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AbstractPurpose:Viral hemorrhagic fevers (VHFs), such as Ebola virus disease, Marburg virus disease, and Lassa fever, are associated with significant morbidity and mortality and the potential for person-to-person transmission. While most individuals in whom VHF is suspected will ultimately be diagnosed with a non-VHF illness, such patients may present to any United States healthcare facility (HCF) for initial evaluation; therefore, all HCFs must be prepared to evaluate and initiate care for suspect VHF patients, especially if they are acutely ill. Included within this evaluation is the ability to perform basic routine laboratory testing before VHF-specific diagnostic test results are available, as well as rapid malaria testing to assess for a common, dangerous “VHF mimic.”Objective:To improve laboratory preparedness and readiness in the initial care of suspect VHF patients who may present to acute care hospitals.Design:Plan-Do-Study-Act quality improvement model.Setting:Frontline healthcare facilities and their clinical laboratories.Methods:We describe the development of a laboratory testing toolkit for a suspect VHF patient that can assist frontline HCFs in providing basic laboratory testing required for the care of these patients.Results:The toolkit provides guidance on infection prevention and control, waste management, occupational health, laboratory test collection, processing, and resulting, in the context of suspect VHF patient evaluation.Conclusions:The toolkit is designed to be readily adapted by any frontline HCF in the US. With the guidance provided, facilities will be able to support safer initial evaluation of VHF suspects and ensure high-quality patient care.

ABSTRACTObjectiveTo investigate the effect of the Coronavirus pandemic on the report of psychological status, bruxism, and TMD symptoms.MethodsAn online survey was drafted to report the presence of psychological status, bruxism activities, and reported symptoms of TMDs perceived during the COVID-19 pandemic in a population of 506 individuals.ResultsMental health is not positive during the Coronavirus pandemic: almost half the subjects reported an increase in bruxism behaviors, while up to one-third reported an increase in their symptoms involving the TMJ and jaw muscles. Specifically, 36% and 32.2% of participants reported increased pain in the TMJ and facial muscles, respectively, and almost 50% of the subjects also reported more frequent migraines and/or headaches.ConclusionIncreased psychosocial distress during the COVID-19 pandemic can increase the frequency of TMD symptoms and bruxism behaviors, which, in turn, constitute a triangle of mutually interacting factors with the psychological and emotional status.

Youth—people ages of 15–24 years—are at the forefront of present-day social movements focused on climate justice, civic activation, gun reform, and racial justice. Social movements occur when people with a shared purpose come together to take collective action in order to achieve a social justice goal. This article examines how youth-organized social movements not only propel individual and collective action but also actively support and sustain youth well-being. We define well-being as feeling positive, socially connected, and purposeful. We explore social movement practices for promoting individual and collective youth well-being. This research builds on dual insights: (1) the well-being practices of youth social movement organizers and (2) the extant literature in consumer research and its associated disciplines. Finally, we highlight insights from consumer research that advance our understanding of youth well-being and raise questions to encourage more researchers to investigate how social movements support youth well-being and well-doing.

Streamwise micro-groove surfaces (‘riblets’) are well-known as a passive surface treatment to reduce drag, which may assist in increasing overall gas turbine efficiency. The first direct numerical simulation of micro-scaled riblets on an axial high pressure compressor blade at engine-relevant conditions (Kozul et al., GT2023-101038) demonstrated the ability of riblets to reduce the skin-friction along most of the chord of a high pressure compressor blade, at both on- and off-design inflow incidences. However this previous study only considered riblets with fixed physical dimensions. The present work considers a ‘locally optimal’ riblet geometry applied to the high pressure compressor blade, where the riblet geometry is smoothly adjusted along the chord to target optimal riblet dimensions in viscous units, known from fundamental fluid mechanics studies. The present locally-optimal riblets do indeed reduce the skin friction on the surface of the high pressure compressor blade at both design and off-design inflow incidences, and are generally at least as effective as the previous fixed-geometry riblets. Yet the present riblet surfaces tend to increase pressure wake losses. In particular, at positive incidence, although the locally-optimal riblets generally further reduce the skin friction compared to the fixed riblets, the wake loss increases by a significant 20% with respect to the reference smooth-blade case. A complex flow interaction with the suction side separation bubble at the leading edge may be responsible for the significantly increased loss at positive inflow incidence.

