Citations

Lactococcosis has emerged as an economically and ecologically significant disease in aquatic animals worldwide. This study employed multilocus sequence typing (MLST) to investigate the genetic diversity of Lactococcus spp. strains from Brazilian fish species and evaluate their phylogenetic relationships with global isolates to elucidate potential epidemiological connections involving multiple host species and distinct geographic regions. A total of 55 isolates from different laboratories had their DNA extracted, followed by the amplification and sequencing of the internal fragments of seven housekeeping genes (als, atpA, tuf, gapC, gyrB, rpoC and galP). Sequence types (STs) and clonal complexes (CCs) were defined. An unrooted neighbor-joining phylogenetic tree was generated using allele profiles from this study and those previously reported from other aquatic animal species. The isolates comprised 29 STs (11 previously reported, 18 novel ones), which were grouped into species-specific CCs: CC5 (L. formosensis); CC4, CC17, CC62 (L. garvieae); CC24, CC29, CC97 (L. petauri). Considerable genetic divergence was observed, with L. formosensis and L. garvieae forming heterogeneous populations, while L. petauri was more homogeneous. These findings describe the MLST structure of the sampled isolates and should be interpreted as hypothesis-generating rather than population-level estimates of genotype prevalence. Phylogenetics confirmed groupings within the CCs and revealed additional phylogenetic clustering patterns. In conclusion, the Brazilian Lactococcus spp. strains analyzed in this study constitute a genetically diverse population based on their STs. MLST and phylogenetic analysis demonstrated genetic relatedness between the L. garvieae and L. formosensis isolates from this study and those from other aquatic animal species. In contrast, all the STs identified for L. petauri in this study were unrelated to the MLST lineages responsible for outbreaks in Brazilian Nile tilapia (Oreochromis niloticus) and North American rainbow trout (Oncorhynchus mykiss). This suggests that piscine L. petauri populations in the Americas evolved from distinct ancestral origins.

Abstract Glioblastoma progression is spatially heterogeneous, but conventional imaging provides limited information about where subsequent tumor progression is likely to occur. We developed a directional magnetic resonance elastography (MRE) framework to test whether local post-treatment tumor–brain interface mechanics are associated with later spatial tumor progression. In a secondary analysis of a prospectively acquired glioblastoma cohort, wedge-level viscoelastic instability features were extracted from the first post-treatment MRE scan and related to novel tumor burden on the second post-treatment scan after excluding tumor already present on pretreatment or first post-treatment imaging. Nine patients had longitudinal imaging suitable for spatial comparison; six lesions showed net interval growth and were included in the primary wedge-level directional analysis, while three non-growing lesions were retained for descriptive comparison. In growing lesions, several directional mechanical features were descriptively associated with later novel tumor burden. In cluster-aware models accounting for within-patient dependence among wedges, mean Δtanδ showed the most consistent association with later wedge-level novel tumor fraction across mixed-effects and generalized estimating equation analyses. Associations were directionally stable across wedge-width sensitivity analyses. These findings provide proof of principle that post-treatment glioblastoma interface mechanics contain spatially resolved information related to where later tumor emergence occurs, supporting further validation of directional MRE as a framework for longitudinal mapping of progression geometry.

ABSTRACT Background Uremic toxins are a growing area of research in nephrology, with significant implications in the progression and treatment of chronic kidney disease (CKD) and the management of end‐stage kidney disease (ESKD). This bibliometric analysis aims to evaluate the global research trends, key contributors, and the impact of publications in the field of uremic toxins from 1991 to 2024. Methods The data were retrieved from the Science Citation Index Expanded (SCI‐EXPANDED) database. The study analyzed 2210 articles using various bibliometric indicators, including total publications ( TP ), average number of citations per publication ( CPP 2024 ), and the Y ‐index for author contributions. Publication trends were examined across countries, institutions, and authors. The analysis included document types, languages, Web of Science categories, and journals. Results The study revealed a steady increase in uremic toxin research publications. Japan, the USA, and China remained the most productive countries, with Japan maintaining the highest output, while Belgium achieved the highest citation impact. Citations of uremic toxin‐related research peaked 2 years following publication and plateaued after approximately 6 years. The research foci evolved, with CKD, ESKD, indoxyl sulfate, protein‐bound solutes, and gut microbiota gaining prominence. Studies on oxidative stress, inflammation, metabolomics, and advanced adsorption‐based toxin removal strategies increased markedly. International collaboration and interdisciplinary integration across nephrology, microbiology, and biochemistry correlated with higher citation performance and research visibility. Conclusion This bibliometric study provides an in‐depth analysis of uremic toxin research trends, identifies major contributors, and suggests future research priorities. The findings can inform future research directions, guide funding allocation, and strengthen global collaborative efforts towards improved management of toxin‐related kidney disease.

