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The optimization workflow for airfoil shapes, crucial for maximizing the lift/drag ratio, involves numerous computational fluid dynamics (CFD) simulations. Convolutional neural networks (CNNs) expedite this process by creating fast reduced order models. However, using uniformly spaced grids for CNN training is inadequate for complex scenarios, like those with wall-bounded turbulence, due to their inability to represent spatial variability effectively. A novel method addresses this limitation by preliminarily transforming flow fields into a new computational space, enabling concise representation of crucial information. The developed neural network architectures, comprising fully connected and transposed convolution layers, accurately infer transformed field maps for incompressible flow around a NACA0012 airfoil based on Reynolds (Re) number and angle of attack. In particular, the performance of a traditional transposed convolutional neural network (TCNN) architecture is compared with that of a conditional generative adversarial network (cGAN) with a TCNN generator. The most important aspect of the proposed spatial transformation lies in the ability to transfer the learned weights onto new geometries, allowing for training with fewer CFD data than would be required for training from scratch. By applying transfer learning to cGAN models trained with 15 cases for the prediction of velocity fields around the NACA4412 airfoil, the average error is up to 70% lower than training without weight transfer. This approach streamlines the optimization process by facilitating rapid model training and precise inference of flow fields, overcoming challenges posed by complex aerodynamic scenarios. [ABSTRACT FROM AUTHOR]

Helical structures are a hallmark of hydrodynamic turbulence, and they play a key role in determining the transport and diffusion properties of the flow. Helicity, defined by the linking of velocity and vorticity, is, thus, of primary significance, particularly in systems such as propelled jet wakes. In this paper, we present a novel approach for determining helicity in turbulence, based on one-dimensional filtering methods. First, we test our new technique using analytical solutions and numerical simulations and find that the model can identify high-helicity patterns qualitatively well. Then, we employ the technique in experiments with propelled, helical turbulent flows. The model reliance on single-point velocity measurement may be especially advantageous for measurements with limited acquisition dimensionality. [ABSTRACT FROM AUTHOR]

This paper focuses on a morphological study of the MnTe-like structures, carried out by the evaluation of the tortuosity tensor and other related parameters using a computational fluid dynamics approach recently developed by our research group. The present work focuses on all possible crystals—existing or not developed yet—having the same structure as that of the manganese telluride. This analysis provides new information not present yet in the open literature. The motivation behind this study lies in the importance of this type of structure in physics and material science. In particular, the structures investigated are anisotropic and bi-disperse, with two independent geometrical parameters controlling the structure shape: the ratio of the particle diameters (r1) and the normalised inter-particle distance (r2). Exploiting this fact, several different structures of the same family are created, changing these two parameters independently, also allowing inter-penetration of particles to enlarge the study's applicability. The results are primarily obtained in terms of the tortuosity tensor, needed to catch and quantify the anisotropy of the structures. Then, other morphological parameters, such as connectivity, principal diffusion directions, and anisotropy factors, are evaluated, obtaining in this way a novel morphological characterisation of the structure. It is found that high values of tortuosity are observed at lower and higher values of {r1, r2}, which means that there exists a minimum value between them. Additionally, the anisotropy factor is found to be higher at lower values of {r1, r2} and lower at higher ones. This is in accordance with the fact that, as the inter-particle distance and the ratio between particle diameters increase, the structure enlarges, which implies a lower influence of the particle distribution and, thus, a gradually more isotropic structure. [ABSTRACT FROM AUTHOR]

