155155 research outputs found
Sort by
New Generation Self-Replicating RNA Vaccines Derived from Pestivirus Genome.
No full textWhile mRNA vaccines have shown their worth, they have the same failing as inactivated vaccines, namely they have limited half-life, are non-replicating, and therefore limited to the size of the vaccine payload for the amount of material translated. New advances averting these problems are combining replicon RNA (RepRNA) technology with nanotechnology. RepRNA are large self-replicating RNA molecules (typically 12-15 kb) derived from viral genomes defective in at least one essential structural protein gene. They provide sustained antigen production, effectively increasing vaccine antigen payloads over time, without the risk of producing infectious progeny. The major limitations with RepRNA are RNase-sensitivity and inefficient uptake by dendritic cells (DCs), which need to be overcome for efficacious RNA-based vaccine design. We employed biodegradable delivery vehicles to protect the RepRNA and promote DC delivery. Condensing RepRNA with polyethylenimine (PEI) and encapsulating RepRNA into novel Coatsome-replicon vehicles are two approaches that have proven effective for delivery to DCs and induction of immune responses in vivo
Prevalence of right-left shunt in stroke patients with cancer.
No full textBACKGROUND AND OBJECTIVES
Cancer is associated with an increased risk of acute ischemic stroke (AIS) and venous thromboembolism. The role of a cardiac right-left shunt (RLS) as a surrogate parameter for paradoxical embolism in cancer-related strokes is uncertain. We sought to investigate the relationship between the presence of a RLS and cancer in AIS patients.
METHODS
We included consecutive AIS patients hospitalized at our tertiary stroke center between January 2015 and December 2020 with available RLS status as detected on transesophageal echocardiography (TEE). Active cancers were retrospectively identified and the association with RLS was assessed with multivariable logistic regression and inverse probability of treatment weighting to minimize the ascertainment bias of having a TEE obtained.
RESULTS
Of the 2236 AIS patients included, 103 (4.6%) had active cancer, of whom 24 (23%) were diagnosed with RLS. A RLS was present in 774 out of the 2133 AIS patients without active cancer (36%). After adjustment and weighting, the absence of RLS was associated with active cancer (adjusted odds ratio [aOR], 2.29; 95% confidence interval [CI], 1.14-4.58). When analysis was restricted to patients younger than 60 years or those with a high-risk RLS (Risk of Paradoxical Embolism Score ≥6), there was no association between RLS and cancer (aOR, 3.07; 95% CI, 0.79-11.88 and aOR, 0.56; 95% CI 0.10-3.10, respectively).
CONCLUSIONS
RLS was diagnosed less frequently in AIS patients with cancer than in cancer-free patients, suggesting that arterial sources may play a larger role in cancer-related strokes than paradoxical venous embolization. Future studies are needed to validate these findings and evaluate potential therapeutic implications such as the general indication, or lack thereof, for PFO closure in this patient population
Evaluation of Ambient Sensor Systems for the Early Detection of Heart Failure Decompensation in Older Patients Living at Home Alone: Protocol for a Prospective Cohort Study.
Get PDFBACKGROUND
The results of telemedicine intervention studies in patients with heart failure (HF) to reduce rehospitalization rate and mortality by early detection of HF decompensation are encouraging. However, the benefits are lower than expected. A possible reason for this could be the fact that vital signs, including blood pressure, heart rate, heart rhythm, and weight changes, may not be ideal indicators of the early stages of HF decompensation but are more sensitive for acute events triggered by ischemic episodes or rhythm disturbances. Preliminary results indicate a potential role of ambient sensor-derived digital biomarkers in this setting.
OBJECTIVE
The aim of this study is to identify changes in ambient sensor system-derived digital biomarkers with a high potential for early detection of HF decompensation.
