated leaves were removed from the field up to 20 days after application and both organisms were exposed to them as in the first experiment. Our concentration-response bioassay indicated that seven insecticides caused mortality ≥80% of P. xylostella: bifenthrin, chlorfenapyr, chlorantraniliprole, cyantraniliprole, indoxacarb, spinetoram, and spinosad. However, only chlorantraniliprole and cyantraniliprole caused mortality ≤30% of S. saevissima. The residual bioassay indicated that four insecticides had a long-lasting effect, causing mortality of 100% to P. xylostella 20 days after application: chlorantraniliprole, cyantraniliprole, spinetoram, and spinosad. For S. saevissima, bifenthrin caused mortality of 100% during the evaluated period. Additionally, mortality rates below 30% occurred four days after the application of spinetoram and spinosad. Thus, chlorantraniliprole and cyantraniliprole are safe options for P. xylostella management since their efficacy favor S. saevissima.

Information is presented on the conceptualization, experimental study, and numerical process simulation of tailor heat treated aluminum alloy blanks. This concept is intended to improve the forming behavior of aluminum parts in challenging conditions. The implementation requires precise control of laser heat treatment parameters within a suitable industrial framework. The study details material properties, heat treatment parameters, and experimental results for the strength and elongation properties of an AA6063-T6 aluminum alloy. Constitutive modeling is applied using the Hocket–Sherby equation, which allowed us to establish a correlation between laser heat treatment maximum temperature and the corresponding material softening degree. Based on the generated flow stress–strain curves, a numerical simulation of a representative case study was performed with Abaqus finite element software highlighting potential improvements of tailor heat treated blanks (THTB). The influence and effectiveness of heat-affected zone (HAZ) dimensions and material softening were analyzed.

Magnetic nanoparticles (MNPs) present outstanding properties making them suitable as therapeutic agents for hyperthermia treatments. Since the main safety concerns of MNPs are represented by their inherent instability in a biological medium, strategies to both achieve long-term stability and monitor hazardous MNP degradation are needed. We combined a dynamic approach relying on flow field flow fractionation (FFF)-multidetection with conventional techniques to explore frame-by-frame changes of MNPs injected in simulated biological medium, hypothesize the interaction mechanism they are subject to when surrounded by a saline, protein-rich environment, and understand their behaviour at the most critical point of intravenous administration. In the first moments of MNPs administration in the patient, MNPs change their surrounding from a favorable to an unfavorable medium, i.e., a complex biological fluid such as blood; the particles evolve from a synthetic identity to a biological identity, a transition that needs to be carefully monitored. The dynamic approach presented herein represents an optimal alternative to conventional batch techniques that can monitor only size, shape, surface charge, and aggregation phenomena as an averaged information, given that they cannot resolve different populations present in the sample and cannot give accurate information about the evolution or temporary instability of MNPs. The designed FFF method equipped with a multidetection system enabled the separation of the particle populations providing selective information on their morphological evolution and on nanoparticle–proteins interaction in the very first steps of infusion. Results showed that in a dynamic biological setting and following interaction with serum albumin, PP-MNPs retain their colloidal properties, supporting their safety profile for intravenous administration.

Developments in the nanotechnology area occur ensuring compliance with regulatory requirements, not only in terms of safety requirements, but also to meet sustainability goals. Hence, safer and sustainable-by-design (SSbD) materials are also aimed for during developmental process. Similar to with any new materials their safety must be assessed. Nanobiomaterials can offer large advantages in the biomedical field, in areas such as tissue repair and regeneration, cancer therapy, etc. For example, although hydroxyapatite-based nanomaterials (nHA) are among the most studied biomaterials, its ecotoxicological effects are mostly unknown. In the present study we investigated the toxicity of seven nHA-based materials, covering both different biomedical applications, e.g., iron-doped hydroxyapatite designed for theragnostic applications), hybrid collagen/hydroxyapatite composites, designed for bone tissue regeneration, and SSbD alternative materials such as titanium-doped hydroxyapatite/alginate composite, designed as sunscreen. The effects were assessed using the soil model Enchytraeus crypticus (Oligochaeta) in the natural standard LUFA 2.2 soil. The assessed endpoints included the 2, 3 and 4 days avoidance behavior (short-term), 28 days survival, size and reproduction (long term based on the OECD standard reproduction test), and 56 days survival and reproduction (longer-term OECD extension). Although overall results showed little to no toxicity among the tested nHA, there was a significant decrease in animals’ size for Ti-containing nHA. Moreover, there was a tendency for higher toxicity at the lowest concentrations (i.e., 100 mg/kg). This requires further investigation to ensure safety.

