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Abstract Introduction The 2023 nomenclature defined criteria for steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and the overlapping MASLD/ALD (MetALD). We aimed to assess racial and ethnic disparities in the SLD prevalence among United States (US) adults based on this new nomenclature. Methods We undertook a cross-sectional study employing the 2017–2018 National Health and Nutrition Examination Survey (NHANES) database. We identified SLD according to a controlled attenuation parameter ≥288 dB/m, liver stiffness ≥7.2 kPa, or elevated aminotransferase levels. Alcohol use thresholds were established according to the updated SLD definition. We estimated prevalences using the complex design of the NHANES survey. Multivariable logistic regressions with complex design weights were employed. Results A total of 5532 individuals are included. The mean age is 45.4 years, and 50.9% are women. The adjusted estimated prevalence of MASLD is 42.4% (95% CI: 41.1–43.8%), MetALD 1.7% (95% CI: 1.3–2.0%), and ALD 0.6% (95% CI: 0.3–0.8%). Hispanics exhibit a higher prevalence of SLD, but there are no significant differences in advanced fibrosis prevalence due to SLD among racial/ethnic groups. In MASLD, men, individuals aged 40–64 and ≥65 years, Hispanics, those with health insurance, higher BMI, diabetes, hypertension, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol or use of lipid-lowering agents are independently associated with a higher risk, while Blacks have the lowest risk. In MetALD, men and higher BMI are independently associated with a higher risk of MetALD in adjusted multivariable analysis. In ALD, the adjusted multivariable analysis shows that only health insurance is independently associated with a lower ALD risk. Conclusions MASLD prevalence is high in the US, especially in men, older individuals, and Hispanics. MetALD and ALD prevalence was substantial but could be underestimated.

Abstract We analysed a large dataset consisting of 457 soil profiles of Andisols and Ultisols of volcanic origin compared to 60 non-volcanic soils. We hypothesised that soil pH has a greater impact on the development of Al-organomineral complexes in volcanic soils compared to non-volcanic soils, in the latter, the silt and clay fractions play a crucial role. Soil pH >4.5 strongly influenced the formation of Al-organomineral complexes in volcanic soils, while an increase in allophane content led to a decrease in SOC. Ultisols with more crystalline clays, such as halloysite and disordered kaolinite, the pH had a weaker impact and there was no effect on non-volcanic soils. Instead, a positive correlation (R2 = 0.63, p

Abstract The ability of serum biomarkers to predict the prognosis and response to deep-brain stimulation (DBS) therapy in Parkinson’s disease (PD) patients is promising. Here, we showed that NfL differed between healthy individuals and PD patients and that changes in NfL, GFAP, and BDNF occurred only transiently after DBS surgery. Therefore, subthalamic stimulation does not promote neurodegeneration, and these biomarkers do not serve as clinical improvement endpoints in PD DBS patients.

Abstract Background Hand osteoarthritis (HOA) is a highly prevalent disease that may be impacted by social inequalities. Few studies in HOA are from underdeveloped regions. We intend to contribute to fill this gap presenting clinical characteristics of our low-income HOA cohort (LIHOA). Methods Data from 119 patients with a HOA diagnosis fulfilling ACR criteria seen between August 2019 and May 2023 in Fortaleza/Brazil. Evaluations included pain (VAS, visual analogue scale), X-ray (KL, Kellgren-Lawrence), grip and pinch strength (KgF), Cochin hand functional scale (CHFS), FIHOA, and SF-12 scores. Social data included monthly (4 IF nodes. OA in other joints: 37 (36.2%) spine, 28 (29.4%) knee, 21 (20.5%) bunions. Functional impairment was mild [8 (5–14) median FIHOA]. Median serum CRP was 0.2 mg/dL (0.1–0.4) with 14 (20%) patients above reference value. Mean total KL score was 27.6 ± 13.6 with 21 (23%), 38 (41.7%), and 33 (36.2%) KL2, KL3, and KL4, respectively; 51 (54.8%) and 42 (45.2%) patients declared 9SY including 37.2% with a university degree. Individuals earning

Abstract Background Sarcopenia and low areal bone mineral density (aBMD) are prevalent musculoskeletal complications after paediatric cancer treatment. However, their relationship has not been examined in young paediatric cancers survivors. This study aimed to evaluate aBMD differences according to sarcopenia status and the risk of low aBMD Z‐score in young paediatric cancer survivors with sarcopenia confirmed/probable. Methods This cross‐sectional study included 116 paediatric cancer survivors (12.1 ± 3.3 years old; 42.2% female). Handgrip strength was used to assessed muscle strength. Dual‐energy X‐ray absorptiometry estimated aBMD (g/cm2) and appendicular lean mass index (ALMI, kg/m2). ‘No sarcopenia’ was defined when muscle strength was >decile 2. ‘Sarcopenia probable’ was defined when muscle strength was ≤ decile 2 and ALMI Z‐score was > −1.5 standard deviation (SD). ‘Sarcopenia confirmed’ was defined when muscle strength was ≤ decile 2 and ALMI Z‐score ≤ −1.5 SD. Analysis of covariance and logistic regression, adjusted for time from treatment completion, radiotherapy exposure, calcium intake, and physical activity, was used to evaluate aBMD and estimate the odds ratios (ORs) of low aBMD (aBMD Z‐score < −1.0). Results Survivors with sarcopenia confirmed had significantly lower aBMD than those without sarcopenia at total body (−1.2 [95% CI: −1.5 to −0.8] vs. 0.2 [−0.2 to 0.6], P

This study presents a simple, low-cost, and efficient route to obtain zinc oxide by adopting the thermal decomposition method of zinc acetate at 300 (Gr@ZnO_300), 400 (Gr@ZnO_400), 500 (Gr@ZnO_500), and 600 °C (Gr@ZnO_600) for 1 h. The diffraction patterns collected for the samples indicated the majority formation of the hexagonal phase (P63mc) for zinc oxide and residual amounts for graphitic carbon, which has a hexagonal structure of space group P63/mmc. The images collected by scanning electron microscopy (SEM) revealed the formation of sub-microcrystals with elongated rod-shaped morphology, with dimensions between 0.223 and 1.09 μm. The optical and colourimetric properties of the obtained materials indicate the presence of graphitic carbon in the samples, corroborating the analysis by XRD and Raman spectroscopy, with an optical bandgap close to 3.21 eV, and energies of the valence (EVB) and conduction (ECB) bands of 2.89 eV and −0.31 eV, respectively. The photocatalytic performance at 20 min of exposure time under UV light of all prepared samples in the decolourisation of rhodamine B (RhB) dye solutions follows the order Gr@ZnO_300 (95.6%) > Gr@ZnO_600 (92.8%) > Gr@ZnO_400 (84.0%) > Gr@ZnO_500 (78.1%), where the photocatalytic performance of Gr@ZnO_300 sample was 16.5 times more effective than the photolysis test. Moreover, the results confirmed that the best performance was archived at pH = 10, and the holes (h+) and superoxide (O2•−) radicals are the main species involved in the discolouration of RhB dye molecules in an aqueous medium. Finally, the reusability experiment shows high stability of the Gr@ZnO_300 sample as a solid photocatalyst and cycling capability, which obtained total discolouration of RhB of a solution under five cycling experiments of 60 min of exposure to UV light at room temperature.