METHODS
This is a prospective interventional cohort study. A total of 24 consecutive patients with HF aged 70 years and older, living alone, and hospitalized for HF decompensation will be included. Physical activity in the apartment and toilet visits are quantified using a commercially available, passive, infrared motion sensing system (DomoHealth SA). Heart rate, respiration rate, and toss-and-turns in bed are recorded by using a commercially available Emfit QS device (Emfit Ltd), which is a contact-free piezoelectric sensor placed under the participant's mattress. Sensor data are visualized on a dedicated dashboard for easy monitoring by health professionals. Digital biomarkers are evaluated for predefined signs of HF decompensation, including particularly decreased physical activity; time spent in bed; increasing numbers of toilet visits at night; and increasing heart rate, respiration rate, and motion in bed at night. When predefined changes in digital biomarkers occur, patients will be called in for clinical evaluation, and N-terminal pro b-type natriuretic peptide measurement (an increase of >30% considered as significant) will be performed. The sensitivity and specificity of the different biomarkers and their combinations for the detection of HF decompensation will be calculated.
RESULTS
The study is in the data collection phase. Study recruitment started in February 2024. Data analysis is scheduled to start after all data are collected. As of manuscript submission, 5 patients have been recruited. Results are expected to be published by the end of 2025.
CONCLUSIONS
The results of this study will add to the current knowledge about opportunities for telemedicine to monitor older patients with HF living at home alone by evaluating the potential of ambient sensor systems for this purpose. Timely recognition of HF decompensation could enable proactive management, potentially reducing health care costs associated with preventable emergency presentations or hospitalizations.
TRIAL REGISTRATION
ClinicalTrials.gov NCT06126848; https://clinicaltrials.gov/study/NCT06126848.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
PRR1-10.2196/55953
Anaphylaxis in a Swiss university emergency department: clinical characteristics and supposed triggers.
Get PDFBACKGROUND
Anaphylaxis is the most severe form of acute systemic and potentially life-threatening reactions triggered by mast and basophilic cells. Recent studies show a worldwide incidence between 50 and 112 occurrences per 100,000 person-years. The most identified triggers are food, medications, and insect venoms. We aimed to analyze triggers and clinical symptoms of patients presenting to a Swiss university emergency department for adults.
METHODS
Six-year retrospective analysis (01/2013 to 12/2018) of all patients (> 16 years of age) admitted with moderate or severe anaphylaxis (classification of Ring and Messmer ≥ 2) to the emergency department. Patient and clinical data were extracted from the electronic medical database of the emergency department.
RESULTS
Of the 531 includes patients, 53.3% were female, the median age was 38 [IQR 26-51] years. The most common suspected triggers were medications (31.8%), food (25.6%), and insect stings (17.1%). Organ manifestations varied among the different suspected triggers: for medications, 90.5% of the patients had skin symptoms, followed by respiratory (62.7%), cardiovascular (44.4%) and gastrointestinal symptoms (33.7%); for food, gastrointestinal symptoms (39.7%) were more frequent than cardiovascular symptoms (36.8%) and for insect stings cardiovascular symptoms were apparent in 63.8% of the cases.
CONCLUSIONS
Average annual incidence of moderate to severe anaphylaxis during the 6-year period in subjects > 16 years of age was 10.67 per 100,000 inhabitants. Medications (antibiotics, NSAID and radiocontrast agents) were the most frequently suspected triggers. Anaphylaxis due to insect stings was more frequently than in other studies. Regarding clinical symptoms, gastrointestinal symptoms need to be better considered, especially that initial treatment with epinephrine is not delayed
Hepatic venous pressure gradient predicts risk of hepatic decompensation and liver-related mortality in patients with MASLD.
Get PDFBACKGROUND & AIMS
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of advanced chronic liver disease (ACLD). Portal hypertension drives hepatic decompensation and is best diagnosed by hepatic venous pressure gradient (HVPG) measurement. Here we investigate the prognostic value of HVPG in compensated (cACLD) MASLD.
METHODS
This European multicentre study included MASLD-cACLD patients characterised by HVPG at baseline. Hepatic decompensation (variceal bleeding/ ascites/hepatic encephalopathy) and liver-related mortality were considered the primary events of interest.
