Emergence of Quantum Dots as Innovative Tools for Early Diagnosis and Advanced Treatment of Breast Cancer.

Quantum dots (QDs) semiconducting nanomaterials, have garnered attention due to their distinctive properties, including small size, high luminescence, and biocompatibility. In the context of triple-negative breast cancer (TNBC), notorious for its resistance to conventional treatments, QDs exhibit promising potential for enhancing diagnostic imaging and providing targeted therapies. This review underscores recent advancements in the utilization of QDs in imaging techniques, such as fluorescence tomography and magnetic resonance imaging, aiming at the early and precise detection of tumors. Emphasis is placed on the significance of QD design, synthesis and functionalization processes as well as their use in innovative strategies for targeted drug delivery, capitalizing on their ability to selectively deliver therapeutic agents to cancer cells. As the research in this field advances rapidly, this review covers a classification of QDs according to their composition, the characterization techniques than can be used to determine their properties and, subsequently, emphasizes recent findings in the field of TNBC-targeting, highlighting the imperative need to address challenges, like potential toxicity or methodologies standardization. Collectively, the findings explored thus far suggest that QDs could pave the way for early diagnosis and effective therapy of TNBC, representing a significant stride toward precise and personalized strategies in treating TNBC.

Mortality, Functional Status, and Quality of Life after 5 Years of Patients Admitted to Critical Care for Spontaneous Intracerebral Hemorrhage.

BACKGROUND: The objective of this study was to assess long-term outcome in patients with spontaneous intracerebral hemorrhage admitted to the intensive care unit. METHODS: Mortality and Glasgow Outcome Scale, Barthel Index, and 5-level EQ-5D version (EQ-5D-5L) scores were analyzed in a multicenter cohort study of three Spanish hospitals (336 patients). Mortality was also analyzed in the Medical Information Mart for Intensive Care III (MIMIC-III) database. RESULTS: The median (25th percentile-75th percentile) age was 62 (50-70) years, the median Glasgow Coma Score was 7 (4-11) points, and the median Acute Physiology and Chronic Health disease Classification System II (APACHE-II) score was 21 (15-26) points. Hospital mortality was 54.17%, mortality at 90 days was 56%, mortality at 1 year was 59.2%, and mortality at 5 years was 66.4%. In the Glasgow Outcome Scale, a normal or disabled self-sufficient situation was recorded in 21.5% of patients at 6 months, in 25.5% of patients after 1 year, and in 22.1% of patients after 5 years of follow-up (4.5% missing). The Barthel Index score of survivors improved over time: 50 (25-80) points at 6 months, 70 (35-95) points at 1 year, and 90 (40-100) points at 5 years (p < 0.001). Quality of life evaluated with the EQ-5D-5L at 1 year and 5 years indicated that greater than 50% of patients had no problems or slight problems in all items (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). In the MIMIC-III study (N = 1354), hospital mortality was 31.83% and was 40.5% at 90 days and 56.2% after 5 years. CONCLUSIONS: In patients admitted to the intensive care unit with a diagnosis of nontraumatic intracerebral hemorrhage, hospital mortality up to 90 days after admission is very high. Between 90 days and 5 years after admission, mortality is not high. A large percentage of survivors presented a significant deficit in quality of life and functional status, although with progressive improvement over time. Five years after the hemorrhagic stroke, a survival of 30% was observed, with a good functional status seen in 20% of patients who had been admitted to the hospital.

Graph-Based Audio Classification Using Pre-Trained Models and Graph Neural Networks.

Sound classification plays a crucial role in enhancing the interpretation, analysis, and use of acoustic data, leading to a wide range of practical applications, of which environmental sound analysis is one of the most important. In this paper, we explore the representation of audio data as graphs in the context of sound classification. We propose a methodology that leverages pre-trained audio models to extract deep features from audio files, which are then employed as node information to build graphs. Subsequently, we train various graph neural networks (GNNs), specifically graph convolutional networks (GCNs), GraphSAGE, and graph attention networks (GATs), to solve multi-class audio classification problems. Our findings underscore the effectiveness of employing graphs to represent audio data. Moreover, they highlight the competitive performance of GNNs in sound classification endeavors, with the GAT model emerging as the top performer, achieving a mean accuracy of 83% in classifying environmental sounds and 91% in identifying the land cover of a site based on its audio recording. In conclusion, this study provides novel insights into the potential of graph representation learning techniques for analyzing audio data.

