Profiles, exposure assessment and expanded screening of PAHs and their derivatives in one petroleum refinery facility of China.

This study investigated environmental distribution and human exposure of polycyclic aromatic hydrocarbons (PAHs) and their derivatives in one Chinese petroleum refinery facility. It was found that, following with high concentrations of 16 EPA PAHs (∑Parent-PAHs) in smelting subarea of studied petroleum refinery facility, total derivatives of PAHs [named as XPAHs, including nitro PAHs (NPAHs), chlorinated PAHs (Cl-PAHs), and brominated PAHs (Br-PAHs)] in gas (mean= 1.57 × 104 ng/m3), total suspended particulate (TSP) (mean= 4.33 × 103 ng/m3) and soil (mean= 4.37 × 103 ng/g) in this subarea had 1.76-6.19 times higher levels than those from other subareas of this facility, surrounding residential areas and reference areas, indicating that petroleum refining processes would lead apparent derivation of PAHs. Especially, compared with those in residential and reference areas, gas samples in the petrochemical areas had higher ∑NPAH/∑PAHs (mean=2.18), but lower ∑Cl-PAH/∑PAHs (mean=1.43 × 10-1) and ∑Br-PAH/∑PAHs ratios (mean=7.49 × 10-2), indicating the richer nitrification of PAHs than chlorination during petrochemical process. The occupational exposure to PAHs and XPAHs in this petroleum refinery facility were 24-343 times higher than non-occupational exposure, and the ILCR (1.04 × 10-4) for petrochemical workers was considered to be potential high risk. Furthermore, one expanded high-resolution screening through GC Orbitrap/MS was performed for soils from petrochemical area, and another 35 PAHs were found, including alkyl-PAHs, phenyl-PAHs and other species, indicating that profiles and risks of PAHs analogs in petrochemical areas deserve further expanded investigation.

Assessment of internal exposure risk from metals pollution of occupational and non-occupational populations around a non-ferrous metal smelting plant.

Non-ferrous metal smelting poses significant risks to public health. Specifically, the copper smelting process releases arsenic, a semi-volatile metalloid, which poses an emerging exposure risk to both workers and nearby residents. To comprehensively understand the internal exposure risks of metal(loid)s from copper smelting, we explored eighteen metal(loid)s and arsenic metabolites in the urine of both occupational and non-occupational populations using inductively coupled plasma mass spectrometry with high-performance liquid chromatography and compared their health risks. Results showed that zinc and copper (485.38 and 14.00 µg/L), and arsenic, lead, cadmium, vanadium, tin and antimony (46.80, 6.82, 2.17, 0.40, 0.44 and 0.23 µg/L, respectively) in workers (n=179) were significantly higher compared to controls (n=168), while Zinc, tin and antimony (412.10, 0.51 and 0.15 µg/L, respectively) of residents were significantly higher than controls. Additionally, workers had a higher monomethyl arsenic percentage (MMA%), showing lower arsenic methylation capacity. Source appointment analysis identified arsenic, lead, cadmium, antimony, tin and thallium as co-exposure metal(loid)s from copper smelting, positively relating to the age of workers. The hazard index (HI) of workers exceeded 1.0, while residents and control were approximately at 1.0. Besides, all three populations had accumulated cancer risks exceeding 1.0 × 10-4, and arsenite (AsIII) was the main contributor to the variation of workers and residents. Furthermore, residents living closer to the smelting plant had higher health risks. This study reveals arsenic exposure metabolites and multiple metals as emerging contaminants for copper smelting exposure populations, providing valuable insights for pollution control in non-ferrous metal smelting.

Estudo longitudinal de famílias / Longitudinal study of families / Estudio longitudinal de familias