Light downconversion films can modulate incident light wavebands on crops, converting less utilised wavebands in an efficient way. In this experiment, red (conversion of green into red light wavebands), pink (conversion of UV and green into blue and red light but to a smaller degree than red film), and blue (conversion of UV into blue light) light downconversion films were used to cover blackberry plants throughout all phenological stages (from leaf emergence to fruit harvesting). The plants' physiological and biometric performance, and fruit yield and quality were evaluated. Plants under blue and red films showed a higher net photosynthetic rate with +23.1% and +14.9%, respectively, and a higher stomatal conductance with +56.0% and +23.6%, respectively, with respect to controls, maintaining stability across stages, except for a decrease under the red film during fruiting. Both films significantly boosted the fruit yield, with the red film increasing the fruit number (+49.8%) and the blue film enhancing the berry shape (+10.7) and fresh weight (+36.6). Notably, no significant differences in nutraceutical quality, including total flavonoid and anthocyanin content, were observed. These findings suggest that light downconversion films, particularly red and blue films, can effectively enhance the photosynthetic performance and fruit production in blackberry plants without compromising the fruit quality. Future research on this topic should focus on balancing plant growth, fruit productivity, and enhancing fruit nutraceutical properties. [ABSTRACT FROM AUTHOR]

Background: This study aimed at (1) delivering generalizable estimates of the prevalence of frontotemporal-spectrum disorders (FTSDs) in non-demented ALS patients and (2) exploring their motor-functional correlates. Methods: N = 808 ALS patients without FTD were assessed for motor-functional outcomes—i.e., disease duration, severity (ALSFRS-R), progression rate (ΔFS), and stage (King's and Milano–Torino—MiToS—systems)—cognition—via the cognitive section of the Edinburgh Cognitive and Behavioural ALS Screen (ECAS)—and behaviour—via the ECAS-Carer Interview. Neuropsychological phenotypes were retrieved via Strong's revised criteria—i.e., ALS cognitively and behaviourally normal (ALScbn) or cognitively and/or behaviourally impaired (ALSci/bi/cbi). Results: Defective ECAS-Total performances were detected in ~ 29% of patients, with the ECAS-Executive being failed by the highest number of patients (~ 30%), followed by the ECAS-Language, -Fluency, and -Memory (~ 15–17%) and -Visuospatial (~ %8). Apathy was the most frequent behavioural change (~ 28%), followed by loss of sympathy/empathy (~ 13%); remaining symptoms were reported in < 4% of patients. The distribution of Strong's classifications was as follows: ALScbn: 46.7%; ALSci/bi/cbi: 22.9%/20.0%/10.4%. Multinomial regressions on Strong's classifications revealed that lower ALSFRS-R scores were associated with a higher probability of ALSbi and ALScbi classifications (p ≤.008). Higher King's and MiToS stages were associated with a higher probability of ALSbi classification (p ≤.031). Conclusions: FTSDs affect ~ 50% of non-demented ALS patients, with cognitive deficits being as frequent as behavioural changes. A higher degree of motor-functional involvement is associated with worse behavioural outcomes—with this link being weaker for cognitive deficits. [ABSTRACT FROM AUTHOR]

Introduction: It has been recently acknowledged that deficits in experiencing and processing one's own emotions, also termed alexithymia, may possibly feature the frontotemporal-spectrum disorders. This study aims to determine whether alexithymia could be included within the frontotemporal syndromes of amyotrophic lateral sclerosis (ALS). Methods: Alexithymic traits were estimated in a cohort of 68 non-demented ALS patients with the 20-item Toronto Alexithymia Scale (TAS-20). Patients were assessed for the identification of motor-phenotypes and frontotemporal syndromes based on current classification criteria. Spearman's coefficients explored the correlates of TAS-20 measures with motor-functional profiles, global cognitive, social-cognitive (emotion recognition and empathy) and behavioral status. Results: Abnormal TAS-20 scores were found in 13% of patients, and their distribution did not vary within motor and frontotemporal phenotypes. Significant associations were detected between TAS-20 and executive (p ≤.011), memory (p =.006), state-anxiety (p ≤.013) and depression measures (p ≤.010). By contrast, TAS-20 scores were unrelated to social-cognitive performances, dysexecutive and apathetic profiles. Disease duration was the only motor-functional feature being related to the TAS-20 (p ≤.008). Conclusions: Alexithymia of potential clinical relevance occur in a minority of ALS patients, and its neuropsychological correlates mostly resemble those featuring the general population. Hence, it is unlikely that alexithymia is a specific feature of frontotemporal-spectrum characterizing ALS, rather it could be an expression of psychogenic factors as a reaction to the disease. [ABSTRACT FROM AUTHOR]

