Multi-omics data elucidate parasite-host-microbiota interactions and resistance to Haemonchus contortus in sheep.

BACKGROUND: The integration of molecular data from hosts, parasites, and microbiota can enhance our understanding of the complex biological interactions underlying the resistance of hosts to parasites. Haemonchus contortus, the predominant sheep gastrointestinal parasite species in the tropics, causes significant production and economic losses, which are further compounded by the diminishing efficiency of chemical control owing to anthelmintic resistance. Knowledge of how the host responds to infection and how the parasite, in combination with microbiota, modulates host immunity can guide selection decisions to breed animals with improved parasite resistance. This understanding will help refine management practices and advance the development of new therapeutics for long-term helminth control. METHODS: Eggs per gram (EPG) of feces were obtained from Morada Nova sheep subjected to two artificial infections with H. contortus and used as a proxy to select animals with high resistance or susceptibility for transcriptome sequencing (RNA-seq) of the abomasum and 50 K single-nucleotide genotyping. Additionally, RNA-seq data for H. contortus were generated, and amplicon sequence variants (ASV) were obtained using polymerase chain reaction amplification and sequencing of bacterial and archaeal 16S ribosomal RNA genes from sheep feces and rumen content. RESULTS: The heritability estimate for EPG was 0.12. GAST, GNLY, IL13, MGRN1, FGF14, and RORC genes and transcripts were differentially expressed between resistant and susceptible animals. A genome-wide association study identified regions on chromosomes 2 and 11 that harbor candidate genes for resistance, immune response, body weight, and adaptation. Trans-expression quantitative trait loci were found between significant variants and differentially expressed transcripts. Functional co-expression modules based on sheep genes and ASVs correlated with resistance to H. contortus, showing enrichment in pathways of response to bacteria, immune and inflammatory responses, and hub features of the Christensenellaceae, Bacteroides, and Methanobrevibacter genera; Prevotellaceae family; and Verrucomicrobiota phylum. In H. contortus, some mitochondrial, collagen-, and cuticle-related genes were expressed only in parasites isolated from susceptible sheep. CONCLUSIONS: The present study identified chromosome regions, genes, transcripts, and pathways involved in the elaborate interactions between the sheep host, its gastrointestinal microbiota, and the H. contortus parasite. These findings will assist in the development of animal selection strategies for parasite resistance and interdisciplinary approaches to control H. contortus infection in sheep.

Thyroid dysfunction alters gene expression of proteins related to iron homeostasis and metabolomics in male rats.

Thyroid hormones (THs) are crucial in bodily functions, while iron is essential for processes like oxygen transport. Specialized proteins maintain iron balance, including ferritin, transferrin, ferroportin, and hepcidin. Research suggests that THs can influence iron homeostasis by affecting mRNA and protein expression, such as ferritin and transferrin. Our study focused on male rats to assess mRNA expression of iron homeostasis-related proteins and metabolomics in thyroid dysfunction. We found altered gene expression across various tissues (liver, duodenum, spleen, and kidney) and identified disrupted metabolite patterns in thyroid dysfunction. These findings highlight tissue-specific effects of thyroid dysfunction on essential iron homeostasis proteins and provide insights into associated metabolic changes. Our research contributes to understanding the intricate interplay between thyroid hormones and iron balance. By unveiling tissue-specific gene expression alterations and metabolic disruptions caused by thyroid dysfunction, our work lays a foundation for future investigations to explore underlying mechanisms and develop targeted strategies for managing iron-related complications in thyroid disorders.

Improving the performance and versatility of microfluidic thread electroanalytical devices by automated injection with electronic pipettes: a new and powerful 3D-printed analytical platform.

