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Xanthan gum production from sugarcane bagasse and its potential for biodegradable food packaging films
No full textImprovement of Diagnostics in NSCLC Patients with <i>MET</i> Exon 14 Mutations Using Complementary DNA/RNA-NGS and Identification of Two Novel Exonic Splicing Mutations
No full textMET exon 14 (METex14) skipping mutations differ from other non-small cell lung cancer (NSCLC) genomic biomarkers as they result in aberrantly spliced MET transcripts and increased MET-signaling. However, the most accurate method for their detection remains debated. We conducted a retrospective study of previously identified METex14 skipping NSCLC samples by using different, commercially available, diagnostic targeted DNA- /RNA-Next-Generation Sequencing (NGS) panels. We primarily used small DNA-NGS panels covering the 5 ' splice site of METex14 and supplemented by targeted RNA sequencing for selected cases. Using this approach, we identified <0.2% patients with METex14 mutations. Due to this low frequency, we validated and introduced complementary NGS testing using combined DNA/RNA-panels. This resulted in an increased number of METex14-positive patients (3.5%) and allowed us to identify METex14 skipping transcripts. Collectively, data from our cohort (n = 34) demonstrated that optimal diagnostics of METex14 variants require a complementary DNA-NGS performed with targeted panels covering both METex14 splice sites, and RNA-NGS. Consequently, we propose a new workflow for interpretation of concordant and discordant findings in METex14 detection. Finally, the potential of DNA-identified METex14 variants to cause aberrant splicing was in silico assessed by the MaxEntScan tool, providing a quantitative approach to splicing disruption. Interestingly, we also identified two novel variants located inside METex14, which also produced the METex14 skipping transcript despite being located outside the canonical splice sites. The altered binding site resulting from these exonic mutations was in silico determined by SpliceTransformer
Proposal for room-temperature superradiant echoes induced by multiple re-phasing of frequency-grated NV spin sub-ensembles
No full textGenome-wide identification of tissue-specific fitness genes in murine models of <i>Staphylococcus aureus</i> infection
No full textStaphylococcus aureus must dynamically rewire its metabolism to persist within distinct host tissues during infection. We applied in vivo transposon-directed insertion site sequencing (TraDIS) in murine models of skin, kidney, and spleen infections to define tissue-specific fitness landscapes for the epidemic USA300 lineage. We identified 46, 76, and 69 fitness genes in the skin, kidney, and spleen, respectively. The core gluconeogenesis gene fbp was essential across all tissues, whereas pckA and gapB showed organ-specific essentiality in the kidney and spleen. Skin infection required oxidative stress and DNA repair genes (ahpC, ahpF, dps, uvrC, and xseA), consistent with elevated genotoxic pressure. In contrast, kidney and spleen relied on branched-chain amino acid catabolism (bkdAB), lipid metabolism (SAUSA300_0355), and putative polyamine biosynthesis (SAUSA300_0458). Competition assays in vivo and under oxidative (H2O2) and gluconeogenic (M9) conditions validated these tissue-specific dependencies. These results reveal how S. aureus remodels metabolic networks and identifies context-specific vulnerabilities for therapeutic targeting.</p
Evaluating the role of mavacamten in symptomatic non-obstructive hypertrophic cardiomyopathy:the ODYSSEY-HCM trial
No full textNon-obstructive hypertrophic cardiomyopathy (nHCM) is defined by exertional limitation without left ventricular outflow tract obstruction and lacks approved targeted therapies. ODYSSEY-HCM was a phase 3, randomized, double-blind, placebo-controlled trial that enrolled adults with symptomatic nHCM and left ventricular ejection fraction ≥ 60% to receive mavacamten, a selective cardiac myosin inhibitor, or placebo for 48 weeks with dose titration guided by serial echocardiography. The co-primary endpoints were the change in peak oxygen uptake and the 23-item Kansas City Cardiomyopathy Questionnaire clinical summary score. Mavacamten produced clear pharmacodynamic effects manifested by reductions in circulating markers of myocardial stress and imaging indices consistent with modest reverse remodelling, but it did not produce statistically significant improvement in the prespecified co-primary clinical endpoints at 48 weeks. Treatment was associated with an increased incidence of reversible reductions in ejection fraction necessitating protocol-mandated dose interruption, indicating a constrained therapeutic window in this cohort. Collectively, the data demonstrate target engagement without definitive patient-centered benefit over the study interval. Further evaluation is required, including randomized trials of agents with alternative pharmacokinetic and titration properties, studies with extended exposure, and phenotype-enriched enrollment, to determine whether biomarker and imaging responses can be translated into sustained improvements in functional capacity and health-related quality of life in patients with nHCM.</p