Autosomal dominant Kabuki syndrome (KS) is a rare multiple congenital anomalies/neurodevelopmental disorder caused by heterozygous inactivating variants or structural rearrangements of the lysine-specific methyltransferase 2D (KMT2D) gene. While it is often recognizable due to a distinctive gestalt, the disorder is clinically variable, and a phenotypic scoring system has been introduced to help clinicians to reach a clinical diagnosis. The phenotype, however, can be less pronounced in some patients, including those carrying postzygotic mutations. The full spectrum of pathogenic variation in KMT2Dhas not fully been characterized, which may hamper the clinical classification of a portion of these variants. DNA methylation (DNAm) profiling has successfully been used as a tool to classify variants in genes associated with several neurodevelopmental disorders, including KS. In this work, we applied a KS-specific DNAm signature in a cohort of 13 individuals with KMT2DVUS and clinical features suggestive or overlapping with KS. We succeeded in correctly classifying all the tested individuals, confirming diagnosis for three subjects and rejecting the pathogenic role of 10 VUS in the context of KS. In the latter group, exome sequencing allowed to identify the genetic cause underlying the disorder in three subjects. By testing five individuals with postzygotic pathogenic KMT2Dvariants, we also provide evidence that DNAm profiling has power to recognize pathogenic variants at different levels of mosaicism, identifying 15% as the minimum threshold for which DNAm profiling can be applied as an informative diagnostic tool in KS mosaics.

It is observed that there is a significant increase in scientific publications on the subject of spirituality and religiosity in the health area. Such studies show that patients would like this topic to be addressed in their psychotherapy care, but it is identified that there is a lack of adequate training to carry out these issues for psychologists. So, this article aims to verify the effectiveness of an online training on the clinical management of religiosity, spirituality, secularity, and unusual experiences in psychotherapy for 46 Brazilian psychotherapist psychologists. As a result, we were able to observe the statistically significant increase in the total CRESEAP score, indicating that the competencies measured were satisfactorily developed. The P-DUREL (IR) scale was positively correlated in the pre-test with the CRESEAP subscale “Therapist’s Spirituality in the Therapeutic Relationship” before training and after, ceased to exist, demonstrating that the participants’ spiritual and religious beliefs were no longer interfering in the clinical practice. The ARES scale was positively related to the “Differential Diagnosis” subscale in the pre-test, and in the post-test, this association ceased to exist, indicating that all psychotherapists can perform the differential diagnosis, regardless of their faith. Therefore, the online training proved to be effective for developing spiritual and religious competencies in Brazilian psychotherapists, offering evidence-based resources to support professional performance on this topic. It is suggested that other studies be carried out with a larger number of participants and with comparative groups of therapists (working with different clinical approaches of psychotherapy, clinical experiences, and atheists).

Stories can inspire and propel people’s individual and collective action to unite social movements. In this article, we outline key social movement storytelling practices and integrate them with insights from academic research to build a framework for understanding how stories unite social movements. This framework includes research-supported storytelling practices for two types of essential social movement stories: individual meand movement westories. Stories of meare the personal stories of individual changemakers. Stories of weare the stories that these individuals tell about the movement. We identify how individual changemakers’ mestories intersect with and strengthen a movement’s westory. Finally, we highlight insights that deepen our conceptual and practical understanding of social movement storytelling.

Very often in the past, innovations from research communities have been disconnected from industry adoption, leading to a lack of exploitation of research projects. To overcome this issue, in the view of future 6G systems, the Hexa-X project is putting in place an innovation management (IM) process, aiming to facilitate and promote innovation opportunities based on project outcomes and ensure that all the ideas emerging from the project are captured and tracked, not “lost.” The focus of IM is on supporting the project to promptly identify innovations and engage with emerging innovation needs in the sector, for identifying gaps and potentials with strategic value. This article presents the IM approach in Hexa-X and selected innovations (some of which also awarded by the EC Innovation Radar), with particular emphasis on the technical aspects of these findings coupled with their identified strategic value for future 6G market exploitation.

