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Locally advanced breast cancers: the EUSOMA experience
Get PDFBackground The aim of this study was to assess clinicopathologic characteristics, treatment modalities used and outcome of patients with locally advanced breast cancer (LABC). Materials and methodswe searched the European Society of Breast Cancer Specialists (EUSOMA) data warehouse for clinically LABC cT4a-d – in the 2013–2022 timeframe. ResultsOf a total of 132269 patients, we identified 2427 patients with cT4abc BC (1.83 %) and 977 with inflammatory (T4d) BCs (0.74 %), of whom 542/2427 (20.1 %) and 251/977 (25.6 %), respectively, had metastatic disease at presentation (p = 0.054. Ninety percent of patients with cT4abcM0 and 88.8 % of patients with cT4dM0 disease had surgery (p = 0.369) and 90.9 % and 88.7 % (p = 0.187) endocrine therapy. Neoadjuvant chemotherapy (CT), adjuvant CT, biological drugs and radiotherapy were given in 33.2 %, 47.0 %, 67.1 % and 61.1 % of cT4abcM0 cases compared to 77.3 %, 80.4 %, 87.7 % and 80.2 % of cT4dM0 cases (all p < 0.001). Multivariable analysis showed that age <70 years, luminal A and HER-2 pure subtype, surgical treatment, radiotherapy, and systemic treatment (all p ≤ 0.034) were determinants of better overall survival (OS). Local recurrence rate (LRR) was significantly lower in patients receiving radiotherapy or endocrine therapy (p ≤ 0.012). Cox analyses showed no difference in OS or LRR between patients with cT4abc and those with T4d BCs, neither at univariable or multivariable analysis. Conclusions The current study confirms well-known features of cLABCs and underscores the importance of multimodal treatment, which is often underused in these patients
Diabetes management using a clinical guideline versus usual practice: a feasibility trial-based qualitative study among Ayurvedic practitioners and patients in Nepal
No full textBackground: Type 2 diabetes mellitus (T2DM) is common in Nepal, where many people seek primary care through Ayurveda, a widely practiced traditional medical system. However, concerns remain about variability in clinical practice and the quality of care provided by Ayurvedic practitioners. No evidence-based clinical practice guideline (EB-CPG) currently exists for managing T2DM in Ayurveda. To address this, an EB-CPG was developed, and a feasibility trial was conducted to inform a future definitive cluster randomized controlled trial evaluating whether the EB-CPG would improve T2DM management compared to usual clinical practice. Objectives: To explore the experiences and perspectives of Ayurvedic practitioners and patients regarding the two treatment groups (EB-CPG-based care versus usual clinical practice) and participation in the feasibility trial. Design: Constructivist qualitative study. Methods: Semistructured interviews were conducted with Ayurvedic practitioners and patients. Data were analyzed thematically using an inductive approach and the framework method. Results: A total of 41 Ayurvedic practitioners and patients were interviewed. Common themes identified across both groups included facilitators and challenges in the trial patient recruitment, challenges in usual clinical care, experiences with EB-CPG-based care (predominantly positive), ease and difficulties of monthly follow-ups, and pros and cons of patient diaries for assessing medication compliance. Practitioner-specific themes included the diverse populations they serve; patients’ motivations for choosing Ayurveda over Western medicine; their motivations for trial participation; balancing clinical duties with the trial demands; confusion about trial roles and responsibilities; and other trial-related issues such as understanding processes and documentation, support and communication, coordination with data collectors, and finances and other resources. Conclusion: The EB-CPG-based approach for managing T2DM by Ayurvedic practitioners in Nepal was well-received and perceived as more beneficial than usual clinical practice. Trial experiences and perspectives were largely positive; however, several challenges related to trial conduct should be addressed in future studies, including the definitive cluster trial
Bank CSR Engagement, Institutional Environments, and Corruption
No full textThis study examines the effect of bank engagement in corporate social responsibility (CSR) on corruption across 39 countries from 2002 to 2021. We build on the view that CSR enables banks to act as active agents influencing national corruption, rather than passive agents of institutional norms. Our results indicate that stronger bank CSR significantly reduces corruption, with robust findings across measures and specifications. CSR mitigates corruption through enhanced regulatory compliance, stakeholder protection, governance diversity, and improved information flows. It also complements formal institutions and informal societal norms, highlighting the potential of embedding CSR into banking regulation to advance both anti-corruption and financial stability