Effect of the SARS-CoV-2 pandemic on metabolic control in patients with type 2 diabetes: a 5-year cohort follow-up managed by a dynamic multidisciplinary team in Northeastern Mexico.

BACKGROUND: The SARS-CoV-2 pandemic brought a radical shift in the healthcare system and suboptimal care for vulnerable patients, such as those with Type 2 Diabetes Mellitus (T2D). Therefore, we compared metabolic control and macro/microvascular complications of patients with T2D before and throughout the three-year SARS-CoV-2 pandemic. RESEARCH DESIGN AND METHODS: A retrospective observational cohort of subjects with T2D studied from 2018 to 2022 in Northern Mexico was treated by a dynamic multidisciplinary team. Levels of Glycated hemoglobin (HbA1c), fasting serum glucose (FG), LDL-Cholesterol (LDL-C), blood pressure (BP), albuminuria, triglycerides, Body Mass Index (BMI), and FIB-4 score, micro and macrovascular complications were evaluated. RESULTS: A total of 999 patients were studied, 51.7% males with a mean (SD) age of 60.1 (12.7) years. Adequate glycemic control based on HbA1c increased by 15.2% and 42.3% in FSG (p < 0.001) between the beginning 2018 and the end of 2022. LDL-C control decreased by 5.1% between 2018 and 2022 (p < 0.001). Systolic BP control decreased by 2.6% (p < 0.001), whereas diastolic BP control increased by 1.8% (p = 0.01) between 2018 and 2022. Albuminuria control increased by 8.5% (p = 0.002). When comparing the Area Under the Curve (AUC) of metabolic parameters between patients who developed SARS-CoV-2 vs. those who did not, AUC was statistically higher in those who developed SARS-CoV-2 (p < 0.05). Diabetic neuropathy was the most prevalent microvascular complication (n = 35; 3.6%); ischemic heart disease was the most frequent macrovascular complication (n = 11;1.1%). CONCLUSIONS: A multidisciplinary dynamic team that adapts to the pandemic SARS-CoV-2 maintains and increases metabolic control in subjects with type 2 diabetes in Mexico. This represents a low percentage of chronic complications. The AUC of metabolic parameters of subjects with SARS-CoV-2 infection is higher, reflecting more variability in metabolic control.

Influence of Service Conditions and Mix Design on the Physical-Mechanical Properties of Roller-Compacted Concrete for Pavement.

This research focuses on the behavior of roller-compacted concrete (RCC) used in pavements, which are prone to deterioration affecting their performance. These deteriorations result from various causes, including traffic load, errors during construction, mix design, and ambient conditions. Among these, ambient conditions could lead to a marked variable impact on material behavior and durability depending on the conditions associated with each region. Accordingly, this study aims to deepen the understanding of the effect, which a broader range of ambient conditions and different mix designs have on the physical and mechanical properties of RCC. Measurements such as the amount of water vapor per kilogram of air were used to apply the findings comprehensively. The RCC analysis encompassed experimentation with different compositions, altering the cement water ratio amount, and adding a superplasticizer. The impact of curing on the materials was evaluated before subjecting them to various humidity and temperature conditions. Laboratory tests were conducted to measure performance, including moisture, shrinkage, compressive strength, and the progression of flexural fracture resistance over curing periods of up to 90 days. The results revealed a logarithmic correlation between shrinkage and ambient humidity, which is the most determining factor in performance. Mix optimization through increased cement and reduced water enhanced the tensile strength of the material. Furthermore, the curing process was confirmed to increase resistance to shrinkage, especially in the long term, establishing it as a crucial element for the structural stability of RCC, which is relatively insensitive to variations in ambient conditions.