An exhalation delivery system for fluticasone (EDS-FLU) is designed to deposit drug into sinonasal regions above the inferior turbinate, particularly sinus drainage pathways not reached by standard nasal steroid sprays. We evaluated the efficacy and safety of EDS-FLU for chronic rhinosinusitis (CRS). We reviewed four independent randomized controlled trials derived from three published articles identified through searches of PubMed, Embase, SCOPUS, Google Scholar, Web of Science, and the Cochrane Library up to April 2024. Outcomes included 22-item Sinonasal Outcome Test (SNOT-22) scores, nasal symptom scores, nasal polyp scores, patient global impression of change (PGIC), responder and surgical indication rates, and adverse events. Compared with EDS-placebo, EDS-FLU produced greater reductions in nasal polyp scores and SNOT-22 scores over 6 months. At 3 months, nasal congestion, facial pain, rhinorrhea, and olfactory dysfunction improved more with EDS-FLU, and PGIC responder and complete response rates were higher at 3 and 6 months. EDS-FLU reduced surgical indication and increased overall responder rates at 3 months but not at 6 months. Epistaxis and nasal septal erosion or ulceration occurred more frequently with EDS-FLU, whereas rates of headache, nasal congestion, nasopharyngitis, and upper respiratory infection were similar between groups. EDS-FLU provides clinically meaningful improvements in subjective and objective outcomes in CRS but is associated with an increased risk of local nasal adverse events, warranting individualized risk-benefit assessment.

Abstract Background For many evidence criteria within v3.0 of the ACMG/AMP guidelines, methodologies have been developed to empower their use outside the stipulated evidence strengths. However, no such methodology has been established for case-control data (PS4). With the release of large-scale unselected case-control datasets and expansion of nationally-collected laboratory datasets enriched for pathogenic variant carriers, there is potential to combine datasets across ascertainment contexts in a more quantitative manner using novel likelihood ratio tools. Methods Using our published PS4-LR-Calculator, we calculated a combined log likelihood ratio (PS4-LLR) across five datasets (three unselected, and two enriched), and estimated enrichment of pathogenic variants in clinically-ascertained laboratory data using truncating variant prevalence. Results Data were combined for 10,817 missense variants from 325,345 female breast cancer patients and 671,006 controls of Western European ancestry for five breast cancer susceptibility genes ( BRCA1, BRCA2, PALB2, ATM, CHEK2 ). A combined LLR was produced for 4,690 missense variants; 927 variants received evidence towards pathogenicity (LLR≥ 1), and 3,242 received evidence towards benignity (LLR≤ -1). Conclusion This flexible, variant-level methodology combines nationally-collected ‘enriched’ datasets with unselected case-control cohorts, expanding the available information for case-control analysis, boosting power, enabling exploration of atypical penetrance and empowering variant classification.

