Optical and structural properties of float-type soda–lime–silica (SLS) glasses doped with 0·2 mol % TiO₂, ZrO₂, HfO₂, Nb₂O₅, Ta₂O₅, MoO₃ or WO₃ have been studied. Under ultraviolet excitation all d⁰ doped glasses exhibit broadband visible emission centred between 19000 and 25000 cm^–1 (400–525 nm) due to a transition from the 2p orbital of O^2– to the metal d⁰ orbital. Dopant additions lead to shifts in the ultraviolet absorption edge to lower energies, with doped glasses having an absorption edge 2000 cm^–1 (~20 nm), and in the case of MoO₃, 4000 cm^–1 (~40 nm), shifted relative to the corresponding undoped glass. Combined ultraiolet-visible absorption and X-band EPR spectroscopy analyses confirm that dopant cations occur in the studied glasses in the expected oxidation states of Ti⁴⁺, Zr⁴⁺, Hf⁴⁺, Nb⁵⁺, Ta⁵⁺, Mo⁶⁺ and W⁶⁺, although very low levels of Mo⁵⁺ are also observed, as demonstrated by the EPR resonance at g=1·92 (3·7 T). The incorporation of the studied dopants into SLS glasses may find applications as cover glasses in photovoltaic (PV) applications, providing ultraviolet protection of polymers and solar cell materials in PV units whilst enhancing solar cell efficiency through downconversion/fluorescence of absorbed ultraviolet photons with re-emission as visible photons, available for absorption and conversion by the solar cell material.

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system (CNS) caused by reactivation of the polyomavirus JC (JCV) typically in immunocompromised individuals. The risk of PML among rheumatic diseases may be higher for systemic lupus erythematosus (SLE), without, however, a clear association with the type and intensity of background therapy. We present the development and outcome of PML in a 32-year-old female lupus patient under mild immunosuppressive treatment, yet with marked B-cell lymphopenia in the peripheral blood and bone marrow (<1% of total lymphocytes). Despite treatment with the immune checkpoint inhibitor pembrolizumab, the patient showed progressive neurological and brain imaging deterioration and eventually died 15 months after PML diagnosis. To unveil possible underlying genetic liabilities, whole exome sequencing was performed which identified deleterious variants in GATA2 and CDH7 genes, which both have been linked to defective T- and/or B-lymphocyte production. These findings reiterate the possible role of disease-/patient-intrinsic factors, rather than that of drug-induced immunosuppression, in driving immune dysregulation and susceptibility to PML in certain patients with SLE.

Liquid biopsy assays are transforming precision oncology by providing a less invasive alternative to tissue biopsies. These assays screen for tumor genetic alterations in circulating free DNA, which typically requires detecting variants at low allele frequencies and, therefore, a high sensitivity and specificity. This international, multicenter analytical performance study evaluated the Hedera Profiling 2 circulating tumor DNA test panel (HP2), a hybrid capture-based next-generation sequencing assay for the detection of somatic alterations in circulating free DNA. Covering 32 genes, HP2 enables the detection of single-nucleotide variants (SNVs), insertions and deletions (Indels), fusions, copy number variations, and microsatellite instability status from a single DNA-only workflow. The analytical performance was assessed using reference standards and a diverse cohort of 137 clinical samples precharacterized by orthogonal methods. In reference standards with variants spiked in at 0.5% allele frequency, sensitivity and specificity were 96.92% and 99.67%, respectively, for SNVs/Indels and 100% for fusions. In clinical samples, SNV/Indel detection showed high concordance (94% for European Society for Medical Oncology Scale of Clinical Actionability for Molecular Targets level I variants) with orthogonal methods. Evidence for solid sensitivity was also found for copy number variation detection and microsatellite instability status determination. Overall, the HP2 assay showed significant potential as a sensitive and efficient pan-cancer test for liquid biopsy testing in a decentralized molecular pathology laboratory setting.

Background: Liquid biopsy (LBx) assays are transforming precision oncology by the screening of genomic alterations in cfDNA. These assays provide a less invasive alternative to tissue biopsies, which are not always feasible. Molecular pathology laboratories require LBx assays that detect variants at low allele frequencies using standardized methods. Methods: This study evaluated the Hedera Profiling 2 ctDNA test panel (HP2) (Hedera Dx, Epalinges, Switzerland), a hybrid capture-based NGS assay for the detection of somatic alterations from cfDNA. Covering 32 genes, HP2 enables the detection of SNVs, Indels, Fusions, CNVs, and MSI status from a single DNA-only workflow. The analytical performance was assessed using reference standards and a diverse cohort of 137 clinical samples pre-characterized by orthogonal methods. Results: In reference standards at 0.5% VAF, detection sensitivity and specificity for SNVs/Indels were 96.92% and 99.67%, respectively, and 100% each for Fusions. For MSI with VAFs of ≥1% and CNVs with VAFs of ≥ 2% both achieved 100% sensitivity. Conclusion: This international, multicenter analytical performance evaluation study across a large number of hospital laboratories demonstrated high concordance of HP2 assay with orthogonal methods, confirming its significant potential as a highly sensitive, and efficient Pan-Cancer test for future decentralized LBx testing.

Background: Immune checkpoint blockade (ICB) targeting the PD-1/PD-L1 axis has improved outcomes in non-small cell lung cancer (NSCLC), although reliable biomarkers for predicting benefit are still limited. Methods: In this exploratory study, we conducted a longitudinal analysis of the peripheral T-cell receptor (TCR) β repertoire in 28 patients with unresectable stage IIIb non-small cell lung cancer (NSCLC) who received anti-PD-L1 immunotherapy following chemoradiotherapy. Blood samples were collected at baseline and three months after treatment initiation. Results: At the cohort level, global TCR repertoire features such as diversity and richness did not change significantly over time. However, when looking at individual patients, more specific patterns became evident. Patients could be broadly separated based on changes in clonotype richness, with reductions generally accompanied by lower diversity and decreased convergent TCR frequency. We also observed differences in TRBV gene usage in relation to clinical outcome, with higher TRBV20-1 and lower TRBV28 frequencies tending to associate with improved survival and delayed disease progression. Interestingly, the disappearance of dominant clonotypes from the peripheral blood during treatment was linked to longer progression-free survival (PFS). In addition, patients with higher baseline blood plasma tumor mutational burden (bTMB) showed greater clonotype richness and were more likely to exhibit this clonotype loss. The combination of high bTMB and clonotype disappearance identified a subgroup of patients with particularly favorable outcomes. Conclusions: Overall, these results suggest that early responses to PD-L1 blockade may be reflected less in global TCR repertoire shifts, including clonality and diversity measures, and more in subtle changes in clonotype composition and dynamics, since the frequencies of certain TRBV genes and the disappearance of dominant clonotypes following ICB were associated with clinical outcomes integrating TCR profiling with bTMB and could therefore help refine patient stratification and improve the understanding of immune responses in NSCLC. Nevertheless, due to the small number of recruited patients, our study is exploratory and hypothesis-generating, and further validation in larger patient cohorts is warranted.