Hydroxyapatite (HA) is a calcium phosphate used in many fields, including biomedical applications. In particular, ion-doped HA nanomaterials (nHA) are developed for their increased bioactivity, particularly in the fields of regenerative medicine and nanomedicine. In this study, we assessed the ecotoxicological impact of five nHA materials: a synthesized calcium hydroxyapatite (CaP-HA), superparamagnetic iron-doped hydroxyapatite (Fe-HA), titanium-doped hydroxyapatite (Ti-HA), alginate/titanium-doped hydroxyapatite hybrid composite (Ti-HA-Alg), and a commercial HA. The soil ecotoxicology model species Folsomia candida (Collembola) was used, and besides the standard reproduction test (28 days), an extension to the standard for one more generation was performed (56 days). Assessed endpoints included the standard survival and reproduction, and additionally, growth. Exposure via the standard (28 days) did not cause toxicity, but reproduction increased in commercial HA (significantly at 320 mg HA/kg) whereas via the extension (56 days) it decreased in all tested concentrations. Juveniles’ size (56 days) was reduced in all tested nHA materials, except commercial HA. nHA materials seem to trigger a compromise between reproduction and growth. Long-term effects could not be predicted based on the standard shorter exposure; hence, the testing of at least two generations (56 days) is recommended to assess the toxicity of nanomaterials, particularly in F. candida. Further, we found that the inclusion of size as additional endpoint is highly relevant.

Heme oxygenase-1 (HO-1) is an enzyme that catalyzes the degradation of heme, releasing equimolar amounts of carbon monoxide (CO), biliverdin (BV), and iron. The anti-inflammatory and antioxidant properties of HO-1 activity are conferred in part by the release of CO and BV and are extensively characterized. However, iron constitutes an important product of HO-1 activity involved in the regulation of several cellular biological processes. The macrophage-mediated recycling of heme molecules, in particular those contained in hemoglobin, constitutes the major mechanism through which living organisms acquire iron. This process is finely regulated by the activities of HO-1 and of the iron exporter protein ferroportin. The expression of both proteins can be induced or suppressed in response to pro- and anti-inflammatory stimuli in macrophages from different tissues, which alters the intracellular iron concentrations of these cells. As we discuss in this review article, changes in intracellular iron levels play important roles in the regulation of cellular oxidation reactions as well as in the transcriptional and translational regulation of the expression of proteins related to inflammation and immune responses, and therefore, iron metabolism represents a potential target for the development of novel therapeutic strategies focused on the modulation of immunity and inflammation.

Bioelectrochemical systems (BES) are emerging as a suite of versatile sustainable technologies to produce electricity and added-value compounds from renewable and carbon-neutral sources using electroactive organisms. The incomplete knowledge on the molecular processes that allow electroactive organisms to exchange electrons with electrodes has prevented their real-world implementation. In this manuscript we investigate the extracellular electron transfer processes performed by the thermophilic Gram-positive bacteria belonging to the Thermincola genus, which were found to produce higher levels of current and tolerate higher temperatures in BES than mesophilic Gram-negative bacteria. In our study, three multiheme c-type cytochromes, Tfer_0070, Tfer_0075, and Tfer_1887, proposed to be involved in the extracellular electron transfer pathway of T. ferriacetica, were cloned and over-expressed in E. coli. Tfer_0070 (ImdcA) and Tfer_1887 (PdcA) were purified and biochemically characterized. The electrochemical characterization of these proteins supports a pathway of extracellular electron transfer via these two proteins. By contrast, Tfer_0075 (CwcA) could not be stabilized in solution, in agreement with its proposed insertion in the peptidoglycan wall. However, based on the homology with the outer-membrane cytochrome OmcS, a structural model for CwcA was developed, providing a molecular perspective into the mechanisms of electron transfer across the peptidoglycan layer in Thermincola.

