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Skin sensitization is a significant concern for chemical safety assessments. Traditional animal assays often fail to predict human responses accurately, and ethical constraints limit the collection of human data, necessitating a need for reliable in silico models of skin sensitization prediction. This study introduces HuSSPred, an in silico tool based on the Human Predictive Patch Test (HPPT). HuSSPred aims to enhance the reliability of predicting human skin sensitization effects for chemical agents to support their regulatory assessment. We have curated an extensive HPPT database and performed chemical space analysis and grouping. Binary and multiclass QSAR models were developed with Bayesian hyperparameter optimization. Model performance was evaluated via five-fold cross-validation. We performed model validation with reference data from the Defined Approaches for Skin Sensitization (DASS) app. HuSSPred models demonstrated strong predictive performance with CCR ranging from 55 to 88%, sensitivity between 48 and 89%, and specificity between 37 and 92%. The positive predictive value (PPV) ranged from 84 to 97%, versus negative predictive value (NPV) from 22 to 65%, and coverage was between 75 and 93%. Our models exhibited comparable or improved performance compared to existing tools, and the external validation showed the high accuracy and sensitivity of the developed models. HuSSPred provides a reliable, open-access, and ethical alternative to traditional testing for skin sensitization. Its high accuracy and reasonable coverage make it a valuable resource for regulatory assessments, aligning with the 3Rs principles. The publicly accessible HuSSPred web tool offers a user-friendly interface for predicting skin sensitization based on chemical structure.

Introduction: Androgenic alopecia (AGA) staging is still based on macroscopic scales, yet the introduction of trichoscopy is gradually bringing an important change, even though it remains an eye-based method. However, recently developed artificial intelligence-assisted programs can execute automated count of trichoscopic patterns. Nevertheless, to interpret data elaborated by these programs can be complex. Machine learning algorithms might represent an innovative solution. Among them, support vector machine (SVM) models are among the best methods for classification. Objectives: Our aim was to develop a SVM algorithm, based on three trichoscopic patterns, able to classify AGA patients and to calculate a severity index. Methods: We retrospectively analyzed trichoscopic images from 200 AGA patients using Trichoscale Pro® software, calculating the number of vellus hair, empty follicles and single hair follicular units. Then, we elaborated a SVM model, based on these three patterns and on sex, able to classify patients as affected by mild AGA or moderate-severe AGA, and able to calculate the probability of the classification being correct, expressed as percentage (from 50% to 100%). This probability estimate is higher in patients with more AGA trichoscopic patterns and, thus, it might serve as a severity index. Results: For training and test datasets, accuracy was 94.3% and 90.0% respectively, while the Area Under the Curve was 0.99 and 0.95 respectively. Conclusions: We believe our SVM model could be of great support for dermatologists in the management of AGA, especially in better assessing disease severity and, thus, in prescribing a more appropriate therapy.

BackgroundHematological malignancies (HMs) represent a heterogeneous group of diseases with diverse etiology, pathogenesis, and prognosis. HMs’ accurate registration by Cancer Registries (CRs) is hampered by the progressive de-hospitalization of patients and the transition to molecular rather than microscopic diagnosis.Material and methodsA dedicated software capable of automatically identifying suspected HMs cases by combining several databases was adopted by Reggio Emilia Province CR (RE-CR). Besides pathological reports, hospital discharge archives, and mortality records, RE-CR retrieved information from general and biomolecular laboratories. Incidence, mortality, and 5-year relative survival (RS) reported according to age, sex, and 4 HMs’ main categories, were noted.ResultsOverall, 7,578 HM cases were diagnosed from 1996 to 2020 by RE-CR. HMs were more common in males and older patients, except for Hodgkin Lymphoma and Follicular Lymphoma (FL). Incidence showed a significant increase for FL (annual percent change (APC)=3.0), Myeloproliferative Neoplasms (MPN) in the first period (APC=6.0) followed by a significant decrease (APC=-7.4), and Myelodysplastic Syndromes (APC=16.4) only in the first period. Over the years, a significant increase was observed in 5-year RS for Hodgkin -, Marginal Zone -, Follicular - and Diffuse Large B-cell-Lymphomas, MPN, and Acute Myeloid Leukemia. The availability of dedicated software made it possible to recover 80% of cases automatically: the remaining 20% required direct consultation of medical records.ConclusionsThe study emphasizes that HM registration needs to collect information from multiple sources. The digitalization of CRs is necessary to increase their efficiency.

