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Aquatic anthropogenic noise is on the rise, with growing concern about its impact on species that are sensitive to low-frequency sounds (e.g. most fish and invertebrates). We investigated whether the reef fish Halichoeres bivittatus living in both noisy and quiet areas had differing levels of baseline stress (measured as whole-body cortisol) and whether they would exhibit a physiological stress response when exposed to boat noise playbacks. While the playback experiments significantly increased cortisol levels in fish from our experiment compared to baseline levels, there were minimal pairwise differences across treatments and no difference in baseline stress for fish living in noisy vs. quiet areas. These results may be explained by low overall auditory sensitivity, habituation to a fairly noisy environment (due to biological sounds), or that boat noise simply may not represent an immediate threat to survival in this species. These findings contrast recent studies that have shown elevated stress responses in fishes when exposed to boat noise and highlights that inter-specific differences must be considered when evaluating potential impacts of anthropogenic noise on marine life.

Highly aggressive, metastatic, neuroendocrine prostate cancer, which typically develops from prostate cancer cells acquiring resistance to androgen deprivation therapy, is associated with limited treatment options and hence poor prognosis. We have previously demonstrated that the αVβ3 integrin is over-expressed in neuroendocrine prostate cancer. We now show that LM609, a monoclonal antibody that specifically targets the human αVβ3 integrin, hinders the growth of neuroendocrine prostate cancer patient-derived xenografts in vivo. Our group has recently identified a novel αVβ3 integrin binding partner, NgR2, responsible for regulating the expression of neuroendocrine markers and for inducing neuroendocrine differentiation in prostate cancer cells. Through in vitro functional assays, we here demonstrate that NgR2 is crucial in promoting cell adhesion to αVβ3 ligands. Moreover, we describe for the first time co-fractionation of αVβ3 integrin and NgR2 in small extracellular vesicles derived from metastatic prostate cancer patients plasma. These prostate cancer patient-derived small extracellular vesicles have a functional impact on human monocytes, increasing their adhesion to fibronectin. The monocytes incubated with small extracellular vesicles do not show an associated change in conventional polarization marker expression and appear to be in an early stage that may be defined as adhesion competent. Overall, these findings allow us to better understand integrin-directed signaling and cell-cell communication during cancer progression. Furthermore, our results pave the way for new diagnostic and therapeutic perspectives for patients affected by neuroendocrine prostate cancer.

Anthropogenic warming and nutrient over-enrichment of our oceans have resulted in significant, and often catastrophic, reductions in dissolved oxygen (deoxygenation). Stress on water-breathing animals from this deoxygenation has been shown to occur at all levels of biological organization: cellular, organ, individual, species, population, community, and ecosystem. Most climate forecasts predict increases in ocean deoxygenation; thus, it is essential to develop reliable biological indicators of low-oxygen stress that can be used by regional and global oxygen monitoring efforts to detect and assess the impacts of deoxygenation on ocean life. This review focuses on responses to low-oxygen stress that are manifest at different levels of biological organization and at a variety of spatial and temporal scales. We compare particular attributes of these biological indicators to the dissolved oxygen threshold of response, timescales of response, sensitive life stages and taxa, and the ability to scale the response to oxygen stress across levels of organization. Where there is available evidence, we discuss the interactions of other biological and abiotic stressors on the biological indicators of low-oxygen stress. We address the utility, confounding effects, and implementation of the biological indicators of oxygen stress for research and societal applications. Our hope is that further refinement and dissemination of these oxygen stress indicators will provide more direct support for environmental managers, fisheries and mariculture scientists, conservation professionals, and policymakers to confront the challenges of ocean deoxygenation. An improved understanding of the sensitivity of different ocean species, communities, and ecosystems to low-oxygen stress will empower efforts to design monitoring programs, assess ecosystem health, develop management guidelines, track conditions, and detect low-oxygen events.