Prevalence and anatomical distribution of MRI lesions in axSpA and differences between patients with and without peripheral involvement:results from the ASAS classification cohort
No full textObjective To evaluate the prevalence and anatomical distribution of inflammatory and structural MRI lesions in axial spondyloarthritis (axSpA) and compare these between patients with isolated axial involvement and those with peripheral manifestations.Methods Data from the Assessment of SpondyloArthritis International Society (ASAS) Classification Cohort were analysed. Peripheral involvement was defined as past or current arthritis/dactylitis/enthesitis. Sacroiliac joint (SIJ) and spinal MRI lesions typical of axSpA were classified per ASAS lesion definitions and centrally read with multi-reader majority agreement (lesion present if called by the majority; SIJ ≥4/7, spine ≥5/9 readers). Comparisons between patients with and without peripheral manifestations were made.ResultsAmong 199 axSpA patients with SIJ MRI, 67 also had spinal MRI. Subchondral SIJ bone marrow oedema (BMO) was observed in 49%, without quadrant preference or subgroup differences. Other SIJ inflammatory lesions ranged from 4%–18%. Erosions (35%) and fat lesions (22%) were the most frequent structural lesions. In the spine, BMO, fat lesions and syndesmophytes/ankylosis were detected in 38%, 25% and 5%, respectively, with similar subgroup frequencies. Among 40 patients with both SIJ and whole spine MRI, inflammatory lesions were observed in both sites in 18%, SIJ only in 38%, and spine only in 20%. Structural lesions occurred in both sites in 19%, SIJ only in 30%, and spine only in 5%, with no subgroup differences.Conclusion The prevalence and anatomical distribution of ASAS-defined MRI lesions was similar across axSpA subgroups. Notably, 20% exhibited spine-only inflammation, suggesting potential added diagnostic and monitoring value of spinal MRI, warranting further study.OBJECTIVE: To evaluate the prevalence and anatomical distribution of inflammatory and structural MRI lesions in axial spondyloarthritis (axSpA) and compare these between patients with isolated axial involvement and those with peripheral manifestations.METHODS: Data from the Assessment of SpondyloArthritis International Society (ASAS) Classification Cohort were analysed. Peripheral involvement was defined as past or current arthritis/dactylitis/enthesitis. Sacroiliac joint (SIJ) and spinal MRI lesions typical of axSpA were classified per ASAS lesion definitions and centrally read with multi-reader majority agreement (lesion present if called by the majority; SIJ ≥4/7, spine ≥5/9 readers). Comparisons between patients with and without peripheral manifestations were made.RESULTS: Among 199 axSpA patients with SIJ MRI, 67 also had spinal MRI. Subchondral SIJ bone marrow oedema (BMO) was observed in 49%, without quadrant preference or subgroup differences. Other SIJ inflammatory lesions ranged from 4%-18%. Erosions (35%) and fat lesions (22%) were the most frequent structural lesions. In the spine, BMO, fat lesions and syndesmophytes/ankylosis were detected in 38%, 25% and 5%, respectively, with similar subgroup frequencies. Among 40 patients with both SIJ and whole spine MRI, inflammatory lesions were observed in both sites in 18%, SIJ only in 38%, and spine only in 20%. Structural lesions occurred in both sites in 19%, SIJ only in 30%, and spine only in 5%, with no subgroup differences.CONCLUSION: The prevalence and anatomical distribution of ASAS-defined MRI lesions was similar across axSpA subgroups. Notably, 20% exhibited spine-only inflammation, suggesting potential added diagnostic and monitoring value of spinal MRI, warranting further study.</p
Hypersensitivity to Opioids:Prevalence, Mechanisms, Diagnosis and Management
No full textMany patients report being allergic to opioids and/or have allergy warnings documented in their medical records. However, the reasoning behind these warnings is often unclear and frequently lacks clinical validation. Reported reactions may include skin rashes, itching, severe vomiting, fainting or respiratory arrest occurring during postoperative recovery where opioids were administered. In many cases, there is also uncertainty about which specific opioid was used. An allergy warning to one opioid further raises the question of whether the patient can tolerate other opioids. In this review, we address the exceedingly rare IgE-mediated opioid allergy and cross-reactivity between opioids, along with non–immune-mediated histamine release and other adverse effects of opioids that patients or clinicians may mistake for allergic reactions. We propose a simple risk stratification algorithm for the clinical management of patients labelled as opioid allergic—helping to distinguish who should be referred for allergy evaluation and who can safely be treated with opioids with or without antihistamine pre-treatment.</p
