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Divergent functionalization of alkenes enabled by photoredox activation of CDFA and α-halo carboxylic acids.
No full textHerein we present our studies on the solvent-controlled difunctionalization of alkenes utilizing chlorodifluoroacetic acid (CDFA) and α-halo carboxylic acids for the synthesis of γ-lactones, γ-lactams and α,α-difluoroesters. Mechanistic insights revealed that photocatalytic reductive mesolytic cleavage of the C-X bond delivers elusive α-carboxyl alkyl radicals. In the presence of an olefin molecule, this species acts as a unique bifunctional intermediate allowing for stipulated formation of C-O, C-N and C-H bonds on Giese-type adducts via single electron transfer (SET) or hydrogen atom transfer (HAT) events. These protocols exhibit great efficiency across a broad spectrum of readily available α-halo carboxylic acids and are amenable to scalability in both batch and flow. To demonstrate the versatility of this concept, the synthesis of (±)-boivinianin A, its fluorinated analog and eupomatilone-6 natural products was successfully accomplished
A safe, effective and adaptable live-attenuated SARS-CoV-2 vaccine to reduce disease and transmission using one-to-stop genome modifications.
Get PDFApproved vaccines are effective against severe COVID-19, but broader immunity is needed against new variants and transmission. Therefore, we developed genome-modified live-attenuated vaccines (LAV) by recoding the SARS-CoV-2 genome, including 'one-to-stop' (OTS) codons, disabling Nsp1 translational repression and removing ORF6, 7ab and 8 to boost host immune responses, as well as the spike polybasic cleavage site to optimize the safety profile. The resulting OTS-modified SARS-CoV-2 LAVs, designated as OTS-206 and OTS-228, are genetically stable and can be intranasally administered, while being adjustable and sustainable regarding the level of attenuation. OTS-228 exhibits an optimal safety profile in preclinical animal models, with no side effects or detectable transmission. A single-dose vaccination induces a sterilizing immunity in vivo against homologous WT SARS-CoV-2 challenge infection and a broad protection against Omicron BA.2, BA.5 and XBB.1.5, with reduced transmission. Finally, this promising LAV approach could be applicable to other emerging viruses
Assessing large language models' accuracy in providing patient support for choroidal melanoma.
No full textPURPOSE
This study aimed to evaluate the accuracy of information that patients can obtain from large language models (LLMs) when seeking answers to common questions about choroidal melanoma.
METHODS
Comparative study comparing frequently asked questions from choroidal melanoma patients and queried three major LLMs-ChatGPT 3.5, Bing AI, and DocsGPT. Answers were reviewed by three ocular oncology experts and scored as accurate, partially accurate, or inaccurate. Statistical analysis compared the quality of responses across models.
RESULTS
For medical advice questions, ChatGPT gave 92% accurate responses compared to 58% for Bing AI and DocsGPT. For pre/post-op questions, ChatGPT and Bing AI were 86% accurate while DocsGPT was 73% accurate. There were no statistically significant differences between models. ChatGPT responses were the longest while Bing AI responses were the shortest, but length did not affect accuracy. All LLMs appropriately directed patients to seek medical advice from professionals.
CONCLUSION
LLMs show promising capability to address common choroidal melanoma patient questions at generally acceptable accuracy levels. However, inconsistent, and inaccurate responses do occur, highlighting the need for improved fine-tuning and oversight before integration into clinical practice
Participatory Visioning and Future Planning. Backcasting with Myanmar Farmers for a more Sustainable Future. Methodological Report
Get PDFThis report describes the methodology of participatory visioning and future planning, including a technique called backcasting. Based on literature and experience, we developed and applied this methodology to support smallholder farmers in southern Myanmar. In a highly participatory bottom-up approach, we co-created and documented the vision of these farmers – in direct collaboration with them – including their desirable futures, and we jointly explored possible pathways and action plans to reach these futures. We also co-implemented needs-based actions including concrete trainings, study trips, and a community-led micro-loan system to strengthen their agriculture – their main source of livelihood. Unfortunately, beginning in 2020, Myanmar experienced two overlapping waves of crisis: the health crisis as a result of the COVID-19 pandemic; and the political crisis following the coup d’etat in 2021. The final two years of the project were implemented under these extremely challenging conditions. We frequently had to adapt our operationalization to the very dynamic, changing circum-stances. Fortunately, our methodology allowed for this kind of adaptive management. Despite the challenging circumstances, the farmers were positive in their assessment of the project outcomes. This suggests that the methodology of participatory visioning and future planning can be effective even under difficult circumstances. We conclude the report by presenting lessons learnt and recommendations. Firstly, we reflect on how useful this methodology was and how it can be applied in similar or different projects (research, development, etc.). Secondly, we share our practical insights and recommendations regarding the application of the methodology in the given or similar contexts. Finally, we provide practical recommendations for project planning for those who want to include participatory visioning and future planning in their projects
Utility of gingival crevicular fluid components for periodontal diagnosis.