Introdução: O desenvolvimento da família é influenciado por diversos fatores de sua organização interna e de ordem ambiental, social, cultural, econômica e política. Em contexto de pobreza os riscos são maiores. Fatores de proteção, como boa organização familiar e rede social de apoio podem diminuir as consequências negativas da pobreza. São escassas as pesquisas longitudinais sobre vulnerabilidade e resiliência nas famílias. Objetivo: Este artigo descreve o desenvolvimento de três famílias ao longo de 15 anos, estudadas por meio de entrevistas em casa, parte de uma coorte populacional de um bairro de Porto Alegre (RS). Buscaram-se associações entre a qualidade das relações nessas famílias e sua saúde física e mental, especialmente a do filho, foco da pesquisa. Métodos: Selecionaram-se no arquivo da pesquisa as três primeiras famílias (do total de 148) das quais se tinham os resultados completos das cinco visitas realizadas aos quatro meses e aos dois, quatro, nove e 15 anos de um filho. Realizou-se análise qualitativa dos registros em busca de categorias para compreender a vida e as relações interpessoais nas famílias. O estudo foi realizado em conjunto por duas pesquisadoras, médicas especialistas em desenvolvimento humano. As categorias identificadas na análise e estudadas nas cinco etapas foram: configuração familiar, situação socioeconômica, situações traumáticas, saúde física, saúde relacional e mental, evolução cognitiva e escolar do filho. Resultados: As três famílias, todas de classe C, com filhos sem problemas de saúde física, tiveram evolução suficientemente boa, apesar de todas enfrentarem múltiplos problemas, inclusive separações e mortes precoces. A relação com o sistema de saúde e escola era boa e similar para as três. A jovem com menos problemas de saúde mental foi aquela que sofreu perdas mais importantes: morte dos pais. Tinha uma estrutura familiar multigeracional sólida desde a primeira infância, com relações interpessoais predominantemente colaborativas e amorosas. Conclusões: O artigo busca avançar na compreensão da resiliência nas famílias em situações de vulnerabilidade. Concluímos que essas três famílias, uma delas mais que as outras, foram suficientemente saudáveis na tarefa de educar seus filhos sem desenvolverem problemas mentais graves. Propomos que o bom desenvolvimento se associa com a adequação e amorosidade dos cuidados com a etapa do ciclo vital, mesmo enfrentando situações problemáticas. Essas qualidades precisam estar associadas à estabilidade socioeconômica básica e a bons serviços de saúde e escola.

Introduction: Family development is influenced by it's internal organization and environmental factors, socioeconomic, cultural and political. In poor contexts there are more risks to development. Protection factors like good family organization and social network may decrease the risks. Longitudinal research about vulnerability and resilience in families is scarse. Objective: This article describes the development of three families over 15 years through interviews at home. The families were part of a populational cohort of a neighborhood in Porto Alegre (RS). We looked for links between the quality of relationships and the physical and mental health of these families, especially of the child focus of the research. Methods: We selected in the research archives the first three families (of a total of 148) for which we had full results of the five interviews at four months and two, four, nine and fifteen years of a child. We did a qualitative analysis of the records looking for parameters to understand the life and interpersonal relationships of these families. This study was done by two researchers, both experts in Human Development. The categories identified in the analysis of the five phases were: family structure, socioeconomic situation, traumatic experiences, physical, mental and relational health and cognitive evolution of the child. Results: All three families belonged to economical class C. The children were in good physical health and had sufficiently good general development, having faced multiple problems, including parental separation and early parental death. The relationship with the health and school systems was good in all of them. The youth with less mental health problems was the one who suffered the heaviest loss: early death of both parents. Her family had strong multigenerational ties since her early days, with predominant collaborative and loving relationships. Conclusions: This article aims to contribute to the comprehension of resilience in families in the context of vulnerability. We can say that these three families were healthy enough in the task of bringing up children without any serious mental health problem. We suggest that healthy development is associated with loving interfamily relationships adequate to each phase of development, notwithstanding dramatic events. This needs to be supported by basic economic stability and adequate school and health systems.

Introducción: El desarrollo de la familia es influenciado por su organización interna y factores ambientales, sociales, culturales, económicos y políticos. En contextos pobres los riesgos son mayores. Factores de protección como buena organización familiar y red social de apoyo pueden disminuir las consecuencias negativas de la pobreza. Son pocas las investigaciones longitudinales de vulnerabilidad y resiliencia de las familias. Objetivo: Este artículo describe el estudio del desarrollo de tres familias a lo largo de 15 años, a través de entrevistas en domicilio, parte de una cohorte poblacional de un barrio de Porto Alegre (RS). Se buscaron correlaciones entre la calidad de las relaciones de esas familias y su salud física y mental, especialmente la del hijo foco de la investigación. Métodos: Fueron seleccionadas en el archivo de la investigación las tres primeras familias (de un total de 148) de las cuales se tenían los resultados completos de las cinco visitas realizadas, a los 4 meses, y a los 2, 4, 9, y 15 años de un hijo. Fue realizado un análisis cualitativo de los registros en busca de categorías para comprender la vida y las relaciones interpersonales en las familias. El estudio fue hecho en conjunto por dos investigadoras, médicas especialistas en desarrollo humano. Las categorías identificadas en el análisis y estudiadas en las cinco etapas fueron: configuración familiar, situación socioeconómica, situaciones traumáticas, salud física, salud relacional y mental, evolución cognitiva y escolar del hijo. Resultados: Las tres familias, todas de clase C, con hijos sin problemas de salud física, tuvieron evolución suficientemente buena, a pesar de que todas enfrentaron múltiples problemas, incluso separaciones y muertes precoces. La relación con el sistema de salud y escuela era buena y similar para las tres. La joven con menos problemas de salud mental fue aquella que sufrió las mayores pérdidas: muerte de los padres. Tenía una estructura familiar multigeneracional sólida desde la primera infancia, con relaciones interpersonales predominantemente colaborativas y amorosas. Conclusiones: El artículo pretende avanzar en la comprensión de la resiliencia en las familias en situaciones de vulnerabilidad. Concluimos que esas tres familias, una de ellas más que las otras, fueron suficientemente saludables en la tarea de educar a sus hijos sin que desarrollaran problemas mentales graves. Proponemos que el buen desarrollo se asocia con el amor y adecuación de los cuidados a la etapa del ciclo vital, aun enfrentando situaciones problemáticas. Esas calidades necesitan estar asociadas a la estabilidad socioeconómica básica y buenos servicios de salud y escuela.