We describe one new species from Ceará state, Brazil: Wedelia figueiredoana. It is morphologically associated with W. bonplandiana, but distinguished by 0.25–1.05 cm leaf blade width (vs. 1.5–2.6 cm), linear to narrow oblong leaf blade (vs. elliptic to spatulate), 3-seriate involucre (vs. 2-seriate), and cypselae 3.9–4 mm long (vs. 6–7 mm). An anatomical analysis of cypselae is provided, and we propose a more accurate terminology to describe similar wings to Wedelia species. We also provide a scientific illustration of the new species, photos of habitat, a map of its geographic occurrence, and its taxonomic affinities are discussed with a taxonomic key to the Wedelia species with the apically pronounced wings in the cypselae.

Abstract To investigate the effect of physical activity (PA) (both general and its type) on self-esteem during and after cancer treatment. A systematic search was conducted across PubMed, Web of Science, Scopus, SPORTDiscuss, and PsycINFO from their inception to February 2024. The systematic review included 32 studies, with 15 studies (13 RCT and 2 quasi-experimental) and 3604 participants (66.7% female) included in the meta-analysis involving controlled trials using a control group and at least one PA intervention group. The study was registered in PROSPERO (CRD42022309771). Risk of bias for RCTs was assessed using the Cochrane Collaboration’s tool for assessing risk of bias (RoB2), and quasi-experimental studies with the Joanna Briggs Institute critical appraisal tool. PA significantly improved self-esteem during and after cancer treatment (pooled SMD = 0.32, p

Abstract Identifying biomarkers able to discriminate individuals on different health trajectories is crucial to understand the molecular basis of age-related morbidity. We investigated multi-omics signatures of general health and organ-specific morbidity, as well as their interconnectivity. We examined cross-sectional metabolome and proteome data from 3,142 adults of the Cooperative Health Research in South Tyrol (CHRIS) study, an Alpine population study designed to investigate how human biology, environment, and lifestyle factors contribute to people’s health over time. We had 174 metabolites and 148 proteins quantified from fasting serum and plasma samples. We used the Cumulative Illness Rating Scale (CIRS) Comorbidity Index (CMI), which considers morbidity in 14 organ systems, to assess health status (any morbidity vs. healthy). Omics-signatures for health status were identified using random forest (RF) classifiers. Linear regression models were fitted to assess directionality of omics markers and health status associations, as well as to identify omics markers related to organ-specific morbidity. Next to age, we identified 21 metabolites and 10 proteins as relevant predictors of health status and results confirmed associations for serotonin and glutamate to be age-independent. Considering organ-specific morbidity, several metabolites and proteins were jointly related to endocrine, cardiovascular, and renal morbidity. To conclude, circulating serotonin was identified as a potential novel predictor for overall morbidity.

Abstract Vitamin D (vitD) deficiency is frequently observed in patients with pulmonary arterial hypertension (PAH) and, in these patients, low levels of vitD correlate with worse prognosis. The aim of this study was to examine the expression and the antiproliferative role of vitD receptor (VDR) and its signalling pathway in the human pulmonary vasculature. VDR presence and expression was analyzed in lungs, pulmonary artery smooth muscle cells (PASMC) and endothelial cells (PAEC) from controls and PAH-patients. VDR expression and VDR-target genes were examined in PASMC treated with calcitriol. The antiproliferative effect of 48 h-calcitriol was studied in PASMC by MTT and BrdU assays. VDR is expressed in PASMC. It is downregulated in lungs and in PASMC, but not in PAEC, from PAH-patients compared to non-hypertensive controls. Calcitriol strongly upregulated VDR expression in PASMC and the VDR target genes KCNK3 (encoding TASK1), BIRC5 (encoding survivin) and BMP4. Calcitriol produced an antiproliferative effect which was diminished by silencing or by pharmacological inhibition of survivin or BMPR2, but not of TASK1. In conclusion, the expression of VDR is low in PAH-patients and can be rescued by calcitriol. VDR exerts an antiproliferative effect in PASMC by modulating survivin and the BMP signalling pathway.

Abstract In this work, we design and implement a new bifocal diffractive spiral lens within an optical tweezers system. The proposed diffractive optical element coined Kolokaski Kinoform Spiral Lens (KKSL), generates twin optical vortices along the propagation direction. The axial positions, as well as the diameters of the generated vortex beams, are correlated with the Kolakoski aperiodic sequence introduced in the design of the diffractive lens. The unique properties of KKSLs make it ideal for optical trapping applications, allowing independent multiple trapping and particle displacement within each optical vortex beam. We present both the focusing properties of KKSL and the experimental results of its integration into the optical tweezer setup.

Abstract Background Merkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer characterized by high rates of metastasis. Emerging evidence suggests that PD-L1/PD1 blockade holds promise as a therapeutic option for MCC. However, the efficacy and safety of this approach in treating MCC remain incompletely understood. This systematic review and meta-analysis aims to analyze the efficacy and safety of PD-1/PD-L1 blockade for patients with MCC. Methods PubMed, Cochrane, and Embase were searched for studies evaluating patients with MCC undergoing PD-1/PD-L1 treatment. The estimated outcomes were overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). We performed the meta-analysis using RStudio v4.4.2 software. Results A total of 14 reports of 13 different studies encompassing 615 patients were included. The median age ranged from 64 to 77 years. Median follow-up ranged from 7.9 months to 59.3 months. Pooled OS rates at 24 and 36 months were 65.05% (95% CI 44.04–81.49) and 59.58% (95% CI 39.62–76.81), respectively, while pooled PFS rates at 6, 12, and 36 months were 51.78% (95% CI 37.83–65.45), 46.12% (95% CI 29.44–63.72), and 28.73% (95% CI 16.57–45.02), in the same order. DCR proportion was 61.65% (95% CI 54.85–68.03) and ORR was 53.79% (95% CI 47.80-59.68). The frequency of TRAEs of any grade was 61.72% (95% CI 45.75–75.51) and for TRAEs of grade ≥ 3 was 17.60% (95% CI 12.28 to 24.57). Conclusions This systematic review and meta-analysis revealed that patients with MCC undergoing treatment with PD-1/PDL-1 showed durable responses with continuous and clinically meaningful survival outcomes. Graphical Abstract

Abstract Background Sustainable Development Goals (SDGs) are universally recognised targets designed to combat poverty, inequality, and climate change. However, there exists limited awareness and understanding of these goals among nursing and midwifery students. To address this knowledge gap, a co-designed audio podcast was introduced as an educational tool to enhance students’ comprehension of SDGs and their relevance to the healthcare profession. Methods A prospective study was conducted at Queen’s University Belfast, involving 566 first-year nursing and midwifery students. A 60-minute SDG podcast, co-designed with students and stakeholders, was made accessible within the university’s learning management system. Pre- and post-test questionnaires were administered to assess changes in students’ knowledge levels and attitudes toward SDGs. Additionally, 37 participants engaged in focus group interviews six months after listening to the podcast to explore their experiences and reflections. Quantitative data was analysed using paired t-tests and descriptive statistics, while qualitative data was analysed thematically. Results The podcast significantly increased students’ awareness of SDGs and their understanding of the goals’ relevance to their profession and personal lives. Post-test scores showed substantial improvements across all three sub-scales: knowledge, professional relevance, and personal relevance. Moreover, participants rated the podcast as a valuable learning resource with high acceptability, although some expressed uncertainty about replay intentions. Focus group interviews revealed three themes, including 1) More than you know’, which described how participants developed new knowledge and understanding about SDGs, 2) ‘Nurse-Midwife Nudges’, which illuminated how participants made minor changes to their behaviour and 3) ‘Fitting Format’, which highlighted how participants favoured the use of an audio podcast to learn about SDGs. Discussion This study demonstrates the potential of audio podcasts as an effective and engaging tool for increasing awareness and understanding of SDGs among nursing and midwifery students. The results suggest that such interventions can positively impact students’ knowledge, attitudes, and behavioural intentions regarding the SDGs. The findings also emphasise the importance of co-design in developing educational resources tailored to the specific needs and preferences of students.

