Search Results (16,625)

Advances in drug development continue to play a critical role in addressing diseases, including those with unmet medical needs. In 2024, the FDA approved 50 novel drugs, 16 of which were biologics. For context, during the first half of 2024 alone, the agency approved six biologics. By mid-2025, six additional biologics have received the green light, indicating that the pace of approvals of this class of drugs this year may be on par with 2024. This paper analyzes all biologics that received FDA authorization in 2024, examining their mechanisms, clinical trials, and expedited review pathways. Key approvals included the highest number of monoclonal antibodies (mAbs) since 2015 (13 mAbs, 6 indicated for oncology), while no antibody–drug conjugates were authorized—continuing with the trend in 2023. In addition, a new chimeric mAb has been approved since the last chimeric mAb approved in 2022, and a new mAb for Alzheimer’s disease. Nine biologics are first-in-class therapies, while ten received Orphan Drug Designation. The biologics considered herein fall into the categories of mAbs and proteins. Full article

Background: The prevalence of inflammatory bowel disease (IBD) is increasing worldwide, while the incidence is tending to stabilize. Moreover, the use of biological treatments is increasing; some studies suggest that surgeries and hospitalizations are decreasing instead. Methods: A population-based, retrospective cohort study was conducted using data from the Catalan Health Surveillance System (CHSS). All patients diagnosed with IBD were included between 2017 and 2023. Crude incidence and prevalence rates were calculated for the Catalan population. Data on pharmacological therapy, surgical procedures, hospitalizations, and mortality were analyzed. Trends in age-sex-adjusted rates were also estimated, and logistic regression was used to calculate the adjusted mortality odds ratio (OR). Data for Crohn’s disease (CD) and ulcerative colitis (UC) were analyzed separately. Results: The number of prevalent IBD cases rose from 28,752 in 2017 to 41,423 in 2023. Despite incidence rates remaining stable (30.8 in 2017 and 29.9 per 100,000 inhabitants in 2023), prevalence rates increased (386.9 and 510.9 per 100,000 inhabitants, respectively). The use of biologics significantly increased (from 13.5% in 2017 to 21.0% in 2023), particularly ustekinumab and vedolizumab. In parallel, a decline in the use of immunosuppressants was observed. IBD-related surgeries and hospitalizations decreased during the study period, particularly among CD patients. Mortality remained low but was higher among IBD patients compared to the general population. Conclusions: The incidence of IBD in Catalonia has stabilized, while its prevalence continues rising, suggesting a transition to Stage 3 (compounding prevalence). The use of biological treatments is increasing steadily, whereas rates of surgeries and hospitalizations are consistently decreasing. Full article

Halting liver fibrosis progression is a key goal in treating liver disease, yet effective antifibrotic drugs remain unavailable. This study explores the use of precision-cut liver slices (PCLS) as an ex vivo model to evaluate new therapies. Researchers tested how different oxygen levels affect viability, tissue integrity, and inflammatory response in PCLS from healthy and fibrotic rats. Fibrotic PCLS maintained their pathological gene signature under 40% oxygen and responded to inflammatory stimuli, indicating preserved functionality. Exposure to high oxygen levels increased oxidative stress and pro-inflammatory gene expression. Cirrhotic PCLS showed early signs of reduced viability and the upregulation of fibrosis-related genes including Col1α2, Col3α1, αSMA, Timp1, Timp2, Mmp2, Pdgfrβ, Nos2, Cox2, and Il6. Lipopolysaccharide (LPS) exposure induced the marked overexpression of Nos2 and Il1β mRNA and confirmed the model’s responsiveness to external injury. Fibrotic PCLS retained fibrogenic activity for at least 48 h. Additionally, the adenoviral delivery of a dominant-negative soluble PDGFRβ effectively blocked fibrotic signaling. Human fibrotic PCLS also remained viable for 72 h and showed an increased mRNA expression of fibrosis markers such as COL1A1, αSMA, and MMP2. These results highlight the potential of PCLS as a promising platform for future therapeutic testing, pending further validation with functional interventions. Full article