The construction sector is currently undergoing a deep digital transformation resulting from the prioritization of emerging technologies, among which are digital twins. New goals and opportunities are appearing that minimize the impact on a building's lifecycle, reduce economic, environmental, and extra-social costs, optimize energetic performance, decrease energy consumption and emissions, and enhance the durability and service life of buildings and their components. Among the research activities that have led to the development of a maintenance management model (MMM), this paper deals with the digital-twin approach, considering it instrumental to the innovative governance of the building environment from a lifecycle-based and sustainable perspective. It includes paying attention to efficiency in terms of resource use, energy consumption, and the energy performance of buildings, supporting decarbonization processes, and environmental vulnerability due to natural disasters, extreme weather, and seismic events. Its current implementation is presented here. In this scenario, the authors, operating at BIG srl, an academic spinoff of the Mediterranean University of Reggio Calabria, Italy, working together with the startup Sysdev, based in Torino, Italy, the company Berna Engineering srl, based in Reggio Calabria, Italy, and ACCA Software spa, based in Avellino, Italy, introduce the experimental application of the DT4SEM for safety and well-being in buildings, which is specifically oriented to seismic behavior monitoring. The proposal, while highlighting the innovative character of DT approaches, responds to the need for reliable data for increasingly effective forecasts and the control of the seismic behavior of buildings, facilitating informed decision-making for building management while also optimizing maintenance schedules. [ABSTRACT FROM AUTHOR]

Sicilian protohistory was characterized by a progressive flow of indigenous populations towards the hills of the western Sicilian hinterland. Especially during the Late Bronze Age and the Iron Age, the island's hinterland was marked by isolated settlements due to Siculi, Ausoni, Morgeti, and Elimi invasions and Phoenician and Greek colonization. In this scenario, Mokarta is an example of territorial autonomy and ethnic isolation (Sicanian) within an area of Elimi colonization. Its demise in the 11th century B.C.E, presumably at the hands of the Elimi, was rapid and violent as the settlement was suddenly abandoned following its destruction by fire. Symbolic of this event is an individual found at the entrance of a burned and collapsed hut who appears to have died from a cranial injury. This paper focuses on the osteological analysis of this skeleton, highlighting the perimortem injury, related to his death, and places the results within a forensic archeological context. The morphological pattern of the lesion is the result of a high‐energy impact by a circular blunt object. The fracture, involving both the meningeal vessels and the brain, could have led to a fatal neurological trauma. The analysis of the cranial fracture and an anatomical evaluation of the affected area led us to conclude that the perimortem injury, inflicted on the right parietal, probably was the cause of death. The case proposed highlights how an integrated approach based on bioarcheology and forensic anthropology helps in interpreting an archeological scenario and formulating hypotheses about the circumstances of an individual's death. [ABSTRACT FROM AUTHOR]

Score-driven models have recently been introduced as a general framework to specify time-varying parameters of conditional densities. The score enjoys stochastic properties that make these models easy to implement and convenient to apply in several contexts, ranging from biostatistics to finance. Score-driven parameter updates have been shown to be optimal in terms of locally reducing a local version of the Kullback–Leibler divergence between the true conditional density and the postulated density of the model. A key limitation of such an optimality property is that it holds only locally both in the parameter space and sample space, yielding to a definition of local Kullback–Leibler divergence that is in fact not a divergence measure. The current paper shows that score-driven updates satisfy stronger optimality properties that are based on a global definition of Kullback–Leibler divergence. In particular, it is shown that score-driven updates reduce the distance between the expected updated parameter and the pseudo-true parameter. Furthermore, depending on the conditional density and the scaling of the score, the optimality result can hold globally over the parameter space, which can be viewed as a generalization of the monotonicity property of the stochastic gradient descent scheme. Several examples illustrate how the results derived in the paper apply to specific models under different easy-to-check assumptions, and provide a formal method to select the link function and the scaling of the score. [ABSTRACT FROM AUTHOR]