Get PDFPeriodontal diseases are highly prevalent chronic diseases, and severe periodontitis creates functional and esthetic problems and decreases self-esteem for a large percentage of the older population worldwide. In many cases of periodontitis, there is no distinct tell-tale pain that motivates a patient to seek treatment, rather the signs become clinically detectable late, and typically when the disease has progressed to a problematic level for the life of the dentition. Early periodontal screening and diagnostics tools will provide early recognition of periodontal diseases and facilitate timely management of the disease to reduce tooth loss. To this goal, gingival crevicular fluid is easily sampled, can be repeatedly and non-invasively collected, and can be tested for potential biomarkers. Moreover, the site specificity of periodontal diseases enhances the usefulness of gingival crevicular fluid sampled from specific sites as a biofluid for diagnosis and longitudinal monitoring of periodontal diseases. The present review aimed to provide up-to-date information on potential diagnostic biomarkers with utility that can be assayed from gingival crevicular fluid samples, focusing on what is new and useful and providing only general historic background textually and in a tabulated format
Correlation-aware active learning for surgery video segmentation
Get PDFSemantic segmentation is a complex task that relies heavily on large amounts of annotated image data. However, annotating such data can be time-consuming and resource-intensive, especially in the medical domain. Active Learning (AL) is a popular approach that can help to reduce this burden by iteratively selecting images for annotation to improve the model performance. In the case of video data, it is important to consider the model uncertainty and the temporal nature of the sequences when selecting images for annotation. This work proposes a novel AL strategy for surgery video segmentation, COWAL, COrrelation-aWare Active Learning. Our approach involves projecting images into a latent space that has been fine-tuned using contrastive learning and then selecting a fixed number of representative images from local clusters of video frames. We demonstrate the effectiveness of this approach on two video datasets of surgical instruments and three real-world video datasets. The datasets and code will be made publicly available upon receiving necessary approvals
Deep Learning Reconstruction of Accelerated MRI: False-Positive Cartilage Delamination Inserted in MRI Arthrography Under Traction.
Get PDFOBJECTIVES
The radiological imaging industry is developing and starting to offer a range of novel artificial intelligence software solutions for clinical radiology. Deep learning reconstruction of magnetic resonance imaging data seems to allow for the acceleration and undersampling of imaging data. Resulting reduced acquisition times would lead to greater machine utility and to greater cost-efficiency of machine operations.
MATERIALS AND METHODS
Our case shows images from magnetic resonance arthrography under traction of the right hip joint from a 30-year-old, otherwise healthy, male patient.
RESULTS
The undersampled image data when reconstructed by a deep learning tool can contain false-positive cartilage delamination and false-positive diffuse cartilage defects.
CONCLUSIONS
In the future, precision of this novel technology will have to be put to thorough testing. Bias of systems, in particular created by the choice of training data, will have to be part of those assessments
REINTERVENTION RATE AFTER TREATMENT WITH THE INCRAFT AAA ULTRA-LOW-PROFILE STENT GRAFT SYSTEM.
Get PDFOBJECTIVE
The INCRAFT stent graft system is an ultra-low profile endograft for the exclusion of infrarenal aortic aneurysms. In the market approval studies, an increased rate of device-related complications was observed and the endograft was approved with mandated postmarketing investigations. Our aim was to analyze midterm outcomes of a real-world patient cohort treated with the INCRAFT endograft.