Prediction of the Physical-Mechanical Properties of Roller-Compacted Concrete Pavements under Different Service and Mix Conditions Based on Cement and Water Content.

Roller-compacted concrete (RCC) for pavements has experienced problems with its physical-mechanical performance over extended periods due to ambient and in situ curing conditions. Accordingly, this study aimed to present multiple regression equations for calculating the physical-mechanical properties of RCC for pavements under different service and mix conditions. For this purpose, the research included two cement and two water contents, one reduced with admixture, and four combinations of temperature and relative humidity. For model calibration and definition of the equations, cubic and beam samples were fabricated to carry out physical-mechanical tests, such as moisture content, shrinkage, and modulus of rupture. Laboratory-obtained data were studied with the Response Surface Methodology (RSM) to determine the best regression equations. The main findings determined that the behavior of a mixture of RCC at a prolonged ambient exposure time is possible because the surface models and the RSM were consistent with the different service and mix conditions. The models showed an accuracy of 98.99% in detecting shrinkage changes from 12 to 16% cement with 5.65% water in dry to wet ambient conditions. Similarly, moisture content and modulus of rupture had a 98.27 to 98.88% fit. Finally, the drying shrinkage, with mixes of 12% cement and water content variations with water-reducing admixture and superplasticizer effects, had an adjustment of 94.87%.

IFITM5-related (type V) osteogenesis imperfecta with evidence of perinatal involvement: A case report.

Osteogenesis imperfecta (OI) is a rare hereditary disorder characterized by bone fragility and frequent fractures. While most cases are attributed to variations in collagen-coding genes COL1A1 and COL1A2, other genes such as IFITM5 have also been associated with the disease, accounting for up to 5 % of cases. Here, we report a case of a 3-month-old female with a femur fracture and limb deformity. X-rays revealed evidence of osteopenia and previous fractures in the arms, clavicle, ribs, and left limb, alongside prenatal bone deformities detected by ultrasound. Initial clinical evaluation suggested progressively deforming (Sillence's type III) osteogenesis imperfecta (OI). Molecular testing led to the diagnosis of IFITM5-related OI, identifying the c.-14C>T (rs587776916) variant. Although this variant has been previously reported in patients with IFITM5-related OI, prenatal involvement had not been associated with this variant.

Silvopastoral systems benefit invertebrate biodiversity on tropical livestock farms in Caquetá, Colombia.

In the Colombian Amazon, there has been long-term and sustained loss of primary forest threatening biodiversity and climate change mitigation. Silvopastoral practices that integrate trees into livestock production could help address both local economic and wider environmental challenges.We aimed to assess the effects of silvopastoral practices on invertebrate communities on smallholder farms in Caquetá, Colombia. Using sweep nets and malaise trapping, invertebrate communities were compared between traditional pasture, silvopasture and forest edge habitats.Invertebrate communities collected using sweep nets were contrasting among habitat types, communities were significantly different between traditional pasture and forest edge habitats and diversity and evenness were greatest in forest edges compared to traditional pastures. It appears that silvopasture areas, by supporting similar invertebrate assemblages to both traditional pasture and forest edges, may be acting as an intermediate habitat.When individual invertebrate orders were compared, Lepidoptera and Coleoptera were found in greater abundance in the forest edge habitats, while Hemiptera were more abundant in traditional pasture. Hemipterans are often pests of forage plants in pasture systems and these differences in abundance may have implications for ecosystem services and disservices.Silvopastoral approaches cannot replace the unique biodiversity supported by native forests but could deliver benefits for invertebrate conservation and ecosystem services if integrated into landscapes.