Glaciers in the Alps are losing mass at unprecedented and accelerating rates. Monitoring of glacier mass change as well as relevant atmospheric parameters plays an important role in improving understanding of local and downstream impacts. We present sub-seasonal, seasonal, and annual glaciological mass balance data and meteorological observations from Mullwitzkees and Venedigerkees, two glacier monitoring sites in the Hohe Tauern range of the Austrian Alps. Ablation stake networks were established on Mullwitzkees in 2006/07 and on Venedigerkees in 2011/12. Monitoring is ongoing. In addition to stake readings at sub-seasonal intervals, accumulation measurements (snow pits and probing) are carried out seasonally. The glaciological dataset consists of sub-seasonal floating-date measurements as well as fixed-date seasonal and annual values. The fixed-date glacier-wide mass balance was derived from annual point mass balance values. Automatic weather stations measuring standard meteorological parameters were installed near Mullwitzkees and Venedigerkees in 2020 and 2019, respectively. Meteorological data are provided in 10 min intervals. Uncertainties in individual point mass balance measurements were computed following the approach of the Swiss Glacier Monitoring (GLAMOS) programme, taking into account estimated density and reading errors. The sub-seasonal mass balance records highlight shorter-term variability in mass loss and the linkage with meteorological conditions. The most negative annual point mass balance recorded in the period of record was -5.8 ± 0.66 m w.e. at an elevation of 2536 m on Venedigerkees, and 2022 stands out as the most negative mass balance year to date in both time series, particularly at higher elevations. The cumulative specific mass balances (glacier-wide) over the period of record were -14.68 m w.e. at Mullwitzkees and -8.79 m w.e. at Venedigerkees. Data are available in the PANGAEA publication series and the associated datasets. The main publication series are updated annually. The Mullwitzkees mass balance datasets can be found in (10.1594/PANGAEA.965660) and (10.1594/PANGAEA.965719). The Venedigerkees data can be found in (10.1594/PANGAEA.965648) and (10.1594/PANGAEA.965729). [ABSTRACT FROM AUTHOR]

In the last ten years, technological innovations have led to the development of new, advanced sensory stimulation (SS) tools, such as PC-based rehabilitative programs or virtual reality training. These are meant to stimulate residual cognitive abilities and, at the same time, assess cognition and awareness, also in patients with a minimally conscious state (MCS). Our purpose was to evaluate the clinical and neurophysiological effects of multi-sensory and emotional stimulation provided by Neurowave in patients with MCS, as compared to a conventional SS treatment. The psychological status of their caregivers was also monitored. In this retrospective study, we have included forty-two MCS patients and their caregivers. Each MCS subject was included in either the control group (CG), receiving a conventional SS, or the experimental group (EG), who was submitted to the experimental training with the Neurowave. They were assessed before (T0) and after the training (T1) through a specific clinical battery, including both motor and cognitive outcomes. Moreover, in the EG, we also monitored the brain electrophysiological activity (EEG and P300). In both study groups (EG and CG), the psychological caregiver’s aspects, including anxiety levels, were measured using the Zung Self-Rating Anxiety Scale (SAS). The intra-group analysis (T0-T1) of the EG showed statistical significances in all patients’ outcome measures, while in the CG, we found statistical significances in consciousness and awareness outcomes. The inter-group analysis between the EG and the CG showed no statistical differences, except for global communication skills. In conclusion, the multi-sensory stimulation approach through Neurowave was found to be an innovative rehabilitation treatment, also allowing the registration of brain activity during treatment.