Understanding solute transport across interfaces between different porous materials is crucial for subsurface applications. Column tracer experiments have suggested solute accumulation at these interfaces. This effect cannot be explained by standard models based on Fickian flux continuity and the advection–dispersion equation. To analyze this phenomenon, we present reactive transport experiments in a 2D intermediate-scale horizontal tank to visualize and evaluate the spatiotemporal evolution of a solute plume crossing a sharp interface between coarse and fine materials. The plume results from the reaction of two fluid solutions entering the tank in parallel through inlet ports. The reaction product is analyzed using mixing and reaction metrics. Results show the reaction product encounters anomalous resistance when the plume crosses the coarse-to-fine (CF) interface. This effect is less pronounced in the fine-to-coarse (FC) transition. This asymmetric resistance does not produce solute accumulation behind the interface, a difference from the results obtained with the one-dimensional model. Instead, results show enhanced transverse spread of the reaction product in the coarse-to-fine transition, with slow release in the fine material. A sudden decrease in the longitudinal concentration profile across the interface is observed. Mixing metrics show that as apparent transverse dispersivity increases closer to the interface in the CF transition, the scalar dissipation rate and total mass reacted increase, indicating that the CF configuration promotes greater solute reactivity near the interface compared to the FC configuration. Full article

Obesity is one of the most challenging metabolic disorders affecting more than 800 million people around the world, according to the World Health Organization (WHO). In recent years, our knowledge and understanding of this multifactorial disease have been exponentially increasing, and many studies have been focusing on one of the main organs affected by obesity: adipose tissue (AT). It is known that AT undergoes remodeling due to the abnormal fat accumulation that accompanies obesity, characterized by increased immune cell infiltration, extracellular matrix (ECM) overproduction, and decreased adipogenesis, among others. Few studies have focused on adipocyte intercommunication, even though it is essential for AT homeostasis and function. In this context, GAP junction, adherens junction, and tight junction proteins can be found in these depots. In some cases, their function is well established, but in most cases it remains unknown. Claudins are the main proteins that form tight junctions (TJs), and, in recent years, studies have revealed a more extensive role of claudin proteins in intracellular signaling and control of a wide set of biological processes. This review aims to gather the main scientific evidence on the role of claudins in cell signaling, as well as what is known about these proteins in the field of obesity and adipose tissue physiology. Full article

Objective: Anifrolumab is approved for systemic lupus erythematosus (SLE). Its off-label use in non-systemic cutaneous lupus erythematosus (NSCLE) remains poorly characterized. We aimed to assess its effectiveness and safety in refractory NSCLE, supported by a literature review and exploratory immunologic analysis. Methods: This multicenter observational study included patients with NSCLE treated with anifrolumab. Skin disease was assessed using the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). CLASI scores at baseline were compared to months 1, 3, and 6. A narrative literature review was also conducted. In a subset of three patients, peripheral blood immunophenotyping was performed before and after treatment to explore immunologic surrogate markers associated with clinical response. Results: Fifteen patients (11 women; mean age 52.1 ± 11.7 years) were included. All had received topical corticosteroids and hydroxychloroquine. Most of them had failed multiple systemic therapies. Anifrolumab (300 mg IV every 4 weeks) was used in combination (n = 12) or as monotherapy (n = 3). All patients improved. Median CLASI-A decreased from 16 to 1 (p < 0.001); CLASI-D decreased from 5 to 4 (p < 0.001). The literature review identified 6 publications reporting 14 additional cases of NSCLE with similar outcomes and minimal adverse effects. Immunologic profiling pointed to an increase in intermediate and non-classical and decreased PD-1 expression in monocytes and NK cells after 12 weeks of treatment. Conclusions: Anifrolumab appears effective and relatively safe in refractory NSCLE. Preliminary immunologic data suggest changes in peripheral blood monocyte subsets and NK cells. However, these findings must be confirmed in prospective, controlled clinical trials. Full article