Strong and weak alignment of large language models with human values.

Minimizing negative impacts of Artificial Intelligent (AI) systems on human societies without human supervision requires them to be able to align with human values. However, most current work only addresses this issue from a technical point of view, e.g., improving current methods relying on reinforcement learning from human feedback, neglecting what it means and is required for alignment to occur. Here, we propose to distinguish strong and weak value alignment. Strong alignment requires cognitive abilities (either human-like or different from humans) such as understanding and reasoning about agents' intentions and their ability to causally produce desired effects. We argue that this is required for AI systems like large language models (LLMs) to be able to recognize situations presenting a risk that human values may be flouted. To illustrate this distinction, we present a series of prompts showing ChatGPT's, Gemini's and Copilot's failures to recognize some of these situations. We moreover analyze word embeddings to show that the nearest neighbors of some human values in LLMs differ from humans' semantic representations. We then propose a new thought experiment that we call "the Chinese room with a word transition dictionary", in extension of John Searle's famous proposal. We finally mention current promising research directions towards a weak alignment, which could produce statistically satisfying answers in a number of common situations, however so far without ensuring any truth value.

Novel crossover and recombination hotspots massively spread across primate genomes.

BACKGROUND: The recombination landscape and subsequent natural selection have vast consequences forevolution and speciation. However, most of the crossover and recombination hotspots are yet to be discovered. We previously reported the relevance of C and G trinucleotide two-repeat units (CG-TTUs) in crossovers and recombination. METHODS: On a genome-wide scale, here we mapped all combinations of A and T trinucleotide two-repeat units (AT-TTUs) in human, consisting of AATAAT, ATAATA, ATTATT, TTATTA, TATTAT, and TAATAA. We also compared a number of the colonies formed by the AT-TTUs (distance between consecutive AT-TTUs < 500 bp) in several other primates and mouse. RESULTS: We found that the majority of the AT-TTUs (> 96%) resided in approximately 1.4 million colonies, spread throughout the human genome. In comparison to the CG-TTU colonies, the AT-TTU colonies were significantly more abundant and larger in size. Pure units and overlapping units of the pure units were readily detectable in the same colonies, signifying that the units were the sites of unequal crossover. We discovered dynamic sharedness of several of the colonies across the primate species studied, which mainly reached maximum complexity and size in human. CONCLUSIONS: We report novel crossover and recombination hotspots of the finest molecular resolution, massively spread and shared across the genomes of human and several other primates. With respect to crossovers and recombination, these genomes are far more dynamic than previously envisioned.

Extracellular vesicles may provide an alternative detoxification pathway during skeletal muscle myoblast ageing.

Skeletal muscle (SM) acts as a secretory organ, capable of releasing myokines and extracellular vesicles (SM-EVs) that impact myogenesis and homeostasis. While age-related changes have been previously reported in murine SM-EVs, no study has comprehensively profiled SM-EV in human models. To this end, we provide the first comprehensive comparison of SM-EVs from young and old human primary skeletal muscle cells (HPMCs) to map changes associated with SM ageing. HPMCs, isolated from young (24 ± 1.7 years old) and older (69 ± 2.6 years old) participants, were immunomagnetically sorted based on the presence of the myogenic marker CD56 (N-CAM) and cultured as pure (100% CD56+) or mixed populations (MP: 90% CD56+). SM-EVs were isolated using an optimised protocol combining ultrafiltration and size exclusion chromatography (UF + SEC) and their biological content was extensively characterised using Raman spectroscopy (RS) and liquid chromatography mass spectrometry (LC-MS). Minimal variations in basic EV parameters (particle number, size, protein markers) were observed between young and old populations. However, biochemical fingerprinting by RS highlighted increased protein (amide I), lipid (phospholipids and phosphatidylcholine) and hypoxanthine signatures for older SM-EVs. Through LC-MS, we identified 84 shared proteins with functions principally related to cell homeostasis, muscle maintenance and transcriptional regulation. Significantly, SM-EVs from older participants were comparatively enriched in proteins involved in oxidative stress and DNA/RNA mutagenesis, such as E3 ubiquitin-protein ligase TTC3 (TTC3), little elongation complex subunit 1 (ICE1) and Acetyl-CoA carboxylase 1 (ACACA). These data suggest SM-EVs could provide an alternative pathway for homeostasis and detoxification during SM ageing.

