Integration of chromosome locations and functional aspects of enhancers and topologically associating domains in knowledge graphs enables versatile queries about gene regulation.

Knowledge about transcription factor binding and regulation, target genes, cis-regulatory modules and topologically associating domains is not only defined by functional associations like biological processes or diseases but also has a determinative genome location aspect. Here, we exploit these location and functional aspects together to develop new strategies to enable advanced data querying. Many databases have been developed to provide information about enhancers, but a schema that allows the standardized representation of data, securing interoperability between resources, has been lacking. In this work, we use knowledge graphs for the standardized representation of enhancers and topologically associating domains, together with data about their target genes, transcription factors, location on the human genome, and functional data about diseases and gene ontology annotations. We used this schema to integrate twenty-five enhancer datasets and two domain datasets, creating the most powerful integrative resource in this field to date. The knowledge graphs have been implemented using the Resource Description Framework and integrated within the open-access BioGateway knowledge network, generating a resource that contains an interoperable set of knowledge graphs (enhancers, TADs, genes, proteins, diseases, GO terms, and interactions between domains). We show how advanced queries, which combine functional and location restrictions, can be used to develop new hypotheses about functional aspects of gene expression regulation.

Efficient electrochemical advanced degradation of Red CL and Red WB dyes from the tanning industry using a boron-doped diamond anode.

Electrochemical oxidation (EO), electro-Fenton (EF), and photoelectro-Fenton (PEF) with a BDD anode have been comparatively assessed to remediate solutions of Red CL and/or Red WB azo dyes from real raw water. For the EO process in 50 mM Na2SO4 at pH 3.0, the main oxidant was the heterogeneous •OH generated at the anode, whereas in EF and PEF, the cathodic production of H2O2 and the addition of 0.50 mM Fe2+ catalyst additionally originated homogeneous •OH that enhanced the oxidation of organics. In PEF, the solution was illuminated with a 6 W UVA light. An almost total discoloration was always found operating with a 1:1 mixture of 200 mg L-1 of both dyes in 60 min, whose efficiency increased in the order of EO < EF < PEF. The HPLC analysis of the dye mixture treated by PEF disclosed that its degradation process agreed with its discoloration. A high 74% of COD was reduced due to the oxidative action of hydroxyl radicals and the photolysis of final Fe(III)-carboxylate species with UVA irradiation. The process was accompanied by an energy consumption of 0.76 kWh (g COD)-1, a value similar to the energy consumed by the applied UVA light.

Survival at 3, 6 and 12 months in patients diagnosed with community-acquired pneumonia in Colombia: a retrospective cohort study.

BACKGROUND: The primary aim of this study is to assess the survival rates of individuals diagnosed with Community-Acquired Pneumonia (CAP) post-hospitalization in Colombia. Additionally, explore potential risk factors associated with decreased long-term survival. METHODS: A retrospective cohort study was conducted in a hospital in Colombia, evaluating survival at 3, 6 and 12 months in CAP patients, using the Kaplan-Meier method. Stratifications were made by age, sex, comorbidity, and severity. The comparison of survival curves was performed using the Log-Rank test, a multivariate analysis with Cox regression was performed to study possible risk factors that affected 12-month survival in patients with CAP. RESULTS: 3688 subjects were admitted, with a mortality of 16.3 % per year. Survival at three, six, and twelve months was 92.9 % (95 % CI 92-93 %), 88.8 % (95 % CI 87-90 %), and 84.2 % (95 % CI 82-85 %), respectively. Analysis stratified by pneumonia severity index, 12-month survival was 98.7 % in Class I, 95.6 % in Class II, 87.41 % in Class III, 77.1 % in Class IV, and 65.8 % in class-V (p < 0.001). Cox-regression showed that being male (HR = 1.44; 95 % CI 1.22‒1.70; p < 0.001), an elevated pneumonia severity index (HR = 4.22; 95 % CI 1.89‒9.43; p < 0.001), a high comorbidity index (HR = 2.29; 95 % CI 1.89‒2.84; p < 0.001) and vasopressor requirement (HR = 2.22; 95 % CI < 0.001) were associated with a lower survival at twelve months of follow-up. CONCLUSION: Survival in patients with CAP who require hospitalization decreases at 3, 6, and 12 months of follow-up, being lower in patients older than 65 years, men, high comorbidity, and in subjects with severe presentation of the disease.

Exploring the Association Between Systemic Lupus Erythematosus and High-Density Lipoproteins: A Systematic Review and Meta-Analysis.

OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease with inflammation as a critical feature. Recently, high-density lipoprotein cholesterol (HDLc) have been evidenced to have anti-inflammatory effects, suggesting a potential link between HDL and SLE that needs to be thoroughly studied. The aim was to explore the association between SLE and HDLc through a systematic review with meta-analysis. METHODS: A systematic review with meta-analysis was conducted to assess mean differences in HDL levels between patients with SLE and healthy controls. Both qualitative and quantitative syntheses were performed, including an assessment of heterogeneity using I2, a publication bias evaluation, a methodologic quality assessment, and a forest plot under a random effects model. Subgroup analyses were conducted based on disease activity and the report of corticosteroid dosage. RESULTS: A total of 53 studies were included in the qualitative synthesis, and 35 studies were included in the quantitative synthesis, comprising 3,002 patients with SLE and 2,123 healthy controls. Mean HDL levels were found to be lower in patients with SLE as follows: in the meta-analysis including all articles -6.55 (95% confidence interval [CI] -8.77 to -4.33); in patients with mild disease activity -5.46 (95% CI -8.26 to -2.65); in patients with moderate or severe disease activity -9.42 (95% CI -15.49 to -3.34); in patients using corticosteroids -5.32 (95% CI -10.35 to -0.29); and in studies with excellent methodologic quality -8.71 (95% CI -12.38 to -5.03). CONCLUSION: HDL levels appear to be quantitatively altered in patients with SLE, suggesting a potential contribution to immune dysregulation, highlighting the importance of HDL in autoimmune diseases.

Radical cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal sarcomatosis: Results from a reference center and considerations based on current evidence.

INTRODUCTION: Peritoneal sarcomatosis is a rare disease, with multiple histological origins and poor overall prognosis. The option of radical cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) is controversial. The results of a surgical team experienced in these procedures are analyzed and discussed based on the available evidence. METHODS: Study on a prospective database of patients with peritoneal sarcomatosis who underwent CRS and HIPEC, from 2016 to 2022, in a national reference center for sarcomas and peritoneal oncological surgery, who met the established inclusion/exclusion criteria. RESULTS: 23 patients were included in the study, with a median age of 53 years (6-68). Recurrent/persistent clinical presentation predominated (78.3%). Visceral origin (including GIST and non-GIST peritoneal) accounted for 47.8% of patients, compared to 43.5% uterine and 8.7% retroperitoneal. The median PCI was 17 (3-36), with CC0 cytoreduction of 87%. Postoperative morbidity (Dindo Clavien III-IV) of 13%, with no postoperative mortality in the series. Overall survival and disease-free survival at 5 years were 64% and 34%, respectively. Histological grade was the most influential prognostic factor for survival. CONCLUSIONS: The results of the series, with low morbidity, support the benefit of radical peritoneal oncological surgery in patients with peritoneal sarcomatosis after adequate selection, as long as it is performed in high-volume centers, experienced surgeons and expert multidisciplinary teams. However, the role of HIPEC remains to be demonstrated and pending future studies.

Hemorrhagic shock secondary to ruptured hypogastric artery pseudoaneurysm. A rare complication of colorectal anastomotic leakage.

Massive bleeding due to rupture of hypogastric artery pseudoaneurysm is an exceptional complication of colorectal anastomotic leakage. A 41-year-old woman with history of rectal cancer surgery, who debuted with massive rectorrhagia and hypovolemic shock due to rupture of a hypogastric artery pseudoaneurysm as a late complication of a colorectal anastomosis leak. The ruptured hypogastric artery pseudoaneurysm should be taken into account in the differential diagnosis of patients with massive rectorrhagia and history of colorectal anastomosis leak. Endovascular embolization is considered the first-line treatment.

La hemorragia masiva por rotura de un pseudoaneurisma de la arteria hipogástrica es una complicación muy rara de la fuga anastomótica colorrectal. Mujer de 41 años con antecedentes de cirugía por cáncer de recto, que debutó con un cuadro de rectorragias masivo y shock hipovolémico secundario a la rotura de un pseudoaneurisma de la arteria hipogástrica como complicación tardía de una fuga de la anastomosis colorrectal. La rotura de un pseudoaneurisma de la arteria hipogástrica se debe tener presente en el diagnostico diferencial de pacientes con rectorragia masiva y antecedentes de dehiscencia de anastomosis colorrectal. La embolización endovascular es actualmente el tratamiento de elección.

Frailty and Cancer Prognosis.