Abstract Background Although second-generation antipsychotics (SGAs) have proven to be effective therapeutic options for patients with schizophrenia, there is a notable lack of evidence on patients’ subjective perspectives regarding their well-being, quality of life, and satisfaction with these medications. This study aimed to evaluate the treatment satisfaction and effectiveness of lurasidone on quality of life and functioning in adult patients with schizophrenia in real-world Italian clinical practice. Methods This was a multicentre, national, non-interventional, single-arm, 3-month prospective study. Patients who were naive to lurasidone treatment and whose treating physician had decided to start them on this medication were enrolled and evaluated over a 3-month period. Eligible patients were adults (≥ 18 years of age) with a primary diagnosis of schizophrenia who were being treated with lurasidone (for the first time [i.e., they were lurasidone naive]) as part of routine clinical practice. Efficacy endpoints were changes in patient/caregiver treatment satisfaction (seven-point Likert scale from the Treatment Satisfaction Questionnaire for Medication), patient quality of life and functioning (QLS), investigator-rated global assessment of functioning (CGI-S, IAQ) after 6 weeks and 3 months of lurasidone, and number of relapses and hospitalizations. Results Sixty-one patients were enrolled and 59 completed the study. The median dosage of lurasidone at baseline was 37.00 mg/day. The median duration of titration was 86.0 days (Min 28; Max 115 days); the median number of dosage changes was 1.0. At the end of 3-month observation period, the median dose of lurasidone was 74.00 mg/day. QoL and Functioning Score showed a trend of improvement over time, reaching a mean change from baseline of 9.8 at the end of the study. According to the CGI-S, the percentage of patients who were “markedly or severely ill” showed a continuous decrease from baseline to 3 months, from 62.29% to 8.20%. Patient satisfaction increased over time, with 80.32% of patients reporting that they were somewhat, fairly, or very satisfied (including 63.93% who were completely or very satisfied) at the end of the study. No relapses/hospitalizations for psychiatric reasons were reported. Lurasidone was well tolerated with no safety concerns or discontinuations due to AEs. Conclusions Lurasidone represents a valid option for the treatment of schizophrenia and positively affects subjective well-being, quality of life and satisfaction. Trial registration NCT06527885 retrospectively registered (01/08/2024).

This review explores the transformative potential of precision agriculture and proximal sensing in revolutionizing crop management practices. By delving into the complexities of these cutting-edge technologies, it examines their role in mitigating the adverse impacts of agrochemical usage while bringing crop health monitoring to a high precision level. The review explains how precision agriculture optimizes production while safeguarding environmental integrity, thus offering a viable solution to both ecological and economic challenges arising from excessive agrochemical application. Furthermore, it investigates various proximal sensing techniques, including spectral imaging, thermal imaging, and fluorescence sensors, showcasing their efficacy in detecting and diagnosing crop health indicators such as stress factors, nutrient deficiencies, diseases, and pests. Through an in-depth analysis of relevant studies and successful practical applications, this review highlights that it is essential to bridge the gap between monitoring sensors and real-time decision-making and to improve image processing and data management systems to fully realize their potential in terms of sustainable crop management practices.

Abstract Background A number of Italian grape berry varieties, such as Fiano (F) and Pallagrello Nero (P), represent National strategic products. Therefore, it is important to identify soil conditions emphasizing their peculiar characteristics as well as find innovative and sustainable treatments improving their compositional and nutraceutical quality. The field spray preparation 500 is a biodynamic product that is presumed to serve as biostimulant on the vine. However, so far, the scientific results probing its effectiveness are still lacking. Moreover, it is necessary to establish a reliable relationship between the grape quality and the spatial microvariability of the vineyard’s soil. On this basis, the main objective of this work consisted in correlating structural and morphological characteristics (via MRI), the primary metabolome (via semi-solid state HRMAS NMR) and important nutraceutical parameters (total phenols and antioxidants via DPPH assay) of F and P grapes with both the action of preparation 500 biostimulant and the vineyard soil microvariability, based on soil apparent electrical conductivity. Results HRMAS enabled the identification of the primary metabolome of F and P. The elaboration of 1H NMR spectra through chemometrics revealed significant changes in F and P grapes, accounting for both soil microvariability and the application of field spray (the latter also confirmed by PLS-DA and Heat-map clustering). Interestingly, for both F and P it was observed a significantly lower content of carbohydrates after biostimulant treatment while MRI revealed diagnostic structural and internal details of intact grapes. The combined use of proton parametric indices, such as relaxation times and diffusion coefficients, indicated alterations induced in grapes by both the spatial microvariability of the soil and the effects of investigated biostimulant. Interestingly, a tight correlation was found between MRI transverse relaxation time and the contents in total phenols and antioxidants. Conclusions Our results have proven that both soil spatial microvariability and the application of field spray preparation 500 significantly affect the structural, metabolomic and nutraceutical characteristics of grapes. Moreover, the preparation 500 treatment has increased the nutraceutical value of grapes. Importantly, these data may be potentially used to promote and protect biodynamic grape and predict the quality of the resulting wines. Graphical Abstract