Heme oxygenase-1 (HO-1) catalyzes the degradation of heme molecules releasing equimolar amounts of biliverdin, iron and carbon monoxide. Its expression is induced in response to stress signals such as reactive oxygen species and inflammatory mediators with antioxidant, anti-inflammatory and immunosuppressive consequences for the host. Interestingly, several intracellular pathogens responsible for major human diseases have been shown to be powerful inducers of HO-1 expression in both host cells and in vivo. Studies have shown that this HO-1 response can be either host detrimental by impairing pathogen control or host beneficial by limiting infection induced inflammation and tissue pathology. These properties make HO-1 an attractive target for host-directed therapy (HDT) of the diseases in question, many of which have been difficult to control using conventional antibiotic approaches. Here we review the mechanisms by which HO-1 expression is induced and how the enzyme regulates inflammatory and immune responses during infection with a number of different intracellular bacterial and protozoan pathogens highlighting mechanistic commonalities and differences with the goal of identifying targets for disease intervention.

The International Agency for Research on Cancer has classified the consumption of “very hot” beverages (temperature >65 °C) as “probably carcinogenic to humans”, but there is no information regarding the serving temperature of Brazil’s most consumed hot beverage—coffee. The serving temperatures of best-selling coffee beverages in 50 low-cost food service establishments (LCFS) and 50 coffee shops (CS) were studied. The bestsellers in the LCFS were dominated by 50 mL shots of sweetened black coffee served in disposable polystyrene (PS) cups from thermos flasks. In the CS, 50 mL shots of freshly brewed espresso served in porcelain cups were the dominant beverage. The serving temperatures of all beverages were on average 90% and 68% above 65 °C in the LCFS and CS, respectively (P95 and median value of measurements: 77 and 70 °C, LCFS; 75 and 69 °C, CS). Furthermore, the cooling periods of hot water systems (50 mL at 75 °C and 69 °C in porcelain cups; 50 mL at 77 °C and 70 °C in PS cups) to 65 °C were investigated. When median temperatures of the best-selling coffees are considered, consumers should allow a minimum cooling time before drinking of about 2 min at both LCFS and CS.

Dengue is considered to be the most important mosquito-borne viral disease in the world. The Aedes aegypti mosquito, its vector, is highly anthropophilic and is very well adapted to urban environments. Although several vaccine candidates are in advanced stages of development no licensed dengue vaccine is yet available. As a result, controlling the spread of dengue still requires that mosquitoes be targeted directly. We review the current methods of dengue vector control focusing on recent technical advances. We first examine the history of Brazil’s National Dengue Control Plan in effect since 2002, and we describe its establishment and operation. With the persistent recurrence of dengue epidemics, current strategies should be reassessed to bring to the forefront a discussion of the possible implementation of new technologies in Brazil’s mosquito control program.

When employed as an engine fuel, ethanol can accumulate in the lubricant during use. Previous work has shown that ethanol contamination affects friction and elastohydrodynamic lubrication (EHL) film formation, and also the growth and stability of anti-wear tribofilms. The present work uses spacer-layer ultrathin interferometry and MTM tests to investigate how ethanol (both hydrated and anhydrous) interacts with friction modifiers in model lubricants. Small proportions (5 wt %) of ethanol were added to solutions of friction modifiers (one MoDTC and three organic friction modifiers) in a Group I base oil. For the three organic friction modifiers, the presence of ethanol promoted the formation of thick viscous boundary films so that very low friction coefficients were measured at low entrainment speeds. For the MoDTC additive, the presence of ethanol prevented the formation of a low friction film at low speeds at 70 °C, but this effect disappeared at 100 °C, probably due to ethanol evaporation.

The accuracy of photogrammetric and Lidar dataset integration is dependent on the quality of a group of parameters that models accurately the conditions of the system at the moment of the survey. In this sense, this paper aims to study the effect of the sub-block position in the entire image block to estimate the interior orientation parameters (IOP) in flight conditions to be used in integrated sensor orientation (ISO). For this purpose, five sub-blocks were extracted in different regions of the entire block. Then, in situ camera calibrations were performed using sub-blocks and sets of Lidar control points (LCPs), computed by a three planes’ intersection extracted from the Lidar point cloud on building roofs. The ISO experiments were performed using IOPs from in situ calibrations, the entire image block, and the exterior orientation parameters (EOP) from the direct sensor orientation (DSO). Analysis of the results obtained from the ISO experiments performed show that the IOP from the sub-block positioned at the center of the entire image block can be recommended.