Axial fans may be equipped with passive flow control devices to enhance rotor efficiency or minimize noise emissions. In this regard, blade designs influenced by biomimicry, such as rotors with sinusoidal leading edges (LEs), have gained popularity in recent years. However, their design is predominantly driven by a trial-and-error approach, with limited systematic studies on the influence of rotor performance. Furthermore, their effectiveness is typically evaluated under controlled conditions that may significantly differ from operations in real installation layouts. In this work, a systematic review of the design process for sinusoidal LE axial fan rotors is provided, aiming to summarize previous design experiences. Then, a modified sinusoidal LE is designed and fitted to a 7.3 m low-speed axial fan for air-cooled condensers (ACCs). These fans operate at environmental conditions, providing a quasi-zero static pressure rise, often with inflow non-uniformities. A series of RANS computations were run to simulate the performance of the baseline fan and that of the sinusoidal leading edge, considering a real installation setup at Stellenbosh University, where the ACC is constrained between buildings and has a channel running on the ground below the fan inlet. The aim is to explore the nonbalanced inflow condition effects in both rotor geometries and to test the effect of the installation layout on fan performance. The results show that the modification to the rotor allows for a more even distribution of flow in the blade-to-blade passages with respect to the baseline geometry.

Background: Ruxolitinib (RUX) is a JAK1/2 inhibitor approved for the therapy of myelofibrosis (MF) based on clinical trials including only intermediate2‐high risk (INT2/HIGH) patients. However, RUX is commonly used in intermediate‐1 (INT1) patients, with scarce information on responses and outcome. Methods: The authors investigated the benefit of RUX in 1055 MF patients, included in the "RUX‐MF" retrospective study. Results: At baseline (BL), 595 (56.2%) patients were at INT1‐risk according to DIPSS (PMF) or MYSEC‐PM (SMF). The spleen was palpable at <5 cm, between 5 and 10 cm, and >10 cm below costal margin in 5.9%, 47.4%, and 39.7% of patients, respectively; 300 (54.1%) were highly symptomatic (total symptom score ≥20). High‐molecular‐risk (HMR) mutations (IDH1/2, ASXL‐1, SRSF2, EZH2, U2AF1Q157) were detected in 77/167 patients. A total of 101 (19.2%) patients had ≥1 cytopenia (Hb < 10 g/dL: n.36; PLT <100 x 109/L: n = 43; white blood cells <4 x 109/L: n = 40). After 6 months on RUX, IWG‐MRT–defined spleen and symptoms response rates were 26.8% and 67.9%, respectively. In univariate analysis, predictors of SR at 6 months were no HMR mutations odds ratio [OR], 2.0, p =.05], no cytopenia (OR, 2.10; p =.01), and blasts <1% (OR, 1.91; p =.01). In multivariate analysis, absence of HMR maintained a significant association (OR, 2.1 [1.12–3.76]; p =.01). Conclusions: In INT1 patients, responses were more frequent and durable, whereas toxicity rates were lower compared to INT2/high‐risk patients. Presence of HMR mutations, cytopenia, and peripheral blasts identified less‐responsive INT1 patients, who may benefit for alternative therapeutic strategies. Overall survival and event‐free survival rates are significantly superior, whereas rate of ruxolitinib discontinuations is significantly lower in intermediate‐1 patients, confirming the benefits of ruxolitinib in patients with less advanced disease. [ABSTRACT FROM AUTHOR]