A tournament graph is a complete directed graph, which can be used to model a round-robin tournament between $n$n players. In this paper, we address the problem of finding a champion of the tournament, also known as Copeland winner, which is a player that wins the highest number of matches. In detail, we aim to investigate algorithms that find the champion by playing a low number of matches. Solving this problem allows us to speed up several Information Retrieval and Recommender System applications, including question answering, conversational search, etc. Indeed, these applications often search for the champion inducing a round-robin tournament among the players by employing a machine learning model to estimate who wins each pairwise comparison. Our contribution, thus, allows finding the champion by performing a low number of model inferences. We prove that any deterministic or randomized algorithm finding a champion with constant success probability requires $\Omega (\ell n)$Ω(ℓn) comparisons, where $\ell$ℓ is the number of matches lost by the champion. We then present an asymptotically-optimal deterministic algorithm matching this lower bound without knowing $\ell$ℓ, and we extend our analysis to three variants of the problem. Lastly, we conduct a comprehensive experimental assessment of the proposed algorithms on a question answering task on public data. Results show that our proposed algorithms speed up the retrieval of the champion up to $13\times$13× with respect to the state-of-the-art algorithm that perform the full tournament.

Purpose: Adrenocortical carcinoma (ACC), a rare malignancy of the adrenocortex, is characterized by a crosstalk between the adipose microenvironment and tumor. Here, we assessed the involvement of carbonic anhydrase (CA) enzymes III and IX (CAIII and CAIX), in the metabolic alterations of the adipose tissue characterizing obesity and in the local crosstalk between the tumor adipose microenvironment and ACC. Results/methods: CAIII and CAIX expression is altered in visceral adipose tissue (VAT) in obesity and in ACC. A significant CAIX upregulation was present in ACC at advanced stages (n= 14) (fold increase FI = 7.4 ± 0.1, P< 0.05) associated with lower CAIII levels (FI = 0.25 ± 0.06, P< 0.001), compared with lower stages (n= 9). In vitro coculture between visceral adipose stem cells (ASCs) and ACC cell lines, H295R and MUC-1, mimicking the interaction occurring between VAT and advanced ACC, showed a significant CAIX upregulation in H295R but not in MUC-1 cells, and a decreased expression of CAIII. The effect on adipose cells was different when cocultured with H295R or MUC-1 cells. Coculture did not modulate CAIII expression in ASCs, which, however, was significantly downregulated with H295R (FI = 0.34 ± 0.11, P< 0.05) and upregulated by MUC-1 when cocultured ASCs were induced to differentiate toward adipocytes, with an expression profile similar to what found in VAT of obese subjects. CAIX expression was markedly increased in ASCs cocultured with H295R and to a less extent following adipogenesis induction (FI = 150.9 ± 46.5 and FI = 4.6 ± 1.1, P< 0.01, respectively). Conclusion: Our findings highlight a modulation of CAIII and CAIX in the metabolic crosstalk between ACC and its local adipose microenvironment, suggesting that CAs might represent a potential target for novel anticancer therapies.

Recent studies in Learning to Rank have shown the possibility to effectively distill a neural network from an ensemble of regression trees. This result leads neural networks to become a natural competitor of tree-based ensembles on the ranking task. Nevertheless, ensembles of regression trees outperform neural models both in terms of efficiency and effectiveness, particularly when scoring on CPU. In this paper, we propose an approach for speeding up neural scoring time by applying a combination of Distillation, Pruning and Fast Matrix multiplication. We employ knowledge distillation to learn shallow neural networks from an ensemble of regression trees. Then, we exploit an efficiency-oriented pruning technique that performs a sparsification of the most computationally-intensive layers of the neural network that is then scored with optimized sparse matrix multiplication. Moreover, by studying both dense and sparse high performance matrix multiplication, we develop a scoring time prediction model which helps in devising neural network architectures that match the desired efficiency requirements. Comprehensive experiments on two public learning-to-rank datasets show that neural networks produced with our novel approach are competitive at any point of the effectiveness-efficiency trade-off when compared with tree-based ensembles, providing up to 4x scoring time speed-up without affecting the ranking quality.