Resumen: En la Amazonía colombiana ha habido una pérdida sostenida y a largo plazo de bosque primario que amenaza la biodiversidad y la mitigación del cambio climático. Las prácticas silvopastoriles que integran los árboles en la producción ganadera podrían ayudar a abordar tanto los desafíos económicos locales como los ambientales.Nuestro objetivo fue evaluar los efectos de las prácticas silvopastoriles en comunidades de invertebrados en pequeñas fincas en Caquetá, Colombia. Las comunidades de invertebrados se compararon entre las pasturas nativas, el sistema silvopastoril y los hábitats del borde del bosque mediante el uso redes entomológicas de barrido y trampas Malaise.Las comunidades de invertebrados recolectadas usando redes entomológicas de barrido contrastaban entre los tipos de hábitat. Las comunidades eran significativamente diferentes entre las pasturas nativas y el borde de bosque. Pareciera que las áreas de silvopastoreo, al soportar conjuntos de invertebrados similares tanto a las pasturas nativas como a los bordes del bosque, pueden estar actuando como un hábitat intermedio.Cuando se compararon los órdenes individuales de invertebrados, los lepidópteros y los coleópteros se encontraron en mayor abundancia en los hábitats del borde del bosque, mientras que los hemípteros eran más abundantes en las pasturas nativas. Los hemípteros son a menudo plagas de plantas forrajeras en sistemas de pastoreo y estas diferencias en abundancia pueden tener implicaciones y perjuicios para los servicios ecosistémicos.Los sistemas silvopastoriles no pueden reemplazar la biodiversidad única apoyada por los bosques nativos, pero podrían ofrecer beneficios para la conservación de invertebrados y los servicios ecosistémicos si se integran en los paisajes.

Risk factors for intubation and mortality in patients treated with high flow nasal cannula due to COVID-19 infection. Survival Analysis Study in a Northern Mexican Population.

BACKGROUND: COVID-19-related acute hypoxic respiratory failure patients often use high-flow nasal cannula (HFNO) oxygen therapy. COVID-19 HFNO intubation and mortality risk factors are understudied in the Mexican population, so the aim was to study them. METHODS: This retrospective study searched electronic medical records from March 2020 to June 2022 for patients with COVID-19 who required hospitalization and HFNO. Descriptive statistics, a survival curve analysis, and Cox proportional hazard models were used to determine predictor factors for intubation and mortality in patients with HFNO and COVID-19, respectively. RESULTS: A total of 134 patients received HFNO treatment. Ninety-one (67.9%) were men with a mean (SD) age of 54.5 (17.9) years. Common medical history included obesity (n = 89, 66.4%) with a Body Mass Index (BMI) mean (SD) of 31.8 (5.9), hypertension (n = 67, 50.0%), type 2 diabetes (n = 55, 41.0%), and dyslipidemias (n = 43, 32.1%). The variables associated with a greater risk of requiring intubation after high-flow therapy were age (HR = 1.018, 95% CI 1.003-1.034, p = 0.022) and BMI (HR = 1.071, 95% CI 1.024-1.120, p = 0.003). No variables were associated with lower risk. Increased mortality was associated with increasing age (HR = 1.151, 95% CI 1.102-1.201, p = <0.001), hypertension (HR = 4.092, 95% CI 1.369-12.236, p = 0.012), and dyslipidemia (HR = 3.954, 95% CI 1.395-11.209, p = 0.010). Patients with type 2 diabetes had a lower risk of mortality (HR = 0.235, 95% CI 0.080-0.688, p = 0.008). CONCLUSIONS: A higher age and BMI were associated with an increased risk of intubation in patients with HFNO and COVID-19. Hypertension and dyslipidemias were associated with a higher risk of mortality.

Safety of inhaled nitric oxide withdrawal in severe chronic pulmonary hypertension.

Inhaled nitric oxide (iNO) is a potent and selective pulmonary vasodilator with a safety concern due to rebound pulmonary hypertension (PH) associated with its withdrawal. We report short-term pulsed iNO in patients with severe pulmonary arterial hypertension (PAH) and nonoperable chronic thromboembolic PH (nCTEPH). This is a retrospective analysis of 33 patients: 22 with PAH and 11 with nCTEPH. We assessed hemodynamic, echocardiographic, and other noninvasive variables to evaluate safety and efficacy of iNO. We performed an iNO withdrawal test during right heart catheterization and after 3 days of iNO treatment. iNO significantly improved all variables examined in 22 patients with PAH and 11 with nCTEPH. Two patterns of response were observed after sudden iNO withdrawal. Twenty-nine patients (88%) showed minimal hemodynamic, oxygenation and clinical changes. Four patients (12%) had a reduction in cardiac index ≥20% and PaO2 ≥ 5%, three patients did not show clinical deterioration, and one patient developed hemodynamic collapse that needed iNO administration. This retrospective study suggests that short-term iNO improves hemodynamics and clinical conditions in some patients with PAH an nCTPEH. However, pulsed iNO withdrawal PH rebound could be a serious concern in these patients. Given the lack of evidence, we do not recommend the use of pulsed iNO in the treatment of patients with chronic PH.