PURPOSE OF REVIEW: This review aims to summarize the current evidence regarding the prognostic role of frailty in older patients diagnosed with cancer and to explore the evidence regarding its prognostic implications in cancer survivors. RECENT FINDINGS: Frailty has been consistently associated with mortality/overall survival, postoperative complications, short- and long-term postoperative mortality, length of stay, among other adverse health-related outcomes in several oncological contexts. The possible association between frailty and treatment toxicity has been less explored, however most studies suggest frailty is a predictor of treatment induced toxicity. In addition, in cancer survivors, frailty is a risk factor for cardiovascular disease, incident type 2 diabetes mellitus, mortality, altered cognitive performance and increased symptom severity. Due to its usefulness in establishing prognosis and informing treatment decision making, it is expected that frailty screening and assessment will continue to gain popularity as part of the pretreatment evaluation of older patients with cancer.

From the Microbiome to the Electrome: Implications for the Microbiota-Gut-Brain Axis.

The gut microbiome plays a fundamental role in metabolism, as well as the immune and nervous systems. Microbial imbalance (dysbiosis) can contribute to subsequent physical and mental pathologies. As such, interest has been growing in the microbiota-gut-brain brain axis and the bioelectrical communication that could exist between bacterial and nervous cells. The aim of this study was to investigate the bioelectrical profile (electrome) of two bacterial species characteristic of the gut microbiome: a Proteobacteria Gram-negative bacillus Escherichia coli (E. coli), and a Firmicutes Gram-positive coccus Enterococcus faecalis (E. faecalis). We analyzed both bacterial strains to (i) validate the fluorescent probe bis-(1,3-dibutylbarbituric acid) trimethine oxonol, DiBAC4(3), as a reliable reporter of the changes in membrane potential (Vmem) for both bacteria; (ii) assess the evolution of the bioelectric profile throughout the growth of both strains; (iii) investigate the effects of two neural-type stimuli on Vmem changes: the excitatory neurotransmitter glutamate (Glu) and the inhibitory neurotransmitter γ-aminobutyric acid (GABA); (iv) examine the impact of the bioelectrical changes induced by neurotransmitters on bacterial growth, viability, and cultivability using absorbance, live/dead fluorescent probes, and viable counts, respectively. Our findings reveal distinct bioelectrical profiles characteristic of each bacterial species and growth phase. Importantly, neural-type stimuli induce Vmem changes without affecting bacterial growth, viability, or cultivability, suggesting a specific bioelectrical response in bacterial cells to neurotransmitter cues. These results contribute to understanding the bacterial response to external stimuli, with potential implications for modulating bacterial bioelectricity as a novel therapeutic target.

Factors influencing the health-related quality of life of older men and women living with HIV in Spain.

The number of older people living with HIV (OPLHIV) is increasing worldwide. However, little is known about the factors that better predict their health-related quality of life (HRQoL). We administered the validated WHOQoL-HIV BREF questionnaire to 247 Spanish OPLHIV (192 men and 55 women). In addition to the six domains of the questionnaire, we constructed a seventh domain as theaverage of punctuations of all domains. Multivariable Poisson regression models with robust estimates by sex were constructed for the seven domains (14 in total). The best-subset selection method together with Mallow's Cp metric was used to select the model factors. The percentage of variability explained by Poisson models ranged from15-38% for men and 29-70% for women. The analysis showed that women were most affected by ageing (four domains), mobility impairments (five domains), and mental disorders (five domains). The factors with the greatest negative influence on men were heterosexuality (six domains), mental disorders (six domains), being single (five domains), and poverty risk (three domains). Physical activity was found to improve HRQoL in both men (six domains) and women (four domains). Future OPLHIV programmes would benefit from considering sex specific HRQoL factors. This could also improve the cost-effectiveness of interventions.

Impact of Vancomycin trough levels monitoring on uncomplicated methilcillin-resistant Staphylococcus aureus bacteremia in chronic kidney disease on hemodialysis, retrospective cohort.