Abstract Systems with broken continuous symmetry in ideal lattices cannot be rectified through rearrangement or deformation. Topological metamaterials featuring nontrivial, artificially induced phase transitions have emerged as pivotal constituents for engineering these topological defects, which, until now, have mostly been experimentally realized in linear or planar configurations. Buckminster Fuller lent his name to the C60 ball-shaped carbon allotrope, which is not only the roundest molecule in existence but also embodies 3D topological defects. Here, we construct a C540 metamaterial composed of interspersed pentagons in a hexagonal network of hollow tubes and cavities. By 3D printing this giant closed-cage topology, the nontrivial state-confinements can be fully controlled and visualized, which, in contrast, in synthesized or naturally found fullerenes, is highly challenging. Thanks to our macroscopic metamaterials approach, we are able to map in real-space topological pentagon states probed by sound waves. Our results show how a seemingly unrelated approach can unveil deep physical understanding in carbon allotropes and potentially in a plethora of other complex systems in the near future.

Atherosclerotic cardiovascular disease (ASCVD) remains the major cause of premature death and disability; effective cardiovascular (CV) risk prevention is fundamental. The World Heart Federation (WHF) Cholesterol Roadmap provides a framework for national policy development and aims to achieve ASCVD prevention.At the invitation of the WHF, a group of experts from the Portuguese Society of Cardiology (SPC), addressed the cholesterol burden at nationally and discussed possible strategies to include in a Portuguese cholesterol roadmap. The literature review showed that the cholesterol burden in Portugal is high and especially uncontrolled in those with the highest CV risk. An infographic scorecard was built to include in the WHF collection, for a clear idea about CV risk and cholesterol burden in Portugal, which would also be useful for health policy advocacy.The expert discussion and preventive strategies proposal followed the five pillars of the WHF document: awareness improvement; population-based approaches for CV risk and cholesterol; risk assessment/population screening; system-level approaches; surveillance of cholesterol and ASCVD outcomes. These strategies were debated by all the expert participants, with the goal of creating a national cholesterol roadmap to be used for advocacy and as a guide for CV prevention.Several key recommendations were outlined: include all stakeholders in a multidisciplinary national program; create a structured activities plan to increase awareness in the population; improve the quality of continuous CV health education; increase the interaction between different health professionals and non-health professionals; increment the referral of patients to cardiac rehabilitation; screen cholesterol levels in the general population, especially high-risk groups; promote patient self-care, engage with patients’ associations; use specific social networks to spread information widely; create a national database of cholesterol levels with systematic registry of CV events; redefine strategies based on the evaluation of results; create and involve more patients’ associations – invert the pyramid order.In conclusion, ASCVD and the cholesterol burden remain a strong global issue in Portugal, requiring the involvement of multiple stakeholders in prevention. The Portuguese cholesterol roadmap can provide some solutions to help urgently mitigate the problem. Population-based approaches to improve awareness and CV risk assessment and surveillance of cholesterol and ASCVD outcomes are key factors in this change. A call to action is clearly needed to fight hypercholesterolemia and ASCVD burden. Resumo: A doença aterosclerótica cardiovascular (DACV) mantém-se a maior causa de morte prematura e de incapacidade, sendo uma prevenção eficaz de risco cardiovascular (CV) fundamental. O WHF Cholesterol Roadmap fornece enquadramento para o desenvolvimento de políticas nacionais, tendo como objetivo a prevenção de DACV. A convite da WHF, um grupo de peritos da Sociedade Portuguesa de Cardiologia (SPC) avaliou a carga do colesterol a nível nacional e discutiu possíveis estratégias para um Roadmap português.A revisão da literatura mostrou uma carga elevada de colesterol em Portugal, sobretudo em pessoas de alto risco CV. Uma infografia, Scorecard, foi construída pela WHF, para mostrar claramente o risco CV e o peso do colesterol em Portugal, sendo útil para advocacia em políticas de saúde.A discussão de peritos e proposta das estratégias preventivas seguiram os cinco pilares do documento da WHF: Melhoria da consciencialização; Abordagens do risco CV e do colesterol nas populações; Avaliação de risco/screening das populações; abordagens a nível do sistema; Seguimento do colesterol e complicações da DACV.Várias recomendações chave foram definidas: incluir todos os stakeholders em programa multidisciplinar nacional; criar plano de atividades estruturadas para aumentar a consciencialização da população; aumentar qualidade da educação contínua em saúde CV; aumentar interação entre profissionais de saúde e outros profissionais; aumentar referenciação de doentes para reabilitação cardiovascular; avaliar níveis de colesterol na população geral, especialmente em alto risco; promover autocuidado dos doentes, envolvendo associações de doentes; usar redes sociais específicas para disseminar informação; criar base nacional de níveis de colesterol com registo sistemático de eventos CV; redefinir estratégias baseadas na avaliação de resultados; criar e envolver mais doentes em associações – inverter a ordem da pirâmide!Em conclusão, a DACV e o peso de colesterol permanecem uma questão global forte em Portugal, necessitando o envolvimento de múltiplos stakeholders na prevenção. O Roadmap de colesterol português pode fornecer algumas soluções para urgentemente mitigar o problema. Abordagens a nível das populações para melhorar a consciencialização e avaliar o risco CV, seguimento do colesterol e das complicações de DACV são fatores chave nesta mudança. Uma call to action é claramente necessária para combater a carga da hipercolesterolemia e DACV.

Carcinoma cuniculatum is a variant of squamous cell carcinoma, characterized by a slow growth with progressive crypt-like invasion of deep tissue. This tumor is frequently misdiagnosed as a benign skin lesion both clinically and histopathologically. The final diagnosis is often delayed as it requires a large sample biopsy. We report the case of a 67-year-old patient who presented to us with a recurring chronic ulcer over a surgical scar of 5 years of evolution.