Objectives : Symptoms and motivation may impact adherence to home-based exercise training programs (HETP) during cancer treatment (CT) for lung or head and neck cancer. This study aimed to identify self-reported symptoms and their frequency, as well as motivation towards an HETP during CT for primary lung or head and neck cancer. Associations between symptoms and motivation with HETP adherence were also investigated. Methods : Participants underwent CT combined with an HETP that included aerobic (walk-based) and resistance training (Theraband ® ). Weekly assessment was conducted using a questionnaire developed by the researchers, evaluating the presence of symptoms. A scale (0 to 10) was used to assess motivation towards the HETP. Adherence was defined as the ratio between HETP sessions completed vs. the number prescribed. Symptom frequency was recorded as the number of weeks a symptom was experienced. Linear regression was used to explore associations. Results : Twenty-four participants were included (61 ± 7 yr; 21 males; head and neck cancer n = 18; median treatment duration: 9 [7 to 11] weeks). The most commonly reported symptoms were fatigue (33%), malaise (24%) and dysphagia (23%). Average score for motivation to exercise was 6.4 ± 2.0. Adherence to the HETP was 47%. Malaise was associated with reduced adherence to HETP ( p = 0.002), explaining 35% of the variance. Motivation was associated with increased adherence ( p = 0.008), explaining 28% of the variance. Conclusions : Fatigue, malaise and dysphagia were among the most frequently reported symptoms during treatment. Malaise and self-motivation to exercise can significantly influence adherence to HETPs. Symptom and motivational support might be necessary when implementing HETPs during CT.

Background: Molecular profiling in upper tract urothelial carcinoma (UTUC) with synchronous or metachronous urothelial bladder cancer (UBC) is scarce. We intended to assess immunohistochemical (IHC) and genetic differences between UTUC-only and UTUC with synchronous or metachronous UBC (UTUC + UBC) and evaluate the effect of subsequent UBC on the outcome of UTUC patients stratified by luminal-basal subtypes., Methods: A retrospective cohort of UTUC was divided into UTUC-only ( n = 71) and UTUC + UBC ( n = 43). IHC expression of cytokeratin 5/6 (CK5/6), CK20, GATA3, and p53 was evaluated to assess relevant subtypes. Genetic characterization comprised TERT p, FGFR3 , RAS , and TP53 status. Kaplan-Meier and Cox regression analyses estimated the effect of clinicopathological variables and molecular profiles on progression-free survival (PFS) and overall survival (OS) of UTUC patients., Results: No meaningful differences were detected among both subgroups according to luminal-basal stratification and genetic analysis. UTUC + UBC was independently associated with a worse PFS when stratified by luminal-basal phenotype (HR 3.570, CI 95% 1.508-8.453, p = 0.004) but with no impact in OS (HR 1.279, CI 95% 0.513-3.190, p = 0.597)., Conclusions: This study reveals that both subgroups exhibited equivalent genomic features and luminal-basal subtypes. The involvement of the bladder relates to shorter PFS but does not seem to influence the survival outcome of UTUC, independently of the IHC phenotype.

Repurposing saffron ( Crocus sativus ) waste presents a sustainable strategy for generating high-value products within the bioeconomy framework. Typically, flower components are discarded after stigma harvest, resulting in significant waste-350 kg of tepals per kilogram of stigmas. This research employed a comprehensive approach, integrating bioactivity studies (in vitro and in silico) with Life Cycle Assessment (LCA) evaluations, to extract and assess bioactive compounds from C. sativus tepals sourced in Tuscany, Italy. Phytochemical characterization using UPLC-MS/MS revealed a high abundance and variety of flavonoids in the hydro-ethanolic extract (CST). The antioxidant capacity was validated through various assays, and the ability to mitigate H 2 O 2 -induced oxidative stress and enhance fermentation was demonstrated in Saccharomyces cerevisiae . This study reports that C. sativus tepals extract reduces oxidative stress and boosts ethanol fermentation in yeast, paving the way for applications in the food and biofuels sectors. Further validation in RAW 264.7 macrophages confirmed CST's significant anti-inflammatory effects, indicating its potential for pharmaceutical, cosmeceutical, and nutraceutical applications. In silico studies identified potential targets involved in antioxidant and anti-inflammatory processes, shedding light on possible interaction mechanisms with Kaempferol 3-O-sophoroside (KOS-3), the predominant compound in the extract. The integration of LCA studies highlighted the environmental benefits of this approach. Overall, this research underscores the value of using waste-derived extracts through "green" methodologies, offering a model that may provide significant advantages for further evaluations compared to traditional methodologies and supporting the circular bioeconomy.