Background: Upper tract urothelial carcinoma (UTUC) is a rare and aggressive malignancy with limited prognostic tools to predict disease progression. Due to its low incidence, the molecular pathogenesis of UTUC remains poorly understood, and few studies have explored transcriptomic profiling in this setting. Identifying gene expression biomarkers associated with progression may help improve risk stratification and guide postoperative management. Methods: In this study, we applied a machine learning approach to gene expression data from radical nephroureterectomy (RNU) specimens of 17 consecutive patients with pT2 or pT3 UTUC treated at our institution. RNA was extracted from formalin-fixed paraffin-embedded tissues and sequenced using the Ion AmpliSeq™ Transcriptome Human Gene Expression Kit on an Illumina HiSeq 2500 platform. Differential gene expression was assessed using DESeq2, and results were visualized with volcano plots. Predictive power was evaluated through logistic regression and receiver operating characteristic (ROC) analysis. Gene Ontology enrichment analysis was used to explore biological pathways. Results: A total of 76 genes were differentially expressed between progressive and non-progressive patients. A random forest classifier identified ten key genes with prognostic potential. Validation with logistic regression yielded an area under the ROC curve (AUC) of 0.88, indicating high discriminative ability. These genes were associated with immune regulation, cell cycle control, and tumor progression. Conclusions: This pilot study demonstrates the potential of integrating machine learning with transcriptomic analysis to identify prognostic biomarkers in UTUC. Further validation in larger, independent cohorts is needed to confirm these findings and support their clinical application. Full article

In Paralympic sports, to guarantee fair competition, it is necessary to identify those peculiar abilities that characterize the discipline and the motor limitations that may or may not most affect the athlete’s performance in a specific sports task, assigning an appropriate classification to the level of impairment. This study proposes a minimally invasive assessment system based on a single inertial sensor to support the investigation of the peculiarities of water polo with disabilities by analyzing players’ trunk inclinations during a simulated match and angular speeds in swimming tests. By comparing a small group of athletes of various classes and those without disabilities, we intended to evaluate whether athletes with lower limb disabilities may be disadvantaged compared to athletes with upper limb disabilities. The results suggest no difference in the mean percentage of time in vertical and horizontal positions when comparing players with and without disabilities, although specific impairments led to distinct behaviors (Δ = 0.9%, p = 0.841). Interesting insights emerged in swimming and turning situations in the water. Strong correlations (r > 0.7, p < 0.05) were found between swimming performance metrics and classification points. Furthermore, players with spasticity exhibited lower smoothness in turning movements, suggesting less fluid execution than those with other impairments affecting the same limbs. These findings highlight the IMU system’s potential to provide objective, quantitative data for refining WPA classification protocols. Full article

This review article synthesizes recent experimental research on the breaching of noncohesive embankment dams and levees caused by overflow, with a specific focus on coarse-grained soil materials. Despite the high incidence of embankment dam collapses leading to significant socio-economic and environmental impacts, comprehensive understanding of the underlying physical processes remains incomplete. Historically, studies have largely concentrated on embankments made from uniform materials ranging from fine cohesive soils to noncohesive clean rockfill. However, recent shifts in focus to well-graded heterogeneous coarse-grained soil materials underscore the complexity of predicting breach mechanics, given the absence of physically based models for these materials. This review aims to compile and elucidate the factors affecting breaching in an effort to inform future research and practical applications in dam safety assessments. Full article

Residents’ values in social housing retrofit extend beyond energy efficiency targets to encompass complex social and physical considerations, shaping their acceptance and experience of interventions. These values appear to influence retrofit success yet are often overlooked in policy and practice that prioritise technical performance. This paper investigates what residents value in social housing retrofit through a focus group method with the Sutton Estate in London, combining institutional stakeholder (housing association and architect) and resident perspectives. Content analysis of focus group questionnaires, discussions, and consensus-building activities revealed four key resident values: (1) good stakeholder relationships, emphasising trust-building through personal connections; (2) access to information, requiring clear, continuous communication through multiple channels; (3) comfort, health, and safety, integrating physical and mental wellbeing; and (4) building and community longevity, focusing on preserving building character and social sustainability. The findings suggest that social housing retrofit may benefit from a holistic approach integrating residents’ values throughout the project lifecycle, addressing the social, physical, and long-term sustainability of homes and communities. The findings highlight the importance for housing associations, architects, and policymakers to consider residents’ values when developing retrofit strategies, balancing technical requirements with residents’ needs and priorities. Full article