Inhibition of Multifunctional Protein p32/C1QBP Promotes Cytostatic Effects in Colon Cancer Cells by Altering Mitogenic Signaling Pathways and Promoting Mitochondrial Damage.

The protein p32 (C1QBP) is a multifunctional and multicompartmental homotrimer that is overexpressed in many cancer types, including colon cancer. High expression levels of C1QBP are negatively correlated with the survival of patients. Previously, we demonstrated that C1QBP is an essential promoter of migration, chemoresistance, clonogenic, and tumorigenic capacity in colon cancer cells. However, the mechanisms underlying these functions and the effects of specific C1QBP protein inhibitors remain unexplored. Here, we show that the specific pharmacological inhibition of C1QBP with the small molecule M36 significantly decreased the viability rate, clonogenic capacity, and proliferation rate of different colon cancer cell lines in a dose-dependent manner. The effects of the inhibitor of C1QBP were cytostatic and non-cytotoxic, inducing a decreased activation rate of critical pro-malignant and mitogenic cellular pathways such as Akt-mTOR and MAPK in RKO colon cancer cells. Additionally, treatment with M36 significantly affected the mitochondrial integrity and dynamics of malignant cells, indicating that p32/C1QBP plays an essential role in maintaining mitochondrial homeostasis. Altogether, our results reinforce that C1QBP is an important oncogene target and that M36 may be a promising therapeutic drug for the treatment of colon cancer.

Personalized Versus Non-personalized Nutritional Recommendations/Interventions for Type 2 Diabetes Mellitus Remission: A Narrative Review.

It is a well-evidenced fact that diet significantly impacts type 2 diabetes mellitus (T2DM) prevention and management. However, dietary responses vary among different populations, necessitating personalized recommendations. Substantial evidence supports the role of diet in T2DM remission, particularly low-energy or low-carbohydrate diets that facilitate weight loss, enhance glycemic control, and achieve remission. This review aims to comprehensively analyze and compare personalized nutritional interventions with non-personalized approaches in T2DM remission. We conducted a literature search using the Academy of Nutrition and Dietetics guidelines, focusing on clinical and observational trials published within the past decade. We present the strengths and drawbacks of incorporating personalized nutrition into practice, along with the areas for research in implementing personalized interventions, such as cost-effectiveness and accessibility. The findings reveal consistently higher diabetes remission rates in personalized nutrition studies compared to non-personalized interventions.

Association of vaccine status, reinfections, and risk factors with Long COVID syndrome.

The COVID-19 pandemic had a profound global impact, characterized by a high fatality rate and the emergence of enduring consequences known as Long COVID. Our study sought to determine the prevalence of Long COVID syndrome within a population of Northeastern Mexico, correlating it with patients' comorbidities, number of COVID-19 reinfection, and vaccination status. Employing an observational cross-sectional approach, we administered a comprehensive questionnaire covering medical history, demographics, vaccination status, COVID-related symptoms, and treatment. Our participant cohort included 807 patients, with an average age of 41.5 (SD 13.6) years, and women accounting 59.3% of the cohort. The follow-up was 488 (IQR 456) days. One hundred sixty-eight subjects (20.9%) met Long COVID criteria. Long COVID-19 was more prevalent when subjects had reinfections (p = 0.02) and less frequent when they had a complete vaccination scheme (p = 0.05). Through logistic regression, we found that male gender (OR 0.5, p ≤ 0.001), blood types of AB- (OR 0.48, p = 0.003) and O- (OR 0.27, p ≤ 0.001) in comparison with A+ and two doses of vaccines (OR 0.5, p = 006) to be protective factors against Long COVID; while higher BMI (OR 1.04, p = 0.005) was a risk factor. We saw that the prevalence of Long COVID was different within vaccinated patients and specific blood types, while being female and a higher BMI were associated with an increased risk of having long-COVID.