Antibiotic resistance risk assessment in Mymensingh, Bangladesh: Current scenario from human-animal-environmental interfaces viewpoint.

The imprudent use of antibiotics increases the environmental microflora's resistance to various drugs, particularly antibiotics. Prescription data is crucial for understanding antibiotic usage frequency and dosage. This health-focused study aims to analyze antibiotic prescription patterns in human and veterinary practices to identify emerging trends in environmental antibiotic resistance. For this survey, A total of 6550 prescriptions were randomly collected from hospitals and pharmacies in Mymensingh sadar upazila, Bangladesh, between August and October 2022. Of these, 5123 (78 %) were for human cases and 1427 (22 %) for veterinary purposes. Photos of the prescriptions were taken and analyzed to understand prescribing habits. Additionally, 30 water samples from rivers, ponds, sewage, and households in Mymensingh City Corporation were collected to assess environmental antibiotic levels and resistance patterns of microorganisms. The analysis showed that Cephalosporins were the most prescribed antibiotics, found in 570 (56.27 %) of human prescriptions and 230 (42.99 %) of veterinary prescriptions. Aminoglycosides had the lowest frequency, with 13 (1.2 %) for humans and 46 (8.6 %) for animals. Macrolides (12.24 %), carboxylic acids (1.87 %), and rifamycins (1.28 %) were only found in human prescriptions, while sulfa drugs (10.84 %), tetracyclines (5.42 %), and combinations of antibiotics (14.77 %) were only in animal prescriptions. Quinolones were prescribed 4.06 times more for humans, while aminoglycosides were used 3.54 times more for animals. Environmental samples showed E. coli had the highest resistance (MAR Value: 0.625) against eight antibiotics. This study illuminates the human-animal prescription patterns that are influenced by environmental factors which drive antibiotic stewardship in Bangladesh. It is imperative for practitioners to exercise caution and adhere to guidelines when prescribing antibiotics, both in human and veterinary practices, given the alarming trend of antibiotic resistance. Additionally, measures must be taken to restrict the influx of antibiotics residue into the environment.

The short fiber knobs of human adenovirus in species F elicit cross-neutralizing antibody responses.

Human adenovirus (HAdV) type 40 in species F (HAdV-F40) and HAdV-F41 represent the third most prevalent causative agents of non-bacterial acute gastroenteritis in infants and young children, following norovirus and rotavirus. Despite their significant contribution to global child morbidity, vaccines to preemptively combat these viruses remain elusive. In this study, we investigate the potential for cross-neutralization between HAdV-F40 and HAdV-F41 using immune sera with the short fiber knob (SFK). We implemented a series of assays to evaluate the responses, including enzyme-linked immunosorbent, micro-neutralization, immunofluorescence, and quantitative polymerase chain reaction. Our results demonstrate that immune sera with HAdV-F40 SFK or HAdV-F41 SFK could effectively neutralize both HAdV-F40 and HAdV-F41, indicating a mutual cross-neutralizing effect. Notably, the immune sera with HAdV-F40 SFK demonstrated a stronger neutralization effect, suggesting the potential to develop a subunit vaccine that can simultaneously counteract both viruses. These findings underscore the potential of SFK immunization in evoking a cross-neutralizing antibody response between HAdV-F40 and HAdV-F41. This suggests a promising avenue for developing subunit vaccines against HAdV-F40 and HAdV-F41 and provides a novel perspective on the potential of neutralizing antibodies to protect against these two types of HAdV.

Exploring the antidiabetic and anti-inflammatory potential of Lavandula officinalis essential oil: In vitro and in silico insights.

Medicinal plants have been utilized for centuries in traditional medicine systems worldwide, providing a rich source of bioactive compounds with diverse biological activities. Lavandula officinalis, a member of the Lamiaceae family, has been recognized for its multifaceted pharmacological activities. In this current investigation, our primary objective was to scrutinize the in vitro inhibitory potential of L. officinalis essential oil (LOEO) against alpha-amylase and alpha-glucosidase, with the aim of understanding its antidiabetic effects. Additionally, the assay encompassed tyrosinase and lipoxygenase (LOX) to assess its anti-inflammatory attributes. Unraveling the underlying molecular mechanisms of these activities prompted an in-silico study. The purpose was to establish correlations between in-vitro observations and computational insights derived from molecular docking, which forecasts the interaction of LOEO molecules with their respective targets, alongside ADMET prediction. The Gas Chromatography-Mass Spectrometry (GC-MS) analysis allow to identify eighteen compounds, with the dominance of L-camphor (43.12 %), 1,8-cineole (34.27 %) and borneol (8.60 %) in LOEO. The antidiabetic evaluation revealed that LOEO exhibited noteworthy inhibitory activity against both α-amylase and α-glucosidase, displaying IC50 values of 3.14 ± 0.05 mg/mL and 2.07 ± 0.03 mg/mL, respectively. The subsequent in-silico study highlighted the particularly strong binding affinity of (E)-Farnesene, with a binding score of -7.4 kcal/mol for alpha-glucosidase, while Germacrene D displayed the highest affinity among the ligands (-7.9 kcal/mol) for the alpha-amylase target. Furthermore, the investigation into in vitro anti-inflammatory activity unveiled LOEO efficacy against tyrosinase (IC50 = 42.74 µg/mL) and LOX (IC50 = 11.58 ± 0.07 µg/mL). The in-silico analysis echoed these findings, indicating α-Cadinene's notable binding affinity of 6 kcal/mol with tyrosinase and α-Cedrene's binding score of -6.5 kcal/mol for LOX. Impressively, for both COX-1 and COX-2, α-Cedrene exhibited significant binding affinities of -7.6 and -7.3 kcal/mol, respectively. The convergence between the in vitro and in silico outcomes underscores the potential of LOEO and its constituent compounds as potent inhibitors targeting both diabetes and the inflammatory processes.