RESULTS
340 MASLD-cACLD patients [56.2% men; age: 62 (55-68) years; MELD: 8 (7-9); 71.2% diabetes] were included. Clinically significant portal hypertension (CSPH; i.e., HVPG ≥10 mmHg) was found in 209 patients (61.5%). During a median follow-up of 41.5 (27.5-65.8) months, 65 patients developed hepatic decompensation with a cumulative incidence of 10.0% after 2 years (2Y) and 30.7% after 5 years (5Y) in MASLD-cACLD with CSPH, compared to 2.4% after 2Y and 9.4% after 5Y in patients without CSPH. Variceal bleeding did not occur without CSPH. CSPH (subdistribution hazard ratio, SHR:5.13; p<0.001) was associated with an increased decompensation risk and a higher HVPG remained an independent risk factor in the multivariable model (aSHR per mmHg:1.12; p<0.001). Liver-related mortality occurred in 37 patients with a cumulative incidence of 3.3% after 2Y and 21.4% after 5Y in CSPH. Without CSPH, the incidence after 5Y was 0.8%. Accordingly, a higher HVPG was also independently associated with a higher risk of liver-related death (aSHR per mmHg:1.20; p<0.001).
CONCLUSION
HVPG measurement is of high prognostic value in MASLD-cACLD. While MASLD-cACLD patients without CSPH show a very low short-term risk of decompensation and liver-related mortality is rare, the presence of CSPH substantially increases both risks.
IMPACT AND IMPLICATIONS
While the incidence of compensated advanced chronic liver disease (cACLD) due to metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing worldwide, insights into the impact of clinically significant portal hypertension (CSPH) on the risk of liver-related events in MASLD-cACLD remain limited. Based on the findings of this European multicentre study including 340 MASLD-cACLD, we could show that increasing HVPG values and the presence of CSPH in particular were associated with a significantly higher risk of first hepatic decompensation and liver-related mortality. In contrast, the short-term incidence of decompensation in MASLD-cACLD patients without CSPH was low and the risk of liver-mortality remained negligible. Thus, HVPG measurements can provide important prognostic information for individualised risk-stratification in MASLD-cACLD and may help facilitate the study of novel and promising treatment possibilities for MASLD
Bridging AI and Clinical Practice: Integrating Automated Sleep Scoring Algorithm with Uncertainty-Guided Physician Review.
Get PDFPURPOSE
This study aims to enhance the clinical use of automated sleep-scoring algorithms by incorporating an uncertainty estimation approach to efficiently assist clinicians in the manual review of predicted hypnograms, a necessity due to the notable inter-scorer variability inherent in polysomnography (PSG) databases. Our efforts target the extent of review required to achieve predefined agreement levels, examining both in-domain (ID) and out-of-domain (OOD) data, and considering subjects' diagnoses.
PATIENTS AND METHODS
A total of 19,578 PSGs from 13 open-access databases were used to train U-Sleep, a state-of-the-art sleep-scoring algorithm. We leveraged a comprehensive clinical database of an additional 8832 PSGs, covering a full spectrum of ages (0-91 years) and sleep-disorders, to refine the U-Sleep, and to evaluate different uncertainty-quantification approaches, including our novel confidence network. The ID data consisted of PSGs scored by over 50 physicians, and the two OOD sets comprised recordings each scored by a unique senior physician.
RESULTS
U-Sleep demonstrated robust performance, with Cohen's kappa (K) at 76.2% on ID and 73.8-78.8% on OOD data. The confidence network excelled at identifying uncertain predictions, achieving AUROC scores of 85.7% on ID and 82.5-85.6% on OOD data. Independently of sleep-disorder status, statistical evaluations revealed significant differences in confidence scores between aligning vs discording predictions, and significant correlations of confidence scores with classification performance metrics. To achieve κ ≥ 90% with physician intervention, examining less than 29.0% of uncertain epochs was required, substantially reducing physicians' workload, and facilitating near-perfect agreement.
CONCLUSION
Inter-scorer variability limits the accuracy of the scoring algorithms to ~80%. By integrating an uncertainty estimation with U-Sleep, we enhance the review of predicted hypnograms, to align with the scoring taste of a responsible physician. Validated across ID and OOD data and various sleep-disorders, our approach offers a strategy to boost automated scoring tools' usability in clinical settings
Lehren aus dem „hölzernen Zeitalter“
No full textDie Begrenztheit von Ressourcen zur Energiegewinnung sowie saisonale Schwankungen waren schon vor der Industriellen Revolution prägende Themen und erforderten vorausschauendes Denken. Auch der Begriff der Nachhaltigkeit taucht in diesem Kontext erstmals auf
Potential Mediating Role of Iron Biomarkers in the Association of Sex With Glucose, Insulin, and Type 2 Diabetes.
