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    A Sequential Segmentation and Classification Learning Approach for Skin Lesion Images

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    This study investigates how the learning order between segmentation and classification tasks influences performance and generalization in medical image analysis. We propose a Sequential Swin Transformer framework that reuses a shared Transformer backbone with alternating task-specific heads to compare two sequential strategies: (i) segmentation followed by classification and (ii) classification followed by segmentation. Unlike conventional multitask or preprocessing-based pipelines, the proposed framework isolates the impact of task ordering on feature transfer under an identical architecture. Evaluated on the HAM10000 skin lesion dataset, the segmentation-then-classification configuration achieves the highest multiclass accuracy (up to 86.9%) while maintaining strong segmentation performance (Jaccard index ≈ 86%). Statistical tests confirm its superiority in accuracy and macro F1 score, whereas Grad-CAM and t-distributed stochastic neighbor embedding (t-SNE) analyses reveal that segmentation-first training yields more lesion-centered attention and a more discriminative latent space. Cross-domain evaluation on gastrointestinal endoscopy images further demonstrates robust segmentation (Jaccard index ≈ 91%) and multiclass accuracy (≈94.5%), confirming the generalizability of the sequential paradigm. Overall, the proposed method provides a theoretically grounded, clinically interpretable, and reproducible alternative to joint multitask learning approaches, enhancing feature transfer and generalization in medical imaging

    Inclisiran for fast-track lipid-lowering treatment early after an acute coronary syndrome: a pilot study

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    Background: Elevated low-density lipoprotein cholesterol (LDL-C) after acute coronary syndrome (ACS) significantly increases cardiovascular risk. Timely reduction of LDL-C is crucial, but it takes several weeks to achieve optimal LDL-C levels with standard therapy. Monoclonal antibodies that inhibit PCSK9 have been demonstrated in some small randomised trials to rapidly abate LDL-C levels when used early after hospital admission for ACS. Inclisiran, a PCSK9-inhibiting siRNA, has recently been introduced into clinical practice; however, no information is available about its effectiveness and safety as a fast-track lipid-lowering agent in this clinical context. Methods: We conducted a prospective, real-world study evaluating a fast-track lipid-lowering approach starting inclisiran on top of standard therapy in 16 consecutive ACS patients admitted to our cardiac intensive care unit with a high baseline LDL-C level (147.2 ± 35.7 mg/dL). Patients started inclisiran as add-on therapy as soon as baseline LDL-C levels were available. We assessed LDL-C levels and the mean change of LDL-C at baseline, discharge, 15-day and 30-day follow-up. Results: Inclisiran, added to standard therapy, reduced LDL-C levels to 30.3 ± 13.0 mg/dL at 30-day follow-up. The guideline-recommended LDL-C levels (≤55 mg/dL, ≥50 % reduction) were achieved in 73.3 % of patients at 15 days and in 100 % of patients at 30 days, with no adverse effects. Conclusion: This pilot study shows promise for inclisiran as a novel therapeutic option to improve cardiovascular outcomes in patients with ACS by contributing to achieving an early and sustained reduction in LDL-C levels

    An update on SARS-CoV-2 prevention strategy in solid organ transplant recipients: an expert opinion

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    Compared to immunocompetent individuals, solid organ transplant recipients (SOTRs) develop a weaker immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and vaccination. Although anti-SARS-CoV-2 vaccines can prevent symptomatic and severe disease, the SOTR population remains at risk as long as SARS-CoV-2 continues to circulate. To protect transplanted patients against severe COVID-19, two primary preventive strategies have been proposed: anti-SARS-CoV-2 vaccination and pre-exposure prophylaxis (PrEP) with monoclonal antibodies that possess neutralizing activity against SARS-CoV-2. The effectiveness of vaccination varies depending on the type of organ transplanted and the immunosuppressive therapy used, whereas the effectiveness of PrEP does not depend on these factors. The timing of vaccination and PrEP administration is also crucial. A stronger immune response is observed when vaccination is conducted during the nadir of immunosuppressive therapy. However, when PrEP is administered concomitantly with the vaccine, the efficacy of the vaccination could be reduced, both in terms of antibody production and cell-mediated immunity. Therefore, PrEP should be administered at least 15 days after vaccine administration. In addition to the availability of various preventive measures against COVID-19 for the most vulnerable transplant patients, the scientific community strongly recommends adhering to protective measures, such as wearing masks, practicing hand hygiene, and maintaining social distancing. These expert recommendations offer crucial guidance on preventing SARS-CoV-2 infection in solid organ transplant patients and are applicable to everyday clinical practice