Cobalt (Co) is an essential trace element for humans and other animals, but high doses can be harmful to human health. It is present in some foods such as green vegetables, various spices, meat, milk products, seafood, and eggs, and in drinking water. Co is necessary for the metabolism of human beings and animals due to its key role in the formation of vitamin B12, also known as cobalamin, the biological reservoir of Co. In high concentrations, Co may cause some health issues such as vomiting, nausea, diarrhea, bleeding, low blood pressure, heart diseases, thyroid damage, hair loss, bone defects, and the inhibition of some enzyme activities. Conversely, Co deficiency can lead to anorexia, chronic swelling, and detrimental anemia. Co nanoparticles have different and various biomedical applications thanks to their antioxidant, antimicrobial, anticancer, and antidiabetic properties. In addition, Co and cobalt oxide nanoparticles can be used in lithium-ion batteries, as a catalyst, a carrier for targeted drug delivery, a gas sensor, an electronic thin film, and in energy storage. Accumulation of Co in agriculture and humans, due to natural and anthropogenic factors, represents a global problem affecting water quality and human and animal health. Besides the common chelating agents used for Co intoxication, phytoremediation is an interesting environmental technology for cleaning up soil contaminated with Co. The occurrence of Co in the environment is discussed and its involvement in biological processes is underlined. Toxicological aspects related to Co are also examined in this review.

Background. Urban planning is a key tool to promote health in cities. The COVID-19 emergency accelerated several social, environmental, and digital challenges, stressing the importance of some issues regarding housing, urban mobility, green areas, and health service networks, urban health policies, and actions. These issues were the subject of an intensive residential course (the 57th) held in Erice, Sicily, in June 2021 in the “International School of Epidemiology and Preventive Medicine G. D’Alessandro”, and the main findings are described here. Methods. Lectures presented the topics, subsequently developed them, and argued them in parallel practical sessions using the World Café technique, since it is well suited for the interaction of participants and the involvement of groups. Results. The World Café provides new insights into how to improve the livability and health of urban spaces, and a set of strategies and actions were proposed for each topic. Discussion and Conclusions. All attendees agreed on the importance of participation in the planning processes, but also on the need for strong political support to ensure the resources needed and a full integration of health with other local policies. A multidisciplinary approach to developing systemic operational capacities and health literacy is considered pivotal to raising awareness and participation.

CDK-1 and PARP-1 play crucial roles in breast cancer progression. Compounds acting as CDK-1 and/or PARP-1 inhibitors can induct cell death in breast cancer with a selective synthetic lethality mechanism. A mixed treatment by means of CDK-1 and PARP-1 inhibitors resulted in radical breast cancer cell growth reduction. Inhibitors with a dual target mechanism of action could arrest cancer progression by simultaneously blocking the DNA repair mechanism and cell cycle, resulting in advantageous monotherapy. To this aim, in the present work, we identified compound 645656 with a significant affinity for both CDK-1 and PARP-1 by a mixed ligand- and structure-based virtual screening protocol. The Biotarget Predictor Tool was used at first in a Multitarget mode to filter the large National Cancer Institute (NCI) database. Then, hierarchical docking studies were performed to further screen the compounds and evaluate the ligands binding mode, whose putative dual-target mechanism of action was investigated through the correlation between the antiproliferative activity data and the target proteins’ (CDK-1 and PARP-1) expression pattern. Finally, a Molecular Dynamics Simulation confirmed the high stability of the most effective selected compound 645656 in complex with both PARP-1 and CDK-1.