Abstract Ruminants have the ability to digest human-inedible plant materials, due to the symbiotic relationship with the rumen microbiota. Rumen microbes supply short chain fatty acids, amino acids, and vitamins to dairy cows that are used for maintenance, growth, and lactation functions. The main goal of this study was to investigate gene-microbiome networks underlying feed efficiency traits by integrating genotypic, microbial, and phenotypic data from lactating dairy cows. Data consisted of dry matter intake (DMI), net energy secreted in milk, and residual feed intake (RFI) records, SNP genotype, and 16S rRNA rumen microbial abundances from 448 mid-lactation Holstein cows. We first assessed marginal associations between genotypes and phenotypic and microbial traits through genomic scans, and then, in regions with multiple significant hits, we assessed gene-microbiome-phenotype networks using causal structural learning algorithms. We found significant regions co-localizing the rumen microbiome and feed efficiency traits. Interestingly, we found three types of network relationships: (1) the cow genome directly affects both rumen microbial abundances and feed efficiency traits; (2) the cow genome (Chr3: 116.5 Mb) indirectly affects RFI, mediated by the abundance of Syntrophococcus, Prevotella, and an unknown genus of Class Bacilli; and (3) the cow genome (Chr7: 52.8 Mb and Chr11: 6.1–6.2 Mb) affects the abundance of Rikenellaceae RC9 gut group mediated by DMI. Our findings shed light on how the host genome acts directly and indirectly on the rumen microbiome and feed efficiency traits and the potential benefits of the inclusion of specific microbes in selection indexes or as correlated traits in breeding programs. Overall, the multistep approach described here, combining whole-genome scans and causal network reconstruction, allows us to reveal the relationship between genome and microbiome underlying dairy cow feed efficiency.

Abstract Heart failure is a highly prevalent disease, which courses with frequent readmissions, mainly by Acute Heart Failure (AHF). Reduced renal function is associated with increased mortality in patients with HF. Therefore, an accurate and precise evaluation of renal function in patients with HF is crucial. The error of estimated GFR (eGFR) is wide and common, showing a ± 30% variability compared to measured GFR (mGFR). However, there is no evidence on the error of formulas in reflecting real renal function and particularly the consequences of this error in patients with AHF. This is a prospective study comparing the impact of mGFR versus eGFR in the onset of cardiovascular (CV) outcomes in patients with AHF. This was tested with cox survival analysis. Measured GFR was determined by the plasma clearance of iohexol-dbs and eGFR by Cockroft-Gould, MDRD, CKD-EPI creatinine, CKD-EPI cystatin-C and CKD-EPI creatinine + cystatin-C equations formulas. Also the agreement between mGFR and eGFR was analyzed. A total of 90 patients were included. Average age was 66 (± 12 years) and 52 (58%) were male. Of them 53 patients (59%) had a cardiovascular event during follow-up, 22 fatal (41%). The agreement between mGFR and eGFR indicated moderate precision and accuracy (concordance correlation coefficient of 0.77; CI = 0.73–0.82). In multiple cox survival analysis, mGFR was significantly associated with cardiovascular events together with NTproBNP, BMI, LVEF and previous coronary artery disease (p = 0.037; HR = 0.98, 95% CI = 0.95–0.99). Estimated GFR by formulas was not significant. In patients with AHF the error of formulas is large, frequent and random, also, mGFR and not eGFR predicted future CV events. The error of eGFR may have clinical consequences in specific subpopulations.

Abstract We present a type IIB 4D string model with stabilised moduli which is able to describe the history of the universe from inflation to quintessence. The underlying Calabi-Yau volume is controlled by two moduli which are stabilised by perturbative effects. The lighter of them drives Fibre Inflation at a large energy scale. The two associated axions are ultra-light since they are lifted only at the non-perturbative level. The lighter of them can drive quintessence if its decay constant is large enough to prevent quantum diffusion during inflation from ruining the initial conditions. The right dark energy scale can be obtained via a large suppression from poly-instanton effects. The heavier axion gives a negligible contribution to dark matter since it starts oscillating after matter-radiation equality. If instead none of the two axions has a large decay constant, a mild alignment allows the lighter axion to drive quintessence, while the heavier can be at most a few percent of dark matter due to isocurvature and UV bounds. In both cases dark matter can also come from either primordial black holes or the QCD axion.

Abstract Background Lung cancer constitutes the leading cause of cancer mortality. High levels of endothelin-1 (ET-1), its cognate receptor ETAR and its activating enzyme, the endothelin-converting enzyme-1 (ECE-1), have been reported in several cancer types, including lung cancer. ECE-1 comprises four isoforms, which only differ in their cytoplasmic N-terminus. Protein kinase CK2 phosphorylates the N-terminus of isoform ECE-1c, increasing its stability and leading to enhanced invasiveness in glioblastoma and colorectal cancer cells, which is believed to be mediated by the amino acid residue Lys-6, a conserved putative ubiquitination site neighboring the CK2-phosphorylated residues Ser-18 and Ser-20. Whether Lys-6 is linked to the acquisition of a cancer stem cell (CSC)-like phenotype and aggressiveness in human non–small cell lung cancer (NSCLC) cells has not been studied. Methods In order to establish the role of Lys-6 in the stability of ECE-1c and its involvement in lung cancer aggressiveness, we mutated this residue to a non-ubiquitinable arginine and constitutively expressed the wild-type (ECE-1cWT) and mutant (ECE-1cK6R) proteins in A549 and H1299 human NSCLC cells by lentiviral transduction. We determined the protein stability of these clones alone or in the presence of the CK2 inhibitor silmitasertib, compared to ECE-1cWT and mock-transduced cells. In addition, the concentration of secreted ET-1 in the growth media was determined by ELISA. Expression of stemness genes were determined by Western blot and RT-qPCR. Chemoresistance to cisplatin was studied by MTS viability assay. Migration and invasion were measured through transwell and Matrigel assays, respectively, and the side-population was determined using flow cytometry. Results ECE-1cK6R displayed higher stability in NSCLC cells compared to ECE-1cWT-expressing cells, but ET-1 secreted levels showed no difference up to 48 h. Most importantly, ECE-1cK6R promoted expression of the stemness genes c-Myc, Sox-2, Oct-4, CD44 and CD133, which enhance cellular self-renewal capability. Also, the ECE-1cK6R-expressing cells showed higher cisplatin chemoresistance, correlating with an augmented side-population abundance due to the increased expression of the ABCG2 efflux pump. Finally, the ECE-1cK6R-expressing cells showed enhanced invasiveness, which correlated with the regulated expression of known EMT markers. Conclusions Our findings suggest an important role of ECE-1c in lung cancer. ECE-1c is key in a non-canonical ET-1-independent mechanism which triggers a CSC-like phenotype, leading to enhanced lung cancer aggressiveness. Underlying this mechanism, ECE-1c is stabilized upon phosphorylation by CK2, which is upregulated in many cancers. Thus, phospho-ECE-1c may be considered as a novel prognostic biomarker of recurrence, as well as the CK2 inhibitor silmitasertib as a potential therapy for lung cancer patients.

Abstract Artificial Intelligence (AI) will have a major social impact in the coming years, affecting today’s professions and our daily routines. In the short-term, education is one of the most impacted areas. The autonomous decision making that can be achieved with tools based on AI implies that some of the traditional methodologies associated with the fundamentals of the learning process in students, must be reviewed. Consequently, the role of teachers in the classroom may change, as they will have to deal with such AI tools performing parts of their work, and with students making a common use of them. In this scope, the AI in Education (AIEd) community agrees on the key relevance of developing AI literacies to train teachers and students of all educational levels in the fundamentals of this new technological discipline, so they can understand how these tools based on AI work and pilot the adaptation in an informed way. This implies teaching students about the fundamentals of topics like perception, representation, reasoning, learning, and the impact of AI, with the aim of delivering a solid formation in this area. To support them, formal teaching and learning resources must be developed and tested with students, properly adapted to different educational levels. The main contribution of this proposal lies in the presentation of the Robobo Project, a technological tool based on intelligent robotics that supports such formal AI literacy training for a wide range of ages, from secondary school to higher education. The core part of this paper is focused on showing the possibilities the Robobo Project offers to teachers in a simple way, and how it can be adapted to different levels and skills, leading to a long-term educational proposal. Validation results that support the feasibility of this technology in the education about AI, obtained with students and teachers in different educational levels during a period of six years, are presented and discussed.