Skin sensitization is a significant concern for chemical safety assessments. Traditional animal assays often fail to predict human responses accurately, and ethical constraints limit the collection of human data, necessitating a need for reliable in silico models of skin sensitization prediction. This study introduces HuSSPred, an in silico tool based on the Human Predictive Patch Test (HPPT). HuSSPred aims to enhance the reliability of predicting human skin sensitization effects for chemical agents to support their regulatory assessment. We have curated an extensive HPPT database and performed chemical space analysis and grouping. Binary and multiclass QSAR models were developed with Bayesian hyperparameter optimization. Model performance was evaluated via five-fold cross-validation. We performed model validation with reference data from the Defined Approaches for Skin Sensitization (DASS) app. HuSSPred models demonstrated strong predictive performance with CCR ranging from 55 to 88%, sensitivity between 48 and 89%, and specificity between 37 and 92%. The positive predictive value (PPV) ranged from 84 to 97%, versus negative predictive value (NPV) from 22 to 65%, and coverage was between 75 and 93%. Our models exhibited comparable or improved performance compared to existing tools, and the external validation showed the high accuracy and sensitivity of the developed models. HuSSPred provides a reliable, open-access, and ethical alternative to traditional testing for skin sensitization. Its high accuracy and reasonable coverage make it a valuable resource for regulatory assessments, aligning with the 3Rs principles. The publicly accessible HuSSPred web tool offers a user-friendly interface for predicting skin sensitization based on chemical structure. [ABSTRACT FROM AUTHOR]

Wind turbines play a major role in the European Green Deal for clean energy transition. Noise is a critical aspect among open technological issues, as it determines the possibility of onshore installations near inhabited places and the possible detrimental effects on wildlife when offshore. This paper assesses the accuracy of different approaches to predicting the sound pressure level (SPL) of a wind turbine. The 2.75 MW Neg Micon NM80 horizontal axis wind turbine (HWAT) was simulated in OpenFOAM, modeling the turbine with the actuator line method (ALM) implemented in the turbinesFoam library. Two different inflow conditions were considered: a stationary inflow with a typical atmospheric boundary layer profile and a time-dependent inflow derived from a precursor channel with fully turbulent conditions. The surrogate model for noise prediction used for this work is based on the synthetic/surrogate acoustics models (SAMs) of Amiet and Brooks-Pope-Marcolini (BPM). This approach allows for blade motion modeling and the prediction of the SPL of the URANS postprocessing results. The SPL spectrum obtained was then compared to the results from the other aeroacoustic solvers of IEA Task 39 participants, showing the best performance in the fully turbulent case. The results demonstrate that coupling between the ALM and surrogate acoustics provides more accurate results than the blade element momentum (BEM) approach.

Introdução: O uso dos implantes osseointegrados para reabilitação de pacientes com dificuldade de adaptação de próteses convencionais mostra-se mais frequente a cada dia. Um grande grupo candidato à reabilitação com essa modalidade são os pacientes tratados para as neoplasias de cabeça e pescoço (CP). A irradiação na região de CP pode ser limitante para a instalação de implantes, porém a literatura apresenta evidências de técnicas e planejamentos favoráveis ao procedimento nesse grupo de pacientes. As técnicas menos traumáticas para intervenções na cavidade oral devem ser avaliadas, e os guias cirúrgicos para colocação de implantes podem ser aliados nesses procedimentos. Relato do caso: Paciente do sexo feminino, 64 anos, tratada com cirurgia, quimioterapia e radioterapia em cavidade oral para um carcinoma espinocelular (CEC) em língua e, em um segundo momento, diagnosticada e tratada com cirurgia para CEC em região de rebordo alveolar maxilar esquerdo por meio de hemipalatecmia, necessitava de reabilitação com implantes osseointegrados na região onde havia sido tratada com radiação primariamente. Realizou-se a cirurgia de colocação dos implantes com a tecnologia guiada para acarretar o mínimo trauma às estruturas bucais. Conclusão: O procedimento cirúrgico foi executado com sucesso. Atualmente, aguarda-se o período de osseointegração para a posterior reabilitação protética.