Microfluidic cotton thread-based electroanalytical devices (µTEDs) are analytical systems with attractive features such as spontaneous passive flow, low cost, minimal waste production, and good sensitivity. Currently, sample injection in µTEDs is performed by hand using manual micropipettes, which have drawbacks such as inconstant speed and position, dependence of skilled analysts, and need of physical effort of operator during prolonged times, leading to poor reproducibility and risk of strain injury. As an alternative to these inconveniences, we propose, for the first time, the use of electronic micropipettes to carry out automated injections in µTEDs. This new approach avoids all disadvantages of manual injections, while also improving the performance, experience, and versatility of µTEDs. The platform developed here is composed by three 3D-printed electrodes (detector) attached to a 3D-printed platform containing an adjustable holder that keeps the electronic pipette in the same x/y/z position. As a proof-of-concept, both injection modes (manual and electronic) were compared using three model analytes (nitrite, paracetamol, and 5-hydroxytryptophan) on µTED with amperometric detection. As result, improved analytical performance (limits of detection between 2.5- and 5-fold lower) was obtained when using electronic injections, as well as better repeatability/reproducibility and higher analytical frequencies. In addition, the determination of paracetamol in urine samples suggested better precision and accuracy for automated injection. Thus, electronic injection is a great advance and changes the state-of-art of µTEDs, mainly considering the use of more modern and versatile electronic pipettes (wider range of pre-programmed modes), which can lead to the development of even more automated systems.

Economic inequality increases the number of hours worked and decreases work-life balance perceptions: longitudinal and experimental evidence.

International institutions' attention to work-life balance (WLB) demonstrates the global breadth of this issue. Yet the scientific community has thus far paid little attention to its structural underpinnings and to the interplay between these macro-level underpinnings and individual psychological factors. We examine the contextual role of economic inequality at the national level as a significant factor influencing working time and WLB perceptions using multiple empirical strategies. In the first set of studies (1a and 1b), we compared countries with different levels of inequality (Study 1a with 37 countries, Study 1b with longitudinal data from 34 countries, N = 254) and found increased working time and reduced WLB in highly unequal countries. In a pilot study (N = 81) and in the pre-registered Studies 2 (N = 338) and 3 (N = 499) we corroborated this evidence with an experimentally induced inequality perception, reporting an indirect effect of inequality on WLB (Studies 2 and 3) and working time (Study 3) through status anxiety and competitiveness. In Study 2, we manipulated socio-economic class in addition to economic inequality, showing that the detrimental effect of inequality on WLB is especially marked for participants assigned to a low-class condition. This research contributes to an integrated understanding of the impact of economic inequality and socio-economic class in shaping WLB and provides useful insights for organizations to develop context-specific policies to improve employees' WLB that take both individual and structural factors into account.

Ruminal and feces metabolites associated with feed efficiency, water intake and methane emission in Nelore bulls.

The objectives of this study were twofold: (1) to identify potential differences in the ruminal and fecal metabolite profiles of Nelore bulls under different nutritional interventions; and (2) to identify metabolites associated with cattle sustainability related-traits. We used different nutritional interventions in the feedlot: conventional (Conv; n = 26), and by-product (ByPr, n = 26). Thirty-eight ruminal fluid and 27 fecal metabolites were significantly different (P < 0.05) between the ByPr and Conv groups. Individual dry matter intake (DMI), residual feed intake (RFI), observed water intake (OWI), predicted water intake (WI), and residual water intake (RWI) phenotypes were lower (P < 0.05) in the Conv group, while the ByPr group exhibited lower methane emission (ME) (P < 0.05). Ruminal fluid dimethylamine was significantly associated (P < 0.05) with DMI, RFI, FE (feed efficiency), OWI and WI. Aspartate was associated (P < 0.05) with DMI, RFI, FE and WI. Fecal C22:1n9 was significantly associated with OWI and RWI (P < 0.05). Fatty acid C14:0 and hypoxanthine were significantly associated with DMI and RFI (P < 0.05). The results demonstrated that different nutritional interventions alter ruminal and fecal metabolites and provided new insights into the relationship of these metabolites with feed efficiency and water intake traits in Nelore bulls.