Drug repurposing is a highly active research area, aiming at finding novel uses for drugs that have been previously developed for other therapeutic purposes. Despite the flourishing of methodologies, success is still partial, and different approaches offer, each, peculiar advantages. In this composite landscape, we present a novel methodology focusing on an efficient mathematical procedure based on gene similarity scores and biased random walks which rely on robust drug-gene-disease association data sets. The recommendation mechanism is further unveiled by means of the Markov chain underlying the random walk process, hence providing explainability about how findings are suggested. Performances evaluation and the analysis of a case study on rheumatoid arthritis show that our approach is accurate in providing useful recommendations and is computationally efficient, compared to the state of the art of drug repurposing approaches.

Neuroblastoma (NB) is a heterogeneous extracranial tumor occurring in childhood. A distinctive feature of NB tumors is their neuroendocrine ability to secrete catecholamines, which in turn, viaβ-adrenergic receptors ligation, may affect different signaling pathways in tumor microenvironment (TME). It was previously demonstrated that specific antagonism of β3-adrenergic receptor (β3-AR) on NB tumor cells affected tumor growth and progression. Here, in a murine syngeneic model of NB, we aimed to investigate whether the β3-AR modulation influenced the host immune system response against tumor. Results demonstrated that β3-AR antagonism lead to an immune response reactivation, partially dependent on the PD-1/PD-L1 signaling axis involvement. Indeed, β3-AR blockade on tumor-infiltrating lymphocytes (TILs) dampened their ability to secrete IFN-γ, which in turn reduced the PD-L1 expression, caused by TILs infiltration, on NB tumor cells. Further investigations, through a genomic analysis on NB patients, showed that high ADRB3 gene expression correlates with worse clinical outcome compared to the low expression group, and that ADRB3 gene expression affects different immune-related pathways. Overall, results indicate that β3-AR in NB TME is able to modulate the interaction between tumor and host immune system, and that its antagonism hits multiple pro-tumoral signaling pathways.

Recent research has demonstrated the effectiveness of riblets (streamwise aligned grooves) in reducing the profile loss of low-pressure turbine (LPT) blades under high-lift (HL) loading. In this research, we pursue the efficacy of riblets in reducing the blade profile loss under various design and off-design conditions. We adopt a strategy in which surface roughness is employed in the transitional regime to minimize the separation bubble-related losses and flush-mounted riblets downstream to further mitigate the skin-friction drag and boundary layer losses due to an increase in the turbulent wetted area. Several high-fidelity scale-resolving simulations are carried out to test the efficacy of this ‘rough-ribbed’ LPT blade for loadings ranging from low-lift (LL), HL, and ultra high-lift (UHL) conditions. Furthermore, two exit Reynolds numbers—83,000 and 166,000—pertaining to engine relevant design and off-design conditions, respectively, are considered. The streamwise evolution of skin-friction coefficient and boundary layer integral parameters are compared and contrasted among different test cases. The instantaneous flow features and second-order statistics such as the Reynolds stress and turbulent kinetic energy are analyzed to determine the design and off-design performance of riblets. It is found that the efficacy of scallop-shaped riblets in reducing the profile loss improves with loading. Specifically, the net skin-friction reduction increases from 3.4% under LL to 8% under UHL loading at cruise Re. There is a corresponding reduction in the trailing edge momentum thickness (θTE) from 10% to 15%. A further reduction in θTE is attained from design to off-design Re under UHL loading. Thus, the effect of riblets in reducing mixing losses improves with increasing Re. It is also found that the riblets reduce flow blockage due to boundary layers. Furthermore, the necessity to optimize riblet ramp to achieve skin-friction reduction under off-design conditions is highlighted.

