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A silica volume Bragg grating (VBG) is used to filter the light of a mid-infrared (mid-IR) supercontinuum laser. The VBG with a 7 µm period was inscribed with 800 nm pulses with a 100 fs duration and the phase-mask technique over a glass thickness of 3 mm. Despite silica's absorption, the VBG allows obtaining a narrowband light source tunable from 2.9 to 4.2 µm with a full width at half maximum (FWHM) of 29 nm. This demonstrates the great potential of using femtosecond-written VBGs as highly tunable, yet selective, spectral filters in the mid-IR.
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PURPOSE: Accurate risk stratification of thyroid nodules is essential for optimal patient management. This study aimed to assess the suitability of ChatGPT for risk stratification of thyroid nodules using a text-based evaluation. METHODS: A dataset was compiled comprising 50 anonymized clinical reports and associated risk assessments for thyroid nodules. The Chat Generative Pre-trained Transformer (ChatGPT) was used to classify sonographic patterns in accordance with the Thyroid Imaging Reporting and Data System (TI-RADS). The model's performance was assessed using various criteria, including sensitivity, specificity, and accuracy. A comparative analysis was conducted, evaluating the model against investigator-based risk stratification as well as histology. RESULTS: With an overall agreement rate of 42 % in comparison with examiner-based evaluation (TI-RADS 1-5), the results show that ChatGPT has moderate potential for predicting the risk of malignancy in thyroid nodules using text-based reports. The chatbot model achieved a sensitivity of 86.7 %, a specificity of 10.7 %, and an overall accuracy of 68 % when distinguishing between low-risk (TI-RADS 2 and 3) and high-risk (TI-RADS 4 and 5) categories. Interrater reliability was calculated with a Cohen's kappa of 0.686. CONCLUSION: This study highlights the potential of ChatGPT in assisting clinicians with risk stratification of thyroid nodules. The results suggest that ChatGPT can facilitate personalized treatment decisions, although the agreement rate is still low. Further research and validation studies are necessary to establish the clinical applicability and generalizability of ChatGPT in routine practice. The integration of ChatGPT into clinical workflows has the potential to enhance thyroid nodule risk assessment and improve patient care.
Subject(s)
Thyroid Nodule , Humans , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/pathology , Reproducibility of Results , Retrospective Studies , Ultrasonography/methods , Risk AssessmentABSTRACT
PURPOSE: Post-stroke depression (PSD) is a common complication after stroke and has a substantial effect on the quality of life of patients. Nevertheless, reliable individual prediction of PSD is not possible. As depressive symptoms have been associated with brainstem raphe (BR) hypoechogenicity on transcranial sonography (TCS), we aimed to explore the association of BR hypoechogenicity and the occurrence of PSD. MATERIALS AND METHODS: The Prognostic Markers of Post-Stroke Depression (PROMoSD) study is a prospective, observational, single-center, investigator-initiated study that included patients with acute ischemic stroke (AIS) to investigate the presence of BR hypoechogenicity by TCS early after symptom onset. The primary outcome was the presence of PSD assessed at the three-month follow-up investigation by a blinded psychiatrist and defined according to the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-V criteria). RESULTS: From 105 included AIS patients, 99 patients completed the study. AIS patients with a hypoechogenic BR developed a PSD at three months more frequently compared to patients with normal echogenicity (48.0% versus 4.1%, P <0.001). After adjustment for confounders (sex, mRS at follow-up, previous depressive episode), a hypoechogenic BR remained independently associated with a substantial increase in the appearance of PSD (adjusted OR: 6.371, 95%-CI: 1.181-34.362). CONCLUSION: A hypoechogenic BR is a strong and independent predictor of PSD at three months after AIS. TCS could be a routine tool to assess PSD risk in clinical practice, thereby streamlining diagnostic and therapeutic algorithms.
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Due to the widespread use of high-resolution sonography, numerous thyroid nodules are diagnosed, often as incidental findings. The challenge lies in evaluating various criteria such as size, shape, and echogenicity to assess the nodules' malignancy risk. Risk stratification systems have been developed to enable systematic assessment as well as to avoid unnecessary medical interventions and malignant findings being overlooked. This article provides an overview of the current diagnostic standards in primary assessment of thyroid nodules.