Urbanization profoundly alters environmental conditions (e.g., temperature, artificial light at night (ALAN), and precipitation) that strongly influence vegetation phenology. However, the rate and extent of vegetation phenological responses to urbanization, as well as their underlying mechanisms, remain underexplored, particularly the roles of CO₂ emissions and PM₂.₅ concentrations, as well as the interactions among environmental conditions. We first used road network density (RND) to represent urbanization effects and quantified the phenological response rate and extent across 31 cities in China (2014–2022) using slope and range metrics derived from linear regressions of phenostages (start of season (SOS), end of season (EOS), length of season (LOS)) against RND. Partial least squares structural equation modeling was applied to assess the direct and indirect effects of RND on phenology via all five key environmental factors. Our results identified substantial differences in the urban phenological responses across latitudinal, hydrothermal, and land−cover gradients. And the impact of urbanization on phenology was most pronounced during early expansion (at a RND threshold of 2.02 ± 0.41 km/km²) but diminished with continued growth. Environmental factors distinctly affected phenological response rate and extent through RND; temperature, ALAN, and CO₂ emissions were the dominant drivers of slope, negatively affecting SOS (β = −0.37 to −0.69) but positively affecting EOS and LOS (β = 0.31 to 0.68). PM₂.₅ played a crucial role in determining the range of SOS (β = −0.31), and precipitation had the largest impact on the range of EOS (β = −0.37). Our study innovatively uses RND to quantify urbanization intensity and improve understanding of the combined effects of multiple drivers, especially PM₂.₅ and CO₂, on phenological responses, which may offer a useful reference for future urban planning strategies that aim to balance development with ecosystem functioning. Full article

Background/Objectives: Endometrial cancer (EC) is the most common gynecological tumor in developed countries, and presents a wide variety of histological and molecular characteristics that make its treatment increasingly complex. In recent years, advances in molecular imaging, particularly with [¹⁸F]FDG-PET/CT and PET/MRI, have changed clinicians’ management of diagnosis, treatment planning, and prognosis of EC. Methods: In this narrative review, a search was conducted for current evidence on the role of [¹⁸F]FDG-PET/CT and PET/MRI throughout the treatment of EC, focusing on their diagnostic performance, clinical relevance, and prognostic implications. Their use in areas such as initial staging, treatment monitoring, recurrence detection, and individualized risk assessment was also discussed. Results: [¹⁸F]FDG-PET/CT is effective in detecting lymph node and distant metastases, while [¹⁸F]FDG-PET/MRI offers greater accuracy for T and N staging. In addition, [¹⁸F]FDG-PET/CT provides early metabolic indicators of therapeutic response and facilitates differentiation between viable tumors and post-treatment changes. Radiomics-derived parameters have shown promising associations with tumor aggressiveness and lymphovascular invasion and survival, supporting their role as prognostic imaging biomarkers. In addition, the use of non-FDG radiotracers, as well as predictive models based on machine learning, can further refine preoperative stratification and treatment planning in certain subtypes of EC. Conclusions: Molecular imaging enhances the accuracy of TNM staging in EC. The incorporation of molecular imaging biomarkers into daily clinical practice could significantly improve personalized decision-making in EC. However, large prospective studies are needed to confirm their efficacy. Full article