Concurrent high risk HPV35, HPV45, and HPV59 infections in prostate and bladder cancer tissues of a single patient: A case report.

Human papillomavirus (HPV) infections, primarily transmitted through sexual contact, have been linked to various cancers, including cervical, penile, anal, oropharynx, breast, and prostate cancers. This study presents a unique case of concurrent high-risk HPV35, HPV45, and HPV59 infections in both prostate and bladder cancer tissues from a single patient, representing the first documented instance worldwide with identical HPV types detected in two adjacent organs of the same individual. Employing a multiplex-PCR approach, gel electrophoresis, and Sanger sequencing, we confirmed the presence of these high-risk HPV types. Additionally, Western blot analysis using an HPV E7 antibody demonstrated the active expression of HPV oncoproteins in both cancer types. This discovery underscores the potential for HPV intra-organ transmission and necessitates further exploration of alternative transmission routes. The implications of our results offer new insights into the complex dynamics of HPV transmission in cancer pathogenesis. In conclusion our study reveals concurrent HPV infections in both prostate and bladder cancers within a single patient and highlights the potential intra-organ spread of HPV and the need for further investigation of alternative transmission routes.

The effect of pregnancy-related hormones on hepatic transporters: studies with premenopausal human hepatocytes.

Introduction: Pregnancy results in significant changes in drug pharmacokinetics (PK). While previous studies have elucidated the impact of pregnancy-related hormones (PRH) on mRNA or protein expression and activity of major hepatic metabolizing enzymes, their effect on hepatic drug transporters remains largely unexplored. Therefore, we investigated the effect of a cocktail of PRH on the mRNA expression and activity of hepatic transporters. Methods: Plated human hepatocytes (PHH) from 3 premenopausal donors were incubated, in triplicate, for 72 h, with vehicle (DMSO < 0.01%), rifampin (10 µM; positive control) or a cocktail of PRH consisting of estrone, estradiol, estriol, estetrol, progesterone, cortisol, testosterone, oxytocin, and placental growth hormone. The PRH concentrations replicated 0.1×, 1×, or 10× of the plasma concentrations of these hormones observed during each of the three trimesters of pregnancy. After treatment, mRNA expression (quantified by qPCR) of hepatic influx and efflux transporters as well as the activity of influx transporters was quantified (uptake of a selective substrate ± corresponding transporter inhibitor). The data were expressed relative to that in the control (vehicle) group. Significance was evaluated by ANOVA (followed by Dunn's multiple comparisons) or unpaired t-test when the within-lot data were analyzed, or repeated measures ANOVA (followed by Dunn's multiple comparisons) or paired t-test when data from all 3 lots were analyzed (p < 0.05). Results and Discussion: In general, a) PRH cocktails significantly induced transporter mRNA expression in the following order OAT2 ≈ NTCP ≈ OCT1 > OATP2B1 and repressed mRNA expression in the following order OATP1B3 > OATP1B1; b) these changes translated into significant induction of OAT2 (T1-T3) and NTCP (T2-T3, in only two lots) activity at the 1× PRH concentration. Compared with the influx transporters, the induction of mRNA expression of efflux transporters was modest, with mRNA expression of MRP2 and BSEP being induced the most. Conclusion: Once these data are verified through in vivo probe drug PK studies in pregnancy, they can be populated into physiologically based pharmacokinetic (PBPK) models to predict, for all trimesters of pregnancy, transporter-mediated clearance of any drug that is a substrate of the affected transporters.

Association of serum lipid profile with liver fibrosis in HCV­coinfected HIV patients on suppressive anti­retroviral therapy.