In this retrospective comparative study, we evaluated the effectiveness of remdesivir (RDSV) in patients with SARS-CoV-2 pneumonia. Individuals hospitalized between March 2020 and August 2022 at S.M. Goretti Hospital, Latina, with a positive test for SARS-CoV-2 and, concomitantly, pneumonia, were included. The overall survival was the primary endpoint. The composite secondary endpoint included death or progression in severe ARDS at 40 days. The study population was stratified according to treatment into two groups: the RDSV group (patients treated with RDSV-based regimens) and the no-RDSV group (patients treated with any other, not RDSV-based, regimens). Factors associated with death and progression to severe ARDS or death were assessed by multivariable analysis. A total of 1153 patients (632 belonging to the RDSV group and 521 to the no-RDSV group) were studied. The groups were comparable in terms of sex, PaO2/FiO2 at admission, and duration of symptoms before hospitalization. Further, 54 patients (8.5%) in the RDSV group and 113 (21.7%) in the no-RDSV group (p < 0.001) died. RDSV was associated with a significantly reduced hazard ratio (HR) of death (HR, 0.69 [95% CI, 0.49–0.97]; p = 0.03), compared to the no-RDSV group, as well as a significantly reduced OR of progression in severe ARDS or death (OR, 0.70 [95% CI 0.49–0.98]; p = 0.04). An overall significantly higher survival rate was observed in the RDSV group (p < 0.001, by log-rank test). These findings reinforce the survival benefit of RDSV and support its routine clinical use for the treatment of COVID-19 patients.

In 2022, three antiviral drugs—molnupiravir, remdesivir and nirmatrelvir/ritonavir—were introduced for treatment of mild-to-moderate COVID-19 in high-risk patients. The aim of this study is the evaluation of their effectiveness and tolerability in a real-life setting. A single-center observational study was set up, with the involvement of 1118 patients, with complete follow-up data, treated between the 5th of January and the 3rd of October 2022 at Santa Maria Goretti’s hospital in Latina, Central Italy. A univariable and a multivariable analysis were performed on clinical and demographic data and composite outcome, the persistence of symptoms at 30 days and time to negativization, respectively. The three antivirals showed a similar effectiveness in containing the progression of the infection to severe COVID-19 and a good tolerability in the absence of serious adverse effects. Persistence of symptoms after 30 days was more common in females than males and less common in patients treated with molnupiravir and nirmatrelvir/r. The availability of different antiviral molecules is a strong tool and, if correctly prescribed, they can have a significant role in changing the natural history of infection for frail persons, in which vaccination could be not sufficient for the prevention of severe COVID-19.

Recent flood disasters caused by extreme meteorological events highlight the need of fast and reliable tools for flooding forecast. For our purposes, the danger associated with floods is embodied in a single risk-level flag which considers both local water depth and velocity. The methodology here derived is applied and validated for the case study of the St. Lucia island in the eastern Caribbean Sea that experiences flash flooding as a result of combined intense rainfall and steep slopes, difficult to predict with traditional early-warning systems. A multi-layer perceptron neural network is trained on a high-fidelity dataset generated through full two-dimensional shallow water simulations of real and synthetic events. The dataset is validated against social markers obtained from real events. The predictive capabilities of the neural network model are tested on the out-of-box case of the Dean and Tomas hurricanes and compared with the solutions of the shallow water solver. The surrogate solver allows a significant speed-up in the prediction time with respect to traditional CFD (seconds vs hours), showing a high precision and accuracy, with accuracy, precision and F1-score above 0.99. [ABSTRACT FROM AUTHOR]

Air-cooled condensers (ACCs) are commonly found in power plants working with concentrated solar power or in steam power plants operated in regions with limited water availability. In ACCs, the flow of air is driven toward the heat exchangers by axial fans that are characterized by large diameters and operate at very high mass flow rates with a near-zero static pressure rise. Given the overall requirements in steam plants, these fans are subjected to inflow distortions, unstable operations, and are characterized by high noise emissions. Previous studies show that leading edge bumps in the tip region of axial fans can effectively reduce the sound pressure levels without affecting the static efficiency. Nevertheless, the effects of this treatment in terms of flow patterns and heat exchange in the whole ACC system were not investigated. In this work, the effect of leading edge bumps on the flow patterns is analyzed. Two RANS simulations were carried out using OpenFOAM on a simplified model of the air-cooled condenser. The fans are simulated using a frozen rotor approach. Turbulence modeling relies on the RNG k-epsilon model. The fan is characterized by a diameter of 7.3 m and a 333 m3/s volumetric flow rate at the design point. The presence of the heat exchanger is modeled using a porous medium. The comparison between the flow fields clearly exerts that the modified blade is responsible for the redistribution of radial velocities in the rotor region. This drastically reduces the losses related to the installation of the fan in a real configuration.