Subject(s)
Hydro-Lyases , Hydro-Lyases/metabolism , Hydro-Lyases/chemistry , Peptides/chemistry , Peptides/metabolism , HumansABSTRACT
Novel discoveries in natural product biosynthesis reveal hidden bioactive compounds and expand our knowledge in enzymology. Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly growing class of natural products featuring diverse non-canonical amino acids introduced by maturation enzymes as a class-defining characteristic. Underexplored RiPP sources, such as the human microbiome, the oceans, uncultured microorganisms, and plants are rich hunting grounds for novel enzymology. Unusual α- and ß-amino acids, peptide cleavages, lipidations, diverse macrocyclizations, and other features expand the range of chemical groups that are installed in RiPPs by often promiscuous enzymes. This review highlights the search for novelty in RiPP enzymology in the past two years, with respect to the discovery of new biochemical modifications but also towards novel applications.
Subject(s)
Peptides , Protein Processing, Post-Translational , Humans , Peptides/metabolism , Peptides/chemistry , Ribosomes/metabolism , Biological Products/metabolism , Biological Products/chemistry , Animals , Enzymes/metabolism , Enzymes/chemistryABSTRACT
Two common approaches to study the composition of environmental protist communities are metabarcoding and metagenomics. Raw metabarcoding data are usually processed into Operational Taxonomic Units (OTUs) or amplicon sequence variants (ASVs) through clustering or denoising approaches, respectively. Analogous approaches are used to assemble metagenomic reads into metagenome-assembled genomes (MAGs). Understanding the correspondence between the data produced by these two approaches can help to integrate information between the datasets and to explain how metabarcoding OTUs and MAGs are related with the underlying biological entities they are hypothesised to represent. MAGs do not contain the commonly used barcoding loci, therefore sequence homology approaches cannot be used to match OTUs and MAGs. We made an attempt to match V9 metabarcoding OTUs from the 18S rRNA gene (V9 OTUs) and MAGs from the Tara Oceans expedition based on the correspondence of their relative abundances across the same set of samples. We evaluated several metrics for detecting correspondence between features in these two datasets and developed controls to filter artefacts of data structure and processing. After selecting the best-performing metrics, ranking the V9 OTU/MAG matches by their proportionality/correlation coefficients and applying a set of selection criteria, we identified candidate matches between V9 OTUs and MAGs. In some cases, V9 OTUs and MAGs could be matched with a one-to-one correspondence, implying that they likely represent the same underlying biological entity. More generally, matches we observed could be classified into 4 scenarios: one V9 OTU matches many MAGs; many V9 OTUs match many MAGs; many V9 OTUs match one MAG; one V9 OTU matches one MAG. Notably, we found some instances in which different OTU-MAG matches from the same taxonomic group were not classified in the same scenario, with all four scenarios possible even within the same taxonomic group, illustrating that factors beyond taxonomic lineage influence the relationship between OTUs and MAGs. Overall, each scenario produces a different interpretation of V9 OTUs, MAGs and how they compare in terms of the genomic and ecological diversity they represent.