EGFRaberrations are reported in a subset of myofibroblastic lesions with kinase domain duplication (EGFR-KDD) and exon 20 mutations being assigned to infantile fibrosarcomas (IFS), mesoblastic nephroma, and fibrous hamartoma of infancy (FHI), respectively. In this retrospective study, we correlated molecular findings with the histomorphology of 14 myofibroblastic lesions harboring such genetic changes identified by NGS. We additionally performed DNA methylation profiling (DNAmp) and immunohistochemistry. Lesions were from 10 males and 4 females with a mean age of 3 years (range, 0.3-14) and occurred subcutaneously in the upper limbs (n = 5), lower limbs (n = 3), back/thorax (n = 5), and the nasal cavity (n = 1). Eleven were cured by surgery, including 1 relapsed case. Two patients were lost to follow-up. One case was very recent, and the patient was biopsied. Histologically, the lesions showed a wide spectrum varying from classic FHI (n = 9) to IFS (n = 1) or lipofibromatosis-like tumors (LFT-like) (n = 2) or dermatofibrosarcoma protuberans-like (DFSP-like) (n = 1) to a predominantly myxoid spindle cell lesion (n = 1). Immunohistochemically, all neoplasms stained with CD34, whereas S100 was positive in 2/14. EGFR expression was observed in 9/10 cases. Molecularly, the IFS and 1 LFT-like harbored EGFR-KDD, whereas an exon 20 mutation was identified in all FHI, 1 LFT-like, the DFSP-like, and in predominant myxoid spindle cell lesion. By DNAmp, all but 2 cases formed a well-defined cluster, demonstrating that these lesions are also epigenetically related. In conclusion, EGFRkinase domain aberrations found in FHI, IFS, LFT-like, DFSP-like, and a spindle cell lesion with a predominant myxoid stroma of children and adolescents showed that these neoplasms with a broad morphologic spectrum belong to the group of protein kinase–related lesions with a distinct epigenetic signature. Molecular analyses, including DNAmp, help to identify and characterize this emerging category and become mandatory when targeted treatment is considered.

Due to the mismatch between energy demand and energy production, in the last years the study of latent thermal energy storage systems has been significantly growing. This work aims to provide an overview of the studies and the experiments carried out on thermal energy storage systems, that use phase change materials combined with metal foams. A histogram that shows how the number of works on these subjects has been increasing over the years is reported; consequently, a general survey on phase change materials is conducted, identifying the temperature ranges and the latent heat which are most used in thermal energy storage systems and defining the strengths and weaknesses of the various types of phase change materials. Furthermore, the paper illustrates the models and methods currently used to describe the phase transition of phase change materials in metal foams. Subsequently, how metal foams improve the desirable characteristics of phase change materials is described, and then it is represented in what percentage the different pore sizes (PPI) are used and what the most functional porosity is for individual works. Lastly, through the summary of the analyzed papers some specific articles are considered, in order to explain the state-of-the-art and to clarify some fundamental concepts.

•Utilization of nanofluids allows to reduce the device dimensions.•The addition of nanoparticles determines a notable increase in the operating energy.•The addition of nanoparticles provokes a monotonic increase in entropy generation.

•Demonstration of mcr-1circulation in poultry birds in a wide area of Southeast Nigeria.•Novel allelic variant (mcr-1.22) was detected.•Among 22 mcr-1-positive E. coli, MLST distinguished 11 fingerprints, with 3 of them being novel.•Urgent need for educational projects and strategies to regulate colistin use in Nigeria.

Objective Plication of the diaphragm is a life-changing procedure for patients affected by diaphragm paralysis. Traditionally, this procedure is performed through a thoracotomy. Access to the diaphragm via this incision is poor and the indications for surgery are limited to patients who can actually sustain such an invasive approach and associated morbidities. A minimally invasive approach was developed to improve the surgical management of diaphragm paralysis.Methods Patients underwent minimally invasive diaphragm plication either by video-assisted or robotic surgery through a 3-port technique with CO2insufflation. Patients were followed at the routine 6-week clinic and also by telephone consultation 6 to 12 months postoperatively. Data were collected on postoperative complications, postoperative pain or numbness, symptomatic improvement, and change to quality of life following surgery.Results Forty-eight patients underwent 49 minimally invasive diaphragm plication. Median postoperative length of hospital stay was 4 days (range: 2 to 34 days) and there were no cases of mortality. Mean reduction in Medical Research Council dyspnea score per patient was 2.2 points (mode: 3 points). Twenty-eight patients (77.8%) reported a significant symptomatic improvement enabling improvements in quality of life, and 97.2% (n= 35) were satisfied with the surgical outcome.Conclusions Minimally invasive diaphragm plication is a safe procedure associated with prompt postoperative recovery. It is effective at reducing debilitating dyspnea and improving quality of life.