First-in-human demonstration of floating EMG sensors and stimulators wirelessly powered and operated by volume conduction.

BACKGROUND: Recently we reported the design and evaluation of floating semi-implantable devices that receive power from and bidirectionally communicate with an external system using coupling by volume conduction. The approach, of which the semi-implantable devices are proof-of-concept prototypes, may overcome some limitations presented by existing neuroprostheses, especially those related to implant size and deployment, as the implants avoid bulky components and can be developed as threadlike devices. Here, it is reported the first-in-human acute demonstration of these devices for electromyography (EMG) sensing and electrical stimulation. METHODS: A proof-of-concept device, consisting of implantable thin-film electrodes and a nonimplantable miniature electronic circuit connected to them, was deployed in the upper or lower limb of six healthy participants. Two external electrodes were strapped around the limb and were connected to the external system which delivered high frequency current bursts. Within these bursts, 13 commands were modulated to communicate with the implant. RESULTS: Four devices were deployed in the biceps brachii and the gastrocnemius medialis muscles, and the external system was able to power and communicate with them. Limitations regarding insertion and communication speed are reported. Sensing and stimulation parameters were configured from the external system. In one participant, electrical stimulation and EMG acquisition assays were performed, demonstrating the feasibility of the approach to power and communicate with the floating device. CONCLUSIONS: This is the first-in-human demonstration of EMG sensors and electrical stimulators powered and operated by volume conduction. These proof-of-concept devices can be miniaturized using current microelectronic technologies, enabling fully implantable networked neuroprosthetics.

Physical Activity, Body Composition, Physical Fitness, and Body Dissatisfaction in Physical Education of Extremadura Adolescents: An Exploratory Study.

In recent years, physical activity levels among youths have declined significantly. This has led to a decline in adherence to physical activity recommendations. In this sense, physical education offers an ideal environment that contributes positively to improving adherence to physical activity recommendations, as it teaches students movement-related skills and knowledge. The objective of the present research was to investigate the relationship between physical activity levels, body composition, fitness in Physical Education, and body dissatisfaction levels, and to analyse sex differences in relation to the study variables. The sample was formed of 1166 participants from the 1st and 2nd secondary compulsory education, of which 642 were boys (age 13.16 ± 0.91), and 524 girls (age 13.08 ± 0.85). The measure of physical activity was the Physical Activity Questionnaire for Adolescents (PAQ-A). Body composition was assessed using weight and height to calculate their body mass index. Cardiorespiratory capacity was assessed using the Course-Navette test in Physical Education lessons. The results showed the relationship between physical activity and body mass index, cardiorespiratory capacity, and body satisfaction. It was also confirmed that higher levels of physical activity were associated with a lower body mass index, improvements in cardiorespiratory fitness, and lower levels of body dissatisfaction to a greater extent in boys than in girls. The study concludes that improvements in the study variables were associated with increased physical activity. In addition, it seems necessary to promote healthy lifestyles in physical education lessons, especially during adolescence, as they could serve as a gateway for the improvement of health-related fitness in future generations. Increasing the amount of physical activity among young people is vital. Therefore, it would be essential to develop intervention programs in physical education classes, especially during adolescence, aimed at promoting and increasing physical activity and its benefits.

Efficacy and safety of a structured de-escalation from antipseudomonal ß-lactams in bloodstream infections due to Enterobacterales (SIMPLIFY): an open-label, multicentre, randomised trial.