    A Possible Case of β‐Thalassemia From the Cemetery of Santa Maria Maggiore in Vercelli (Piedmont, Northern Italy,18th Century)

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    In Italy's Piedmont region, the city of Vercelli has a history of malaria transmission due to favorable conditions for Anopheles mosquitoes, which may have influenced the genetic prevalence of thalassemia. This study investigates the skeletal remains of a nonadult individual from the Church of Santa Maria Maggiore in Vercelli, dating to the 18th century, and suggests possible pathological changes indicative of β-thalassemia. The skeletal analysis reveals extensive pitting, marrow hyperplasia, cortical thinning, scalloped epiphyses, and a distinctive “rib-within-a-rib” radiological appearance, which could be consistent with β-thalassemia major and intermedia. While thalassemia is currently prevalent in Piedmont, no prior paleopathological evidence of the condition has been reported. This study highlights the diagnostic challenges in identifying β-thalassemia in ancient populations due to similarities with other anemias and the absence of ancient DNA. The importance of combining skeletal analysis with historical and environmental contexts is emphasized to improve diagnostic accuracy. This research provides new insights into the historical presence of β-thalassemia in Vercelli and underscores the potential influence of environmental factors and genetic disorders

    SIEGE: IV. Compact star clusters in cosmological simulations with a high star formation efficiency and subparsec resolution

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    The formation of compact high-redshift star-forming clumps, along with the physical processes driving their evolution and their potential connection to present-day globular clusters (GCs), are key open questions in studies of galaxy formation. In this work, we aim to shed light on these aspects using the SImulating the Environment where Globular clusters Emerged (SIEGE) project, a suite of cosmological zoom-in simulations with subparsec resolution that is specifically designed to investigate the physical conditions behind the origin of compact stellar systems in high-redshift environments. The simulations analyzed in this study are focused on a dwarf galaxy with a virial mass of a few 109 M' at z = 6.14, where the spatial resolution reaches 0.3 pc h'1. Individual stars are formed directly by sampling the initial mass function, with a 100% star formation efficiency. This setup is designed to explore the impact of a high star formation efficiency under high-redshift conditions. The simulation reveals the emergence of numerous stellar clumps with sizes of 1'3 pc, stellar surface densities up to almost 104 M' pc'2, and masses predominantly spanning 103 M' to several 104 M', with a few reaching 105 M' and up to 106 M'. All clumps form during intense, short bursts of star formation lasting less than a megayear, without noticeable signs of second peaks of star formation or accretion, often with negligible dark matter content (i.e., dark-to-stellar mass ratios below 1 within three times their effective radii). We measured a clear correlation between mass and size, with a clump mass function described by a power law with a slope of '2. Star formation conditions in the simulation reveal a behaviour that is similar to that of a feedback-free starburst scenario, where dense clumps form due to inefficient stellar feedback over small timescales. Notably, some clumps exhibit properties that closely resemble those of present-day globular clusters, highlighting their potential evolutionary connection

    Comparative Enzymatic and Stability Assays Reveal GPLG as an Effective Cathepsin B Cleavable Linker for Tumor-Targeting Drug Conjugates

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    In the past decade, targeted drug delivery systems have significantly advanced cancer therapy. A key component of these constructs is the chemical linker that covalently connects a targeting unit to a potent cytotoxic payload. Among approved and investigational antibody-drug conjugates (ADCs) and small molecule-drug conjugates (SMDCs), lysosomal-cleavable peptide sequences such as Val-Cit (VCit), Val-Ala (VA), and Gly-Phe-Leu-Gly (GFLG) are widely used for tumor-specific drug release. However, premature drug release and instability often cause off-target toxicity and poor selectivity. Since lysosomal proteases are still considered optimal for the drug release within the tumor site, the quest for new and more stable lysosomal-sensitive peptide sequences is currently an ongoing challenge. This work investigates the enzymatic susceptibility, cleavage kinetics, and metabolic stability of the peptide sequence Gly-Pro-Leu-Gly (GPLG) as a novel Cathepsin B-cleavable linker for tumor-targeting drug conjugates. Compared to GFLG, VCit, and VA, all conjugated to paclitaxel via a PABC-N,N '-dimethylethylenediamine spacer, GPLG exhibited the fastest Cathepsin B cleavage within the first 30 min of the assay, and higher stability at pH 5.4 and in both human and rat plasma samples. These results highlight GPLG as a promising lysosomal-sensitive linker for next-generation SMDCs and ADCs

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