Subject(s)
DNA Barcoding, Taxonomic , Metagenome , DNA Barcoding, Taxonomic/methods , Eukaryota/genetics , Eukaryota/classification , RNA, Ribosomal, 18S/genetics , Metagenomics/methodsABSTRACT
BACKGROUND: The treatment of ischemic stroke (IS) has changed considerably in recent years. Particularly the advent of mechanical thrombectomy (MTE) has revolutionized the available treatment options. Most patients in developed countries have access to intravenous thrombolysis (IVT). However access to MTE remains restricted in some regions despite efforts to increase its availability. We performed an evaluation of national datasets to monitor improvements made in access to revascularization therapies for IS patients in Germany. METHODS: We analyzed national datasets on German Diagnosis-Related Groups and structured quality reports by extracting information of patients admitted with stroke with and without IVT and MTE for the period of 2019-2021. Data from 2016 and limited data for 2022 were also included for comparison. RESULTS: Admissions with ischemic stroke declined during the years of the COVID 19 pandemic by 4.5% from 227,258 in 2019 to 216,923 in 2021. IVT rates were stable with 16.3% being treated with IVT in 2019 and 2021. MTE rates continued to increase from 7.1 to 8.4% and the number of MTE centers increased by 14.8% in the same period. Over 87.3% of MTEs were performed in centers with a case volume exceeding 50 cases per year in 2021. The largest increase in the relative share of MTEs was seen in large MTE centers (n ≥ 200). Patient age for MTEs surpassed the age for IVTs in 2019 and the proportion of patients ≥ 80 years receiving MTE continued to increase. The proportion of regions in Germany with poor MTE rates (≤ 4.1%) decreased significantly from 2019 (12.3%) to 2021 (5.3%) (p < 0.001). CONCLUSIONS: We found strong evidence that while IVT rates reached a temporary ceiling effect, both the absolute number of and access to MTEs continued to increase in Germany. Regional disparities have become less significant and the majority of MTEs are performed in centers with medium or high case volumes.
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Ancestral reconstruction is a widely used technique that has been applied to understand the evolutionary history of gain and loss of gene families. Ancestral gene content can be reconstructed via different phylogenetic methods, but many current and previous studies employ Dollo parsimony. We hypothesize that Dollo parsimony is not appropriate for ancestral gene content reconstruction inferences based on sequence homology, as Dollo parsimony is derived from the assumption that a complex character cannot be regained. This premise does not accurately model molecular sequence evolution, in which false orthology can result from sequence convergence or lateral gene transfer. The aim of this study is to test Dollo parsimony's suitability for ancestral gene content reconstruction and to compare its inferences with a maximum likelihood-based approach that allows a gene family to be gained more than once within a tree. We first compared the performance of the two approaches on a series of artificial data sets each of 5,000 genes that were simulated according to a spectrum of evolutionary rates without gene gain or loss, so that inferred deviations from the true gene count would arise only from errors in orthology inference and ancestral reconstruction. Next, we reconstructed protein domain evolution on a phylogeny representing known eukaryotic diversity. We observed that Dollo parsimony produced numerous ancestral gene content overestimations, especially at nodes closer to the root of the tree. These observations led us to the conclusion that, confirming our hypothesis, Dollo parsimony is not an appropriate method for ancestral reconstruction studies based on sequence homology.
Subject(s)
Evolution, Molecular , Phylogeny , Likelihood FunctionsABSTRACT
Protists are key players in the biosphere. Here, we provide a perspective on integrating protist culturing with omics approaches, imaging, and high-throughput single-cell manipulation strategies, concluding with actions required for a successful return of the golden age of protist culturing.
Subject(s)
Eukaryota , Eukaryota/genetics , MultiomicsABSTRACT
Osteopenia and osteoporosis are common long-term complications of the cytotoxic conditioning regimen for hematopoietic stem cell transplantation (HSCT). We examined mesenchymal stem and progenitor cells (MSPCs) that include skeletal progenitors from mice undergoing HSCT. Such MSPCs showed reduced CFU-F frequency, increased DNA damage and enhanced occurrence of cellular senescence, while there was a reduced bone volume in animals that underwent HSCT. This reduced MSPC function correlated with elevated activation of the small RhoGTPAse Cdc42, disorganized F-actin distribution, mitochondrial abnormalities and impaired mitophagy in MSPCs. Changes and defects similar to those in mice were also observed in MSPCs from humans undergoing HSCT. A pharmacological treatment that attenuated the elevated activation of CDC42 restored F-actin fiber alignment, mitochondrial function, and mitophagy in MSPCs in vitro. Finally, targeting CDC42 activity in vivo in animals undergoing transplants improved MSPC quality to increase both bone volume and trabecular bone thickness. Our study shows that attenuation of CDC42 activity is sufficient to attenuate reduced function of MSPCs in a BM transplant setting.