METHODS
Consecutive patients treated with the INCRAFT endograft between February 2015 and December 2022 at a single institution were included. In accordance with the Society for Vascular Surgery reporting standards, safety endpoints were reported and outcome endpoints included reinterventions, technical success, aortic-related and overall-mortality, endoleak, stent fracture, and endograft migration >5 mm.
RESULTS
Eighty patients (85% male) with a mean age of 76 ± 7 years were included. Fifty-two patients (65%) were treated within the endograft's instruction for use (IFU). Mean aortic diameter was 59 ± 10 mm and 91% of the procedures were performed percutaneously. Mean follow-up was 37 ± 25 months and there was no aortic- or procedure-related mortality. Reinterventions occurred in 25 patients (31%) with a freedom from reintervention at 1, 3 and 5 years of 84%, 66% and 55%. The most frequent reinterventions were limb graft stenting (23%) and type II endoleak embolization (14%). Limb occlusion rate was 9% and in three patients (4%) distal endograft migrations >5 mm occurred. Persisting type II endoleaks were observed in 29% and aneurysm diameter was stable in 41% and had shrunk in 38%. Three type III endoleaks (4%) developed during follow-up and four open conversions (5%) were necessary. No known risk factors, including treatment outside IFU, were predictive for reinterventions.
CONCLUSION
Treatment of infrarenal aortic aneurysms with the INCRAFT stent graft system was safe and successful. Nevertheless, a substantial rate of reinterventions was necessary during follow-up to maintain endograft patency and prevent aneurysm growth
Epidemiology of maxillofacial trauma in elderly patients receiving oral anticoagulant or antithrombotic medication; a Swiss retrospective study.
Get PDFBACKGROUND
The percentage of elderly trauma patients under anticoagulation and antiplatelet agents has been rising lately. As newer agents are introduced, each comes with its own advantages and precautions. Our study covered elderly patients admitted to the ED with maxillofacial trauma while on anticoagulation (AC) or antiplatelet therapy (APT). We aimed to investigate the demographic characteristics, causes, and types of maxillofacial trauma, along with concomitant injuries, duration of hospitalisation, haemorrhagic complications, and the overall costs of care in the emergency department (ED).
METHODS
Data were gathered from the ED of Bern University Hospital. In this retrospective analysis, patients over 65 of age were included, who presented at our ED with maxillofacial trauma between 2013 and 2019 while undergoing treatment with therapeutic AC/APT.
RESULTS
The study involved 188 patients with a median age of 81 years (IQR: 81 [74; 87]), of whom 55.3% (n=104) were male. More than half (54.8%, n=103) were aged 80 years or older. Cardiovascular diseases were present in 69.7% (n=131) of the patients, with the most common indications for AC/APT use being previous thromboembolic events (41.5%, n=78) and atrial fibrillation (25.5%, n=48). The predominant cause of facial injury was falls, accounting for 83.5% (n=157) of cases, followed by bicycle accidents (6.9%, n=13) and road-traffic accidents (5.3%, n=10). The most common primary injuries were fractures of the orbital floor and/or medial/lateral wall (60.1%, n=113), zygomatic bone (30.3%, n=57), followed by isolated orbital floor fractures (23.4%, n=44) and nasal bone fractures (19.1%, n=36). Fractures of the mandible occurred in 14.9% (n=28). Facial hematomas occurred in 68.6% of patients (129 cases), primarily in the midface area. Relevant facial bleeding complications were intracerebral haemorrhage being the most frequent (28.2%, n=53), followed by epistaxis (12.2%, n=23) and retrobulbar/intraorbital hematoma (9%, n=17). Sixteen patients (8.5%) experienced heavy bleeding that required emergency treatment. The in-hospital mortality rate was 2.1% (4 cases).
CONCLUSIONS
This study indicates that falls are the leading cause of maxillofacial trauma in the elderly, with the most common diagnoses being orbital, zygomatic, and nasal fractures. Haemorrhagic complications primarily involve facial hematomas, especially in the middle third of the face, with intracerebral haemorrhage being the second most frequent. Surgical intervention for bleeding was required in 8.5% of cases. Given the aging population, it is essential to improve prevention strategies and update safety protocols, particularly for patients on anticoagulant/antiplatelet therapy (AC/APT). This can ensure rapid diagnostic imaging and prompt treatment in emergencies
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