Estudo sobre a prevalência de doença carotídea detectada por ultrassonografia nos casos de AVC isquêmico de um hospital público de Santa Catarina / Study on the prevalence of carotid artery disease detected by ultrasonography in cases of ischemic stroke at a public hospital in Santa Catarina

Fundamento: Acidentes Vasculares Cerebrais Isquêmicos (AVCi) representam significativa parcela dentre as causas da morbimortalidade mundial. Estenose das artérias carótidas e vertebrais são consideradas fator de risco para tal desfecho. A Ultrassonografia com Doppler (USG Doppler) das artérias extracranianas pode ser útil na identificação de pacientes com estenose significativa por ser um método inócuo e acessível. Objetivos: avaliar a prevalência de estenose nas artérias extracranianas diagnosticadas através do estudo com USG Doppler e a prevalência de fatores associados em pacientes com quadro de AVCi. Métodos: Trata-se de estudo retrospectivo, transversal, a partir da análise de prontuários dos pacientes internados com quadro de AVCi no Hospital Regional de São José, Santa Catarina, Brasil. O estudo ocorreu entre janeiro de 2020 e dezembro de 2021. A análise ultrassonográfica foi realizada por médicos radiologistas habilitados, a partir do uso de aparelho validado (GE Logic P9 com transdutor linear multifrequencial 6-15MHz). Resultados: Dentre os 239 pacientes incluídos, destaca-se a significativa prevalência de comorbidades associadas ao AVCi, como hipertensão arterial sistêmica (78,2%) e tabagismo (40,6%). A distribuição entre os sexos foi homogênea (58,2 versus 41,8%) e 70,3% dos pacientes possuíam idade superior a 60 anos de idade. A taxa de pacientes com alterações hemodinamicamente significativas (estenose >50% da luz do vaso) das artérias carótidas e vertebrais foi de 29,2%. O tabagismo foi o único fator de risco que se correlacionou estatisticamente com a ocorrência de AVCi decorrente do acometimento das artérias carótidas ou vertebrais (RP 1,708; IC 1,057-2,761; p=0,028). Conclusão: O USG com Doppler das artérias extracranianas é ferramenta útil na investigação dos casos de AVCi, visto que a prevalência de doença significativa dos grandes vasos extracranianos (estenose>50%) se aproxima de 30%.

Background: Ischemic Strokes represent a sizable portion among the causes of morbidity and mortality worldwide. Stenosis of the carotid and vertebral arteries represent a risk factor to this outcome. Ultrasonography with Doppler of the extracranial arteries can be useful in identifying patients with significant stenosis because it is a harmless and accessible method. Objectives: To assess the prevalence of stenosis in the extracranial arteries diagnosed through Doppler ultrasound examination and the prevalence of associated factors in patients with ischemic stroke Methods: This is a retrospective, cross-sectional study based on the analysis of medical records of patients admitted with ischemic stroke at the Regional Hospital of São José, Santa Catarina, Brazil. The study was conducted between January 2020 and December 2021. Ultrasonographic analysis was performed by qualified radiologists, using a validated device (GE Logic P9 with a multi-frequency linear transducer 6-15MHz). Results: Among the 239 included patients, there is a significant prevalence of comorbidities associated with ischemic stroke, such as systemic arterial hypertension (78.2%) and smoking (40.6%). The distribution between genders was homogeneous (58.2% versus 41.8%), and 70.3% of the patients were over 60 years old. The rate of patients with hemodynamically significant alterations (stenosis >50% of the vessel lumen) in the carotid and vertebral arteries was 29.2%. Smoking was the only risk factor that statistically correlated with the occurrence of ischemic stroke resulting from the involvement of the carotid or vertebral arteries (PR 1.708; CI 1.057-2.761; p=0.028). Conclusion: Ultrasonography with Doppler of the extracranial arteries is a useful tool in the investigation of ischemic stroke cases, given that the prevalence of significant disease in the large extracranial vessels (stenosis >50%) approaches 30%.

