The human genome comprises 8% sequences of retroviral origin, so-called human endogenous retroviruses (HERVs). Most of these proviral sequences are defective, but some possess open reading frames. ...They can lead to the formation of viral transcripts, when activated by intrinsic and extrinsic factors. HERVs are thought to play a pathological role in inflammatory diseases and cancer. Since the consequences of activated proviral sequences in the human body are largely unexplored, selected envelope proteins of human endogenous retroviruses associated with inflammatory diseases, namely HERV-K18, HERV-K113, and HERV-Fc1, were investigated in the present study. A formation of glycosylated envelope proteins was demonstrated in different mammalian cell lines. Nevertheless, protein maturation seemed to be incomplete as no transport to the plasma membrane was observed. Instead, the proteins remained in the ER where they induced the expression of genes involved in unfolded protein response, such as
and
. Furthermore, low expression levels of native envelope proteins were increased by codon optimization. Cell-free expression systems showed that both the transcriptional and translational level is affected. By generating different codon-optimized variants of HERV-K113 envelope, the influence of single rare t-RNA pools in certain cell lines was demonstrated. The mRNA secondary structure also appears to play an important role in the translation of the tested viral envelope proteins. In summary, the formation of certain HERV proteins is basically possible. However, their complete maturation and thus full biologic activity seems to depend on additional factors that might be disease-specific and await elucidation in the future.
Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may ...benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome.
PROTEUS is a randomized, multicenter, 2-armed, noninferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomized 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis.
This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE.
Clinicaltrials.gov registration number NCT05028179, registered on 31 August 2021; ISRCTN: ISRCTN15113915; IRAS ref: 293515; REC ref: 21/NW/0199.
Advanced data encryption requires the use of true random number generators (TRNGs) to produce unpredictable sequences of bits. TRNG circuits with high degree of randomness and low power consumption ...may be fabricated by using the random telegraph noise (RTN) current signals produced by polarized metal/insulator/metal (MIM) devices as entropy source. However, the RTN signals produced by MIM devices made of traditional insulators, i.e., transition metal oxides like HfO2 and Al2O3, are not stable enough due to the formation and lateral expansion of defect clusters, resulting in undesired current fluctuations and the disappearance of the RTN effect. Here, the fabrication of highly stable TRNG circuits with low power consumption, high degree of randomness (even for a long string of 224 − 1 bits), and high throughput of 1 Mbit s−1 by using MIM devices made of multilayer hexagonal boron nitride (h‐BN) is shown. Their application is also demonstrated to produce one‐time passwords, which is ideal for the internet‐of‐everything. The superior stability of the h‐BN‐based TRNG is related to the presence of few‐atoms‐wide defects embedded within the layered and crystalline structure of the h‐BN stack, which produces a confinement effect that avoids their lateral expansion and results in stable operation.
The few‐atoms‐wide and amorphous native defects in multilayer hexagonal boron nitride (h‐BN) synthesized by chemical vapor deposition can drive out‐of‐plane random telegraph noise current signals that are more stable than those traditionally observed in transition metal oxides. The reason is that these defects are confined and completely surrounded by 2D layered and crystalline h‐BN. This allows fabrication of high‐performance true random number generators for advanced data encryption.
MRI Detection of Left Atrial Ablation Lesions. Introduction: We tested the hypothesis that cardiovascular magnetic resonance (CMR) imaging can reliably distinguish the presence or absence of left ...atrial (LA) ablation lesions by blinded analysis of pre‐ and postablation imaging.
Methods:
Consecutive patients at 2 centers undergoing pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation by either wide area circumferential radiofrequency ablation (WACA) or ostial ablation with a cryoballoon underwent CMR late gadolinium enhancement (LGE) imaging pre‐ and 3 months postablation. Imaging was anonymized for blinded analysis of (1) LGE images, and (2) a 3D fusion image with LGE projected onto a segmented LA surface. Scans were categorized using both assessment techniques separately as pre‐ or postablation, and if postablation, whether lesions were in an ostial or WACA distribution.
Results:
LGE imaging was performed in 50 patients (aged 60 ± 10 years, 68% male, 24 underwent WACA and 26 had cryoablation). Sensitivity and specificity for detection of ablation lesions was 60% and 96% on LGE imaging. Sensitivity was higher using 3D fusion imaging (88%; P = 0.003). The proportion in whom lesions were both detected and the distribution correctly assessed as WACA or ostial was higher with 3D fusion imaging compared to LGE imaging (54% vs 28%; P = 0.014). There was no difference in the detection of radiofrequency ablation lesions compared to cryoablation lesions (58% vs 62%; P = 1.000).
Conclusion:
LGE imaging of atrial scar is not yet sufficiently accurate to reliably identify ablation lesions or to determine lesion distribution. (J Cardiovasc Electrophysiol, Vol. 24, pp. 396‐403, April 2013)
Hyperphosphorylation and intraneuronal aggregation of the microtubule-associated protein tau is a major pathological hallmark of Alzheimer's disease (AD) brain. Of special interest is the effect of ...cerebral amyloid beta deposition, the second main hallmark of AD, on human tau pathology. Therefore, studying the influence of cerebral amyloidosis on human tau in a novel human tau knock-in (htau-KI) mouse model could help to reveal new details on their interplay.