The use of arbuscular mycorrhizal fungi (AMF) offers promising benefits to agriculture in the Amazon regions, where soils are characteristically acidic and nutrient-poor. The purpose of this research was to investigate the potential effects of two recently described species of AMF ( Nanoglomus plukenetiae and Rhizoglomus variabile ) native to the Peruvian Amazon for improving the plant growth of Plukenetia volubilis (inka nut or sacha inchi) and protecting the roots against soil pathogens. Two assays were simultaneously conducted under greenhouse conditions in Peru. The first focused on evaluating the biofertilizer effect of AMF inoculation, while the second examined the bioprotective effect against the root knot nematode, Meloidogyne incognita . Overall, the results showed that AMF inoculation of P. volubilis seedlings positively improved their development, particularly their biomass, height, and the leaf nutrient contents. When seedlings were exposed to M. incognita , plant growth was also noticeably higher for AMF-inoculated plants than those without AMF inoculation. Nematode reproduction was significantly suppressed by the presence of AMF, in particular R. variabile , and especially when inoculated prior to nematode exposure. The dual AMF inoculation did not necessarily lead to improved crop growth but notably improved P and K leaf contents. The findings provide strong justification for the development of products based on AMF as agro-inputs to catalyze nutrient use and uptake and protect crops against pests and diseases, especially those that are locally adapted to local crops and cropping conditions.

Background: Severe cases of lymphopenia have been reported during siponimod clinical trials, which may negatively impact its benefit/risk profile., Objective: We aimed to evaluate the incidence of lymphopenia following the initiation of siponimod treatment in clinical practice. The secondary objectives included the analysis of factors predisposing to and the clinical relevance of lymphopenia events., Methods: In this multicenter retrospective cohort study, information collected from the medical records of 129 patients with MS from 15 tertiary hospitals in Spain who initiated treatment with Siponimod were followed-up for at least 3 months, including at least one lymphocyte count evaluation per patient., Results: Of the 129 patients, 121 (93.6%) reported lymphopenia events, including 110 (85.3%) with grade ≤ 3 and 11 (8.5%) with grade 4 lymphopenia, higher than those reported in the pivotal clinical trial (73.3% and 3.3% for grade ≤ 3 and grade 4 lymphopenia, respectively). The study included an unexpectedly high proportion of male subjects (72.9%), which might have led to an underestimation of the actual magnitude of the risk., Conclusions: In this study, the incidence and severity of lymphopenia after starting siponimod treatment were higher than those reported in previous clinical trials. Therefore, our results reinforce the need for the closer monitoring of novel MS drugs in clinical practice, as well as larger and longer follow-up studies to properly characterize this risk.

This single-center study included 68 multiple sclerosis (MS) patients who received the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from one of several approved vaccine preparations in Spain. Blood samples were collected one to three months after the second dose of the vaccine had been administered. Cellular immune responses to the vaccine were assessed using QuantiFERON analysis, and peripheral blood mononuclear cell subsets were assayed using flow cytometry. Response associated with higher percentages of total lymphocytes, naïve CD4+ T-cells ( p = 0.028), CD8+ T-cells ( p = 0.013), and, mostly, naïve CD8+ T-cells ( p = 0.0003). These results were confirmed by analyzing absolute numbers ( p = 0.019; p = 0.002, and p = 0.0003, respectively). Naïve CD8 T-cell numbers higher than 17 cells/μL were closely associated with an optimal cellular response to SARS-CoV-2 vaccination (odds ratio: 24.0, confidence interval: 4.8-460.3; p = 0.0001). This finding clearly shows that independent of the treatment received, higher numbers of naïve CD8+ T-cells yield a strong cellular response to SARS-CoV-2 vaccines in MS patients. If this finding is validated with other viruses/vaccines, it could provide a good tool for identifying MS patients undergoing treatment who will develop strong cellular responses to anti-virus vaccines.

