80936 research outputs found
Sort by
KLF7 is a general inducer of human pluripotency
No full textPluripotency is the capacity to generate all somatic cells and the germ line and is governed by a self-reinforcing network of transcription factors. The forced expression of only some of these factors enables the reprogramming of somatic cells to pluripotency. In murine cells, several Krüppel-like factors (KLFs) have been identified as stabilisers and inducers of pluripotency. Human somatic cells are routinely reprogrammed by expression of KLF4 in combination with OCT4, SOX2 and cMYC (OSKM). An extensive transcriptome analysis revealed, however, that KLF4 is barely expressed in conventional human pluripotent stem cells (PSCs). Here we show that KLF7 is robustly expressed in conventional human PSCs and it allows transcription factor-mediated somatic reprogramming replacing KLF4. Moreover, KLF7 is highly expressed in naive PSCs and its forced expression in conventional hPSCs induces upregulation of naive markers and results in efficient chemical resetting to naive PSCs. KLF7 CRISPRi-mediated silencing, while not affecting maintenance of conventional/primed PSCs, greatly reduces the efficiency of chemical resetting. Our data indicate that KLF7 is a general human pluripotency factor and an inducer of pluripotency
Making a “decorous” working class: Racialized stigmatization and alienation in a gentrifying neighborhood
No full textSince 2018, the municipality of Brescia (Italy) has been carrying out a large-scale project of urban regeneration targeting Via Milano, a 2.5-kilometer road connecting the city’s western neighborhoods to the historical center. This project, inspired by the Italian government’s approach for revitalizing “decaying urban peripheries,” is transforming Via Milano and the surrounding districts. The area, historically inhabited by the city’s industrial working-class, is now home to many migrant residents as well. Drawing from 6 years of ethnographic research, this paper discusses three dynamics emerging from the regeneration. Firstly, it examines how powerful discourses define racialized conditions of membership to Italian society by mobilizing the categories of “decay” and “decorum,” which marginalize non-White residents and stigmatize their practices, deemed as “indecorous.” Secondly, it explores how these racialized definitions of Italianness are mobilized by public authorities to impose their vision and facilitate the emergence of inter-class alliances between white working- and middle-class residents with a “desired gentrifier,” that is, an imagined subject the municipality aims to attract to the regenerated neighborhood. Finally, the paper concludes by discussing how the “working-class subject” itself has been made “decorous,” complicating the relationships between groups forced to coexist in a gentrifying, yet historically class-segregated, neighborhood
Optimizing Tildrakizumab Dosing in Psoriasis: A 52-Week Multicenter Retrospective Study Comparing 100 mg and 200 mg—IL PSO (Italian Landscape Psoriasis)
No full textIntroduction: Tildrakizumab is a monoclonal antibody targeting interleukin (IL)-23 approved for the treatment of moderate-to-severe plaque psoriasis across two different dosages (100 mg and 200 mg). The higher dosage is recommended for patients with a body weight ≥ 90 kg or a high disease burden (Psoriasis Area and Severity Index [PASI] ≥ 16 or the involvement of difficult-to-treat areas). We conducted a 52-week multicenter retrospective study to compare the effectiveness and safety of both dosages and assess their impact on specific patient subgroups. Methods: We enrolled a total of 540 patients with high disease burden or body weight ≥ 90 kg; 177 and 363 were treated with tildrakizumab 200 mg and 100 mg, respectively. The effectiveness was evaluated in terms of PASI 90, PASI 100, and PASI ≤ 2 at weeks 16, 28, and 52. We also performed subanalyses according to the body weight (≥ 90 kg), PASI ≥ 16, prior biologic exposure, involvement of difficult-to-treat areas, and the presence of at least one cardiometabolic comorbidity. Results: After 16 weeks of treatment, a higher proportion of patients in the 200-mg group achieved PASI 90 and PASI 100 compared to those in the 100-mg group (43.5% vs. 34.3% and 36.4% vs. 24.2%, respectively). These results were sustained at 1 year, with PASI 90 and PASI 100 reached by 68.6% and 52.9% of patients in the 200-mg group, respectively, versus 57.3% and 35% in the 100-mg group. All subgroup analyses consistently indicated a trend toward greater effectiveness with tildrakizumab 200 mg, particularly in terms of PASI 90 and PASI 100 achievement at weeks 16 and 52. No differences in the safety profile were observed throughout the study period. Conclusion: Our findings confirm the superior effectiveness of tildrakizumab 200 mg over 100 mg in specific subgroups of patients with a comparable safety profile across the study period
