European Automobile Manufacturers Association

IntroductionHIV prevention and treatment supported by the United States President's Emergency Plan for AIDS Relief (PEPFAR) have saved millions of lives. Rwanda is among the most successful countries worldwide in achieving global targets with PEPFAR support. Abrupt PEPFAR funding uncertainty raises concerns about continued HIV epidemic control. We projected the impact of the Government of Rwanda's (GoR's) capacity to offset PEPFAR funding elimination on adult HIV epidemic and care continuum outcomes over 10 years.MethodsUsing an HIV policy model calibrated to Rwanda, we assessed capacity to sustain HIV services at: 50% (with no capacity by GoR to cover the PEPFAR funding gap), 75%, 90% and 100% (with full capacity by GoR to cover the gap). Scenarios involved reducing the number on antiretroviral therapy (ART), immediately discontinuing ART and proportionally decreasing HIV diagnosis, ART initiation, and care re‐engagement. We projected epidemic outcomes (HIV prevalence, HIV incidence, number with HIV, new HIV infections, deaths) and care continuum outcomes (percentage diagnosed, percentage on ART among those diagnosed, percentage virally suppressed among those on ART). We calculated differences in projected outcomes for partial or no capacity versus full capacity. Secondary analyses assessed the timing of the GoR's response.ResultsCompared to full capacity at 10 years, the model projected a 13.9%–38.7% increase in HIV prevalence and 69.0%–246.7% increase in HIV incidence across coverage capacity scenarios. This translated to 29,000–64,000 additional adults with HIV and 20,000–92,000 cumulative new adult HIV infections. Cumulative projected deaths increased by 10,000–51,200. The model projected continual reductions in percentage diagnosed at 10 years; percentage virally suppressed among those on ART was similar across scenarios. Higher, and more delayed, coverage capacity had projected outcomes similar to lower, and less delayed, coverage capacity. Outcomes for gradual increases in coverage capacity were generally similar to or better than full, but delayed, coverage capacity.ConclusionsEven in countries like Rwanda that have achieved epidemic control, abrupt and persistent elimination of PEPFAR funding could drastically reverse critical gains. Evidence quantifying the consequences of different capacities to sustain HIV services underscores the high stakes of rapid and sufficient action.

Background: Fibromyalgia is a chronic condition characterized by widespread pain, fatigue, and localized tenderness. Its pathophysiology remains unclear, and treatment options are often limited and only partially effective. Recent studies suggest a potential link between vitamin D deficiency and symptom severity, as vitamin D may play a role in modulating pain and inflammation. Methods: This systematic review and meta-analysis assessed the efficacy of vitamin D supplementation in reducing pain and improving quality of life in fibromyalgia patients, focusing on studies up to 31 December 2024. Following PRISMA guidelines, a literature search in PubMed, Web of Science, and Scopus identified 2776 articles; 7 were included in the systematic review and 4 studies in each meta-analysis. Results: Results showed that vitamin D supplementation significantly reduced pain levels compared to the control group, with a statistically significant effect observed using the NRS or VAS (SMD = −0.85; 95% CI: −1.54 to −0.17; p = 0.0148), as well as the FIQ scale (SMD = −0.87; 95% CI: −1.56 to −0.20; p= 0.0115), resulting in an improvement in quality of life. Conclusions: These findings suggest that vitamin D may be a valuable adjunct in fibromyalgia management, particularly for pain. However, further high-quality trials are needed to confirm these effects and identify responsive patient subgroups.

Sonodynamic therapy (SDT) is a new non-invasive and precise tumor treatment method, which is a promising anticancer treatment and is becoming a cutting-edge interdisciplinary research field. Based on the research progress of SDT, this paper reviews the latest situation of metal-organic frameworks (MOF) based sonosensitizer in recent years, and introduces the preparation methods and related properties of MOF materials. By describing the many in-depth observations and understandings of MOF-assisted SDT strategies in anticancer applications, we aim to highlight the advantages and improvements of MOF-enhanced SDT and synergistic therapy. The methods to improve the effect of SDT were discussed by exploring the measures of combining hypoxia activating drugs, improving hypoxia microenvironment, accelerating glutathione consumption, and enhancing cavitation effect. Based on the extensive application of MOF materials in SDT and the related technical challenges, this review hopes to bring some enlightenment to improve the therapeutic effect of cancer and promote the development of nanomedicine.

AimTo assess the frequency of super-responders (≥ 75% reduction in migraine frequency) and absolute responders (100% reduction) to monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) after one year of treatment in individuals with high frequency (HFEM) or chronic migraine (CM).MethodsThis multicenter (n = 16), prospective, real-life study, involved consecutive adults with HFEM or CM and ≥ 3 prior preventive failures, receiving subcutaneous anti-CGRP mAbs for ≥ 12 months. Co-primary endpoints were the 12-month rates of super- and absolute responders. Secondary endpoints included subgroup analyses by migraine type and timing of response, categorized as early (≤ 3 months), late (> 3–6 month), or ultra-late (> 6–12 month).Results572 patients completed 12 months of treatment: 70.0% achieved super-response (HFEM: 64.9%; CM: 71.8%) and 23.4% absolute response (HFEM: 29.9%; CM: 21.0%). Both outcomes exhibited a time-dependent progression. Among super-responders (n = 400), 29.4% were early, 22.6% late, and 18.0% ultra-late. Among absolute responders (n = 134), 3.1% responded early, 3.7% late, and 16.6% ultra-late.ConclusionOne year of anti-CGRP mAbs therapy yields a ≥ 75% response in over two-thirds and a 100% response in nearly one-quarter of patients with HFEM or CM and prior treatment failures. Most super- and absolute responses emerge after six months, supporting long-term continuation treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00415-025-13419-z.

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L’article explore la manière dont Gramsci formule son idée d’émancipation populaire. En partant d’une comparaison avec la manière libérale de concevoir la relation entre les intellectuels et le peuple, l’étude propose de reconnaître le propre de l’idée gramscienne d’émancipation populaire dans la notion d’autoconscience intellectuelle. La première partie propose une reconstruction philologique de la problématique à partir d’une série de notes des Cahiers de prison rédigées à partir de mars 1932, tandis que la seconde propose une analyse politico-philosophique du § 1 du Cahier 11.

Tumor heterogeneity plays a pivotal role in tumor progression and resistance to clinical treatment. Single-cell RNA sequencing (scRNA-seq) enables us to explore heterogeneity within a cell population and identify rare cell types, thereby improving our design of targeted therapeutic strategies. Here, we use a pan-cancer and pan-tissue single-cell transcriptional landscape to reveal heterogeneous expression patterns within malignant cells, precancerous cells, as well as cancer-associated stromal and endothelial cells. We introduce a deep learning framework named Shennong for in silico screening of anticancer drugs for targeting each of the landscape cell clusters. Utilizing Shennong, we could predict individual cell responses to pharmacologic compounds, evaluate drug candidates' tissue damaging effects, and investigate their corresponding action mechanisms. Prioritized compounds in Shennong's prediction results include FDA-approved drugs currently undergoing clinical trials for new indications, as well as drug candidates reporting anti-tumor activity. Furthermore, the tissue damaging effect prediction aligns with documented injuries and terminated discovery events. This robust and explainable framework has the potential to accelerate the drug discovery process and enhance the accuracy and efficiency of drug screening.