Abstract The share of solar power in Brazil’s electrical grid has rapidly increased, relieving GHG emissions and diversifying energy sources for greater energy security. Besides that, solar resource is susceptible to climate change, adding uncertainty to electrical grid resilience. This study uses satellite and reanalysis data to evaluate the performance of CMIP6 models in replicating and predicting surface solar irradiance (SSR) in Brazil. The results from the most reliable models indicate an increase in SSR by 2% to 8% in most regions, with a decrease of around 3% in the South. These findings highlight the potential for increased photovoltaic (PV) yield if backed by supportive public policies while underlining the importance of uncertainty assessment of climate models.

Abstract MicroRNAs (miRNAs) have been implicated in human disorders, from cancers to infectious diseases. Targeting miRNAs or their target genes with small molecules offers opportunities to modulate dysregulated cellular processes linked to diseases. Yet, predicting small molecules associated with miRNAs remains challenging due to the small size of small molecule-miRNA datasets. Herein, we develop a generalized deep learning framework, sChemNET, for predicting small molecules affecting miRNA bioactivity based on chemical structure and sequence information. sChemNET overcomes the limitation of sparse chemical information by an objective function that allows the neural network to learn chemical space from a large body of chemical structures yet unknown to affect miRNAs. We experimentally validated small molecules predicted to act on miR-451 or its targets and tested their role in erythrocyte maturation during zebrafish embryogenesis. We also tested small molecules targeting the miR-181 network and other miRNAs using in-vitro and in-vivo experiments. We demonstrate that our machine-learning framework can predict bioactive small molecules targeting miRNAs or their targets in humans and other mammalian organisms.

Abstract Background Volatile organic compounds (VOCs) released by plants can act as signaling molecules mediating ecological interactions. Therefore, the study of VOCs mediated intra- and interspecific interactions with downstream plant physiological responses is critical to advance our understanding of mechanisms underlying information exchange in plants. Here, we investigated how plant-emitted VOCs affect the performance of an interspecific neighboring plant via induced shifts in root exudate chemistry with implications for root-associated microbiota recruitment. Results First, we showed that VOCs emitted by potato-onion plants stimulate the growth of adjacent tomato plants. Then, we demonstrated that this positive effect on tomato biomass was attributed to shifts in the tomato rhizosphere microbiota. Specifically, we found potato-onion VOCs to indirectly affect the recruitment of specific bacteria (e.g., Pseudomonas and Bacillus spp.) in the tomato rhizosphere. Second, we identified and validated the compound dipropyl disulfide as the active molecule within the blend of potato-onion VOCs mediating this interspecific plant communication. Third, we showed that the effect on the tomato rhizosphere microbiota occurs via induced changes in root exudates of tomato plants caused by exposure to dipropyl disulfide. Last, Pseudomonas and Bacillus spp. bacteria enriched in the tomato rhizosphere were shown to have plant growth-promoting activities. Conclusions Potato-onion VOCs—specifically dipropyl disulfide—can induce shifts in the root exudate of adjacent tomato plants, which results in the recruitment of plant-beneficial bacteria in the rhizosphere. Taken together, this study elucidated a new mechanism of interspecific plant interaction mediated by VOCs resulting in alterations in the rhizosphere microbiota with beneficial outcomes for plant performance. Video Abstract

Abstract Background Neutralizing antibodies against PRRSV are capable of conferring protection against viral reinfection, but they tend to be strain specific and usually have poor cross-reactivity. Nonetheless, it has been described that there are individuals capable of efficiently neutralizing viruses of different origin, so it is expected that there are conserved neutralizing epitopes relevant for broad neutralization. However, although immunodominant regions and neutralizing epitopes have been described in different envelope proteins, their role in broad neutralization is unknown. The main objective of this study was to determine whether the linear epitopes existing in the ectodomains of PRRSV envelope proteins play a role in cross-neutralization. Results A pepscan analysis was carried out using synthetic peptides against the ectodomains of PRRSV envelope proteins and PRRSV-hyperimmune sera of different cross-reactivity. The results obtained confirm the existence of antigenic regions in the ectodomains of the GP2, GP3, GP4 and GP5 that tend to be relatively conserved among different PRRSV isolates. Nonetheless, these antigenic regions have poor immunogenicity since they are only recognized by a limited number of sera. Furthermore, no differences were found between the reactivity of sera with broad cross-neutralization capacity and sera with poor heterologous neutralization activity, which indicate that linear epitopes existing in the ectodomains of PRRSV envelope proteins are not relevant for the development of broadly reactive neutralizing antibodies. Subsequently, some selected peptides were used in competition assays with the virus for binding to the cell receptors and in seroneutralization inhibition assays by incubation with hyperimmune sera. Firstly, some peptides that interfere with virus infectivity were identified in competition assays, but only in the case of one viral isolate, which points to the possible existence of a strain-dependent inhibition. However, the results of the seroneutralization inhibition assay indicate that, under the conditions of our study, none of the peptides used was capable of inhibiting virus neutralization by the hyperimmune sera. Conclusions The results obtained indicate that the linear peptides analyzed in this study do not play a major role in the induction of broadly reactive neutralizing antibodies, which could probably depend on conformational neutralizing.

Abstract Background Increasing evidence supports the role of advanced glycation end products (AGEs) in atherosclerosis in both diabetic and non-diabetic patients, suggesting that therapeutic strategies targeting AGEs may offer potential benefits in this population. The Mediterranean diet is associated with improved biomarkers and anthropometric measurements related with atherosclerosis in addition to its ability to modulate AGE metabolism. Our aim was to determine whether the reduction in atherosclerosis progression (measured by changes in intima-media thickness of both common carotid arteries (IMT-CC)), observed after consumption of a Mediterranean diet compared to a low-fat diet, is associated with a modulation of circulating AGE levels in patients with coronary heart disease (CHD). Methods 1002 CHD patients were divided in: (1) Non-increased IMT-CC patients, whose IMT-CC was reduced or not changed after dietary intervention and (2) Increased IMT-CC patients, whose IMT-CC was increased after dietary intervention. Serum AGE levels (methylglyoxal–MG and Nε-Carboxymethyllysine-CML) and parameters related to AGE metabolism (AGER1 and GloxI mRNA and sRAGE levels) and reduced glutathione (GSH) levels were measured before and after 5-years of dietary intervention. Results The Mediterranean diet did not affect MG levels, whereas the low-fat diet significantly increased them compared to baseline (p = 0.029), leading to lower MG levels following the Mediterranean diet than the low-fat diet (p

Abstract Current influenza vaccines are strain-specific and require frequent updates to combat new strains, making a broadly protective influenza vaccine (BPIV) highly desirable. A promising strategy is to induce T-cell responses against internal proteins conserved across influenza strains. In this study, pH1N1 pre-exposed pigs were immunized by aerosol using viral vectored vaccines (ChAdOx2 and MVA) expressing matrix (M1) and nucleoprotein (NP). Following H3N2 challenge, all immunizations (M1, NP or NPM1) reduced lung pathology, but M1 alone offered the greatest protection. NP or NPM1 immunization induced both T-cell and antibody responses. M1 immunization generated no detectable antibodies but elicited M1-specific T-cell responses, suggesting T cell-mediated protection. Additionally, a single aerosol immunization with the ChAdOx vaccine encoding M1, NP and neuraminidase reduced lung pathology. These findings provide insights into BPIV development using a relevant large natural host, the pig.