Abstract Background and objectives There is an urgent need to discover blood-based biomarkers of multiple sclerosis (MS) to better define the underlying biology of relapses and monitor disease progression. The main goal of this study is to search for candidate biomarkers of MS relapses associated with circulating extracellular vesicles (EVs), an emerging tool for biomarker discovery. Methods EVs, purified from unpaired plasma and CSF samples of RRMS patients by size-exclusion chromatography (SEC), underwent proteomic analysis to discover novel biomarkers associated with MS relapses. The candidate biomarkers of disease activity were detected by comparison approach between plasma- and CSF-EV proteomes associated with relapses. Among them, a selected potential biomarker was evaluated in a cohort of MS patients, using a novel and highly reproducible flow cytometry-based approach in order to detect low abundant EV subsets in a complex body fluid such as plasma. Results The proteomic profiles of both SEC-purified plasma EVs (from 6 patients in relapse and 5 patients in remission) and SEC-purified CSF EVs (from 4 patients in relapse and 3 patients in remission) revealed a set of proteins associated with MS relapses significant enriched in the synaptic transmission pathway. Among common proteins, excitatory amino-acid transporter 2, EAAT2, responsible for the majority of the glutamate uptake in CNS, was worthy of further investigation. By screening plasma samples from 110 MS patients, we found a significant association of plasma EV-carried EAAT2 protein (EV-EAAT2) with MS relapses, regardless of disease-modifying therapies. This finding was confirmed by investigating the presence of EV-EAAT2 in plasma samples collected longitudinally from 10 RRMS patients, during relapse and remission. Moreover, plasma EV-EAAT2 levels correlated positively with Expanded Disability Status Scale (EDSS) score in remitting MS patients but showed a negative correlation with age in patients with secondary progressive (SPMS). Conclusion Our results emphaticize the usefulness of plasma EVs as a source of accessible biomarkers to remotely analyse the CNS status. Plasma EV-EAAT2 showed to be a promising biomarker for MS relapses. Further studies are required to assess the clinical relevance of this biomarker also for disability progression independent of relapse activity and transition from RRMS towards SPMS.

Abstract Kindlin-2 is a cytoskeletal adapter protein that is present in many different cell types. By virtue of its interaction with multiple binding partners, Kindlin-2 intercalates into numerous signaling pathways and cytoskeletal nodes. A specific interaction of Kindlin-2 that is of paramount importance in many cellular responses is its direct binding to the cytoplasmic tails of integrins, an interaction that controls many of the adhesive, migratory and signaling responses mediated by members of the integrin family of cell-surface heterodimers. Kindlin-2 is highly expressed in many cancers and is particularly prominent in prostate cancer cells. CRISPR/cas9 was used as a primary approach to knockout expression of Kindlin-2 in both androgen-independent and dependent prostate cancer cell lines, and the effects of Kindlin-2 suppression on oncogenic properties of these prostate cancer cell lines was examined. Adhesion to extracellular matrix proteins was markedly blunted, consistent with the control of integrin function by Kindlin-2. Migration across matrices was also affected. Anchorage independent growth was markedly suppressed. These observations indicate that Kindlin-2 regulates hallmark features of prostate cancer cells. In androgen expressing cells, testosterone-stimulated adhesion was Kindlin-2-dependent. Furthermore, tumor growth of a prostate cancer cell line lacking Kindlin-2 and implanted into the prostate gland of immunocompromised mice was markedly blunted and was associated with suppression of angiogenesis in the developing tumor. These results establish a key role of Kindlin-2 in prostate cancer progression and suggest that Kindlin-2 represents an interesting therapeutic target for treatment of prostate cancer.