Bimodal ECG and PCG Cardiovascular Disease Detection: Exploring the Potential and Modality Contribution
No full textEarly detection of cardiovascular diseases (CVDs) is crucial for improving patient outcomes and alleviating healthcare burdens. Electrocardiograms (ECGs) and phonocardiograms (PCGs) offer low-cost, non-invasive, and easily integrable solutions for preventive care settings. In this work, we propose a novel bimodal deep learning model that combines ECG and PCG signals to enhance the early detection of CVDs. To address the challenge of limited bimodal data, we fine-tuned a Convolutional Neural Network (CNN) pre-trained on large-scale audio recordings, leveraging all publicly available unimodal PCG datasets. This PCG branch was then integrated with a 1D-CNN ECG branch via late fusion. Evaluated on an augmented version of MITHSDB, currently the only publicly available bimodal dataset, our approach achieved an AUROC of 96.4%, significantly outperforming ECG-only and PCG-only models by approximately 3%pts and 11%pts, respectively. To interpret the model's decisions, we applied three explainability techniques, quantifying the relative contributions of the electrical and acoustic features. Furthermore, by projecting the learned embeddings into two dimensions using UMAP, we revealed clear separation between normal and pathological samples. Our results conclusively demonstrate that combining ECG and PCG modalities yields substantial performance gains, with explainability and visualization providing critical insights into model behavior. These findings underscore the importance of multimodal approaches for CVDs diagnosis and prevention, and strongly motivate the collection of larger, more diverse bimodal datasets for future research
Optimizing critical mineral extraction and processing in single and joint production
No full textIn the context of the energy transition, efficient ore extraction and processing are essential to support clean energy technologies. This study investigates the economic and operational factors shaping the cost structures of single (e.g., copper) versus joint metal producers (e.g., copper and cobalt produced simultaneously). Notably, it addresses the following key questions: What parameters influence the costs of these production systems? Under what conditions can joint production provide cost advantages? How does scaling up ore processing impact cost dynamics?
Using an optimization-based economic model, we show that cost dynamics for single metal producers are influenced by unit costs, tax rates, and output elasticities. In contrast, joint production is further shaped by technical efficiency and metal demand. Our empirical analysis, based on data from 427 mining projects producing copper and two critical metals, i.e. cobalt and nickel, reveals that joint producers typically face higher costs than single metal producers. Our model indicates two novel pathways for cost reduction: enhancing the relative output elasticity of the secondary metal (cobalt or nickel) or achieving economies of scale by increasing ore-processing capacity.
By integrating theoretical modeling with real-world data, this study provides actionable insights and novel frameworks for optimizing metal production to meet the growing demands of the energy transition. Our findings offer a foundation for developing operational benchmarks and designing cost-effective, sustainable metal production strategies
The risk of candidiasis during treatment with bimekizumab for the management of plaque psoriasis: a 16-week multicentre real-world experience - IL PSO (Italian Landscape Psoriasis)
No full textTrends in GVHD Epidemiology, Prophylaxis and Management: The Gruppo Italiano per il Trapianto di Midollo Osseo, Cellule Staminali Emopoietiche e Terapia Cellulare (GITMO) GVHD24 Study
No full text: Compared to historical reports, both aGVHD and cGVHD appeared to have decreased in the recent transplant era, possibly due to the extension of T-cell depletion, the availability of effective second-line approaches in SR/D GVHD and improved anti-infectious prophylaxis and treatments