Electrochemical sensor based on 3D-printed substrate by masked stereolithography (MSLA): a new, cheap, robust and sustainable approach for simple production of analytical platforms.

The development of miniaturized, sustainable and eco-friendly analytical sensors with low production cost is a current trend worldwide. Within this idea, this work presents  the innovative use of masked stereolithography (MSLA) 3D-printed substrates for the easy fabrication of pencil-drawn electrochemical sensors (MSLA-3D-PDE). The use of a non-toxic material such as pencil (electrodes) together with a biodegradable 3D printing resin (substrate) allowed the production of devices that are quite cheap (ca. US$ 0.11 per sensor) and with low environmental impact. Compared to paper, which is the most used substrate for manufacturing pencil-drawn electrodes, the MSLA-3D-printed substrate has the advantages of not absorbing water (hydrophobicity) or becoming crinkled and weakened when in contact with solutions. These features provide more reproducible, reliable, stable, and long-lasting sensors. The MSLA-3D-PDE, in conjunction with the custom cell developed, showed excellent robustness and electrochemical performance similar to that observed of the glassy carbon electrode, without the need of any activation procedure. The analytical applicability of this platform was explored through the quantification of omeprazole in pharmaceuticals. A limit of detection (LOD) of 0.72 µmol L-1 was achieved, with a linear range of 10 to 200 µmol L-1. Analysis of real samples provided results that were highly concordant with those obtained by UV-Vis spectrophotometry (relative error ≤ 1.50%). In addition, the greenness of this approach was evaluated and confirmed by a quantitative methodology (Eco-Scale index). Thus, the MSLA-3D-PDE appears as a new and sustainable tool with great potential of use in analytical electrochemistry.

A world together: Global citizen identification as a basis for prosociality in the face of COVID-19.

How do global citizens respond to a global health emergency? The present research examined the association between global citizen identification and prosociality using two cross-national datasets-the World Values Survey (Study 1, N = 93,338 from 60 countries and regions) and data collected in 11 countries at the start of the COVID-19 pandemic (Study 2, N = 5,427). Results showed that individuals who identified more strongly as global citizens reported greater prosociality both generally (Study 1) and more specifically in the COVID-19 global health emergency (Study 2). Notably, global citizen identification was a stronger predictor of prosociality in response to COVID-19 than national identification (Study 2). Moreover, analyses revealed that shared ingroup identity accounted for the positive association between global citizen identification and prosociality (Study 2). Overall, these findings highlight global citizenship as a unique and promising direction in promoting prosociality and solidarity, especially in the fight against COVID-19.

Do unbiased people act more rationally?-The case of comparative realism and vaccine intention.

Within different populations and at various stages of the pandemic, it has been demonstrated that individuals believe they are less likely to become infected than their average peer. This is known as comparative optimism and it has been one of the reproducible effects in social psychology. However, in previous and even the most recent studies, researchers often neglected to consider unbiased individuals and inspect the differences between biased and unbiased individuals. In a mini meta-analysis of six studies (Study 1), we discovered that unbiased individuals have lower vaccine intention than biased ones. In two pre-registered, follow-up studies, we aimed at testing the reproducibility of this phenomenon and its explanations. In Study 2 we replicated the main effect and found no evidence for differences in psychological control between biased and unbiased groups. In Study 3 we also replicated the effect and found that realists hold more centric views on the trade-offs between threats from getting vaccinated and getting ill. We discuss the interpretation and implication of our results in the context of the academic and lay-persons' views on rationality. We also put forward empirical and theoretical arguments for considering unbiased individuals as a separate phenomenon in the domain of self-others comparisons.

It Matters to Whom You Compare Yourself: The Case of Unrealistic Optimism and Gender-Specific Comparisons.