Phased injection of natural gas into internal combustion marine engines is a promising solution for optimizing performance and reducing harmful emissions, particularly unburned methane, a potent greenhouse gas. This innovative practice distinguishes itself from continuous injection because it allows for more precise control of the combustion process with only a slight increase in system complexity. By synchronizing the injection of natural gas with the intake and exhaust valve opening and closing times while also considering the gas path in the manifolds, methane release into the atmosphere is significantly reduced, making a substantial contribution to efforts to address climate change. Moreover, phased injection improves the efficiency of marine engines, resulting in reduced overall fuel consumption, lower fuel costs, and increased ship autonomy. This technology was tested on a single-cylinder, large-bore, four-stroke research engine designed for marine applications, operating in dual-fuel mode with diesel and natural gas. Performance was compared with that of the conventional continuous feeding method. Evaluation of the effect on equivalent CO2 emissions indicates a potential reduction of up to approximately 20%. This reduction effectively brings greenhouse gas emissions below those of the diesel baseline case, especially when injection control is combined with supercharging control to optimize the air–fuel ratio. In this context, the boost pressure in DF was reduced from 3 to 1.5 bar compared with the FD case.

The Selvicciola necropolis is a large burial site dated to the Copper Age, located on the mid-Tyrrhenian side of Central Italy, in the Fiora river valley. Despite post-depositional disturbances, 32 prehistoric tombs were found, generally in a good state of preservation, with a total number of 119 individuals identified. In the present study, radiocarbon and stable isotope measurements on bone collagen are combined with skeletal data for 71 of these individuals. We aim to investigate possible changes in food practices and burial patterns throughout time. In detail, the results allowed us to define a timeframe for the use of the cemetery of at least 2000 years, with the two most ancient individuals found in tomb 17 and dated to around 3950 cal BC, assigning this a necropolis chronological investigation of the so-called Rinaldone culture. Stable carbon and nitrogen isotope analysis confirmed a predominantly agropastoral subsistence strategy for this prehistoric community. Although the plant intake consisted mainly of C3 species, we further discuss the fact that the stable isotope data suggest an increase in the consumption of C4 plants over time. The integration of radiocarbon and isotopic data with the skeletal evidence and material culture provides an interesting insight into the funerary world of this community, highlighting the importance of Selvicciola for the understanding of life in the Mediterranean at the transition between the fourth and the third millennia BC.

Abstract It has been thought that Io’s many paterae may contain lava lakes, but observations by NASA’s Galileo spacecraft at sufficiently high resolution were limited to a few locations, such as Loki Patera. Data acquired by NASA’s Juno mission in May 2023 reveal a common set of thermal characteristics for at least ten paterae on Io, with bright (hot) “thermal rings” around the perimeter of their floors. Loki, Surt, Fuchi, Amaterasu, Mulungu, Chors, and Dazhbog Patera, and four unnamed paterae, all show the same pattern of surface temperature. This new Juno/JIRAM data suggests that hot rings around paterae are a common phenomenon, and that they are indicative of active lava lakes. All the investigated paterae lack recent lava flows on their flanks, suggesting that at the time of observations, the level of the lake was not high enough to overflow the rim. These observations provide insight about the characteristics of paterae’s activity, which may involve either central upwelling of magma, or up-and-down “piston-like” vertical motion of the lake surface. Tidal forces, which are extreme at Io, could play a role as well. Future observations from Juno, particularly during the closest flybys, may indicate which mechanism is more plausible.

