Real-World Treatment Patterns and Timeliness of Clinical Care Pathway for Non-Small Cell Lung Cancer Patients in Austria: The PRATER Retrospective Study.

This was a retrospective study of the profile and initial treatments of adults diagnosed with early-stage (ES) non-small cell lung cancer (NSCLC) during January 2018-December 2021 at 16 leading hospital institutions in Austria, excluding patients enrolled in clinical trials. In total, 319 patients were enrolled at a planned ~1:1:1 ratio across StI:II:III. Most tested biomarkers were programmed death ligand 1 (PD-L1; 58% expressing), Kirsten rat sarcoma virus (KRAS; 22% positive), and epidermal growth factor receptor (EGFR; 18% positive). Of 115/98/106 StI/II/III patients, 82%/85%/36% underwent surgery, followed by systemic therapy in 9%/45%/47% of those [mostly chemotherapy (ChT)]. Unresected treated StIII patients received ChT + radiotherapy [43%; followed by immune checkpoint inhibitors (ICIs) in 39% of those], ICI ± ChT (35%), and ChT-alone/radiotherapy-alone (22%). Treatment was initiated a median (interquartile range) of 24 (7-39) days after histological confirmation, and 55 (38-81) days after first medical visit. Based on exploratory analyses of all patients newly diagnosed with any stage NSCLC during 2018-2021 at 14 of the sites (N = 7846), 22%/10%/25%/43% had StI/II/III/IV. The total number was not significantly different between pre-COVID-19 (2018-2019) and study-specific COVID-19 (2020-2021) periods, while StI proportion increased (21% vs. 23%; p = 0.012). Small differences were noted in treatments. In conclusion, treatments were aligned with guideline recommendations at a time which preceded the era of ICIs and targeted therapies in the (neo)adjuvant setting.

A novel technique of voice-sparing cricotracheal resection.

Background: Cricotracheal resection (CTR) is considered the standard of care for patients suffering from idiopathic subglottic stenosis (iSGS). Although CTR results in permanent restoration of airway patency, it has a mild to moderate impact on voice quality. Here we propose modifications of the standard CTR technique to make it a voice-preserving procedure. Methods: Five women with iSGS underwent voice-sparing CTR between January 2022 and January 2023. In this procedure, through several technical adaptations, the function of the cricothyroid joint was preserved. Outcomes of these voice-sparing CTRs were compared to outcomes in patients who underwent standard CTR in our institution. All patients underwent full functional preoperative and postoperative workups, including spirometry, voice measurements, patient self-assessment, and fiberoptic endoscopic evaluation of swallowing. Results: All 5 patients in the study group suffered from iSGS with high-grade Myer-Cotton III° stenosis (100%); 1 patient had previously undergone endoscopic laser resection. Voice evaluation demonstrated a nearly unchanged fundamental pitch (mean preoperative, 191 ± 73.1 Hz; postoperative, 182 ± 64.2 Hz) and dynamic voice range (preoperative, 24.4 semitones; postoperative, 20.4 semitones). This was in contrast to the control group, in which significantly reduced voice quality was observed. Conclusions: In selected patients suffering from iSGS, excellent functional results can be obtained with voice-sparing CTR.

An extended DNA-free intranuclear compartment organizes centrosome microtubules in malaria parasites.

Proliferation of Plasmodium falciparum in red blood cells is the cause of malaria and is underpinned by an unconventional cell division mode, called schizogony. Contrary to model organisms, P. falciparum replicates by multiple rounds of nuclear divisions that are not interrupted by cytokinesis. Organization and dynamics of critical nuclear division factors remain poorly understood. Centriolar plaques, the centrosomes of P. falciparum, serve as microtubule organizing centers and have an acentriolar, amorphous structure. The small size of parasite nuclei has precluded detailed analysis of intranuclear microtubule organization by classical fluorescence microscopy. We apply recently developed super-resolution and time-lapse imaging protocols to describe microtubule reconfiguration during schizogony. Analysis of centrin, nuclear pore, and microtubule positioning reveals two distinct compartments of the centriolar plaque. Whereas centrin is extranuclear, we confirm by correlative light and electron tomography that microtubules are nucleated in a previously unknown and extended intranuclear compartment, which is devoid of chromatin but protein-dense. This study generates a working model for an unconventional centrosome and enables a better understanding about the diversity of eukaryotic cell division.

Food-Poisoning Bacteria Employ a Citrate Synthase and a Type†II NRPS To Synthesize Bolaamphiphilic Lipopeptide Antibiotics*.

Mining the genome of the food-spoiling bacterium Burkholderia gladioli pv. cocovenenans revealed five nonribosomal peptide synthetase (NRPS) gene clusters, including an orphan gene locus (bol). Gene inactivation and metabolic profiling linked the bol gene cluster to novel bolaamphiphilic lipopeptides with antimycobacterial activity. A combination of chemical analysis and bioinformatics elucidated the structures of bolagladin A and B, lipocyclopeptides featuring an unusual dehydro-ß-alanine enamide linker fused to an unprecedented tricarboxylic fatty acid tail. Through a series of targeted gene deletions, we proved the involvement of a designated citrate synthase (CS), priming ketosynthases III (KS III), a type II NRPS, including a novel desaturase for enamide formation, and a multimodular NRPS in generating the cyclopeptide. Network analyses revealed the evolutionary origin of the CS and identified cryptic CS/NRPS gene loci in various bacterial genomes.

Performance characteristics of qPCR assays targeting human- and ruminant-associated bacteroidetes for microbial source tracking across sixteen countries on six continents.

Numerous quantitative PCR assays for microbial fecal source tracking (MST) have been developed and evaluated in recent years. Widespread application has been hindered by a lack of knowledge regarding the geographical stability and hence applicability of such methods beyond the regional level. This study assessed the performance of five previously reported quantitative PCR assays targeting human-, cattle-, or ruminant-associated Bacteroidetes populations on 280 human and animal fecal samples from 16 countries across six continents. The tested cattle-associated markers were shown to be ruminant-associated. The quantitative distributions of marker concentrations in target and nontarget samples proved to be essential for the assessment of assay performance and were used to establish a new metric for quantitative source-specificity. In general, this study demonstrates that stable target populations required for marker-based MST occur around the globe. Ruminant-associated marker concentrations were strongly correlated with total intestinal Bacteroidetes populations and with each other, indicating that the detected ruminant-associated populations seem to be part of the intestinal core microbiome of ruminants worldwide. Consequently tested ruminant-targeted assays appear to be suitable quantitative MST tools beyond the regional level while the targeted human-associated populations seem to be less prevalent and stable, suggesting potential for improvements in human-targeted methods.