Mortality trends in chronic obstructive pulmonary disease in 27 countries within Europe from 2011 to 2021
Get PDFBackground: Chronic obstructive pulmonary disease (COPD) incurs significant mortality worldwide. Less is known about the burden in the last decade across Europe. We report trends and variations in mortality for patients with COPD across 27 European countries from 2011 to 2021.Methods: COPD mortality was extracted from the EUROSTAT database, using the International Classification of Diseases 10 codes J43 and J44 for each country. Age-standardised and sex-standardised mortality rates (SMR) were calculated and joinpoint regression identified average annual percentage change (AAPC) in deaths from 2011 to 2021. Global Burden of Disease tobacco prevalence data were used to try and best contextualise the mortality.Results: The overall SMR in Europe for this period was 32.1 (95% CI 32.0 to 32.1) per 100 000 person-years, with substantial geographical heterogeneity. There was a fivefold difference in mortality rates between the countries with the greatest versus the least deaths. Although there was an apparent 3% (95% CI −4.4% to −1.6%) decrease in average annual deaths from 2011 to 2021 across Europe, there was no significant change in deaths from 2011 to 2018, prior to the UK leaving the dataset (a noticeably high outlier in SMR) and the COVID-19 pandemic. A 2% reduction (95% CI −2.6% to −1.2%) in annual mortality rate was noted in males from 2011 to 2018, while females increased (AAPC 1.3% (95% CI 0.1% to 2.6)%) in the same time frame.Conclusion: The plateau in COPD-related deaths across Europe from 2011 to 2018 demands focus. Geographical variation in mortality suggests under-reporting in some countries, which may underestimate the true burden
Microscopic Insights into Firework- and Biomass-Burning-Derived Haze Particles during the Diwali Festival in Delhi, India
Get PDFDelhi, one of the world's most densely populated megacities, experiences extreme haze during the Diwali Festival - a nationwide celebration marked by intense fireworks coinciding with postmonsoon biomass burning. Although bulk measurements routinely show sharp PM 2.5 spikes during Diwali, direct microscopic evidence linking specific aerosol types to these concurrent sources remains limited. Here, we combined transmission electron microscopy (TEM) with bulk chemical analysis to identify particle types and track their physicochemical evolution throughout the Diwali period. Before Diwali, aerosols were dominated by potassium (K)-rich particles (25%), carbonaceous particles (primary organic aerosol (POA) and soot, 29%), and their internal mixtures (K−POA/soot, 37%), with frequent spherical POA (i.e., tar balls), indicating a strong biomass-burning influence. During Diwali, particle populations shifted abruptly to a pyrotechnic signature of fireworks, characterized by abundant Al 2 O 3 monomers (30−300 nm) and their agglomerates, either as bare (36−40%) or uniformly coated by K 2 SO 4 (Al 2 O 3 −K, 46−47%). After Diwali, ultrafine Al 2 O 3 particles (<100 nm) persisted and underwent coagulation with aged biomass-burning particles, forming distinctive Al 2 O 3 −K−POA/soot internal mixtures. Therefore, Al 2 O 3 nanoparticles can serve as a tracer of fireworks and were further internally mixed with carbonaceous particles derived from biomass burning during severe haze events of Diwali. These metal-containing particles warrant particular attention because of their potential toxicity and adverse respiratory health effects in the densely populated megacity
Relevance of Chemokines in Mobilizing γδ T Cells in the Biliary Tract Cancer Microenvironment: Potential for γδ T-Cell–Based Adoptive Cell Therapy
Get PDFObjective: Biliary tract cancer (BTC) has a poor prognosis with limited therapeutic options. γδ T cells represent an MHC-independent immune cell population; however, their therapeutic efficacy in solid tumors is constrained by insufficient tumor infiltration. Chemokine-mediated trafficking is fundamental to T lymphocyte recruitment; however, the chemokine landscape of the BTC tumor microenvironment (TME) remains uncharacterized. Using single-cell RNA sequencing of BTC tissues, we delineated chemokine ligand expression patterns, stratified chemokine producers by lineage, assessed γδ T-cell recruitment mechanisms, and identified chemokine-mediated immune escape.Methods: We analyzed single-cell RNA sequencing data from 3 independent GEO cohorts (GSE210066, GSE201425, and GSE213452; 19 patients) to comprehensively delineate γδ T-cell mobilization-related chemokine expression across the BTC TME using the Seurat v5.0 pipeline in R.Results: Analysis identified a multiaxis chemokine profile