Boron neutron capture therapy (BNCT) is a cellular-level hadron therapy achieving therapeutic effects via the synergistic action of multiple particles, including Lithium, alpha, proton, and photon. However, evaluating the relative biological effectiveness (RBE) in BNCT remains challenging. In this research, we performed a microdosimetric calculation for BNCT using the Monte Carlo track structure (MCTS) simulation toolkit, TOPAS-nBio. This paper reports the first attempt to derive the ionization cross-sections of low-energy (>0.025 MeV/u) Lithium for MCTS simulation based on the effective charge cross-section scalation method and phenomenological double-parameter modification. The fitting parameters λ1=1.101,λ2=3.486 were determined to reproduce the range and stopping power data from the ICRU report 73. Besides, the lineal energy spectra of charged particles in BNCT were calculated, and the influence of sensitive volume (SV) size was discussed. Condensed history simulation obtained similar results with MCTS when using Micron-SV while overestimating the lineal energy when using Nano-SV. Furthermore, we found that the microscopic boron distribution can significantly affect the lineal energy for Lithium, while the effect for alpha is minimal. Similar results to the published data by PHITS simulation were observed for the compound particles and monoenergetic protons when using micron-SV. Spectra with nano-SV reflected that the different track densities and absorbed doses in the nucleus together result in the dramatic difference in the macroscopic biological response of BPA and BSH. This work and the developed methodology could impact the research fields in BNCT where understanding radiation effects is crucial, such as the treatment planning system, source evaluation, and new boron drug development.

The organic carbon (Corg) stored in seagrass meadows is globally significant and could be relevant in strategies to mitigate increasing CO2 concentration in the atmosphere. Most of that stored Corg is in the soils that underlie the seagrasses. We explored how seagrass and soil characteristics vary among seagrass meadows across the geographic range of turtlegrass (Thalassia testudinum) with a goal of illuminating the processes controlling soil organic carbon (Corg) storage spanning 23° of latitude. Seagrass abundance (percent cover, biomass, and canopy height) varied by over an order of magnitude across sites, and we found high variability in soil characteristics, with Corg ranging from 0.08 to 12.59% dry weight. Seagrass abundance was a good predictor of the Corg stocks in surficial soils, and the relative importance of seagrass-derived soil Corg increased as abundance increased. These relationships suggest that first-order estimates of surficial soil Corg stocks can be made by measuring seagrass abundance and applying a linear transfer function. The relative availability of the nutrients N and P to support plant growth was also correlated with soil Corg stocks. Stocks were lower at N-limited sites than at P-limited ones, but the importance of seagrass-derived organic matter to soil Corg stocks was not a function of nutrient limitation status. This finding seemed at odds with our observation that labile standard substrates decomposed more slowly at N-limited than at P-limited sites, since even though decomposition rates were 55% lower at N-limited sites, less Corg was accumulating in the soils. The dependence of Corg stocks and decomposition rates on nutrient availability suggests that eutrophication is likely to exert a strong influence on carbon storage in seagrass meadows.

Objective: To compare the safety profile and clinical outcomes of Altieri-modified Nesbit corporoplasty using two different anesthesia methods including spinal anesthesia and local anesthesia. Materials and methods: A total of 40 patients with congenital penile curvature (CPC) and Peyronie’s disease (PD) underwent Altieri-modified Nesbit corporoplasty. Group 1 (n = 20) received spinal anesthesia, and Group 2 (n = 20) received local anesthesia. The patients were categorized into age groups (< 30 years, 31-45 years, 46-60 years, and 61-75 years) for analysis. Clinical outcomes, post-operative complications, hospital stay, pain levels, and other parameters were assessed. Results: The results showed that 2 patients (10%) reported postoperative complications, including headache, arterial hypotension, and penile foreskin necrosis from the spinal anesthesia group. Whereas, in the local anesthesia group, 1 patient (5%) reported scar phimosis. Further, post-operative pain was predominantly very mild, with 16 patients (80%) in the spinal anesthesia group and 14 patients (70%) in the local anesthesia group experiencing minimal discomfort. Age did not significantly impact hospital stay, post-operative intestinal disorders, constipation, lower urinary tract symptoms, voiding burning, or dysuria. Conclusions: Spinal anesthesia may lead to more post-operative complications and longer hospital stays compared to local anesthesia. Age does not significantly affect most clinical outcomes but can influence post-operative pain in patients receiving local anesthesia.