Fibromyalgia syndrome (FS) is a disorder characterized by widespread musculoskeletal pain and psychopathological symptoms, often associated with central pain modulation failure and dysfunctional adaptive responses to environmental stress. The Radio Electric Asymmetric Conveyer (REAC) technology is a neuromodulation technology. The aim of this study was to evaluate the effects of some REAC treatments on psychomotor responses and quality of life in 37 patients with FS. Tests were conducted before and after a single session of Neuro Postural Optimization and after a cycle of 18 sessions of Neuro Psycho Physical Optimization (NPPO), using evaluation of the functional dysmetria (FD) phenomenon, Sitting and Standing (SS), Time Up and Go (TUG) tests for motor evaluation, Fibromyalgia Impact Questionnaire (FIQ) for quality of life. The data were statistically analyzed, and the results showed a statistically significant improvement in motor response and quality of life parameters, including pain, as well as reduced FD measures in all participants. The study concludes that the neurobiological balance established by the REAC therapeutic protocols NPO and NPPO improved the dysfunctional adaptive state caused by environmental and exposomal stress in FS patients, leading to an improvement in psychomotor responses and quality of life. The findings suggest that REAC treatments could be an effective approach for FS patients, reducing the excessive use of analgesic drugs and improving daily activities.

Increasing intrauterine insemination (IUI) success rates is essential to improve the quality of care for infertile couples. Additionally, straight referral of couples with less probability of achieving a pregnancy through IUI to more complex methods such as in vitro fertilization is important to reduce costs and the time to pregnancy. The aim of the present study is to prospectively evaluate the threshold values for different parameters related to success in intrauterine insemination in order to provide better reproductive counseling to infertile couples, moreover, to generate an algorithm based on male and female parameters to predict whether the couple is suitable for achieving pregnancy using IUI. For that, one hundred ninety-seven infertile couples undergoing 409 consecutive cycles of intrauterine insemination during a two-year period were included. The first year served as a definition of the parameters and thresholds related to pregnancy achievement, while the second year was used to validate the consistency of these parameters. Subsequently, those parameters that remained consistent throughout two years were included in a generalized estimating equation model (GEE) to determine their significance in predicting pregnancy achievement. Parameters significantly associated with the lack of pregnancy through IUI and included in the GEE were ( p < 0.05): (i) male age > 41 years; (ii) ejaculate sperm count < 51.79 x 10 6 sperm; (iii) swim-up alkaline Comet > 59%; (iv) female body mass index > 45 kg/m 2 ; (v) duration of infertility (>84 months), and (vi) basal LH levels > 27.28 mUI/mL. The application of these limits could provide a pregnancy prognosis to couples before undergoing intrauterine insemination, therefore avoiding it in couples with low chances of success. The retrospective application of these parameters to the same cohort of patients would have increased the pregnancy rate by up to 30%.

Background: This study aimed to evaluate short- and long-term humoral and T-cell-specific immune responses to SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs)., Methods: Single-center observational longitudinal study including 102 patients with MS who consecutively received vaccination against SARS-CoV-2. Serum samples were collected at baseline and after receiving the second dose of the vaccine. Specific Th1 responses following in vitro stimulation with spike and nucleocapsid peptides were analyzed by quantifying levels of IFN-γ. Serum IgG-type antibodies against the spike region of SARS-CoV-2 were studied by chemiluminescent microparticle immunoassay., Results: Patients undergoing fingolimod and anti-CD20 therapies had a markedly lower humoral response than those treated with other DMTs and untreated patients. Robust antigen-specific T-cell responses were detected in all patients except those treated with fingolimod, who had lower IFN-γ levels than those treated with other DMTs (25.8 pg/mL vs. 868.7 pg/mL, p = 0.011). At mid-term follow-up, a decrease in vaccine-induced anti-SARS-CoV-2 IgG antibodies was observed in all subgroups of patients receiving DMTs, although most patients receiving induction DMTs or natalizumab and non-treated patients remained protected. Cellular immunity was maintained above protective levels in all DMT subgroups except the fingolimod subgroup., Conclusions: SARS-CoV-2 vaccines induce robust and long-lasting humoral and cell-mediated specific immune responses in most patients with MS.

