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Abstract Background Five species of the Phortica genus (Diptera: Drosophilidae) are known in Europe and the Middle East. Among these, Phortica variegata and Phortica okadai are better known for their role as vectors of the zoonotic eyeworm Thelazia callipaeda. Other species, such as Phortica semivirgo and Phortica oldenbergi, have been studied less. Given the paucity of data about these Phortica spp. vectors, we explored the population dynamics and ecology of Phortica spp. in an area highly endemic for T. callipeada (Manziana, Rome, Central Italy). Methods Phortica spp. flies were collected over a 3-year period (2018–2020) during their active season (April–October) with a sweep net while hovering around fermenting fruits or a human operator acting as baits. Collected flies were morphologically identified and tested for a T. callipeada infection and for the presence of Wolbachia, by polymerase chain reaction (PCR). Population dynamics of species collected was associated to environmental drivers through generalized additive models. Results Of the 5564 flies collected, 90.8% were P. variegata, 9.1% were P. oldenbergi, 0.05% were P. semivirgo, and one specimen was P. okadai. Only P. variegata scored molecularly infected with T. callipeada throughout the 3-year sampling period (1.8%). Phortica oldenbergi, observed consistently during the entire sampling period, exhibited a marked preference for fruit traps, contrasting with the lachryphagous activity of P. variegata. Analysis of environmental drivers of P. oldenbergi and P. variegata population dynamics indicated temperature, wind speed, and pressure as significant factors. In addition, Wolbachia pipientis endosymbiont was detected in P. oldenbergi and P. okadai. Conclusions For the first time, this study analysed several ecological aspects of Phortica species coexisting in a T. callipeada endemic area, highlighting different behaviors in the same environment and their vectorial role. Notably, this is also the first report of the presence of P. oldenbergi in Italy and P. okadai in Europe, underscoring the importance of extensive sampling for detecting potential vectors and alien species with direct implications for vector-borne disease epidemiology. Graphical Abstract

Abstract We construct rigid non-supersymmetric heterotic vacua with reduced rank and no tachyons in six and four dimensions. These configurations are based on asymmetric orbifold compactifications which do not admit neutral deformation moduli and represent, to the best of our knowledge, the first instances of non-tachyonic non-supersymmetric heterotic vacua with reduced rank.

Purpose: The aim of this study is to establish which specific cognitive abilities are phenotypically related to reading skill in adolescence and determine whether this phenotypic correlation is explained by polygenetic overlap. Method: In an Australian population sample of twins and non-twin siblings of European ancestry (734 [less than or equal to] N [less than or equal to] 1542 [50.7% < F < 66%], mean age = 16.7, range = 11-28 years) from the Brisbane Adolescent Twin Study, mixed-effects models were used to test the association between a dyslexia polygenic score (based on genome-wide association results from a study of 51,800 dyslexics versus >1 million controls) and quantitative cognitive measures. The variance in the cognitive measure explained by the polygenic score was compared to that explained by a reading difficulties phenotype (scores that were lower than 1.5 SD below the mean reading skill) to derive the proportion of the association due to genetic influences. Results: The strongest phenotypic correlations were between poor reading and verbal tests R[superscript 2] up to 6.2%); visuo-spatial working memory was the only measure that did not show association with poor reading. Dyslexia polygenic scores could completely explain the phenotypic covariance between poor reading and most working memory tasks and were most predictive of performance on a test of arithmetic (R[superscript 2] = 2.9%). Conclusion: Shared genetic pathways are thus highlighted for the commonly found association between reading and mathematics abilities, and for the verbal short-term/working memory deficits often observed in dyslexia.