Background: Within the broad spectrum of rehabilitation, maxillofacial prostheses are those that are made to restore the appearance of a person who has suffered facial deformation due to cancer, accidents, congenital diseases, among others. Although these are not made to restore functionality, they have a major impact on restoring the patient's quality of life as it is an area so closely linked to their identity. For his reason, they have to be carefully tailored for each patient, which tends to increase cost and production time Objectives: The purpose of this research is to compare different additive manufacturing mechanisms, to evaluate which of them achieves the best reproduction of the leather details and maintains the desired dimensional properties. Methods: The manufacturing equipment will be selected comparing 7 different 3D printing of an oculo-palpebral model for a future maxillofacial prosthesis, obtained from the “Mais Identidade” Method. They were evaluated according to their economic, physical and aesthetic characteristics. Results: The results of the evaluations show that: the highest score in the economic evaluation was obtained by PhotonS; in the physical evaluation it was obtained by PhotonS, Phrozen Suffle XL and PRO95; and in the aesthetic evaluation it was obtained by PRO95 and Objet500. Finally, according to the multi-criteria evaluation, the highest score was obtained by the Photon S and PRO95.

Abstract For 3D neural cultures durable hydrogels are required, which persist over a long differentiation period and thus enable the maturation of neuronal networks (NN). Here, 3D models based on human induced pluripotent stem cell‐derived neural progenitor cells that are embedded in hydrogels of either pure alginate or alginate functionalized with the extracellular matrix protein laminin 111 (L111) are established. This study analyzes material characteristics such as porosity, L111 distribution and shear viscosity, cell compatibility of hydrogels by measuring viability and cytotoxicity, and neural function by monitoring cell migration, differentiation as well as NN formation and activity on multielectrode arrays. The addition of L111 increases neural migration and enhances differentiation into neurons and astrocytes as well as synaptogenesis in alginate hydrogels. NN formed in hydrogels are electrically active for up to 206 d and L111‐supplementation further increases electrical activity, network maturation, and synchronicity compared to 2D controls and NN grown in pure alginate hydrogels. L111 addition to alginate gels further accelerates recovery of electrical activity after blockage of sodium channels with tetrodotoxin. In conclusion, NN grown in alginate‐L111 hydrogel blends are promising models for future long‐term applications in disease modeling, drug or chemical evaluation.

Bitemark analysis is a challenging procedure in the field of criminal case investigation. The unique characteristics of dentition are used to find the best match between the existing patterned injury and the suspected perpetrator in bitemark identification. Bitemark analysis accuracy can be influenced by various factors, including biting pressure, tooth morphology, skin elasticity, dental cast duplication, timing, and image quality. This review article discusses the potential of a smartphone camera as an alternative method for 3D bitemark analysis. Bitemark evidence on human skin and food should be immediately recorded or duplicated to retrieve long-lasting proof, allowing for a sufficient examination period. Various studies utilizing two-dimensional (2D) and three-dimensional (3D) technologies have been developed to obtain an adequate bitemark analysis. 3D imaging technology provides accurate and precise analysis. However, the currently available method using an intraoral scanner (IOS) requires high-cost specialized equipment and a well-trained operator. The numerous advantages of monoscopic photogrammetry may lead to a novel method of 3D bitemark analysis in forensic odontology. Smartphone cameras and monoscopic photogrammetry methodology could lead to a novel method of 3D bitemark analysis with an efficient cost and readily available equipment.