BACKGROUND: CKD patients on hemodialysis (HD) with Staphylococcus aureus (SA) bacteremia present high morbidity, mortality and increased risk of MRSA. Vancomycin is the antibiotic of choice in these cases, it has a narrow therapeutic margin and inadequate dosage generates a risk of toxicity, therefore, the recommendation is to dosage it through serum levels. METHODS: This is a retrospective cohort study in 3 hospitals of third level of complexity in the city of Medellin in which there were differences in the measurement and implementation of vancomycin25 dosage based on trough levels (VL) in patients with chronic kidney disease on hemodialysis (CKD- HD) with uncomplicated bacteremia based infection by methilcillin-resistant Staphyloccocus aureus (MRSA). The primary outcome was the composite of hospital mortality, clinical response (fever, hemodynamic instability and altered consciousness), complications associated with bacteremia, or bacteriological response failure (positive cultures at first week follow-up) at 7 days. The composite variables were analyzed individually as secondary outcomes. RESULTS: The main unadjusted outcome (OR 1.3, CI 0.6 - 2.7) and adjusted for age, Charlson index, loading dose, initial dose, dosing frequency and MIC to vancomycin (OR 1.2, CI 0.5 - 2.7). Regarding adjusted secondary outcomes: clinical response (OR 1.4 CI 0.3 - 5.8), death (OR 1.3 CI 0.3 - 4.6) and complications (OR 0.9, CI 0.37 - 2.2). CONCLUSIONS: We conclude that the measurement of trough levels in patients with HD-CKD does not modify the composite outcome. The main limitation is the sample size and type of study, randomized control trials may be required to confirm the results presented.

Absolute lymphocyte count after BCMA CAR-T therapy is a predictor of response and outcomes in relapsed multiple myeloma.

ABSTRACT: B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor T cells (CAR-Ts) used in multiple myeloma (MM) are rapidly becoming a mainstay in the treatment of relapsed/refractory (R/R) disease, and CAR-T expansion after infusion has been shown to inform depth and duration of response (DoR), but measuring this process remains investigational. This multicenter study describes the kinetics and prognostic impact of absolute lymphocyte count (ALC) in the first 15 days after CAR-T infusion in 156 patients with relapsed MM treated with the BCMA-targeting agents ciltacabtagene autoleucel and idecabtagene vicleucel. Patients with higher maximum ALC (ALCmax) had better depth of response, progression-free survival (PFS), and DoR. Patients with ALCmax >1.0 × 103/µL had a superior PFS (30.5 months vs 6 months; P < .001) compared with those with ≤1.0 × 103/µL, whereas patients with ALCmax ≤0.5 × 103/µL represent a high-risk group with early disease progression and short PFS (hazard ratio, 3.4; 95% confidence interval, 2-5.8; P < .001). In multivariate analysis, ALCmax >1.0 × 103/µL and nonparaskeletal extramedullary disease were the only independent predictors of PFS and DoR after accounting for international staging systemic staging, age, CAR-T product, high-risk cytogenetics, and the number of previous lines. Moreover, our flow cytometry data suggest that ALC is a surrogate for BCMA CAR-T expansion and can be used as an accessible prognostic marker. We report, to our knowledge, for the first time the association of ALC after BCMA CAR-T infusion with clinical outcomes and its utility in predicting response in patients with R/R MM.

Experimental Study of White Light Interferometry in Mach-Zehnder Interferometers Based on Standard Single Mode Fiber.

In this work, we experimentally analyzed and demonstrated the performance of an in-line Mach-Zehnder interferometer in the visible region, with an LED light source. The different waist diameter taper and asymmetric core-offset interferometers proposed used a single-mode fiber (SMF). The visibility achieved was V = 0.14 with an FSR of 23 nm for the taper MZI structure and visibilities of V = 0.3, V = 0.27, and V = 0.34 with FSRs of 23 nm, 17 nm, and 8 nm and separation lengths L of 2.5 cm, 4.0 cm, and 5.0 cm between the core-offset structure, respectively. The experimental investigation of the response to the temperature sensor yielded values from 50 °C to 300 °C; the sensitivity obtained was 3.53 a.u./°C, with R2 of 0.99769 and 1% every 1 °C in the transmission. For a range of 50 °C to 150 °C, 20.3 pm/°C with a R2 of 0.96604 was obtained.

Gut microbiota in cats with inflammatory bowel disease and low-grade intestinal T-cell lymphoma.

In cats and humans, several physiological and environmental factors have been shown to alter the gut microbiota of healthy individuals. Cats share several diseases with humans such as inflammatory bowel diseases and low-grade intestinal T-cell lymphoma. The physiopathology of these chronic enteropathies is poorly understood but may involve disequilibrium of the gut microbiota composition and disruption of normal microbiome activity profiles. These disorders are increasingly diagnosed in the feline species due to improved medicalization and easier access to endoscopy in veterinary practice. This review addresses the current data on the gut microbiota of cats in health and in chronic enteropathies. Such functional analysis will help the advancement of innovative diagnostic tools and targeted therapeutic strategies.