Abstract Background Pyrethroid resistance is one of the major threats for effectiveness of insecticide-treated bed nets (ITNs) in malaria vector control. Genotyping of mutations in the voltage gated sodium channel (VGSC) gene is widely used to easily assess the evolution and spread of pyrethroid target-site resistance among malaria vectors. L1014F and L1014S substitutions are the most common and best characterized VGSC mutations in major African malaria vector species of the Anopheles gambiae complex. Recently, an additional substitution involved in pyrethroid resistance, i.e. V402L, has been detected in Anopheles coluzzii from West Africa lacking any other resistance alleles at locus 1014. The evolution of target-site resistance mutations L1014F/S and V402L was monitored in An. coluzzii and Anopheles arabiensis specimens from a Burkina Faso village over a 10-year range after the massive ITN scale-up started in 2010. Methods Anopheles coluzzii (N = 300) and An. arabiensis (N = 362) specimens collected both indoors and outdoors by different methods (pyrethrum spray catch, sticky resting box and human landing collections) in 2011, 2015 and 2020 at Goden village were genotyped by TaqMan assays and sequencing for the three target site resistance mutations; allele frequencies were statistically investigated over the years. Results A divergent trend in resistant allele frequencies was observed in the two species: 1014F decreased in An. coluzzii (from 0.76 to 0.52) but increased in An. arabiensis (from 0.18 to 0.70); 1014S occurred only in An. arabiensis and slightly decreased over time (from 0.33 to 0.23); 402L increased in An. coluzzii (from 0.15 to 0.48) and was found for the first time in one An. arabiensis specimen. In 2020 the co-occurrence of different resistance alleles reached 43% in An. coluzzii (alleles 410L and 1014F) and 32% in An. arabiensis (alleles 1014F and 1014S). Conclusions Overall, an increasing level of target-site resistance was observed among the populations with only 1% of the two malaria vector species being wild type at both loci, 1014 and 402, in 2020. This, together with the co-occurrence of different mutations in the same specimens, calls for future investigations on the possible synergism between resistance alleles and their phenotype to implement local tailored intervention strategies.

Abstract Environmental pollutants used as plasticizers in food packaging and in thousands of everyday products have become harmful for their impact on human health. Among them, phthalates, recognized as emerging endocrine disruptors (EDs) can induce toxic effects leading to different health disorders. Only few studies evaluated the effects of di-n-hexyl phthalate (DnHP) in in vivo models and no studies have been conducted to investigate the effect of DnHP on the endocannabinoid system (ECS), one of the majors signaling pathways involved in the microbiota–gut–brain axis. Due to the current relevance of probiotic bacteria as beneficial dietary interventions, the present study was aimed at evaluating the potential neuroprotective impact of daily administration of Lactiplantibacillus (Lpb.) plantarum IMC513 on zebrafish adults exposed to DnHP, with a focus on ECS modulation. Gene expression analysis revealed a promising protective role of probiotic through the restoration of ECS genes expression to the control level, in the brain of zebrafish daily exposed to DnHP. In addition, the levels of main endocannabinoids were also modulated. These findings confirm the potential ability of probiotics to interact at central level by modulating the ECS, suggesting the use of probiotics as innovative dietary strategy to counteract alterations by EDs exposure.

ObjectiveThis study aimed to examine the effects of the Mindfulness-Based Health Promotion program on mindfulness, psychological capital, compassion fatigue, and affect in a sample of healthcare workers at a hospital in Colombia.MethodRandomized controlled study with pre-test and post-test measures, in which 33 workers participated (Mage = 35.01, SD = 10.0), assigned to the experimental group (EG, n = 16, Mage = 34.00, SD = 9.59) and the wait-list control group (CG, n = 17, Mage = 36.03, SD = 10.56). The contrast of the program effects was carried out through a mixed factorial ANOVA.ResultsWe found significant effects on observing, non-reacting and mindfulness as a function of the group factor.ConclusionWe concluded the Mindfulness-Based Health Promotion program showed positive effects on mindfulness, this was tested with a novel program designed for the Latin population. This study is pioneering in using this mindfulness program in Colombia. These findings offer valuable insights for leaders of healthcare institutions when developing intervention programs that promote the mental health in the workplace. Future studies with larger samples and mixed-methods are necessary to confirm our results and to identify factors that can predict these findings.