within the BTC TME. High expression of CCL5, CCL4, and CCL3 established predominant CCR5-mediated recruitment axes supporting Vγ9Vδ2 T-cell infiltration, whereas CCL2 and modest CXCL8 supported CCR2+ and CXCR1+ Vδ1 T-cell recruitment. Notably, CXCL16 expression supported epithelial γδ T-cell homing through CXCR6. However, critical deficiencies in CXCL9 and CXCL10 suppress the IFN-γ-driven immunity. Paradoxically, chemokine axes supporting γδ T-cell recruitment (CCL2-CCR2, CXCL8-CXCR1, CXCL12-CXCR4) simultaneously recruit immunosuppressive populations, such as myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and tumor-associated macrophages (TAMs).Conclusion: Comprehensive single-cell analysis identified selective chemokine recruitment signatures supporting γδ T-cell infiltration but revealed paradoxical corecruitment of immunosuppressive populations. Patient stratification through chemokine profiling, combined with γδ T-cell enrichment and targeted chemokine antagonism, represents a rational therapeutic strategy
Identification of significant SNPs and the quantification of correlation using Genomic Informational Field Theory (GIFT)
Get PDFGiven data on genotypes and phenotypes from a sample population, we show how ordering the data by phenotype and analysing the information contained in the corresponding list of genotypes can identify those SNPs which have a significant correlation with phenotype. We derive formulae for p-values to quantify the significance of each SNP, and show how to analyse the correlations between different SNPs. As well as using classical covariance and correlations, we introduce an information-theoretic measure of correlation which is based on Shannon’s informational entropy. This variational formulation also gives rise to other ways of determining the strength of a SNP’s influence on phenotype in a biallelic population using ‘field’ functions which account for the relationship between phenotype and genotype. By computing this field for each SNP, we are able to quantify the correlations between SNPs. The results are shown to depend on the number of each genostate (aa, Aa and AA) in the population in a predictable manner. The methods are illustrated using data on horse height
Recruitment of bifunctional regulator thermospermine to methylated ribosomes directs xylem fate
Get PDFPolyamines are often associated with ribosomes and are thought to stabilize their integrity. In Arabidopsis, the polyamine thermospermine (tSpm) affects xylem cell fate. tSpm induces translation of SUPPRESSOR-OF-ACAULIS51 (SAC51) and SAC51-LIKEs (SACLs), which inhibit heterodimerization of the xylem development proteins LONESOME-HIGHWAY (LHW) and TARGET-OF-MONOPTEROS5. Here, we report a methyltransferase, OVERACHIEVER, that methylates the peptidyl transferase center of the 25S ribosomal RNA (rRNA). Residue m3U2952 promotes functional tSpm binding to a specific site connecting the P-site transfer RNA (tRNA) with rRNA residues in the peptidyl transferase center. This interaction enhances the translation of SACLs but inhibits that of LHW. Our study uncovers the dependency between a conserved rRNA base methylation and a polyamine in orchestrating cell fate decisions, highlighting a role for the ribosome chemical landscape in translational regulation
Investigating the lubricant effect on hydrogen engine particulate emissions – part II: Influence of oil formulation and operating condition
Get PDFThe examination of the morphology and chemical content of lubricating oil-derived particles is essential for understanding the ramifications of our current decarbonisation trajectory, as research on these emissions is notably scarce, particularly in the context of hydrogen as a potential propulsion medium. Consequently, a spark-ignited hydrogen engine was tested under a series of 21 steady state conditions with four different oils (baseline, low & high ash, and high viscosity). The study examines particle elemental composition, morphology, size, count, and influence of oil formulation. A differential mobility spectrometer (DMS500) with a catalytic stripper, transmission electron microscopy (TEM) and energy dispersive X-ray (EDX) spectroscopy were employed to characterise the particles emitted. The solid particle number (SPN) values for each oil and all 21 conditions were near or below the DMS resolution limit of 1 × 104/cm3 with a variety of particles ranging from 10 to 50 nm crystalline structures to agglomerates (10-100 nm) and large clusters (100 nm-4 μm). Across all oil types, many 10–100 nm and >100 nm s particles were found to be rich in Fe, Ni, Mn, Cr, Al (engine wear), C, Mg, Zn, P, S, Ca (oil additives), and K, Na, F, Cl (coolant residues). Large calcium-rich clusters appear in the high-ash oil, while carbon- and sulphur-rich clusters are found in the high-viscosity oil
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