[On-line pornography and minors. Diagnosis, challenges and proposals]. / Pornografía on-line y menores. Diagnóstico, desafíos y propuestas.

The consumption of pornography over the Internet by minors has been increasing exponentially in recent years. The use of digital technologies and the ease of access to these contents are causes that explain this event. Simultaneously, there is concern about the increase in sexual violence, associated with discriminatory behavior, despite the efforts of laws and programs that promote sexual reproductive health (SRH) and the principle of equality. From a bioethical point of view, it is urgent to address this issue, which affects the physical and psychological health of minors and their affective-sexual education. The study addresses whether it is possible to relate the consumption of online pornography by minors and sexual violence. To do this, legal sources, reports from associations, audiovisual councils and scientific studies are consulted. In all of them, the relationship between the consumption of online pornography by adolescents and risky behavior in emotional-sexual matters and gender inequality is evident. In the legal and fiscal sphere, it is alerted to the damage that is occurring and points out the need to propose lines of action that reverse this situation. We propose measures to technically regulate access to content. These measures are based on the precautionary principle, a tool that has been applied in fields such as health and the environment. More studies and political actions are needed to make the Internet a safe place for minors.

Sex differences in health-related quality of life and poverty risk among older people living with HIV in Spain: A cross-sectional study.

BACKGROUND: Current antiretroviral therapies have increased the life expectancy of people living with HIV (PLHIV). There is, however, limited evidence regarding the health-related quality of life (HRQoL) and living conditions of older people living with HIV (OPLHIV) in Spain. METHODS: We implemented a self-administered online questionnaire to identify sex differences in HRQoL and poverty risk among Spanish OPLHIV (PLHIV ≥50 years). Participants were contacted through non-governmental organisations. We used the standardised WHOQoL-HIV BREF questionnaire and the Europe 2020 guidelines to estimate HRQoL and poverty risk respectively. The statistical analysis included multivariable generalised linear models with potential confounding variables and robust estimates. RESULTS: The study included 247 OPLHIV (192 men and 55 women). On the WHOQoL-HIV BREF questionnaire, men scored higher on 84% of items and in all six domains. Women had significantly lower HRQoL in five domains: physical health (ß: -1.5; 95% CI: -2.5, -0.5; p: 0.002), psychological health (ß: -1.0; 95% CI: -1.9, -0.1; p: 0.036), level of independence (ß: -1.1; 95% CI: -1.9, -0.2; p: 0.019), environmental health (ß: -1.1; 95% CI: -1.8, -0.3; p: 0.008), and spirituality/personal beliefs (ß: -1.4; 95% CI: -2.5, -0.3; p: 0.012). No statistical differences were found in the domain of social relations. Poverty risk was considerable for both men (30%) and women (53%), but women were significantly more likely to experience it (OR: 2.9; 95% CI: 1.3, 6.5; p: 0.009). CONCLUSION: The aging of PLHIV is a public health concern. Our findings indicate that HRQoL and poverty risk among Spanish OPLHIV differ significantly by sex. Spain should, therefore, implement specific policies and interventions to address OPLHIV needs. The strategies must place a high priority on the reduction of sex inequalities in HRQoL and the enhancement of the structural conditions in which OPLHIV live.

Bariatric Surgery: An Opportunity to Improve Quality of Life and Healthy Habits.

Bariatric surgery therapy (BST) is an effective treatment for obesity; however, little is known about its impacts on health-related quality of life (HRQoL) and related factors. This study aimed to evaluate changes in HRQoL and its relationship with weight loss, depression status, physical activity (PA), and nutritional habits after BST. Data were obtained before and 18 months postprocedure from 56 obese patients who underwent BST. We administered four questionnaires: Short Form-36 health survey for HRQoL, 14-item MedDiet adherence questionnaire, Rapid Assessment of PA (RAPA) questionnaire, and Beck's Depression Inventory-II. Multivariable linear regression analysis was used to identify factors associated with improvement in HRQoL. After the surgery, MedDiet adherence and HRQoL improved significantly, especially in the physical component. No changes in PA were found. Patients without previous depression have better mental quality of life, and patients who lost more than 25% of %TBWL have better results in physical and mental quality of life. In the multivariable analysis, we found that %TBWL and initial PCS (inversely) were related to the improvement in PCS and initial MCS (inversely) with the MCS change. In conclusion, BST is an effective intervention for obesity, resulting in significant weight loss and improvements in HRQoL and nutritional habits.