Unrealistic Optimism (UO) appears when comparing participants' risk estimates for themselves with an average peer, which typically results in lower risk estimates for the self. This article reports nuanced effects when comparison varies in terms of the gender of the peer. In three studies (total N = 2,468, representative sample), we assessed people's risk estimates for COVID-19 infections for peers with the same or other gender. If a peer's gender is not taken into account, previous studies were replicated: Compared with others, participants perceived themselves as less likely to get infected with COVID-19. Interestingly, this effect was qualified by gender: Respondents perceived women as less threatened than men because women are perceived as more cautious and compliant with medical guidelines.

Tax the élites! The role of economic inequality and conspiracy beliefs on attitudes towards taxes and redistribution intentions.

Taxation is one of the most widely acknowledged strategies to reduce inequality, particularly if based on progressivity. In a high-powered sample study (N = 2119) we investigated economic inequality and conspiracy beliefs as two key predictors of tax attitude and support for progressive taxation. We found that participants in the high economic inequality condition had lower levels of tax compliance and higher levels of conspiracy beliefs and support for progressive taxation. Furthermore, the effect of the experimental condition on tax compliance was mediated by conspiracy beliefs. Finally, conspiracy belief scores were positively associated with support for progressive taxation. Our results provide evidence that attitudes towards taxation are not monolithic but change considering the aims and targets of specific taxes. Indeed, while the perception of economic inequality prompts the desire for equal redistribution, it also fosters conspiracy narratives that undermine compliance with taxes.

Bivariate GWAS reveals pleiotropic regions among feed efficiency and beef quality-related traits in Nelore cattle.

Feed-efficient cattle selection is among the most leading solutions to reduce cost for beef cattle production. However, technical difficulties in measuring feed efficiency traits had limited the application in livestock. Here, we performed a Bivariate Genome-Wide Association Study (Bi-GWAS) and presented candidate biological mechanisms underlying the association between feed efficiency and meat quality traits in a half-sibling design with 353 Nelore steers derived from 34 unrelated sires. A total of 13 Quantitative Trait Loci (QTL) were found explaining part of the phenotypic variations. An important transcription factor of adipogenesis in cattle, the TAL1 (rs133408775) gene located on BTA3 was associated with intramuscular fat and average daily gain (IMF-ADG), and a region located on BTA20, close to CD180 and MAST4 genes, both related to fat accumulation. We observed a low positive genetic correlation between IMF-ADG (r = 0.30 ± 0.0686), indicating that it may respond to selection in the same direction. Our findings contributed to clarifying the pleiotropic modulation of the complex traits, indicating new QTLs for bovine genetic improvement.

Electrochemical study and forensic electroanalysis of fungicide benzovindiflupyr using disposable graphite pencil electrode.

Nowadays, the use of pesticides in world agriculture is fundamental. However, it leads to an increase in the illegal sale and smuggling of these products in various parts of the world, mainly in Brazil. Therefore, the development of new analytical methods for screening and analysis of these kind of substances is a relevant issue. We present in this work, for the first time, an electrochemical study and a novel electroanalytical method for determination of fungicide benzovindiflupyr (BENZO). According to our knowledge, the electrochemical behavior of BENZO, as well as its voltammetric determination, have never been reported before. The sensors used here consisted of disposable pencil graphite electrodes (PGEs). On this electrode surface and at optimal pH, BENZO behaved according to a quasi-reversible system and showed two voltammetric peaks, one anodic at Ep = +0.59 V and another cathodic at Ep = +0.43 V. The analytical studies utilized BENZO anodic sweep and square-wave adsorptive stripping voltammetry (SWAdSV). All experimental and instrumental parameters were fully investigated and optimized. Under the best conditions, a calibration plot was obtained in the concentration range from 0.10 to 12.5 µmol L-1. The limits of detection (LOD) and quantification (LOQ) achieved were 0.023 and 0.076 µmol L-1, respectively. An electrochemical mechanism for BENZO oxidation was also proposed. The method developed here was successfully employed for the qualitative and quantitative forensic analysis of BENZO in smuggled products, showing good accuracy (recoveries ca. 104%) and precision (relative standard deviation < 5%). These data attest the potential for use of this method in forensic area.

