1,824 research outputs found
Retrograde intramedullary headless compression screw fixation for pediatric mid-diaphyseal proximal phalanx malunion: A case study
No full textIntroduction: Proximal phalanx fractures in children, especially mid-diaphyseal fractures, can result in malunion and significant functional impairment. Early malunions require prompt and effective intervention to prevent long-term complications. This case study highlights the use of intramedullary headless compression screw (IMHCS) fixation in addressing a proximal phalanx malunion. Case presentation: A 12-year-old boy presented with a malunion of the mid-diaphyseal proximal phalanx of the fourth finger following conservative treatment of a cycling injury. Initial management involved immobilization followed by buddy taping; however, incomplete radiographic evaluation resulted in an underestimation of the volar angulation. At the four-week follow-up, the patient exhibited 50 degrees volar angulation, clinodactyly, and marked stiffness. The malunion was treated surgically with retrograde IMHCS fixation after osteoclasis. Radiographic evaluation confirmed proper reduction and alignment. The patient began physical therapy immediately, achieved full range of motion within four weeks and maintained excellent functional outcomes at one year postoperatively. Discussion: Retrograde IMHCS fixation is an innovative technique for managing phalangeal malunions, providing stable fixation and enabling early mobilization. This method avoids the physis, minimizing the risk of growth disturbances, eliminates the need for hardware removal, and ensures proper alignment. Conclusion: IMHCS fixation is a promising solution for early malunions and potentially fresh fractures of the proximal phalanx in pediatric patients. It offers stable fixation, preserves physeal integrity, and supports early rehabilitation, contributing to excellent functional recovery. Further studies are needed to evaluate its long-term outcomes.The authors wish to thank the Department of Orthopaedics at AZ Delta Roeselare, Belgium for their assistance in this manuscript
Inheemse bomen en struiken in Nederland en Vlaanderen : herkenning, verspreiding, geschiedenis en gebruik
No full textDerivatization of 1-phenyl substituted 4-amino-2-benzazepin-3-ones: evaluation of Pd-catalyzed coupling reactions
No full textSeveral Pd-catalyzed reactions were explored to further functionalize the bromo-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one scaffold (Aba). We report in this paper suitable reaction conditions for Suzuki, Buchwald–Hartwig, and Heck reactions. The substitution pattern of the starting aminobenzazepinone turned out to be crucial for the success of these transition metal-catalyzed reactions, which often required modifications of standard literature procedures. The Pd-catalyzed methods provide access to novel substitution patterns of the Aba scaffold.Steven Ballet, Rien De Wachter, Bert U.W. Maes, Dirk Tourwéhttp://www.sciencedirect.com/science/journal/0040402
Diagnostic Validation of a Comprehensive Targeted Panel for Broad Mutational and Biomarker Analysis in Solid Tumors
No full textSIMPLE SUMMARY: The analysis of tumor-associated genetic variants and biomarkers is critical for therapy choice, as specific mutations allow for a personalized treatment. Because more and more mutation-treatment combinations become available, screening should be performed on many genes simultaneously. The use of large and comprehensive gene panel screenings in molecular diagnostics, however, requires an extensive and thorough validation to demonstrate the correctness of all clinically relevant data. Here, we describe such validation using a large number of samples and confirmed effective detection of several types of mutations for different validation parameters. Samples of tumor patients thus can be reliably tested with a comprehensive assay to maximize their personalized treatment regimen. ABSTRACT: The use of targeted Next Generation Sequencing (NGS) for the diagnostic screening of somatic variants in solid tumor samples has proven its high clinical value. Because of the large number of ongoing clinical trials for a multitude of variants in a growing number of genes, as well as the detection of proven and emerging pan-cancer biomarkers including microsatellite instability (MSI) and tumor mutation burden (TMB), the currently employed diagnostic gene panels will become vastly insufficient in the near future. Here, we describe the validation and implementation of the hybrid capture-based comprehensive TruSight Oncology (TSO500) assay that is able to detect single-nucleotide variants (SNVs) and subtle deletions and insertions (indels) in 523 tumor-associated genes, copy-number variants (CNVs) of 69 genes, fusions with 55 cancer driver genes, and MSI and TMB. Extensive validation of the TSO500 assay was performed on DNA or RNA from 170 clinical samples with neoplastic content down to 10%, using multiple tissue and specimen types. Starting with 80 ng DNA and 40 ng RNA extracted from formalin-fixed and paraffine-embedded (FFPE) samples revealed a precision and accuracy >99% for all variant types. The analytical sensitivity and specificity were at least 99% for SNVs, indels, CNVs, MSI, and gene rearrangements. For TMB, only values around the threshold could yield a deviating outcome. The limit-of-detection for SNVs and indels was well below the set threshold of 5% variant allele frequency (VAF). This validated comprehensive genomic profiling assay was then used to screen 624 diagnostic samples, and its success rate for adoption in a clinical diagnostic setting of broad solid tumor screening was assessed on this cohort