Infertility is usually defined as the inability of a couple to conceive even after 1 year of unprotected, frequent sexual intercourse. The male is solely responsible in about 20% of cases. Several risk factors as well as urogenital abnormalities,endocrinological disease,enviromental toxines,genetic disorders,immunological factors,urogenitaly infections,sexual dysfunction have been identified as causes of male infertility. Nowadays different studies reported mithocoldrial dysfunction as cause of male infertility and alteration of semen parameters.

El tratamiento de la enfermedad hepática terminal con Cardiomiopatía Cirrótica (CMC) es el trasplante hepático (TH), sin embargo el tratamiento médico con la combinación de diuréticos y beta bloqueantes no selectivos antes y después tienen un rol importante. A diferencia de la insuficiencia cardíaca de otras etiologías, los inhibidores de la enzima convertidora (IECA), los bloqueadores del receptor de angiotensina 2 (ARA-2) o los inhibidores del receptor de angiotensina y de neprilisina (ARNI) no se recomiendan debido a la fisiopatología particular de la CMC. El shunt porto-sistémico intrahepático transyugular (Transjugular intrahepatic porto-systemic shunt: TIPS) tiene sus indicaciones con posibles beneficios y riesgos pero más estudios son necesarios en la CMC. El TH es la opción más eficaz y puede revertir el QTc del ECG y la disfunción diastólica y sistólica; en las últimas décadas, a pesar del aumento de la complejidad en los pacientes (mayor score MELD), con la mejoría de la técnica quirúrgica, cuidados intensivos, drogas inmunosupresoras y diagnóstico por imágenes la sobrevida ha mejorado significativamente.

Abstract Consumers can play critical roles in ecosystem resilience by modifying community resistance and recovery rates. In coral reefs, grazers can increase reef resilience by controlling algae and maintaining open space for coral recruitment, but can also erode the reef framework critical for coral recovery. Here we examine the context‐dependent effects of herbivores on reef persistence in Caribbean Panamá. Using a series of lab and field experiments, we found that the erosional effects of the herbivorous reef urchin (Echinometra viridis) were 2 orders of magnitude greater on dead corals than live corals, and surveys across multiple similarly overfished reefs revealed a positive relationship between urchin densities and percent cover of bare dead coral with urchin densities exceeding 150 m−2 in some reefs. However, we observed that a mat‐forming zoanthid (Zoanthus pulchellus), found exclusively on dead corals, had an inverse spatial relationship with urchins. Through a series of field experiments, we found that zoanthid overgrowth repelled urchins, increased dead coral persistence, and decreased erosion of dead corals making up the reef framework by more than 50% over a 22‐month period. Our findings reveal that zoanthids can provide associational refuge to dead corals by enhancing their persistence under high urchin grazing pressure. We suggest that secondary space‐holders, such as zoanthids, may play increasingly important functional roles in degraded reef systems by shielding coral skeletons from external bioeroders. Moreover, the Stress Gradient Hypothesis, which predicts that the importance of positive interactions such as associational refuges increases with consumer pressure, extends to dead foundation species such as coral skeletons crucial for ecosystem recovery.

BackgroundFacial synkinesis (FS) is a distressing sequela of facial palsy (FP) characterized by involuntary, simultaneous movements of facial muscles occurring during voluntary facial expressions. Treatment of synkinesis is challenging, and preventive methods are needed.AimThis study evaluated the efficacy of physical facial nerve rehabilitation (PFNR) therapy alone vs. PNFR with eyelid surgery to correct lagophthalmos and prevent the onset of synkinesis.MethodsTwenty five outpatients were randomized to receive either PFNR alone (neuromuscular retraining and Kabat proprioceptive neuromuscular facilitation) or PNFR and early (90 days after FP onset) eyelid surgery (involving a conservative oculoplastic correction for lagophthalmos with epiphora or ectropion). Comprehensive otolaryngological assessments and Magnetic Resonance Imaging (MRI) were conducted. Synkinesis progression was measured using Another Disease Scale (ADS) at baseline, 3-, 6-, 12-, and 24-months post-treatment. The data were analyzed with ANOVA, τ-test, Chi-Square analyses.ResultsPatients undergoing eyelid surgery with PFNR showed faster (p