Introdução: A transformação do Linfoma de Hodgkin (LH) é um evento incomum, cujo prognóstico é variável, principalmente quando para linfomas de alto grau. Sua fisiopatologia é incerta. A incidência é maior em Linfoma de Hodgkin Predominância Linfocitária Nodular, mas ocorre em até 1% dos Linfomas de Hodgkin Clássico. Objetivo: Relatar caso de paciente com LHCEN quimiorrefratário com transformação para LDGCB. Material e métodos: Revisão de prontuário eletrônico, relato e discussão de caso clínico a partir de revisão de literatura, utilizando base de dados PUBMED, MEDLINE, BVS, SCIELO. Relato de caso: Paciente C.S.S, feminina, 24 anos, previamente hígida, apresentou nódulo supraclavicular à direita associado à dor local, prurido generalizado e manchas hipocrômicas com 5 meses de evolução. Em biópsia excisional do linfonodo, o anatomopatológico foi sugestivo de infiltração linfoproliferativa de grandes células, confirmada em imunofenotipagem por imunohistoquímica (IHQ) na presença de marcadores CD15 e CD30, com negatividade para CD20, CD3, CD43, CD45 RO, CD79a, LMP e ALK, interpretado como LHC esclerose nodular. Foi realizado estadiamento por PET-CT, com acometimento de múltiplas cadeias linfonodais e maior captação em massa mediastinal (80 × 50 mm, SUVm 9.4), definindo estadio clínico IIIA (Ann Arbor / Lugano) e International Prognostic Score de 0. A paciente recebeu em 1ª linha quimioterapia protocolo ABVD e, após 2 ciclos, sem intercorrências graves, apresentou Deauville 1 em PET-CT. Após o 4° ciclo, a mesma evoluiu com dor abdominal e lesão expansiva retouterina sólido-cística com captação anexial em PET-CT de controle, além de progressão do padrão de captação em relação ao exame prévio. Realizada PAAF anexial guiada por ultrassonografia, mas como o material era escasso foi optado por biópsia via laparotomia, cujo AP foi compatível com doença linfoproliferativa e IHQ positiva para CD45, CD20, BCL6, MUM1, diagnosticado como LDGCB não centro germinativo pela classificação de Hans. A revisão da IHQ inicial assegurou os resultados prévios. A paciente completou 6 ciclos de ABVD durante a investigação, mantendo progressão da doença em PET-CT posterior. Confirmada a transformação, foi optado por quimioterapia de resgate com protocolo R-DHAP e, após 3 ciclos, houve refratariedade e por opção da paciente e recusa a receber nova quimioterapia, seguimento com cuidados paliativos exclusivos. Discussão: A evolução de LH para LDGCB é rara e com poucas publicações sobre sua apresentação, incidência, prognóstico e manejo. A fisiopatologia é pouco esclarecida, porém alguns autores acreditam que ocorra de forma simultânea (casual) ou subsequente (progressão histológica) ao LH, visto que os tumores poderiam originar-se de clones diferentes ou de uma mesma célula em diferentes estágios de diferenciação. Ademais, a presença de leucopenia, estadio avançado e sintomas B são comuns em relatos e podem ser fatores prognósticos para a transformação. Estudos incorporando diagnóstico molecular e citogenético devem melhor elucidar os mecanismos envolvidos. Conclusão: A transformação do LH para LDGCB deve ser aventada quando há evolução agressiva e refratariedade à terapêutica inicial. A vigilância com exames de imagem com alta sensibilidade e a escolha de biópsia excisional para estudo imunohistoquímico são aconselháveis para melhor diagnosticar e tratar este fenômeno.