BACKGROUND: De-escalation from broad-spectrum to narrow-spectrum antibiotics is considered an important measure to reduce the selective pressure of antibiotics, but a scarcity of adequate evidence is a barrier to its implementation. We aimed to determine whether de-escalation from an antipseudomonal ß-lactam to a narrower-spectrum drug was non-inferior to continuing the antipseudomonal drug in patients with Enterobacterales bacteraemia. METHODS: An open-label, pragmatic, randomised trial was performed in 21 Spanish hospitals. Patients with bacteraemia caused by Enterobacterales susceptible to one of the de-escalation options and treated empirically with an antipseudomonal ß-lactam were eligible. Patients were randomly assigned (1:1; stratified by urinary source) to de-escalate to ampicillin, trimethoprim-sulfamethoxazole (urinary tract infections only), cefuroxime, cefotaxime or ceftriaxone, amoxicillin-clavulanic acid, ciprofloxacin, or ertapenem in that order according to susceptibility (de-escalation group), or to continue with the empiric antipseudomonal ß-lactam (control group). Oral switching was allowed in both groups. The primary outcome was clinical cure 3-5 days after end of treatment in the modified intention-to-treat (mITT) population, formed of patients who received at least one dose of study drug. Safety was assessed in all participants. Non-inferiority was declared when the lower bound of the 95% CI of the absolute difference in cure rate was above the -10% non-inferiority margin. This trial is registered with EudraCT (2015-004219-19) and ClinicalTrials.gov (NCT02795949) and is complete. FINDINGS: 2030 patients were screened between Oct 5, 2016, and Jan 23, 2020, of whom 171 were randomly assigned to the de-escalation group and 173 to the control group. 164 (50%) patients in the de-escalation group and 167 (50%) in the control group were included in the mITT population. 148 (90%) patients in the de-escalation group and 148 (89%) in the control group had clinical cure (risk difference 1·6 percentage points, 95% CI -5·0 to 8·2). The number of adverse events reported was 219 in the de-escalation group and 175 in the control group, of these, 53 (24%) in the de-escalation group and 56 (32%) in the control group were considered severe. Seven (5%) of 164 patients in the de-escalation group and nine (6%) of 167 patients in the control group died during the 60-day follow-up. There were no treatment-related deaths. INTERPRETATION: De-escalation from an antipseudomonal ß-lactam in Enterobacterales bacteraemia following a predefined rule was non-inferior to continuing the empiric antipseudomonal drug. These results support de-escalation in this setting. FUNDING: Plan Nacional de I+D+i 2013-2016 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Ciencia, Innovación y Universidades, Spanish Network for Research in Infectious Diseases; Spanish Clinical Research and Clinical Trials Platform, co-financed by the EU; European Development Regional Fund "A way to achieve Europe", Operative Program Intelligence Growth 2014-2020.

Modulation of tumor microenvironment by targeting histone acetylation in bladder cancer.

Alterations in the epigenetic machinery in both tumor and immune cells contribute to bladder cancer (BC) development, constituting a promising target as an alternative therapeutic option. Here, we have explored the effects of a novel histone deacetylase (HDAC) inhibitor CM-1758, alone or in combination with immune checkpoint inhibitors (ICI) in BC. We determined the antitumor effects of CM-1758 in various BC cell lines together with the induction of broad transcriptional changes, with focus on the epigenetic regulation of PD-L1. Using an immunocompetent syngeneic mouse model of metastatic BC, we studied the effects of CM-1758 alone or in combination with anti-PD-L1 not only on tumor cells, but also in the tumor microenvironment. In vitro, we found that CM-1758 has cytotoxic and cytostatic effects either by inducing apoptosis or cell cycle arrest in BC cells at low micromolar levels. PD-L1 is epigenetically regulated by histone acetylation marks and is induced after treatment with CM-1758. We also observed that treatment with CM-1758 led to an important delay in tumor growth and a higher CD8 + T cell tumor infiltration. Moreover, anti-PD-L1 alone or in combination with CM-1758 reprogramed macrophage differentiation towards a M1-like polarization state and increased of pro-inflammatory cytokines systemically, yielding potential further antitumor effects. Our results suggest the possibility of combining HDAC inhibitors with immunotherapies for the management of advanced metastatic BC.

WNT Signaling in Stem Cells: A Look into the Non-Canonical Pathway.