Oral squamous cell carcinoma is the most common malignant epithelial neoplasm affecting the oral cavity. While surgical resection is the cornerstone of a multimodal curative approach, some tumors are deemed recurrent or metastatic (R/M) and often not suitable for curative surgery. This mainly occurs due to the extent of lesions or when surgery is expected to result in poor functional outcomes. Amongst the main non-surgical therapeutic options for oral squamous cell carcinoma are radiotherapy, chemotherapy, molecular targeted agents, and immunotherapy. Depending on the disease setting, these therapeutic approaches can be used isolated or in combination, with distinct efficacy and side effects. All these factors must be considered for treatment decisions within a multidisciplinary approach. The present article reviews the evidence regarding the treatment of patients with R/M oral squamous cell carcinoma. The main goal is to provide an overview of available treatment options and address future therapeutic perspectives.

Multifunctional nano-objects containing a magnetic heater and a temperature emissive sensor in the same nanoparticle have recently emerged as promising tools towards personalized nanomedicine permitting hyperthermia-assisted treatment under local temperature control. However, a fine control of nano-systems' morphology permitting the synthesis of a single magnetic core with controlled position of the sensor presents a main challenge. We report here the design of new iron oxide core-silica shell nano-objects containing luminescent Tb 3+ /Eu 3+ -(acetylacetonate) moieties covalently anchored to the silica surface, which act as a promising heater/thermometer system. They present a single magnetic core and a controlled thickness of the silica shell, permitting a uniform spatial distribution of the emissive nanothermometer relative to the heat source. These nanoparticles exhibit the Tb 3+ and Eu 3+ characteristic emissions and suitable magnetic properties that make them efficient as a nanoheater with a Ln 3+ -based emissive self-referencing temperature sensor covalently coupled to it. Heating capacity under an alternating current magnetic field was demonstrated by thermal imaging. This system offers a new strategy permitting a rapid heating of a solution under an applied magnetic field and a local self-referencing temperature sensing with excellent thermal sensitivity (1.64%·K -1 (at 40 °C)) in the range 25-70 °C, good photostability, and reproducibility after several heating cycles.

The potential of nanomaterials in food technology is nowadays well-established. However, their commercial use requires a careful risk assessment, in particular concerning the fate of nanomaterials in the human body. Bacterial nanocellulose (BNC), a nanofibrillar polysaccharide, has been used as a food product for many years in Asia. However, given its nano-character, several toxicological studies must be performed, according to the European Food Safety Agency's guidance. Those should especially answer the question of whether nanoparticulate cellulose is absorbed in the gastrointestinal tract. This raises the need to develop a screening technique capable of detecting isolated nanosized particles in biological tissues. Herein, the potential of a cellulose-binding module fused to a green fluorescent protein (GFP-CBM) to detect single bacterial cellulose nanocrystals (BCNC) obtained by acid hydrolysis was assessed. Adsorption studies were performed to characterize the interaction of GFP-CBM with BNC and BCNC. Correlative electron light microscopy was used to demonstrate that isolated BCNC may be detected by fluorescence microscopy. The uptake of BCNC by macrophages was also assessed. Finally, an exploratory 21-day repeated-dose study was performed, wherein Wistar rats were fed daily with BNC. The presence of BNC or BCNC throughout the GIT was observed only in the intestinal lumen, suggesting that cellulose particles were not absorbed. While a more comprehensive toxicological study is necessary, these results strengthen the idea that BNC can be considered a safe food additive.