Hepatitis C virus (HCV) coinfection in individuals living with human immunodeficiency virus (HIV) (PLWH) may affect lipid metabolism and accelerate the progression of chronic hepatitis. Therefore, the identification of risk factors for progressive liver disease is needed. The present study aimed to examine the prevalence and clinical features associated with liver fibrosis in HCV-coinfected HIV patients, including metabolic markers. A total of 105 patients coinfected with HIV and HCV were recruited and liver fibrosis was assessed using the fibrosis-4 (FIB-4) score and aspartate aminotransferase-to-platelet ratio index (APRI). Logistic regression analyses indicated that patients aged >50 years and with a CD4+ cell count <350 cells/µl had an 11.4-times higher (P=0.001) and a 5.7-times higher (P=0.017) risk of liver fibrosis, as determined by FIB-4 score, compared to patients aged ≤40 years and a CD4+ cell count of ≥350 cells/µl, respectively. In addition, patients naïve to HCV treatment or receiving treatment had 5.4- and 12.7-times higher risks for liver fibrosis, as determined by APRI, than those with sustained virologic response (SVR) (P=0.003 and P=0.033, respectively). Univariate analysis indicated lower risks of liver fibrosis, as determined by APRI, in the patients with abnormally high levels of cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) than those with normal levels [odds ratio (OR) 0.3, 95% confidence interval (CI) 0.1-0.9, P=0.037; OR 0.4, 95% CI 0.2-0.9, P=0.041; OR 0.2, 95% CI 0.1-0.5, P=0.001] and multivariate analysis suggested only patients with high levels of LDL had a lower risk for liver fibrosis determined by APRI (OR 0.1, 95% CI 0.3-0.8, P=0.029). Consistently, serum levels of cholesterol, HDL and LDL were significantly lower in the patient groups with more advanced fibrosis, evaluated by FIB-4 score and APRI, than those without liver fibrosis and the levels of cholesterol and LDL in the patients achieving SVR were higher than those with no response or not receiving treatment (all P<0.05). In conclusion, the present study identified serum lipid levels as associated factors of hepatic fibrosis, together with age, CD4+ cell count and HCV treatment status, in HCV-coinfected PLWH on long-term suppressive anti-retroviral therapy.

Comprehensive breast cancer risk analysis with whole exome sequencing and the prevalence of BRCA1 and ABCG2 mutations and oncogenic HPV.

Breast cancer is the most prevalent cancer and also the leading cause of cancer death in women worldwide. A comprehensive understanding of breast cancer risk factors and their incidences is useful information for breast cancer prevention and control planning. The present study aimed to provide information on single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) in breast cancer, the allele frequency of two SNPs in breast cancer-related genes BRCA1 DNA repair associated (BRCA1; rs799917) and ATP binding cassette subfamily G member 2 (ABCG2; rs2231142), and the prevalence of human papillomavirus (HPV) infections in a normal population living in Phayao Province, Northern Thailand. One breast cancer and 10 healthy samples were investigated by whole exome sequencing (WES) and compared for genetic variation. The WES data contained SNPs in genes previously implicated in breast cancer and provided data on CNVs. The allele frequencies for SNPs rs799917 and rs2231142 were also examined. The SNP genotype frequencies were 35.88% CC, 46.54% CT, and 17.58% TT for rs799917 and 33.20% CC, 46.88% CA, and 19.92% AA for rs2231142. A total of 825 human whole blood samples were examined for HPV infection by PCR, and the pooled DNA was tested for HPV infection using metagenomic sequencing. No HPV infections were detected among all 825 samples or the pooled blood samples. The incidence of breast cancer among the tested samples was estimated based on acceptable breast cancer risk factors and demographic data and was 1.47%. The present study provided data on SNPs and CNVs in breast cancer-related genes. The associations between SNPs rs2231142 and rs799917 and breast cancer should be further investigated in a case-control study since heterozygous and homozygous variants are more common. Based on the detection of HPV infection in the blood samples, HPV may not be associated with breast cancer, at least in the Northern Thai population.

Do you wanna dance? Tales of trust and driving trust factors in robot medication counseling in the pharmacy context.

Introduction: The sustainable implementation of socially assistive robots in a pharmacy setting requires that customers trust the robot. Our aim was to explore young adults' anticipations of and motives for trusting robot medication counseling in a high-stakes scenario. Methods: Through a co-creation approach, we co-designed a prototype application for the Furhat platform together with young adults. In-lab testing of a pharmacy scenario, where the robot provides medication counseling related to emergency contraceptive pills, was conducted to deepen our understanding of some factors driving young adults' initial trust establishment and anticipations of interacting with a robot in a high-stakes scenario. Qualitative data from interviews with six study participants were analyzed using inductive, reflexive thematic analysis and are presented through a narrative approach. Results: We outline five tales of trust characterized by personas. A continuum of different anticipations for consulting a robot in medication counseling is presented, ranging from low to high expectations of use. Driving factors in the initial trust establishment process are position, autonomy, boundaries, shame, gaze, and alignment. Discussion: The article adds to the understanding of the dimensions of the multifaceted trust concept, of driving trust factors, and of the subsequent anticipation to trust robots in a high-stakes pharmacy context.