Introdução: Mielofibrose (MF) é uma neoplasia mieloproliferativa caracterizada por quadros de anemia, hematopoiese extramedular, fibrose da medula óssea, esplenomegalia e progressão para leucemia mieloide aguda. Seu diagnóstico pode ser um desafio, principalmente em pacientes triplo negativos. Objetivo: Relatar um caso de paciente com suspeita de MF e os desafios em seu diagnóstico. Material e métodos: Revisão de prontuário eletrônico, relato e discussão de caso clínico, utilizando dados do Pubmed, Medline, Google Acadêmico e COSMIC database. Relato de caso: Paciente de 54 anos, sexo masculino, com histórico de hepatite C tratada em 2014, desenvolveu plaquetopenia leve, considerada secundária à infecção. Em 2020, durante internação por COVID-19, nova plaquetopenia leve. Realizou TC abdominal com vasculite intestinal, tratada com corticoide. Em 2022, USG de abdome com esplenomegalia e edema difuso do trato digestivo. Colonoscopia: inflamação moderada de cólon, indicando doença inflamatória intestinal, sendo iniciada mesalazina. Biópsia de medula óssea, compatível com neoplasia mieloproliferativa crônica, com fibrose grau 3. Citogenética normal. Encaminhado ao nosso serviço, mutações JAK2, CARL, MPL e BCR-ABL negativos. Após extensa investigação, mantendo plaquetopenia leve, o diagnóstico hematológico definido foi mielofibrose secundária a processo autoimune. Em 2023, evoluiu com pancitopenia (Hb = 7,3 Leucócitos = 700 Plaquetas = 99.000) e DHL aumentado. Realizou nova BMO com expansão reticulinica difusa (grau 3), compatível com MF primária. Suspensa mesalazina e iniciada prednisona 40 mg/dia (retirada após desmame), evoluindo com normalização do hemograma e da esplenomegalia. Realizado NGS com as mutações BCORL1 S894P (100%) e GATA2 G450A (44,5%), ambas de significado incerto. Mantivemos o diagnóstico de mielofibrose secundária. Discussão: Apesar dos avanços consideráveis na compreensão das bases genéticas, a MF ainda é uma neoplasia complexa. Mutações envolvendo JAK2, CALR ou MPL estão presentes em 90% dos pacientes, chamadas “drivers disease”. Alterações epigenéticas, de vias de sinalização, dentre outras, podem ter papel na patogênese da doença e são chamadas “clonal drivers”. No presente caso, observa-se que, apesar dos critérios clínicos, como BMO compatível, esplenomegalia, DHL aumentado, anemia, as mutações JAK2, CALR e MPL eram negativas (triplo negativo) e a citogenética normal. O NGS foi realizado no intuito de encontrar alterações clonais que pudessem estar associadas a MF. As “drivers disease” mais frequentes estão relacionadas aos seguintes genes: ASXL1, DNMT3A, IDH1, IDH2, EZH2, NRAS, KRAS, CBL, SRSF2, U2AF1, TP53, TET2, RUNX1, SF3B1 (e nem todos os tipos de mutações desses genes podem desenvolver doenças). Mutações do GATA2 e BCORL1 relacionadas a MF são raras, sem descrição das variantes alélicas encontradas em nosso NGS. Consideramos mutações de significado indeterminado, mielofibrose 2aria e seguimos acompanhando o paciente, caso desenvolva novas alterações. Conclusão: O diagnóstico de MF em pacientes triplo negativos pode ser um desafio e o advento de novas tecnologias, com a experiência constantemente adquirida, podem nos auxiliar quanto a clonalidades adicionais que definam o diagnóstico.

Background: Psoriasis is a chronic skin disease driven by immune system dysfunction and associated with increased cardiovascular risk and metabolic disorders. Risankizumab is an anti-interleukin-23 humanized monoclonal antibody approved for the treatment of moderate-to-severe plaque psoriasis.Objective: We conducted a 3-year retrospective study to evaluate the effectiveness and the safety of risankizumab in patients with moderate-to-severe psoriasis, comparing those with and without the presence of at least one cardiometabolic comorbidity (CMD).Results: Our study included 333 patients treated with risankizumab for at least one year. One hundred and sixty-two patients had at least one CMD. After one year of treatment, a reduction of at least 90% and 100% in Psoriasis Area and Severity Index (PASI) score compared with baseline (PASI90 and PASI100, respectively) was observed in 80.3% and 63% of patients with CMDs compared to 83% and 63.2% of patients without CMDs. No statistically significant differences were observed between the two cohorts of patients in terms of effectiveness and rates of adverse events. No significant safety findings were observed throughout the study period. Our study supports data from clinical trials and real-world studies, even in patients with concomitant cardiometabolic comorbidities.

This paper aimed at investigating the relationship between HEXACO personality traits and academic performance in two samples of Italian 10–14 years old middle-school adolescents (N = 714 and N = 1093) using Multilevel Mixed Models. The main results show that: 1) Conscientiousness and Openness to Experience were the most important predictors of school performance, followed by Honesty-Humility; 2) a modest effect was present also for eXtraversion and Emotionality; 3) these influences occurred net of the influence of gender and class and could be generalized to male and female adolescents across 6th, 7th and 8th grade; 5) Perfectionism, Diligence and Prudence within Conscientiousness, Inquisitiveness within Openness, and Sincerity within Honesty-Humility were the facets more correlated with school performance; 6) results were replicated in two studies. Results are discussed and conclusions are drawn.