Get PDFCONTEXT
Sex-specific prevalence and incidence of type 2 diabetes (T2D) have been reported, but the underlying mechanisms are uncertain.
OBJECTIVE
In this study, we aimed to investigate whether iron biomarkers mediate the association between biological sex and glucose metabolism and the incidence of T2D.
METHODS
We used data from the general population enrolled in the prospective Prevention of REnal and Vascular ENd-stage Disease study in Groningen, The Netherlands. We measured ferritin, transferrin saturation (TSAT), hepcidin, soluble transferrin receptor (sTfR), fasting plasma glucose (FPG), fasting plasma insulin (FPI) levels, and incidence of T2D. We used multivariable regression and mediation analyses to investigate our hypothesis. All iron biomarkers, FPG, and FPI were log-transformed.
RESULTS
The mean (SD) age of the 5312 (51.3% female) individuals was 52.2 (11.6) years. Compared with males, females had lower FPG (β = -.01; 95% CI -0.02, -0.01) and FPI (β = -.03; 95% CI -0.05, -0.02) levels. Ferritin, hepcidin, and sTfR showed potential mediating effects on the association between sex and FPG, 21%, 5%, and 7.1%, respectively. Furthermore, these variables mediated 48.6%, 5.7%, and 3.1% of the association between sex and FPI, respectively. Alternatively, TSAT had a suppressive mediating role in the association of sex with FPG and FPI. The incidence of T2D was lower in females than in males (hazard ratio 0.58; 95% CI 0.44, 0.77), with 19.2% of this difference being mediated by ferritin.
CONCLUSION
Iron biomarkers may partially mediate the association between sex and glucose homeostasis. Future studies addressing the causality of our findings are needed
The laminar position, morphology, and gene expression profiles of cortical astrocytes are influenced by time of birth from ventricular/subventricular progenitors.
No full textAstrocytes that reside in superficial (SL) and deep cortical layers have distinct molecular profiles and morphologies, which may underlie specific functions. Here, we demonstrate that the production of SL and deep layer (DL) astrocyte populations from neural progenitor cells in the mouse is temporally regulated. Lineage tracking following in utero and postnatal electroporation with PiggyBac (PB) EGFP and birth dating with EdU and FlashTag, showed that apical progenitors produce astrocytes during late embryogenesis (E16.5) that are biased to the SL, while postnatally labeled (P0) astrocytes are biased to the DL. In contrast, astrocytes born during the predominantly neurogenic window (E14.5) showed a random distribution in the SL and DL. Of interest, E13.5 astrocytes birth dated at E13.5 with EdU showed a lower layer bias, while FT labeling of apical progenitors showed no bias. Finally, examination of the morphologies of "biased" E16.5- and P0-labeled astrocytes demonstrated that E16.5-labeled astrocytes exhibit different morphologies in different layers, while P0-labeled astrocytes do not. Differences based on time of birth are also observed in the molecular profiles of E16.5 versus P0-labeled astrocytes. Altogether, these results suggest that the morphological, molecular, and positional diversity of cortical astrocytes is related to their time of birth from ventricular/subventricular zone progenitors
Data sources:
BORIS Portal Bern Open Repository and I...BAF-Online: Proceedings of the Berner Al...HASBonline – Hefte zur Archäologie des M...Informationswissenschaft: Theorie, Metho...Jahrbuch Diakonie SchweizJournal of Eye Movement ResearchJournal of Radiation Oncology Informatic...BOP SerialsVersants. Revista suiza de literaturas r...BORIS ThesesAccess Repository Dashboard
Do you manage Bern Open Repository and Information System (BORIS)? Access insider analytics, issue reports and manage access to outputs from your repository in the CORE Repository Dashboard!