Objective: Thioalbamide is a ribosomally synthesized and post-translationally modified peptide (RiPP) belonging to the family of thioamitides, a rare class of microbial specialized metabolites with unusual post-translational modifications and promising biological activities. Recent studies have demonstrated the ability of thioalbamide to exert highly selective cytotoxic effects on tumor cells by affecting their energy metabolism, thus causing abnormal ROS production and triggering apoptosis. This study is aimed to investigate the molecular mechanisms underlying the antitumor activity of thioalbamide in order to identify its exact molecular target. Methods: Wild type MCF-7 and MDA-MB-231 breast cancer cell lines as well as cancer cells deprived of mitochondrial DNA (ρ0 cells) were employed in order to assess thioalbamide effects on tumor bioenergetics. In this regard, metabolic profile was evaluated by a Seahorse XFe96 analyzer, and the activity of the enzyme complexes involved in oxidative phosphorylation was quantified by spectrophotometric assays. Thioalbamide effects on tumor invasiveness were assessed by gelatin zymography experiments and invasion assays. In vivo experiments were carried out on breast cancer xenograft and “experimental metastasis” mouse models. Results: Experiments carried out on ρ0 breast cancer cells, together with Seahorse analysis and the application of spectrophotometric enzymatic assays, highlighted the ability of thioalbamide to affect the mitochondrial respiration process, and allowed to propose the FoF1-ATPase complex as its main molecular target in breast cancer cells. Additionally, thioalbamide-mediated OXPHOS inhibition was shown, for the first time, to reduce tumor invasiveness by inhibiting metalloproteinase-9 secretion. Furthermore, this study has confirmed the antitumor potential of thioalbamide in two different in vivo models. In particular, experiments on MCF-7 and MDA-MB-231 xenograft mouse models have confirmed in vivo its high anti-proliferative and pro-apoptotic activity, while experiments on MDA-MB-231 ″experimental metastasis” mouse models have highlighted its ability to inhibit breast cancer cell invasiveness. Conclusions: Overall, our results shed more light on the molecular mechanisms underlying the pharmacological potential of thioamidated peptides, thus reducing the gap that separates this rare class of microbial metabolites from clinical studies, which could validate them as effective tools for cancer treatment.

Tuberculosis (TB) causes 1 in 3 deaths among people living with HIV (PLHIV). Diagnosing and treating latent tuberculosis infection (LTBI) is critical to reducing TB incidence and mortality. Blood-based screening tests (e.g., QuantiFERON-TB Gold Plus (QFT+)) and shorter-course TB preventive therapy (TPT) regimens such as 3HP (3 months weekly isoniazid-rifapentine) hold significant promise to improve TB outcomes. We qualitatively explored barriers and solutions to optimizing QFT+ and 3HP among PLHIV in three cities in Brazil. We conducted 110 in-depth interviews with PLHIV, health care providers (HCP) and key informants (KI). Content analysis was conducted including the use of case summaries and comparison of themes across populations and contexts. LTBI screening and treatment practices were dependent on HCP's perceptions of whether they were critical to improving TB outcomes. Many HCP lacked a strong understanding of LTBI and perceived the current TPT regimen as complicated. HCP reported that LTBI screening and treatment were constrained by clinic staffing challenges. While PLHIV generally expressed willingness to consider any test or treatment that doctors recommended, they indicated HCP rarely discussed LTBI and TPT. TB testing and treatment requests were constrained by structural factors including financial and food insecurity, difficulties leaving work for appointments, stigma and family responsibilities. QFT+ and 3HP were viewed by all participants as tools that could significantly improve the LTBI cascade by avoiding complexities of TB skin tests and longer LTBI treatment courses. QFT+ and 3HP were perceived to have challenges, including the potential to increase workload on over-burdened health systems if not implemented alongside improved supply chains, staffing, and training, and follow-up initiatives. Multi-level interventions that increase understanding of the importance of LTBI and TPT among HCP, improve patient-provider communication, and streamline clinic-level operations related to QFT+ and 3HP are needed to optimize their impact among PLHIV and reduce TB mortality.

IntroductionImmunocompromised patients have been shown to have an impaired immune response to COVID-19 vaccines.MethodsHere we compared the B-cell, T-cell and neutralizing antibody response to WT and Omicron BA.2 SARS-CoV-2 virus after the fourth dose of mRNA COVID-19 vaccines in patients with hematological malignancies (HM, n=71), solid tumors (ST, n=39) and immune-rheumatological (IR, n=25) diseases. The humoral and T-cell responses to SARS-CoV-2 vaccination were analyzed by quantifying the anti-RBD antibodies, their neutralization activity and the IFN-γ released after spike specific stimulation.ResultsWe show that the T-cell response is similarly boosted by the fourth dose across the different subgroups, while the antibody response is improved only in patients not receiving B-cell targeted therapies, independent on the pathology. However, 9% of patients with anti-RBD antibodies did not have neutralizing antibodies to either virus variants, while an additional 5.7% did not have neutralizing antibodies to Omicron BA.2, making these patients particularly vulnerable to SARS-CoV-2 infection. The increment of neutralizing antibodies was very similar towards Omicron BA.2 and WT virus after the third or fourth dose of vaccine, suggesting that there is no preferential skewing towards either virus variant with the booster dose. The only limited step is the amount of antibodies that are elicited after vaccination, thus increasing the probability of developing neutralizing antibodies to both variants of virus.DiscussionThese data support the recommendation of additional booster doses in frail patients to enhance the development of a B-cell response directed against Omicron and/or to enhance the T-cell response in patients treated with anti-CD20.