The association of different types of human milk with bronchopulmonary dysplasia in preterm infants.

Objective: To evaluate the association between different types of human milk feeds and bronchopulmonary dysplasia (BPD) in preterm infants. Methods: Data on dispensed mother's own milk (MOM) and donor human milk (DHM) from Leipzig Milk Bank for hospitalized infants with a gestational age (GA) ≤32 weeks observed from birth to 36 weeks' postmenstrual age or prior discharge were used. BPD was assessed based on documented International Statistical Classification of Diseases and Related Health Problems (ICD) diagnosis and on electronic hospital records (EHR) of data on ventilation and oxygen supplementation. Associations of dispensed milk feed variations with BPD were investigated using logistic regressions in crude and adjusted models. Results: 866 infants were included with a BPD prevalence of 15.4% (EHR) and 23.2% (ICD). The mean GA was 29.1 weeks. The majority (84.4%, n = 746) of infants were nurtured with a mix of MOM, DHM supplemented by formula or parenteral (other) nutrition during hospitalization. For which, MOM comprised the highest median [Q1-Q3] percentage proportion (53[31-81] %) of this mix. Exclusive fresh milk and exclusive MOM feeds were dispensed on a mean of 40 and 34% patient-days, respectively. Statistically significant associations with lower BPD incidence were only observed for 70-80% MOM vs. DHM, and 60% fresh vs. frozen milk, in crude and adjusted models. Conclusion: Our findings suggest a protective association of MOM and fresh milk with lower odds of BPD, which may be dependent on the proportion of MOM or fresh milk administered. These results highlight the importance of MOM as an ideal source of nutrition during early infancy.

Quantitative evaluation of a theoretical-conceptual model based on affective and socio-behavioral dimensions to explain the academic performance of mathematics students.

Objective: There is evidence that suggests that affective dimensions, personality traits, as well as students' cooperative interpersonal interactions, are an important element in the students learning process. In this work we propose a theoretical model, based on evidence, that shows the direct and indirect relationships between these factors and academic performance in mathematics courses, in undergraduate and school students. Methods: To understand the type of relationships between these variables, the PANAS psychometric test of positive and negative affect, the BIG FIVE personality test and the economic decision game DUPLES GAME were applied. The study sample was 130 students between 17 and 22 years of age from undergraduate and school (M ± SD = 20.1 ± 3.99). Results: From a path analysis, statistically significant relationships were found, for example, a direct relationship between neuroticism and positive affect, which in turn is related to academic performance. We also found a direct relationship between neuroticism and negative affect, extraversion and positive affect. This allows us to propose that some of the independent variables of the model directly and indirectly influence the academic performance of students in the subject of mathematics. Conclusion: Positive affect and negative affect directly affect academic performance in mathematics, neuroticism has a direct impact on negative affect and extraversion direct impact on positive affect. Consequently, there are direct and indirect relationships between personality traits and affective dimensions, which affect the academic performance of mathematics students.

T cell trafficking in human chronic inflammatory diseases.

Circulating T cells, which migrate from the periphery to sites of tissue inflammation, play a crucial role in the development of various chronic inflammatory conditions. Recent research has highlighted subsets of tissue-resident T cells that acquire migratory capabilities and re-enter circulation, referred to here as "recirculating T cells." In this review, we examine recent advancements in understanding the biology of T cell trafficking in diseases where T cell infiltration is pivotal, such as multiple sclerosis and inflammatory bowel diseases, as well as in metabolic disorders where the role of T cell migration is less understood. Additionally, we discuss current insights into therapeutic strategies aimed at modulating T cell circulation across tissues and the application of state-of-the-art technologies for studying recirculation in humans. This review underscores the significance of investigating T trafficking as a novel potential target for therapeutic interventions across a spectrum of human chronic inflammatory diseases.

Associations of age at diagnosis of breast cancer with incident myocardial infarction and heart failure: A prospective cohort study.

Background: The associations of age at diagnosis of breast cancer with incident myocardial infarction (MI) and heart failure (HF) remain unexamined. Addressing this problem could promote understanding of the cardiovascular impact of breast cancer. Methods: Data were obtained from the UK Biobank. Information on the diagnosis of breast cancer, MI, and HF was collected at baseline and follow-ups (median = 12.8 years). The propensity score matching method and Cox proportional hazards models were employed. Results: A total of 251,277 female participants (mean age: 56.8 ± 8.0 years), of whom 16,241 had breast cancer, were included. Among breast cancer participants, younger age at diagnosis (per 10-year decrease) was significantly associated with elevated risks of MI (hazard ratio [HR] = 1.36, 95% confidence interval [CI] 1.19-1.56, p<0.001) and HF (HR = 1.31, 95% CI 1.18-1.46, p<0.001). After propensity score matching, breast cancer patients with younger diagnosis age had significantly higher risks of MI and HF than controls without breast cancer. Conclusions: Younger age at diagnosis of breast cancer was associated with higher risks of incident MI and HF, underscoring the necessity to pay additional attention to the cardiovascular health of breast cancer patients diagnosed at younger age to conduct timely interventions to attenuate the subsequent risks of incident cardiovascular diseases. Funding: This study was supported by grants from the National Natural Science Foundation of China (82373665 and 81974490), the Nonprofit Central Research Institute Fund of Chinese Academy of Medical Sciences (2021-RC330-001), and the 2022 China Medical Board-open competition research grant (22-466).