Traditionally, formal education has favored boys, while girls, in the past, were relegated to the domestic sphere. This has been the case for centuries, without considering the possible specific cognitive needs of girls, which have been ignored. In Western countries, this has generated significant educational problems, especially in the learning of more technical subjects, with which girls not only do not identify but also often exclude themselves with the excuse that “it is not for them” (i.e., they tend to display a strong stereotype, a false belief, regarding these disciplines). The consequences have not been long in coming. Currently, in many Western countries, the low percentage of women in technical careers (such as Physics, Engineering, and Computer Science) is alarming. Is it possible to change stereotypes? This article addresses this complex issue, placing particular emphasis on the learning of spatial abilities, so important in all STEM careers (i.e., science, technology, engineering, and mathematics). This study concludes with examples of other stereotypes (mainly cultural) that have been eliminated or significantly reduced thanks to virtual reality (VR) and the help of artificial intelligence (AI). Could the same be achieved in the spatial domain? Full article

This study analyzes the impact of the COVID-19 pandemic on alcohol, cannabis, and tobacco use among adolescents aged 14–19 in Central Catalonia across three periods. Data were obtained from two waves of the DESKcohort project. The first wave (n = 4641) was pre-COVID-19 and the second wave was divided into two phases: post-COVID-19 with restrictions (n = 3478) and post-COVID-19 without restrictions (n = 2900). The prevalence of monthly binge drinking, cannabis use in the last 30 days, and daily tobacco use was calculated. Poisson regression models estimated adjusted prevalence ratios (aPR) comparing two post-pandemic phases to the pre-pandemic baseline. Binge drinking increased during the restrictions among girls [aPR = 1.5 (95%CI: 1.1–2.1)] and boys [aPR = 1.7 (95%CI: 1.3–2.3)]. Cannabis use decreased during restrictions and remained low post-pandemic, especially among girls [aPR = 0.6 (95%CI: 0.5–0.8)] and boys in the 4th Compulsory Secondary Education (CSE) [aPR = 0.4 (95%CI: 0.3–0.6)], and girls in the 2nd Post-Compulsory Secondary Education/Intermediate-Level Training Cycles (PCSE/ILTC) [aPR = 0.7 (95%CI: 0.6–0.9)]. Daily tobacco use also dropped among boys in the 4th year of CSE [aPR = 0.5 (95%CI: 0.3–0.7)] and girls in the 2nd year of PCSE/ILTC [aPR = 0.7 (95%CI: 0.6–0.9)]. The COVID-19 pandemic has created a unique opportunity to reassess patterns of adolescent substance use in a context of sudden social disruption. The findings highlight the need to denormalize alcohol and tobacco use and promote healthier adolescent behavior through education. Full article

This study aimed to evaluate how tidal modulation influences breaking waves on a macrotidal beach along the Amazonian coast under varying climatic conditions. The study utilized medium-term data (2006–2018) from national and international institutions and short-term data (2012–2014) from in situ measurements at Ajuruteua Beach. Offshore winds and waves, predominantly from the northeast, were influenced by severe storms associated with La Niña and El Niño events. During these periods, wave heights exceeded 5 m, with wave periods ranging from 12 to 20 s. Tidal fluctuations (typically 5.0–6.0 m) modulated nearshore wave heights and periods, with variations determined by offshore conditions and climatic influences. Wave heights decreased from 2–5 m offshore to 1–2 m nearshore. At low tide, sandbanks dissipated wave energy, resulting in significantly smaller breaking waves (0.1–0.5 m) compared with high tide (1–1.8 m). The northern part of Ajuruteua Beach experienced a progressive retreat, with a total area loss of 0.15 km² and a shoreline retreat of 0.360 km between 2007 and 2021. The combination of high hydrodynamic energy and unregulated development led to the destruction of 43 buildings between 2007 and 2013 and an additional 44 houses between 2013 and 2021 within the intertidal zone. Moreover, the absence of coastal management strategies has exacerbated erosion, underscoring the urgent need for planning and regulatory frameworks. Based on the findings of this study, it is recommended that land use be regulated and both short- and long-term physical processes be systematically integrated into future coastal protection planning. Full article