Abstract Acute ST‐segment elevation myocardial infarction (STEMI) can typically complicate with the development of cardiogenic shock; nevertheless, other less frequent types of shock may occur, including adrenal crisis (AC). We describe a case of STEMI complicated by AC and, for the first time, AC‐induced focal takotsubo syndrome.

Al norte de la ciudad monumental de Cáceres, a cincuenta metros de la Iglesia de Santiago, se advierte un espacio que clama por un pasaje por el trazado de la trama urbana. Pero no aparece en el callejero ni en la cartografía histórica que manejamos. El ayuntamiento lo contempla como prioridad desde la aprobación del Plan Especial de Protección y Revitalización del Patrimonio Arquitectónico de 1990, incorporándolo al Plan General Municipal de 2010. A partir del trazado grafico se establecen propuestas para la apertura de este paso, con beneficios para todas las partes implicadas.

Predictive models are central to many scientific disciplines and vital for informing management in a rapidly changing world. However, limited understanding of the accuracy and precision of models transferred to novel conditions (their 'transferability') undermines confidence in their predictions. Here, 50 experts identified priority knowledge gaps which, if filled, will most improve model transfers. These are summarized into six technical and six fundamental challenges, which underlie the combined need to intensify research on the determinants of ecological predictability, including species traits and data quality, and develop best practices for transferring models. Of high importance is the identification of a widely applicable set of transferability metrics, with appropriate tools to quantify the sources and impacts of prediction uncertainty under novel conditions.

To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS.

Metaphors can shape how people reason about complex issues,but most studies of metaphor framing rely exclusively onwritten materials. This is a significant limitation, as peopleregularly encounter linguistic metaphors in a variety ofdifferent communicative settings (e.g., read in the newspaper,heard on the radio, or viewed on television). Because researchfinds that variations in communication modality can influencemessage comprehension, retention, and persuasiveness, weexplored the relative power of metaphor framing in differentcommunication modalities. Across two experiments,participants read, heard, or watched a person describe fourdifferent metaphorically framed issues. They had to answer atarget question about each issue by selecting from two responseoptions, one of which was congruent with the metaphor frame.Results revealed a significant, similarly-sized effect ofmetaphor framing in every communication modality,suggesting that communication modality does not moderate theefficacy of metaphor framing.

Abstract Background Omics data, driven by rapid advances in laboratory techniques, have been generated very quickly during the COVID-19 pandemic. Our aim is to use omics data to highlight the involvement of specific pathways, as well as that of cell types and organs, in the pathophysiology of COVID-19, and to highlight their links with clinical phenotypes of SARS-CoV-2 infection. Methods The analysis was based on the domain model, where for domain it is intended a conceptual repository, useful to summarize multiple biological pathways involved at different levels. The relevant domains considered in the analysis were: virus, pathways and phenotypes. An interdisciplinary expert working group was defined for each domain, to carry out an independent literature scoping review. Results The analysis revealed that dysregulated pathways of innate immune responses, (i.e., complement activation, inflammatory responses, neutrophil activation and degranulation, platelet degranulation) can affect COVID-19 progression and outcomes. These results are consistent with several clinical studies. Conclusions Multi-omics approach may help to further investigate unknown aspects of the disease. However, the disease mechanisms are too complex to be explained by a single molecular signature and it is necessary to consider an integrated approach to identify hallmarks of severity.