Monkeypox infection is an emerging problem and a new challenge for modern medicine. With an increasing number of new cases worldwide, new data regarding the clinical manifestations, characteristics of the patients, risk factors and treatment options are coming to light. Knowing more about the disease will allow to elaborate new helpful methods to facilitate its diagnosis. Special attention should be paid to the careful dermatologic and dermoscopic examination of the patient. The analysis of available data also suggests possible strategies for the prevention of Monkeypox virus spread; the vaccine against Smallpox seems to be an effective solution. This case report describes the diagnostic approach and management of a non-vaccinated adult patient with several risk factors and a history of sexually transmitted disease. The patient had no history of travel abroad. Even though a clinical diagnose of Monkeypox can be challenging due to its similarities with skin rashes caused by other Orthopoxviral infections, there are fine differences between the rashes which can be helpful in their differentiation, although laboratory analysis is required for a definitive identification. A careful study of the characteristics of the rash, such as diameter, its presence on palms and soles and its evolution in time, provided important clues for the diagnosis of Monkeypox infection. The lack of vaccinations in the history of the patient was another crucial finding in the diagnostic process.

Features of personality disorders (PDs) have been found to explain meaningful variance in the onset, maintenance, and symptomatic presentation of eating disorders (EDs), and a co-occurent personality pathology is commonly associated with poorer response to ED treatment. The “pathoplasty model” of the relationship between personality and EDs implies that, once both conditions are established, they are likely to interact in ways that modify therapy outcome; however, to date, no studies have explored overall personality functioning, and especially PD clusters, as a mediator of treatment outcome. The present study aimed at conjointly exploring the associations between personality functioning and PDs, respectively, with pre-treatment ED symptomatic impairment and therapy outcome; and the mediating role of personality variables. At treatment onset, a sample of 107 women with ED problems were evaluated using both the Structured Clinical Interview for DSM-5 (SCID-5-CV) and the Shedler-Westen Assessment Procedure-200 (SWAP-200)—a clinician-rated procedure to dimensionally assess personality. Participants were also asked to complete self-report questionnaires on overall ED symptomatology, symptoms of binge eating and purging behaviors, and therapy outcome. The findings showed that, over and above the categorical ED diagnosis, the SWAP-200 healthy personality functioning score mediated the relationship between baseline ED symptom severity and therapy outcome, as well as the association between baseline bulimic symptoms and treatment outcome; furthermore, SWAP-200 Cluster B PD scores mediated the link between baseline binge eating and purging symptoms and therapy outcome, whereas scores in Clusters A and C showed no significant effects. The findings suggest that personality-based outcome research may improve treatment effectiveness in this difficult-to-treat population.

Reduction of gas turbine (GT) carbon emissions relies on a strategy for fueling the engines with pure or blended hydrogen. The major technical challenges to solve are (i) the adjustments to the engine and in particular the combustion chamber and (ii) a series of issues to solve to guarantee safe operations. In fact, compared to natural gas, hydrogen fueling implies higher risks of explosion in case of leak in the turbine enclosure and a more careful design of the ventilation system. Thus, a deeper comprehension of hydrogen leak scenarios is needed to adjust the safe design strategy of the enclosure. To this aim, a series of numerical investigations was carried out to understand how different methane-hydrogen blends (from pure methane to pure hydrogen) behave when leaking from a pipeline with fuel pressure that span from 1.5 to 4.5 MPa. The different fuel blends' leaks in form of underexpanded jets were studied under different cross-flow ventilation conditions, with ventilation velocity spanning from 0 m/s to 5 m/s. When compared to pure methane, the outcome is a three times longer penetration distance for pure hydrogen axisymmetric flammable clouds, whereas in cross-flow conditions a more complex three-dimensional behavior was found, potentially opening a safety-related concerns discussed in the paper. [ABSTRACT FROM AUTHOR]