We studied the effects of a novel human htau-KI under fast-progressing amyloidosis in 5xFAD mice in terms of correlation of gene expression data with human brain regions, development of Alzheimer's-like pathology, synaptic transmission, and behavior.
The main findings are an interaction of human beta-amyloid and human tau in crossbred 5xFADxhtau-KI observed at transcriptional level and corroborated by electrophysiology and histopathology. The comparison of gene expression data of the 5xFADxhtau-KI mouse model to 5xFAD, control mice and to human AD patients revealed conspicuous changes in pathways related to mitochondria biology, extracellular matrix, and immune function. These changes were accompanied by plaque-associated MC1-positive pathological tau that required the htau-KI background. LTP deficits were noted in 5xFAD and htau-KI mice in contrast to signs of rescue in 5xFADxhtau-KI mice. Increased frequencies of miniature EPSCs and miniature IPSCs indicated an upregulated presynaptic function in 5xFADxhtau-KI.
In summary, the multiple interactions observed between knocked-in human tau and the 5xFAD-driven progressing amyloidosis have important implications for future model development in AD.
Migrant birds face a number of threats throughout their annual cycle, including persecution, collision with energy infrastructure, and habitat and climate change. A key challenge for the conservation ...of migrants is the identification of important habitat, including migratory concentration areas, because species survival rates may be determined by events in geographically very limited areas. Remote‐tracking technology is facilitating the identification of such critical habitat, although the strategic identification of important sites and incorporation of such knowledge in conservation planning remains limited. We tracked 45 individuals of an endangered, soaring migrant (Egyptian vulture Neophron percnopterus), over 75 complete migrations that traversed three continents along the Red Sea Flyway. We summarize and contextualize migration statistics by season and age class, including migration start, midpoint, and end dates, as well as linear and cumulative migration distance, migration duration and speed, and route straightness. Then, using dynamic Brownian bridge movement models, we quantified space use to identify the most important migratory bottlenecks and high‐use areas on the flyway. These areas each accounted for < 5% of the overall movement range of the tracked birds, yet > 20% of all tracks passed through bottlenecks, and > 50% of the overall vulture time spent on migration fell within high‐use areas. The most important sites were located at the southeastern Red Sea coast and Bab‐el‐Mandeb Strait (Saudi Arabia, Yemen, Djibouti), the Suez Canal zone (Egypt), and the Gulf of Iskenderun (Turkey). Discouragingly however, none of the area within the major migratory bottlenecks was protected and < 13% of the high‐use areas were protected. This demonstrates a very concerning gap in the protected area network for migratory soaring birds along the Red Sea Flyway. Because reducing threats at migratory concentrations can be a very efficient approach to protect populations, our work provides clear guidelines where conservation investment is urgently needed to benefit as many as 35 migratory soaring‐bird species that regularly use the Red Sea Flyway.
The Eukaryotic Linear Motif (ELM) resource (http://elm.eu.org) is a manually curated database of short linear motifs (SLiMs). In this update, we present the latest additions to this resource, along ...with more improvements to the web interface. ELM 2016 contains more than 240 different motif classes with over 2700 experimentally validated instances, manually curated from more than 2400 scientific publications. In addition, more data have been made available as individually searchable pages and are downloadable in various formats.
Objective
This study was undertaken to improve understanding of late relapse following epilepsy surgery in pharmacoresistant epilepsy.
Methods
Retrospective comparison was made of 99 of 1278 patients ...undergoing surgery during 1999–2015 with seizure relapses after at least 2 years of complete seizure freedom with matched controls experiencing continued long‐term seizure freedom. Univariate and multivariate analyses were performed.
Results
With a mean follow‐up of 9.7 years, mean time to seizure relapse was 56.6 months. In multivariate analysis, incomplete resection based on magnetic resonance imaging (MRI), bilateral lesions on preoperative MRI, and epilepsy onset in the first year of life carried a significantly higher risk of late relapse. In patients with late relapse, additional functional imaging with positron emission tomography had been performed significantly more often. Although the differences were not significant in multivariate analysis, doses of antiepileptic drugs were higher in the relapse group preoperatively and in the first 24 months and complete withdrawal was more frequent in the control group (68% vs. 51%). Regarding seizure frequency, most patients had mild seizure relapse (single relapse seizure or <1/month).
Significance
In our predominantly lesional cohort, complete resection of the MRI lesion is the most important factor to maintain long‐term seizure freedom. Two patterns of recurrence were identified: (1) incomplete resected lesions with seizure generation in proximity to the initial resection and (2) epileptogenic networks not detected preoperatively or evolving in the postoperative interval and manifesting with new clinical and diagnostic features.
Photovoice is a research method that changes perceptions of mental health. However, there is a lack of evidence exploring how Photovoice is used in mental health research involving adolescents. Our ...review aimed to understand the nature and key themes across findings of Photovoice studies exploring mental health among adolescents. We used pre-existing data and updated a search strategy. Popay and colleagues' guidance was used to analyse the studies and the quality of each study was appraised. Our review found that Photovoice studies exploring mental health among adolescents are limited in quality and that Photovoice is a flexible, adaptable, inclusive, and emerging method. Coping; resilience; beliefs about oneself; family; friends; safety; living in a lower socioeconomic area and treatment emerged as key themes across study findings. Our review is the first of its kind and highlights ways Photovoice studies in the future can be developed and is helpful to multiple stakeholders.
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