Probing BERT for Ranking Abilities
No full textContextual models like BERT are highly effective in numerous text-ranking tasks. However, it is still unclear as to whether contextual models understand well-established notions of relevance that are central to IR. In this paper, we use probing, a recent approach used to analyze language models, to investigate the ranking abilities of BERT-based rankers. Most of the probing literature has focussed on linguistic and knowledge-aware capabilities of models or axiomatic analysis of ranking models. In this paper, we fill an important gap in the information retrieval literature by conducting a layer-wise probing analysis using four probes based on lexical matching, semantic similarity as well as linguistic properties like coreference resolution and named entity recognition. Our experiments show an interesting trend that BERT-rankers better encode ranking abilities at intermediate layers. Based on our observations, we train a ranking model by augmenting the ranking data with the probe data to show initial yet consistent performance improvements (The code is available at https://github.com/yolomeus/probing-search/ ).Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Web Information System
BERT Rankers are Brittle: A Study using Adversarial Document Perturbations
No full textContextual ranking models based on BERT are now well established for a wide range of passage and document ranking tasks. However, the robustness of BERT-based ranking models under adversarial inputs is under-explored. In this paper, we argue that BERT-rankers are not immune to adversarial attacks targeting retrieved documents given a query. Firstly, we propose algorithms for adversarial perturbation of both highly relevant and non-relevant documents using gradient-based optimization methods. The aim of our algorithms is to add/replace a small number of tokens to a highly relevant or non-relevant document to cause a large rank demotion or promotion. Our experiments show that a small number of tokens can already result in a large change in the rank of a document. Moreover, we find that BERT-rankers heavily rely on the document start/head for relevance prediction, making the initial part of the document more susceptible to adversarial attacks. More interestingly, we find a small set of recurring adversarial words that when added to documents result in successful rank demotion/promotion of any relevant/non-relevant document respectively. Finally, our adversarial tokens also show particular topic preferences within and across datasets, exposing potential biases from BERT pre-training or downstream datasets. Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Web Information System
Suzuki-Miyaura diversification of amino acids and dipeptides in aqueous media
No full textThe authors gratefully acknowledge the IWT Flanders and Janssen Pharmaceutica for financial support of T.W. This work is supported by the Scientific Research Network (WOG) “Sustainable chemistry for the synthesis of fine chemicals” of the Research Foundation - Flanders (FWO).The Suzuki-Miyaura derivatisation of free amino acids, peptides and proteins is an attractive area with much potential utility for medicinal chemistry and chemical biology. Here we report the modification of unprotected and Boc-protected aromatic amino acids and dipeptides in aqueous media, enabling heteroarylation and vinylation. We systematically investigate the impact of the peptide backbone and adjacent amino acid residues upon the reaction. Our studies reveal that whilst asparagine and histidine hinder the reaction, by utilising dppf, a ferrocene-based bidentate phosphine ligand, cross-coupling of halophenylalanine or halotryptophan adjacent to such a residue could be enabled. Our studies reveal dppf to have good compatibility with all unprotected, proteinogenic amino acid side chains.Peer reviewe
Cover picture : expedient synthesis of bridged bicyclic nitrogen scaffolds via orthogonal tandem catalysis (Angew. Chem. Int. Ed. 40/2021)
No full textAbstract: Escape from flatland. Increased saturation (fraction of sp(3)) is more likely to be successful when moving compounds through the drug development pipeline. Bridged nitrogen heterocycles have a huge potential in drug discovery, although long synthetic sequences are typically required. New step-economic and selective organic syntheses are therefore highly sought after. Bert U. W. Maes et al. describe in their Research Article on page 21988 the synthesis of the normorphan skeleton through challenging tandem catalysis. Cover design by Joris Snaet.
Author Ben Ames Williams first met Searsmont farmer Bert McCorrison in 1918, a m
No full textAuthor Ben Ames Williams first met Searsmont farmer Bert McCorrison in 1918, a meeting which the author said had a profound impact on his professional career. McCorrison died in 1931, leaving Williams his Hardscrabble Farm in Searsmount, which became the author\u27s home until his death in 1953
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