Abstract Background Sinetrol® Xpur is a polyphenolic ingredient rich in citrus flavonoids that has shown weight loss effects in previous studies. The dose dependent nature, gut microbial actions of this product has not been explored previously, thus presented in this study. Methods In this open label study, we evaluated the effect of Sinetrol® Xpur supplementation on healthy but overweight/obese adults (20–50 yrs) for 16 weeks. Participants (n = 20) were randomly allocated to a high dose group (HD, 1800 mg/day) or low dose group (LD, 900 mg/day) of the product for 16 weeks. Fat composition, gut microbial composition, were evaluated using MRI and 16S rDNA sequencing respectively at week 1 and 16. Results We observed HDL, HbA1C, LDL and leptin improved significantly over 16 weeks, irrespective of the dosage. There was a trend for decrease in visceral adipose tissue (VAT), BMI over time and body weight displayed a trend for dose dependent decrease. Eubacterium xylanophilum, Ruminococcacea UCG-004 genus which increased in HD and LD respectively were negatively associated to VAT. Both doses increased butyrate producers such as Eubacterium ruminantium and Ruminococcaceae NK4A214 genus. Conclusions Overall chronic supplementation of Sinetrol® Xpur, irrespective of their dose improved HDL, HbA1c, LDL and leptin and tended to decrease visceral adipose tissue via changes in gut microbiota. Trial registration number NCT03823196.

Abstract Bisphenol A (BPA) is a plasticizer used to synthesize polycarbonate plastics and epoxy resins and is well-known for its endocrine-disrupting action. BPA occurrence in the environment is widespread, and there is a growing concern regarding exposure to this chemical during childhood, given the findings indicating the long-lasting hazards associated with exposure during early life compared to adulthood. We examined urinary BPA concentrations from 319 elementary school-aged Brazilian children, using high-performance liquid chromatography coupled to high-resolution mass spectrometry. We found that urinary BPA was detectable in the majority of children, and that urinary BPA levels were higher among children with lower family income and lower maternal educational levels. BPA levels found herein were compared with those from countries with different regulation policies concerning exposure to BPA. They were similar to those reported from studies conducted in Egypt and Australia. Despite more protective regulatory policies in the European Union, they were similar or lower than those reported in European studies. Our findings indicate that exposure of Brazilian children to BPA is widespread and comparable to or even lower than that of countries with stricter regulatory policies.

Abstract Gold nanoparticles (AuNPs) are potentially applicable in drug/nucleic acid delivery systems. Low toxicity, high stability, and bioavailability are crucial for the therapeutic use of AuNPs and they are mainly determined by their interactions with proteins and lipids on their route to the target cells. In this work, we investigated the interaction of two pegylated gold nanoparticles, AuNP14a and AuNP14b, with human serum proteins albumin (HSA) and transferrin (Tf) as well as dimyristoyl-phosphatidylcholine (DMPC) liposomes, which can be a representative of biomembranes. We showed that AuNP14a/b interacted with HSA and Tf changing their electrical, thermodynamic, and structural properties as evidenced by dynamic light scattering, zeta potential, transmission electron microscopy, circular dichroism, fluorescence quenching, and isothermal titration calorimetry. These nanoparticles penetrated the DMPC membrane suggesting their ability to reach a target inside the cell. In most of the effects, AuNP14b was more effective than AuNP14a, which might result from its more positive charge. Further studies are needed to evaluate whether the interaction of AuNP14a/b with HSA and Tf is safe for the cell/organism and whether they may safely penetrate natural membranes.

Abstract Air pollution poses a significant global concern, notably impacting pregnancy outcomes through mechanisms such as DNA damage, oxidative stress, inflammation, and altered miRNA expression, all of which can adversely affect trophoblast functions. Cleistocalyx nervosum var. paniala, known for its abundance of anthocyanins with diverse biological activities including anti-mutagenic, antioxidant, and anti-inflammatory properties, is the focus of this study examining its effect on Particulate Matter 10 (PM10) soluble extract-induced trophoblast cell dysfunction via miRNA expression. The study involved the extraction of C. nervosum fruit using 70% ethanol, followed by fractionation with hexane, dichloromethane, and ethyl acetate. Subsequent testing for total phenolics, flavonoids, anthocyanins, and antioxidant activity revealed the ethyl acetate fraction (CN-EtOAcF) as possessing the highest phenolic and anthocyanin content along with potent antioxidant activity, prompting its selection for further investigation. In vitro studies on HTR-8/SVneo cells demonstrated that 5–10 µg/mL PM10 soluble extract exposure inhibited cell proliferation, migration, invasion, and induced apoptosis. However, pretreatment with 20–80 µg/mL CN-EtOAcF followed by 5 µg/mL PM10 soluble extract exposure exhibited protective effects against PM10 soluble extract-induced damage, including inflammation inhibition and intracellular ROS suppression. Notably, CN-EtOAcF down-regulated PM10-induced miR-146a-5p expression, with SOX5 identified as a potential target. Overall, CN-EtOAcF demonstrated the potential to protect against PM10-induced harm in trophoblast cells, suggesting its possible application in future therapeutic approaches.

Abstract Background Few studies have attempted to use clinical and laboratory parameters to stratify COVID-19 patients with severe versus non-severe initial disease and evaluate age-specific differences in developing multiple different COVID-19-associated disease outcomes. Methods A retrospective cohort included patients from the electronic health database of Hong Kong Hospital Authority between 1 January 2022 and 15 August 2022 until 15 November 2022. The cohort was divided into three cohorts by age (≤ 40, 41–64, and ≥ 65 years old). Each age cohort was stratified into four groups: (1) COVID-19 critically exposed group (ICU admission, mechanical ventilation support, CRP > 80 mg/L, or D-dimer > 2 g/mL), (2) severely exposed group (CRP 30–80 mg/L, D-dimer 0.5–2 g/mL, or CT value 40) for the disease outcomes in the acute phase of infection (e.g., mortality risk HR (aged ≤ 40): 1.0 (95%CI: 0.5,2.0), HR (aged 41–64): 2.1 (95%CI: 1.8, 2.6), HR (aged > 65): 4.8 (95%CI: 4.6, 5.1)); while in the post-acute phase, these risks were largely insignificant in those aged 65): 1.5 (95%CI: 1.5,1.6)). Fully vaccinated patients were associated with lower risks of disease outcomes than those receiving less than two doses of vaccination. Conclusions The risk of multiple different disease outcomes in both acute and post-acute phases increased significantly with the increasing severity of acute COVID-19 illness, specifically among the elderly. Moreover, future studies could improve by risk-stratifying patients based on universally accepted thresholds for clinical parameters, particularly biomarkers, using biological evidence from immunological studies.