Rumen and fecal microbiomes are related to diet and production traits in Bos indicus beef cattle.

Background: Ruminants harbor a complex microbial community within their gastrointestinal tract, which plays major roles in their health and physiology. Brazil is one of the largest producers of beef in the world and more than 90% of the beef cattle herds are composed of pure and crossbred Nelore (Bos indicus). Despite its importance to the Brazilian economy and human feeding, few studies have characterized the Nelore microbiome. Therefore, using shotgun metagenomics, we investigated the impact of diet on the composition and functionality of the Nelore microbiome, and explored the associations between specific microbial taxa and their functionality with feed efficiency and methane emission. Results: The ruminal microbiome exhibited significantly higher microbial diversity, distinctive taxonomic profile and variations in microbial functionality compared to the fecal microbiome, highlighting the distinct contributions of the microbiomes of these environments. Animals subjected to different dietary treatments exhibited significant differences in their microbiomes' archaeal diversity and in the abundance of 89 genera, as well as in the functions associated with the metabolism of components of each diet. Moreover, depending on the diet, feed-efficient animals and low methane emitters displayed higher microbial diversity in their fecal microbiome. Multiple genera were associated with an increase or decrease of the phenotypes. Upon analyzing the functions attributed to these taxa, we observed significant differences on the ruminal taxa associated with feed efficient and inefficient cattle. The ruminal taxa that characterized feed efficient cattle stood out for having significantly more functions related to carbohydrate metabolism, such as monosaccharides, di-/oligosaccharides and amino acids. The taxa associated with methane emission had functions associated with methanogenesis and the production of substrates that may influence methane production, such as hydrogen and formate. Conclusion: Our findings highlight the significant role of diet in shaping Nelore microbiomes and how its composition and functionality may affect production traits such as feed efficiency and methane emission. These insights provide valuable support for the implementation of novel feeding and biotechnological strategies.

Alteración de la marcha y poliartralgia como manifestación de escorbuto en un niño. Presentación de un caso / Gait disturbance and polyarthralgia as a manifestation of scurvy in a pediatric patient. Case report

La vitamina C o ácido ascórbico es imprescindible para el correcto funcionamiento del organismo. Los seres humanos no pueden sintetizarla; en consecuencia, dependen estrictamente de su aporte exógeno. Su déficit causa escorbuto, un cuadro que se manifiesta con fatiga, mialgias y poliartralgias, hemorragias en la piel y sangrado de las encías. Es una enfermedad infrecuente. La mayoría de los casos publicados corresponden a niños con restricciones alimentarias por trastornos del neurodesarrollo. La respuesta satisfactoria al aporte de ácido ascórbico confirma el diagnóstico. La sospecha de esta enfermedad evitaría exámenes complementarios innecesarios y el tratamiento temprano ayudaría a revertir los síntomas y prevenir complicaciones. Se presenta el caso de un varón de 13 años que consulta por dolor en ambas caderas con progresión hacia las rodillas, sumado a pérdida de la fuerza y hematomas en los miembros inferiores. El objetivo de esta presentación es resaltar la importancia de la anamnesis alimentaria completa y evitar un abordaje tardío con múltiples intervenciones. Nivel de Evidencia: IV

Vitamin C or ascorbic acid is essential for the correct functioning of the organism. As it cannot be synthesized by humans, it is obtained from external food sources. Deficiency of ascorbic acid produces scurvy, which includes symptoms as fatigue, myalgia and polyarthralgia, associated with skin hemorrhage and bleeding gums. Scurvy is a rare entity. Most of the reported cases involve children with food restrictions due to neurodevelopmental disorders. The early detection of the clinical signs of this condition would avoid unnecessary complementary tests, and early treatment would help reverse symptoms and prevent complications. Case Report: a 13-year-old male patient presented with pain in both hips radiating to the knees associated with loss of strength and hematomas in the lower limbs. Objective: to highlight the importance of a complete nutritional assessment to avoid a late approach with multiple interventions. Level of Evidence: IV

Differential Allele-Specific Expression Revealed Functional Variants and Candidate Genes Related to Meat Quality Traits in B. indicus Muscle.