A novel diazaspiro[3.4]octane series was identified from a Plasmodium falciparumwhole-cell high-throughput screening campaign. Hits displayed activity against multiple stages of the parasite lifecycle, which together with a novel sp3-rich scaffold provided an attractive starting point for a hit-to-lead medicinal chemistry optimization and biological profiling program. Structure–activity-relationship studies led to the identification of compounds that showed low nanomolar asexual blood-stage activity (<50 nM) together with strong gametocyte sterilizing properties that translated to transmission-blocking activity in the standard membrane feeding assay. Mechanistic studies through resistance selection with one of the analogues followed by whole-genome sequencing implicated the P. falciparumcyclic amine resistance locus in the mode of resistance.

Background/aimsBest-corrected visual acuity (BCVA) is the most common primary endpoint in treatment trials for choroideremia (CHM) but the long-term natural history of BCVA is unclear.MethodsWe searched in seven databases to identify studies that reported BCVA of untreated eyes with CHM. We sought individual-level data and performed segmented regression between BCVA and age. For eyes followed longitudinally, we introduced a horizontal translation factor to each dataset to account for different ages at onset of a rapid BCVA decline.ResultsWe included 1004 eyes from 23 studies. BCVA of the right and left eyes was moderately correlated (r=0.60). BCVA as a function of age followed a 2-phase decline (slow followed by rapid decline), with an estimated transition age of 39.1 years (95% CI 33.5 to 44.7). After the introduction of horizontal translation factors to longitudinal datasets, BCVA followed a 2-phase decline until it reached 0 letters (r2=0.90). The BCVA decline rate was 0.33 letters/year (95% CI −0.38 to 1.05) before 39 years, and 1.23 letters/year (95% CI 0.55 to 1.92) after 39 years (p=0.004).ConclusionBCVA in eyes with CHM follows a 2-phase linear decline with a transition age of approximately 39 years. Future trials enrolling young patients may not be able to use BCVA as a primary or sole endpoint, but rather, may need to employ additional disease biomarkers that change before age 39. BCVA may still have utility as a primary endpoint for patients older than 39 years who have measurable BCVA decline rates.

Determining the natural history of unifocal versus multifocal geographic atrophy (GA) secondary to nonexudative age-related macular degeneration.

To conduct a systematic review and meta-analysis of the natural history of atrophy secondary to choroideremia (CHM).

Background No published studies have evaluated in pregnant women with HIV weight gain with different antiretroviral drug classes.Methods Data from a national cohort study were used. We compared absolute weight gain and occurrence of excessive weight gain in women with HIV who received during pregnancy integrase inhibitors (INSTI), protease inhibitors (PI), or non-nucleoside reverse transcriptase inhibitors (NNRTI). Excessive weight gain was defined according to the Institute of Medicine recommendations. Possible predictors of weight gain were assessed using univariate and multivariate analyses.Results Among 273 cases (PI: 191, NNRTI: 43, INSTI: 39), the mean weight increase was 11.3 kg, and 25.4% of the mothers had an excessive weight increase. No significant differences were found among the three treatment groups for absolute weight increase, occurrence of excessive weight gain, infant birthweight, and other pregnancy and laboratory outcomes. The comparisons of individual drugs, although based on a limited number of cases, suggested no major differences. A significant positive correlation was found between weight gain and CD4+T-cell increase during pregnancy. In multivariate analyses, drug class and nucleoside backbone were not associated with absolute or excessive weight increase. Excessive weight increase was significantly associated with week of delivery (adjusted odds ratio: 1.74, 95% CI 1.15, 2.63), obesity (5.21, 95% CI 1.85, 14.64), overweight (7.95, 95% CI 3.26, 19.39), recent substance use (5.96, 95% CI 1.13, 31.40) and fasting 2nd trimester hyperglycaemia (3.94, 95% CI 1.14, 13.65).Conclusions No significant differences in absolute weight change or occurrence of excessive weight gain were found among women with HIV who received during pregnancy different classes of antiretroviral drugs.