Abstract Topologically ordered phases of matter elude Landau’s symmetry-breaking theory, featuring a variety of intriguing properties such as long-range entanglement and intrinsic robustness against local perturbations. Their extension to periodically driven systems gives rise to exotic new phenomena that are forbidden in thermal equilibrium. Here, we report the observation of signatures of such a phenomenon—a prethermal topologically ordered time crystal—with programmable superconducting qubits arranged on a square lattice. By periodically driving the superconducting qubits with a surface code Hamiltonian, we observe discrete time-translation symmetry breaking dynamics that is only manifested in the subharmonic temporal response of nonlocal logical operators. We further connect the observed dynamics to the underlying topological order by measuring a nonzero topological entanglement entropy and studying its subsequent dynamics. Our results demonstrate the potential to explore exotic topologically ordered nonequilibrium phases of matter with noisy intermediate-scale quantum processors.

One hundred years after the publication of History and Class Consciousness, it is imperative to revisit the classic work of Georg Lukács to discuss the relevance of his ideas in a world where the capitalist mode of production does not cease to show its devastating effects. To do so, we divide the article into two sections. In the first part, we place Lukács’ work in dialogue with that of Hegel and Marx in order to clarify the status of violence as an ontological condition of history, allowing us to determine the theoretical-practical framework from which social revolution can be conceptualized. In the second section, we analyze Lukács’ notion of class consciousness not as a historical fatality but as an act of self-determination of the proletariat. We compare this proposal with the current situation of gentrification of the proletariat which, far from invalidating the Hungarian author’s proposal, constitutes its reversal and the platform for its actualization. Ultimately, it is about the proletarian still today taking control and becoming, through class consciousness, the subject-object of history. We conclude by reinterpreting Lukács’ terms in a practice that counters a reactionary position in order to combat both the reactionary movements and the hedonistic immobilism of the proletariat.

Abstract The COVID-19 pandemic remains a significant global health threat, with uncertainties persisting regarding the factors determining whether individuals experience mild symptoms, severe conditions, or succumb to the disease. This study presents an NMR metabolomics-based approach, analysing 80 serum and urine samples from COVID-19 patients (34 intensive care patients and 46 hospitalized patients) and 32 from healthy controls. Our research identifies discriminant metabolites and clinical variables relevant to COVID-19 diagnosis and severity. These discriminant metabolites play a role in specific pathways, mainly “Phenylalanine, tyrosine and tryptophan biosynthesis”, “Phenylalanine metabolism”, “Glycerolipid metabolism” and “Arginine and proline metabolism”. We propose a three-metabolite diagnostic panel—comprising isoleucine, TMAO, and glucose—that effectively discriminates COVID-19 patients from healthy individuals, achieving high efficiency. Furthermore, we found an optimal biomarker panel capable of efficiently classify disease severity considering both clinical characteristics (obesity/overweight, dyslipidemia, and lymphocyte count) together with metabolites content (ethanol, TMAO, tyrosine and betaine).

Abstract This work presents a new method called Dimensionless Fluctuation Balance (DFB), which makes it possible to obtain distributions as solutions of Partial Differential Equations (PDEs). In the first case study, DFB was applied to obtain the Boltzmann PDE, whose solution is a distribution for Boltzmann gas. Following, the Planck photon gas in the Radiation Law, Fermi–Dirac, and Bose–Einstein distributions were also verified as solutions to the Boltzmann PDE. The first case study demonstrates the importance of the Boltzmann PDE and the DFB method, both introduced in this paper. In the second case study, DFB is applied to thermal and entropy energies, naturally resulting in a PDE of Boltzmann’s entropy law. Finally, in the third case study, quantum effects were considered. So, when applying DFB with Heisenberg uncertainty relations, a Schrödinger case PDE for free particles and its solution were obtained. This allows for the determination of operators linked to Hamiltonian formalism, which is one way to obtain the Schrödinger equation. These results suggest a wide range of applications for this methodology, including Statistical Physics, Schrödinger’s Quantum Mechanics, Thin Films, New Materials Modeling, and Theoretical Physics.

Abstract Erysipelas still causes large economic losses to pig industry. Maternal immunity is critical to prevent erysipelas in young animals, thus, intensive vaccination protocols or practices focused on the improvement of the maternally derived immunity could provide substantial benefits. The present study evaluates potential changes in antibodies levels in sows and their offspring using two types of tests (commercial ELISA, Ingenasa or rSpaA415 ELISA) when two different vaccination programs (before farrowing or after farrowing) against Erysipelothrix rhusiopathiae were applied to sows from Iberian (A) or conventional Large White-Landrace (B) pig farms. The results showed a statistical correlation between titers found in sows and their one-week old piglets in both tests. The overall mean of (log) antibody titers in farm B measured by the commercial ELISA test was significantly higher in pre-farrowing vaccinated sows compared to the post-farrowing vaccine protocol (p = 0.0278). Additionally, using the rSpaA415 ELISA test, the overall mean of (log) antibody titers was significantly higher in pre-farrowing sows (p = 0.0056) compared to sows following post-farrowing vaccine protocol (p = 0.0003) or non- vaccinated sows. None of the above-mentioned differences were found in farm A. The overall mean of (log) antibody titers in piglets from the pre-farrowing vaccination protocol was significantly higher than piglets from the post-farrowing vaccination protocol in farm A (p = 0.0059; rSpaA415 ELISA) and farm B (p = 0.0168 and p = 0.0098 for the commercial and rSpaA415 ELISA data, respectively). Additionally, higher proportion of piglets from pre-farrowing vaccinated sows remained seropositive during the post-weaning period (days 42 to 84) compared to piglets from non-vaccinated or post-farrowing vaccinated groups in both farms A and B.

Abstract The development of computational tools for the systematic prediction of metabolic vulnerabilities of cancer cells constitutes a central question in systems biology. Here, we present gmctool, a freely accessible online tool that allows us to accomplish this task in a simple, efficient and intuitive environment. gmctool exploits the concept of genetic Minimal Cut Sets (gMCSs), a theoretical approach to synthetic lethality based on genome-scale metabolic networks, including a unique database of synthetic lethals computed from Human1, the most recent metabolic reconstruction of human cells. gmctool introduces qualitative and quantitative improvements over our previously developed algorithms to predict, visualize and analyze metabolic vulnerabilities in cancer, demonstrating a superior performance than competing algorithms. A detailed illustration of gmctool is presented for multiple myeloma (MM), an incurable hematological malignancy. We provide in vitro experimental evidence for the essentiality of CTPS1 (CTPS synthase) and UAP1 (UDP-N-Acetylglucosamine Pyrophosphorylase 1) in specific MM patient subgroups.

Abstract Background Benzodiazepines are frequently prescribed drugs; however, their prolonged use can lead to tolerance, dependence, and other adverse effects. Despite these risks, long-term use remains common, presenting a public health concern. This study aims to explore the beliefs and opinions held by the public regarding benzodiazepines, as understanding these perspectives may provide insights into their usage patterns. Methods We collected public tweets published in English between January 1, 2019, and October 31, 2020, that mentioned benzodiazepines. The content of each tweet and the characteristics of the users were analyzed using a mixed-method approach, including manual analysis and semi-supervised machine learning. Results Over half of the Twitter users highlighted the efficacy of benzodiazepines, with minimal discussion of their side effects. The most active participants in these conversations were patients and their families, with health professionals and institutions being notably absent. Additionally, the drugs most frequently mentioned corresponded with those most commonly prescribed by healthcare professionals. Conclusions Social media platforms offer valuable insights into users’ experiences and opinions regarding medications. Notably, the sentiment towards benzodiazepines is predominantly positive, with users viewing them as effective while rarely mentioning side effects. This analysis underscores the need to educate physicians, patients, and their families about the potential risks associated with benzodiazepine use and to promote clinical guidelines that support the proper management of these medications. Clinical trial number Not applicable.