Traditional transcriptomics approaches have been used to identify candidate genes affecting economically important livestock traits. Regulatory variants affecting these traits, however, remain under covered. Genomic regions showing allele-specific expression (ASE) are under the effect of cis-regulatory variants, being useful for improving the accuracy of genomic selection models. Taking advantage of the better of these two methods, we investigated single nucleotide polymorphisms (SNPs) in regions showing differential ASE (DASE SNPs) between contrasting groups for beef quality traits. For these analyses, we used RNA sequencing data, imputed genotypes and genomic estimated breeding values of muscle-related traits from 190 Nelore (Bos indicus) steers. We selected 40 contrasting unrelated samples for the analysis (N = 20 animals per contrasting group) and used a beta-binomial model to identify ASE SNPs in only one group (i.e., DASE SNPs). We found 1479 DASE SNPs (FDR ≤ 0.05) associated with 55 beef-quality traits. Most DASE genes were involved with tenderness and muscle homeostasis, presenting a co-expression module enriched for the protein ubiquitination process. The results overlapped with epigenetics and phenotype-associated data, suggesting that DASE SNPs are potentially linked to cis-regulatory variants affecting simultaneously the transcription and phenotype through chromatin state modulation.

PSMA PET for the Evaluation of Liver Metastases in Castration-Resistant Prostate Cancer Patients: A Multicenter Retrospective Study.

Background: To evaluate the diagnostic performance of PSMA-PET compared to conventional imaging/liver biopsy in the detection of liver metastases in CRPC patients. Moreover, we evaluated a PSMA-PET/CT-based radiomic model able to identify liver metastases. Methods: Multicenter retrospective study enrolling patients with the following inclusion criteria: (a) proven CRPC patients, (b) PSMA-PET and conventional imaging/liver biopsy performed in a 6 months timeframe, (c) no therapy changes between PSMA-PET and conventional imaging/liver biopsy. PSMA-PET sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy for liver metastases were calculated. After the extraction of radiomic features, a prediction model for liver metastases identification was developed. Results: Sixty CRPC patients were enrolled. Within 6 months before or after PSMA-PET, conventional imaging and liver biopsy identified 24/60 (40%) patients with liver metastases. PSMA-PET sensitivity, specificity, PPV, NPV, and accuracy for liver metastases were 0.58, 0.92, 0.82, 0.77, and 0.78, respectively. Either number of liver metastases and the maximum lesion diameter were significantly associated with the presence of a positive PSMA-PET (p < 0.05). On multivariate regression analysis, the radiomic feature-based model combining sphericity, and the moment of inverse difference (Idm), had an AUC of 0.807 (95% CI:0.686-0.920). Conclusion: For liver metastases assessment, [68Ga]Ga-PSMA-11-PET demonstrated moderate sensitivity while high specificity, PPV, and inter-reader agreement compared to conventional imaging/liver biopsy in CRPC patients.

Allele-specific expression reveals functional SNPs affecting muscle-related genes in bovine.