Background: The frequency of cognitive impairment (CI) reported in neuromyelitis optica spectrum disorder (NMOSD) is highly variable, and its relationship with demographic and clinical characteristics is poorly understood. We aimed to describe the cognitive profile of NMOSD patients, and to analyse the cognitive differences according to their serostatus; furthermore, we aimed to assess the relationship between cognition, demographic and clinical characteristics, and other aspects linked to health-related quality of life (HRQoL). Methods: This cross-sectional study included 41 patients (median age, 44 years; 85% women) from 13 Spanish centres. Demographic and clinical characteristics were collected along with a cognitive z-score (Rao’s Battery) and HRQoL patient-centred measures, and their relationship was explored using linear regression. We used the Akaike information criterion to model which characteristics were associated with cognition. Results: Fourteen patients (34%) had CI, and the most affected cognitive domain was visual memory. Cognition was similar in AQP4-IgG-positive and -negative patients. Gender, mood, fatigue, satisfaction with life, and perception of stigma were associated with cognitive performance (adjusted R2 = 0.396, p < 0.001). Conclusions: The results highlight the presence of CI and its impact on HRQoL in NMOSD patients. Cognitive and psychological assessments may be crucial to achieve a holistic approach in patient care.

We would like to thank you for the opportunity to reply to the comments in regard of the letter by Dr. Weiss [...].

In psoriatic arthritis (PsA) patients with concomitant chronic widespread pain, the differential diagnosis with fibromyalgia syndrome (FMS) can be challenging. We evaluated whether ultrasound (US) examination of entheseal sites can distinguish pain from (PsA) enthesitis versus FMS. PsA and FMS patients underwent clinical evaluation and gray-scale (GS; B-mode) and power Doppler (PD) US examination of the entheses. At least one enthesis with GS- and PD-mode changes was found in 90% and 59.3% of PsA patients ( n = 140) and 62.7% and 35.3% of FMS patients ( n = 51), respectively. GS and PD identified changes in 49.5% and 19.2% of the 840 PsA entheses and 22.5% and 7.9% of the 306 FMS entheses, respectively. Receiver operating characteristic curve analysis showed an area under the curve of 0.77 and 0.66 for B- and PD-mode, respectively, 3.5 being the best cut-off GS-score to discriminate the two conditions. Multivariate regression showed that Achilles and proximal patellar tendon enthesitis (B-mode) were strongly associated with PsA (odds ratio, ~2). Principal component analysis (B-mode) confirmed that PsA patients have a higher number of involved entheses and patterns of entheseal involvement than FMS patients. US evaluation of the entheses may help differentiate chronic widespread pain from PsA versus FMS.

In scoliosis, most of the deformity is in the disc and occurs during the period of rapid growth. The ring apophyses form the insertion of the disc into the vertebral body, they then ossify and fuse to the vertebrae during that same crucial period. Although this must have important implications for the mechanical properties of the spine, relatively little is known of how this process takes place. This study describes the maturation pattern of the ring apophyses in the thoracic and lumbar spine during normal growth. High-resolution CT scans of the spine for indications not related to this study were included. Ossification and fusion of each ring apophysis from T1 to the sacrum was classified on midsagittal and midcoronal images (4 points per ring) by two observers. The ring apophysis maturation (RAM) was compared between different ages, sexes, and spinal levels. The RAM strongly correlated with age (R = 0.892, p < 0.001). Maturation differed in different regions of the spine and between sexes. High thoracic and low lumbar levels fused earlier in both groups, but, around the peak of the growth spurt, in girls the mid-thoracic levels were less mature than in boys, which may have implications for the development of scoliosis.

We report here a novel "one-pot" approach for the controlled growth and organization of Prussian blue nanostructures on three different surfaces: pure Au 0 , cysteamine-functionalized Au 0 , and SiO 2 -supported lipid bilayers with different natures of lipids. We demonstrate that fine control over the size, morphology, and the degree and homogeneity of the surface coverage by Prussian Blue (PB) nanostructures may be achieved by manipulating different parameters, which are the precursor concentration, the nature of the functional groups or the nature of lipids on the surfaces. This allows the growth of isolated PB nanopyramids and nanocubes or the design of thin dense films over centimeter square surfaces. The formation of unusual Prussian blue nanopyramids is discussed. Finally, we demonstrate, by using experimental techniques and theoretical modeling, that PB nanoparticles deposited on the gold surface exhibit strong photothermal properties, permitting a rapid temperature increase up to 90 °C with a conversion of the laser power of almost 50% for power source heat.