Tissue homeostasis is crucial for multicellular organisms, wherein the loss of cells is compensated by generating new cells with the capacity for proliferation and differentiation. At the origin of these populations are the stem cells, which have the potential to give rise to cells with both capabilities, and persevere for a long time through the self-renewal and quiescence. Since the discovery of stem cells, an enormous effort has been focused on learning about their functions and the molecular regulation behind them. Wnt signaling is widely recognized as essential for normal and cancer stem cell. Moreover, ß-catenin-dependent Wnt pathway, referred to as canonical, has gained attention, while ß-catenin-independent Wnt pathways, known as non-canonical, have remained conspicuously less explored. However, recent evidence about non-canonical Wnt pathways in stem cells begins to lay the foundations of a conceivably vast field, and on which we aim to explain this in the present review. In this regard, we addressed the different aspects in which non-canonical Wnt pathways impact the properties of stem cells, both under normal conditions and also under disease, specifically in cancer.

What makes a word a good representative of the category of "emotion"? The role of feelings and interoception.

The words we use to describe emotions vary in terms of prototypicality; that is, some of these words may be more representative of the semantic category of emotion than others (e.g., anger refers more clearly to an emotion than boredom). Based on a multicomponential conception of emotions, the aim of the present study was to examine the contribution of several variables to emotion prototypicality. Some of those variables are related to the distinct components of emotions: evaluation, action, body expression, internal body sensations (interoception), and feelings. Other variables are related to the concreteness/abstractness distinction: sensory experience, social interaction, thought, and morality. We collected ratings for these variables for a large set of words (1,286) which varied in emotion prototypicality. A regression analysis revealed that the variables that most contributed to emotion prototypicality were feelings and interoception. Furthermore, a factor analysis identified two underlying factors: socioemotional polarity and emotional experience. The scores of each word in both factors were used to create a two-dimensional space and a density plot which provides relevant information about the organization of emotion concepts in memory. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Hepatitis B reactivation is a rare event among patients with resolved infection undergoing anti-CD20 antibodies in monotherapy without antiviral prophylaxis: results from the HEBEM study.

INTRODUCTION: Prospective data on the risk of hepatitis B reactivation (HBVr) among patients with resolved HBV infection undergoing anti-CD20 antibodies monotherapy is scarce. We aimed to assess the risk of HBVr in patients with resolved HBV infection treated with rituximab or ocrelizumab in monotherapy for multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) without antiviral prophylaxis. METHODS: HEBEM is a prospective study that included all consecutive adults HBsAg-negative/anti-HBc-positive who initiated anti-CD20 antibodies for MS or NMOSD at Cemcat. Inclusion criteria encompassed undetectable HBV-DNA, absence of other immunosuppressants or antiviral therapy. Every 6 months HBsAg, ALT and HBV-DNA were performed to rule out HBVr (defined by 2-log increase in HBV-DNA or seroconversion to HBsAg+). RESULTS: From August/2019 to August/2022, 540 subjects initiated anti-CD20 antibodies, 28 (5.2%) were anti-HBc-positive and were included. Twenty-two received rituximab and 6 ocrelizumab. The majority (89.3%) had previously received ≥ 1 immunomodulatory drug, with corticosteroids (82.1%) and interferon (42.9%) as the most common. At inclusion, all presented normal transaminases and undetectable HBV-DNA. Median anti-HBs levels were 105.5 mIU/mL (IQR 0-609). Median follow-up was 3.1 years (2.1-4.0). Median number of cycles of anti-CD20 antibodies was 6 (3-7), with a cumulative dose of 8.5 g (5.8-11.2) of rituximab and 3 g (1.8-3.8) of ocrelizumab. Neither cases of HBVr nor changes in anti-HBs titers were observed per 83.6 patient-years treated with monotherapy with anti-CD20 antibodies. CONCLUSIONS: In this cohort of patients with MS or NMOSD and resolved HBV infection, anti-CD20 monotherapy was not associated with detectable risk of HBV reactivation despite the lack of antiviral prophylaxis.