The aim of this study was to assess whether toothbrushing with a dentifrice containing an antimicrobial phthalocyanine derivative (APD) can reduce the intraoral viral load of SARS-CoV-2. Twenty COVID-19-positive dentate patients aged ≥18 years were selected instructed to brush their teeth for 2 min with a dentifrice containing APD. Self-collected samples of unstimulated saliva were carried out three times: T0 (baseline), T5 (5 min after toothbrushing), and T30 (30 min after toothbrushing). The analysis of viral RNA was performed by RT-qPCR for detection of three viral genes (ORF1ab, N and S genes). Results were statistically tested using Friedman’s test and pairwise comparison with Bonferroni corrections, with a significance level of 5%. There was an increase in the cycle threshold (Ct) value from T0 to T5 in 13 patients (72.2%), and from T0 to T30 in 14 patients (77.8%). In two patients (11.1%) no SARS-CoV-2 was detected at T5 and five patients (27.8%) at T30. The Ct values were statistically significantly higher (p=0.020) at T30 in comparison to T0 and T5. This pilot study suggests that toothbrushing with a dentifrice containing APD could reduce the SARS-CoV-2 viral load in the oral cavity. However, further studies are needed to confirm this possible beneficial effect against SARS-CoV-2.

Abstract Medical datasets inherently contain errors from subjective or inaccurate test results, or from confounding biological complexities. It is difficult for medical experts to detect these elusive errors manually, due to lack of contextual information, limiting data privacy regulations, and the sheer scale of data to be reviewed. Current methods for training robust artificial intelligence (AI) models on data containing mislabeled examples generally fall into one of several categories—attempting to improve the robustness of the model architecture, the regularization techniques used, the loss function used during training, or selecting a subset of data that contains cleaner labels. This last category requires the ability to efficiently detect errors either prior to or during training, either relabeling them or removing them completely. More recent progress in error detection has focused on using multi-network learning to minimize deleterious effects of errors on training, however, using many neural networks to reach a consensus on which data should be removed can be computationally intensive and inefficient. In this work, a deep-learning based algorithm was used in conjunction with a label-clustering approach to automate error detection. For dataset with synthetic label flips added, these errors were identified with an accuracy of up to 85%, while requiring up to 93% less computing resources to complete compared to a previous model consensus approach developed previously. The resulting trained AI models exhibited greater training stability and up to a 45% improvement in accuracy, from 69 to over 99% compared to the consensus approach, at least 10% improvement on using noise-robust loss functions in a binary classification problem, and a 51% improvement for multi-class classification. These results indicate that practical, automated a priori detection of errors in medical data is possible, without human oversight.

Abstract The Russian invasion of Ukraine on February 24, 2022, has had devastating effects on the Ukrainian population and the global economy, environment, and political order. However, little is known about the psychological states surrounding the outbreak of war, particularly the mental well-being of individuals outside Ukraine. Here, we present a longitudinal experience-sampling study of a convenience sample from 17 European countries (total participants = 1,341, total assessments = 44,894, countries with >100 participants = 5) that allows us to track well-being levels across countries during the weeks surrounding the outbreak of war. Our data show a significant decline in well-being on the day of the Russian invasion. Recovery over the following weeks was associated with an individual’s personality but was not statistically significantly associated with their age, gender, subjective social status, and political orientation. In general, well-being was lower on days when the war was more salient on social media. Our results demonstrate the need to consider the psychological implications of the Russo-Ukrainian war next to its humanitarian, economic, and ecological consequences.

Tuberculosis (TB) remains an impactful infectious disease, leading to millions of deaths every year. Mycobacterium tuberculosis causes the formation of granulomas, which will determine, through the host–pathogen relationship, if the infection will remain latent or evolve into active disease. Early TB diagnosis is life-saving, especially among immunocompromised individuals, and leads to proper treatment, preventing transmission. This review addresses different approaches to diagnosing TB, from traditional methods such as sputum smear microscopy to more advanced molecular techniques. Integrating these techniques, such as polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP), has significantly improved the sensitivity and specificity of M. tuberculosis identification. Additionally, exploring novel biomarkers and applying artificial intelligence in radiological imaging contribute to more accurate and rapid diagnosis. Furthermore, we discuss the challenges of existing diagnostic methods, including limitations in resource-limited settings and the emergence of drug-resistant strains. While the primary focus of this review is on TB diagnosis, we also briefly explore the challenges and strategies for diagnosing non-tuberculous mycobacteria (NTM). In conclusion, this review provides an overview of the current landscape of TB diagnostics, emphasizing the need for ongoing research and innovation. As the field evolves, it is crucial to ensure that these advancements are accessible and applicable in diverse healthcare settings to effectively combat tuberculosis worldwide.