ABSTRACT: The evaluation of dairy cow feed efficiency using residual feed intake accounts for known energy sinks. However, behavioral traits may also contribute to the variation in feed efficiency. Our objective was to estimate the heritability and repeatability of behavioral traits and their genetic correlations with feed efficiency and its components in lactating Holstein cows. The first dataset consisted of 36,075 daily rumination and lying time records collected using a SMARTBOW ear-tag accelerometer (Zoetis, Parsippany, NJ) and 6,371 weekly feed efficiency records of 728 cows from the University of Wisconsin–Madison. The second dataset consisted of 59,155 daily activity records, measured as number of steps, recorded by pedometers (AfiAct; SAE Afikim, Kibbutz Afikim, Israel) and 8,626 weekly feed efficiency records of 635 cows from the University of Florida. Feed efficiency and its components included DMI, change in BW, metabolic BW, secreted milk energy, and residual feed intake. The statistical models included the fixed effect of cohort, lactation number, and days in milk, and the random effects of animal and permanent environment. Heritability estimates for behavioral traits using daily records were 0.19 ± 0.06 for rumination and activity, and 0.37 ± 0.07 for lying time. Repeatability estimates for behavioral traits using daily data ranged from 0.56 ± 0.02 for activity to 0.62 ± 0.01 for lying time. Both heritability and repeatability estimates were larger when weekly records instead of daily records were used. Rumination and activity had positive genetic correlations with residual feed intake (0.40 ± 0.19 and 0.31 ± 0.22, respectively) and lying time had a negative genetic correlation with this residual feed intake (−0.27 ± 0.11). These results indicate that more efficient cows tend to spend more time lying and less time active. Additionally, less efficient cows tend to eat more and therefore also tend to ruminate longer. Overall, sensor-based behavioral traits are heritable and genetically correlated with feed efficiency and its components and, therefore, they could be used as indicators to identify feed-efficient cows within the herd.

ABSTRACT: The aim of this study was to evaluate the effects of different anti-mycotoxin feed additives on the concentration of mycotoxins in milk, urine, and blood plasma of dairy cows fed diets artificially contaminated with mycotoxins. Secondarily, performance, total-tract apparent digestibility of nutrients, and blood parameters were evaluated. Twelve multiparous cows (165 ± 45 DIM, 557 ± 49 kg BW, and 32.1 ± 4.57 kg/d milk yield at the start of the experiment) were blocked according to parity, milk yield, and DIM and used in a 4 × 4 Latin square design experiment with 21-d periods, where the last 7 d were used for sampling and data analysis. Treatments were (1) mycotoxin group (MTX), basal diet (BD) without anti-mycotoxin feed additives; (2) hydrated sodium calcium aluminosilicate (HSCA), HSCA added to the BD at 25 g/cow per day; (3) mycotoxin deactivator (MD; Mycofix Plus, dsm-firmenich) added to the BD at 15 g/cow per day (MD15); and (4) MD added to the BD at 30 g/cow per day (MD30). Cows from all treatments were challenged with a blend of mycotoxins containing 404 μg of aflatoxin B1, 5,025 μg of deoxynivalenol (DON), 8,046 μg of fumonisins (FUM), 195 μg of T2 toxin (T2), and 2,034 μg of zearalenone (ZEN) added daily to the BD during the last 7 d of each period. Neither performance (milk yield and composition) nor nutrient digestibility was affected by treatments. All additives reduced aflatoxin M1 (AFM1) concentration in milk, whereas MD15 and MD30 group had lower excretion of AFM1 in milk than HSCA. Deoxynivalenol, FUM, T2, or ZEN were not detected in milk of MD15 and MD30. Concentrations in milk of DON, FUM, T2, and ZEN were similar between MTX and HSCA. Except for AFM1, none of the analyzed mycotoxins were detected in urine of MD30 group. Comparing HSCA to MD treatments, the concentration of AFM1 was greater for HSCA, whereas MD30 was more efficient at reducing AFM1 in urine than MD15. Aflatoxin M1, DON, FUM, and ZEN were not detected in the plasma of cows fed MD30, and DON was also not detected in MD15 group. Plasma concentration of FUM was lower for MD15, similar plasma FUM concentration was reported for HSCA and MTX. Plasma concentration of ZEN was lower for MD15 than MTX and HSCA. Serum concentrations of haptoglobin and hepatic enzymes were not affected by treatments. Blood concentration of sodium was lower in HSCA compared with MD15 and MD30 groups. In conclusion, the mycotoxin deactivator proved to be effective in reducing the secretion of mycotoxins in milk, urine, and blood plasma, regardless of the dosage. This reduction was achieved without adverse effects on milk production or total-tract digestibility in cows fed multi-mycotoxin-contaminated diets over a short-term period. Greater reductions in mycotoxin secretion were observed with full dose of MD.

ABSTRACT: The rumen microbiome is crucial for converting feed into absorbable nutrients used for milk synthesis, and the efficiency of this process directly affects the profitability and sustainability of the dairy industry. Recent studies have found that the rumen microbial composition explains part of the variation in feed efficiency traits, including dry matter intake, milk energy, and residual feed intake. The main goal of this study was to reveal relationships between the host genome, the rumen microbiome, and dairy cow feed efficiency using structural equation models. Our specific objectives were to (1) infer the mediation effects of the rumen microbiome on feed efficiency traits, (2) estimate the direct and total heritability of feed efficiency traits, and (3) calculate the direct and total breeding values of feed efficiency traits. Data consisted of dry matter intake, milk energy, and residual feed intake records, SNP genotype data, and 16S rRNA rumen microbial abundances from 448 mid-lactation Holstein cows from 2 research farms. We implemented structural equation models such that the host genome directly affects the phenotype (GP → P) and the rumen microbiome (GM → P), and the microbiome affects the phenotype (M → P), partially mediating the effect of the host genome on the phenotype (G → M → P). We found that 7% to 30% of microbes within the rumen microbial community had structural coefficients different from zero. We classified these microbes into 3 groups that could have different uses in dairy farming. Microbes with heritability

ABSTRACT Introduction: Although nerves and vessels of the penis play important role in erection, there are few studies on their development in human fetus. Therefore, the objective of the present study is to analyze, quantitatively, in the corpora cavernosa and corpus spongiosum, the development of the nerves and vessels in the fetal penis at different gestational ages. Material and Methods: Fifty-six fresh, macroscopically normal human fetuses aged from 13 to 36 weeks post-conception (WPC) were used. Gestational age was determined by the foot length criterion. Penises were immediately fixed in 10% formalin, and routinely processed for paraffin embedding, after which tissue sections from the mid-shaft were obtained. We used immunohistochemical staining to analyze the nerves and vessels in the corpus cavernous and in the corpus spongiosum. These elements were identified and quantified as percentage by using the Image-J software. Results: The quantitative analysis showed that the percentage of nerves varied from 3.03% to 20.35% in the corpora cavernosa and from 1.89% to 23.88% in the corpus spongiosum. The linear regression analysis indicated that nerves growth (incidence) in the corpora cavernosa and corpus spongiosum correlated significantly and positively with fetal age (r2=0.9421, p