Single nucleotide polymorphisms showing allele-specific expression (ASE SNPs) are useful for cis-regulatory variants discovery. Despite this potential, there are expensive costs involved in genome-level ASE analysis for large sample sizes. If different data resolutions are available, genotype imputation can be used to mitigate this limitation. Aiming to increase the power to detect regulatory variants, we used a large dataset (>4 million) of imputed SNP genotypes and RNA-Seq data from 190 Nelore steers. Differences between major and minor allele expressions in muscle were tested with a Binomial Test. We identified 38,177 ASE SNPs (FDR ≤ 0.05) within 7304 linkage disequilibrium blocks. After that, we searched for aseQTLs (i.e., neighboring SNPs potentially regulating the ASE SNPs' allelic expression) by comparing the ASE of heterozygous to homozygous sample groups under a Wilcoxon Rank Sum test. We identified 21,543 aseQTLs potentially regulating 430 ASE SNPs (FDR ≤ 0.05). A total of 3333 cis-eQTLs (being 2098 ASE SNPs and 1075 aseQTLs) were associated with the expression of 758 transcripts (FDR ≤ 0.05), demonstrating the cis-regulatory effect of these ASE SNPs and aseQTLs. Data integration showed reproducibility with previous studies in bovine ASE and genomic imprinting. Furthermore, we identified 36,756 novel ASE regions due to the imputation approach. Comparisons with epigenetics data from Functional Annotation of Animal Genomes (FAANG) suggest a regulatory potential of the ASE-related SNPs. The affected genes were enriched in metabolic pathways essential for muscle homeostasis. These findings reinforce the potential of using ASE for discovering cis-regulatory SNPs that may affect muscle-related traits.

Management of Functional Seizures and Functional Movement Disorder: A Cross-Sectional Comparative Study.

Introduction: Functional neurological disorders (FND) are conditions that cause to alterations in nervous system functions. They are disabling and impair the quality of life of patients but that are potentially reversible provided they have specific management. Functional seizures (FS) and functional movement disorder (FMD) are among the most common subtypes. Studies suggest a strong overlap between FS and FMD; however, there are still no cross-sectional studies that compare the management between these two conditions. Thus, our focus was to carry out a research that compares how these two subtypes of FND are being managed, in addition to assessing rates of understanding and acceptance of a diagnosis of FND. Methods: It is a cross-sectional study with data collected from medical records and interviews with two patients' groups (FS and FMD) treated from a FND clinic of the public health system of Brazil. Results: From 105 medical records of patients with FND analyzed, 60 participants were eligible and agreed to participate in this research, being FS (n = 31) and FMD (n = 29). Statistically significant differences (p < 0.05) were found in the use of antiseizure (FS > FMD), opioids (FMD > FS), multi-professional follow-up (FMD > FS) and rates of understanding and acceptance of an FND diagnosis (FMD > FS). Similarities were found in sociodemographic profiles, medical follow-up, psychiatric comorbidities and use of antidepressants, anxiolytics, antipsychotics and mood stabilizers between two conditions. Conclusion: More similarities than differences in management were found between FS and FMD. Similarities may be related to overlaps in sociodemographic and clinical characteristics between the two groups. Differences may be related to specific issues of each patient and condition. Regardless of the group, patients who perform psychotherapeutic follow-up have higher rates of understanding and acceptance of an FND diagnosis.

Double jeopardy: How lower levels of support during COVID-19 exacerbated the relationship between loneliness and distress.

While the relationship between loneliness and psychological distress is well documented, the mechanisms underlying this relationship are less clear. One factor known to be related to loneliness as well as psychological distress, is social support, with some studies suggesting that support-both received and provided-can serve as a mechanism to reduce the distress associated with loneliness. In this paper we examine the mediating role of both aspects of support in the relationship between loneliness and psychological distress in the COVID-19 context. We used a multi-country dataset collected at two timepoints during the pandemic; the first during the early stages (N = 6,842, 11 countries) and the second collected for a subset of countries (N = 1,299, 3 countries) 3 months later. Across all eleven countries, results revealed significant positive associations between loneliness and distress. Furthermore, using longitudinal data, we investigated the directionality of this relationship and found that increased loneliness over time was associated with increased psychological distress. The data also showed that both feeling unsupported and feeling unable to provide support to others mediated this relationship. These findings point to the need to facilitate people's ability to draw effective social support and help others-particularly at times when social connectedness is threatened-as a way of alleviating the psychological distress that commonly presents with loneliness.