Abstract Background The most compelling advantage that photon counting detectors (PCDs) currently have over energy integrating detectors (EIDs) for CT applications may be their improved spatial resolution. However, PCDs are difficult to manufacture. Next‐generation EIDs using conventional scintillator sensors could be easier to mass produce, but their spatial resolution is thought to be limited by fill factor considerations. Specifically, each EID pixel comprises a block of scintillator surrounded by inactive, optically reflective septa. The minimum width of optically reflective septa is ∼0.1 mm, and unless this is shrunk, decreases in pixel pitch inevitably cause an increasing fraction of dead space. Purpose To propose a modified system geometry in which the detector pixels are tilted by a few degrees, such that rays that are incident on reflective septa would later encounter scintillator. Because reflective septa are nearly transparent to x‐rays compared to scintillator, this geometry restores much of the lost fill factor. Methods Tilting can be achieved in several different ways. We discuss three implementation options: individual detector modules may be tilted, with gaps between modules that are seamless from the perspective of the x‐ray source; the whole detector can be arranged to point towards a “false” focal spot that is offset slightly from the true focal spot; the scintillator wafer can structured differently, e.g. by sawing it at an angle. The pros and cons of each option are discussed. Tilting introduces blurring, but a smaller pixel size improves resolution, and the combination of both improves both resolution and fill factor. We used Monte Carlo simulations to compare a conventional detector with 1.0 mm, 0.75, or 0.5 mm pixel pitch to a tilted detector with 0.5 mm pixel pitch. We assumed negligible optical crosstalk and electronic noise, that the scintillator was 1.5 mm thick with attenuation similar to gadolinium oxysulfide, that the reflective septa was 0.1 mm wide at standard resolution or 0.08 mm at higher resolutions and composed of a low‐attenuating polymer similar to acrylic infused with 20% titanium content. We also compared this to a simple model of a CdTe detector with 1.6 mm thickness, 0.3 mm pixel pitch, and Gaussian charge sharing. Results Tilt increases the aperture of the pixel in an energy‐dependent fashion. With a 1D ASG (85% fill factor) and at 120 kVp, the detection efficiencies (DQE(0)) of a conventional detector at 1.0 mm, conventional detector at 0.5 mm pixel pitch, CdTe detector, and tilted detector at 0.5 mm pixel pitch are 65%, 55%, 66%, and 64%, respectively. With a sparse 2D ASG (1.5 × 3.0 mm openings, 86% fill factor), the DQE(0) of a tilted detector with 0.75 mm is 69%. The DQE(0) of all detectors decreases at higher energy because of punch‐through. Conclusions By tilting detector modules a few degrees, energy‐integrating detectors can provide increases in spatial resolution without the expected losses in fill factor. This architecture could bring the resolution improvements associated with photon counting CT into the domain of energy‐integrating detectors equipped with conventional scintillator sensors.

PURPOSE We tested the hypothesis that adding metastasis-directed therapy (MDT) to standard-of-care (SOC) systemic therapy improves progression-free survival (PFS) among patients with oligometastatic disease. METHODS EXTEND was a multicenter randomized phase II trial. Patients with 1-5 metastases were randomly assigned to MDT + SOC versus SOC in one of the six baskets (breast, pancreas, kidney, two prostate baskets, and an other basket) with basket-specific stratification and powering. PFS, the primary end point, was prespecified in the per-protocol set within each basket, across all baskets, and across all baskets excluding the prostate baskets. Exploratory end points included circulating tumor DNA (ctDNA) and immune profiling. RESULTS From 2018 through 2023, 521 patients were screened, 350 were randomly assigned, and 334 were analyzed per protocol (MDT + SOC, n = 166; SOC, n = 168). Radiotherapy was used as MDT for 98% of metastases (370/379). Overall, after a median follow-up of 53 months, PFS was improved with MDT + SOC (hazard ratio [HR], 0.54 [95% CI, 0.41 to 0.72], P < .001). Similarly, PFS was improved when excluding the prostate baskets (HR, 0.60 [95% CI, 0.40 to 0.89]). Within each basket, PFS superiority was identified for the pancreas, prostate, and other baskets, whereas the breast and kidney baskets were inconclusive. At enrollment, detectable ctDNA correlated with shorter PFS and survival; by contrast, ctDNA clearance 3 months postenrollment correlated with improved survival. MDT + SOC-induced systemic immune activation was most pronounced among baskets demonstrating PFS superiority. CONCLUSION The phase II EXTEND trial supports the addition of MDT to SOC for oligometastatic disease. Histology-specific efficacy signals were identified for phase III testing. Translational insights suggest the potential for optimizing the definition of oligometastasis using ctDNA and point to systemic immune responses as a possible mechanism of benefit from MDT.