Relationship between infant gastrointestinal microorganisms and maternal microbiome within 6 months of delivery.

To investigate the association between the microbiota in mothers and gut microbiota in infants from 0 to 6 months, the microbiotas in infant feces, maternal feces, and breast milk were determined by 16S rRNA gene sequencing. The contribution of each maternal microbiome to the infant was assessed using fast expectation-maximization for microbial source tracking calculations. The levels of short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA) in the feces of infants were also determined using gas chromatography and IDK-sIgA ELISA to gain a more comprehensive understanding of the infant gut microbiome. The results of this study showed that in addition to Firmicutes (E1) and Bifidobacterium (E2), the dominant microorganisms of the intestinal microbiota of infants aged 0-6 months include Proteobacteria, which is different from previous findings. Acetic acid, the most abundant SCFA in the infant gut, was positively correlated with Megasphaera (P < 0.01), whereas sIgA was positively correlated with Bacteroides (P < 0.05) and negatively correlated with Klebsiella and Clostridium_XVIII (P < 0.05). The maternal gut microbiota contributed more to the infant gut microbiota (43.58% ± 11.13%) than the breast milk microbiota, and significant differences were observed in the contribution of the maternal microbiota to the infant gut microbiota based on the delivery mode and feeding practices. In summary, we emphasize the key role of maternal gut health in the establishment and succession of infant gut microbiota.IMPORTANCEThis study aims to delineate the microbial connections between mothers and infants, leveraging the fast expectation-maximization for microbial source tracking methodology to quantify the contribution of maternal microbiota to the constitution of the infant's gut microbiome. Concurrently, it examines the correlations between the infant gut microbiota and two distinctive biomolecules, namely short-chain fatty acids (SCFAs) and secretory immunoglobulin A (sIgA). The findings indicate that the maternal gut microbiota exerts a greater influence on the infant's gut microbial composition than does the microbiota present in breast milk. Infants born via vaginal delivery and receiving mixed feeding display gut microbiota profiles more similar to their mothers'. Notably, the SCFA acetate displays positive associations with beneficial bacteria and inverse relationships with potentially harmful ones within the infant's gut. Meanwhile, sIgA positively correlates with Bacteroides species and negatively with potentially pathogenic bacteria. By delving into the transmission dynamics of maternal-infant microbiota, exploring the impacts of metabolic byproducts within the infant's gut, and scrutinizing how contextual factors such as birthing method and feeding practices affect the correlation between maternal and infant microbiota, this research endeavors to establish practical strategies for optimizing early-life gut health management in infants. Such insights promise to inform targeted interventions that foster healthier microbial development during the critical first 6 months of life.

Genetic Signatures of Positive Selection in Human Populations Adapted to High Altitude in Papua New Guinea.

Papua New Guinea (PNG) hosts distinct environments mainly represented by the ecoregions of the Highlands and Lowlands that display increased altitude and a predominance of pathogens, respectively. Since its initial peopling approximately 50,000 years ago, inhabitants of these ecoregions might have differentially adapted to the environmental pressures exerted by each of them. However, the genetic basis of adaptation in populations from these areas remains understudied. Here, we investigated signals of positive selection in 62 highlanders and 43 lowlanders across 14 locations in the main island of PNG using whole-genome genotype data from the Oceanian Genome Variation Project (OGVP) and searched for signals of positive selection through population differentiation and haplotype-based selection scans. Additionally, we performed archaic ancestry estimation to detect selection signals in highlanders within introgressed regions of the genome. Among highland populations we identified candidate genes representing known biomarkers for mountain sickness (SAA4, SAA1, PRDX1, LDHA) as well as candidate genes of the Notch signaling pathway (PSEN1, NUMB, RBPJ, MAML3), a novel proposed pathway for high altitude adaptation in multiple organisms. We also identified candidate genes involved in oxidative stress, inflammation, and angiogenesis, processes inducible by hypoxia, as well as in components of the eye lens and the immune response. In contrast, candidate genes in the lowlands are mainly related to the immune response (HLA-DQB1, HLA-DQA2, TAAR6, TAAR9, TAAR8, RNASE4, RNASE6, ANG). Moreover, we find two candidate regions to be also enriched with archaic introgressed segments, suggesting that archaic admixture has played a role in the local adaptation of PNG populations.