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At least 163 records · Page 9Linked to original sources
PubMed2002

Fraudulent use of radiographic images.

The aim of this study was to evaluate the ability of trained observers to identify altered radiographic images after modifications using an image-editing software. Based on implantology in 10 radiographs, eight panoramic and one linear tomograph were modified while one tomograph was untouched. Implants were placed or removed and bone levels were altered, and seventy dentists were invited to identify these alterations. The results showed that the percentage of the correct answers was 12.5% or 2 identifications per examiner. The rate of false positives in relation to correct answers was at a level of 6:1. We concluded that the professionals have difficulty in identifying altered radiographs after using an image-editing software and that the seriousness of this situation demands that dentists be warned of the dangers of the use and abuse of this technology.

Brazil↗
PubMed2026

Towards precision medicine for brain arteriovenous malformations.

Recent advances in cerebrovascular genomics, single-cell biology, pharmacology, and gene editing technology are transforming our understanding of brain arteriovenous malformations (bAVMs) - a leading cause of pediatric hemorrhagic stroke. Once considered static anatomical defects, bAVMs are now recognized as dynamic, genetically driven lesions resulting from somatic mutations in KRAS, BRAF, and pathways involved in arteriovenous specification, angiogenesis, and vascular remodeling. By integrating human genetics, animal models, and endovascular innovations, researchers have uncovered convergent mechanisms that link endothelial Ras/MAPK hyperactivation to abnormal vessel growth and higher rupture risk. These insights provide a foundation for precision medicine approaches that combine molecular diagnostics - such as liquid or endoluminal biopsies - with mutation-specific pharmacotherapies and emerging CRISPR-based gene editing strategies. We suggest that genotype-guided interventions, tailored by spatial and developmental cerebrovascular context, could ultimately reclassify bAVMs from surgically incurable malformations to treatable molecular conditions.

Humans↗
PubMed2026

In vivo epigenome editing reduces circulating lipids and attenuates atherosclerosis in mice.

Atherosclerotic cardiovascular disease remains the leading cause of global mortality, with hypercholesterolemia serving as a critical driver of atherogenesis. Although current lipid-lowering therapies substantially improve circulating lipid profiles, strategies that provide more durable, safe, and efficient control of lipid metabolism are still needed. Epigenome editing offers a promising approach for long-lasting repression of disease-modifying genes without altering the underlying DNA sequence. Here, we develop CRISPRoff platforms delivered by adeno-associated virus or lipid nanoparticle to epigenetically silence hepatic Hmgcr or Pcsk9 in vivo. In both C57BL/6J wild-type and ApoE-/- mice, CRISPRoff mediates robust and durable repression of these targets, leading to marked reductions in circulating total cholesterol, low-density lipoprotein cholesterol, and triglycerides. In the ApoE-/- context, epigenetic silencing of Pcsk9 confers pronounced vascular protection, including decreased lipid accumulation in the liver and aortic root, reduced necrotic core formation, diminished macrophage infiltration, and enhanced plaque stability. Together, these results provide proof of principle that CRISPRoff-based epigenome editing enables stable repression of clinically relevant targets and ameliorates key features of atherosclerotic disease. This work lays the foundation for broader therapeutic applications of epigenetic modulation in cardiovascular disorders.

Animals↗
PubMed1986

Observation of the terminal methyl group in fatty acids of the linolenic series by a new 1H NMR pulse sequence providing spectral editing and solvent suppression. Application to excised frog muscle and rat brain.

A new 1H NMR pulse sequence is described that combines water suppression with the selective observation of signals from coupled spin systems. The pulse sequence is easy to set up and compensates for pulse width inhomogeneity in the biological sample. Suppression of the water signal is achieved by pulses that return the water spins to their equilibrium position; spectral editing is based on the J modulation present in spin-echo spectra and its inhibition by coherent decoupling at one of the resonances of the spin system of interest. The pulse sequence, which was designed for 1H NMR spectroscopy of tissue, was tested at 470 MHz on excised frog muscle and rat brain. The lactate methyl resonance of caffeine-treated frog sartorius muscle was observed selectively by irradiation at the position of its alcoholic proton. The terminal methyl signal of linolenic acid, along with other fatty acids of the linolenic series (first double bond in the omega-3 position), was observed selectively by irradiation at the position of its omega-1 methylene group. 1H NMR spectra of rat brain were edited to reveal the terminal methyl of either linolenic series or all other fatty acids. The results suggest that the terminal methyl groups of fatty acids of the linolenic series (mostly docosahexaenoic acid, 22:6) have higher mobility than those of all other fatty acids.

Animals↗
PubMed2026

Genome Editing in Solanaceae: Harnessing CRISPR-Cas Technology for Precision Crop Improvement.

Malnutrition and climate-induced stress remain major constraints to global food and nutritional security despite the yield gains of the Green Revolution. Solanaceae crops such as tomato, potato, brinjal, and pepper are key sources of vitamins, minerals, and bioactive compounds. Yet, their genetic improvement has been limited by narrow diversity and complex polygenic traits. The advent of CRISPR/Cas-mediated genome editing provides a transformative platform for precision crop improvement by enabling targeted modification of genes controlling stress tolerance, yield, and nutritional quality. In Solanaceae, CRISPR/Cas applications have successfully enhanced resistance against major pathogens (SlMlo1, SlPelo, SlDCL2), improved abiotic stress tolerance through editing of SlMAPK3, SlCBF1, and SlBZR1, and optimized fruit quality traits via modulation of Psy1, CrtR-b2, and fiAD2/3. Emerging innovations, such as base and prime editing, and RNP-mediated transgene-free delivery, are expanding the precision and scope of editing. However, challenges persist, including genotype-dependent transformation, low HDR efficiency, and incomplete understanding of off-target and epigenetic effects. Integrating CRISPR with omics-guided gene discovery, efficient transformation systems, and regulatory harmonization can accelerate the development of nutritionally enriched, stress-resilient, and sustainable Solanaceae varieties. This review synthesizes recent advances, identifies critical limitations, and outlines future opportunities for deploying CRISPR/Cas technology to achieve next-generation breeding and food system resilience.

CRISPR/Cas↗
PubMed1999

A localized double-quantum filter for in vivo detection of taurine.

Noninvasive detection of taurine, an important amino acid involved in numerous physiological processes, by in vivo (1)H magnetic resonance (MR) spectroscopy is complicated by severe overlap of the taurine resonances with those of a number of other metabolites. Unambiguous differentiation of the taurine resonances requires spectral editing. In this study, the development of a localized spectral editing technique based on double-quantum filtering optimized for in vivo detection of taurine is described. The sequence recovers the taurine signal while substantially eliminating overlapping resonances and provides excellent three-dimensional spatial localization. The performance of the sequence is demonstrated both in phantoms and in rat brain in vivo. Magn Reson Med 42:454-460, 1999.

Animals↗
PubMed1992

The World Health Organization's Histological Classification of Salivary Gland Tumors. A commentary on the second edition.

The second edition of the World Health Organization's Histological Classification of Salivary Gland Tumors is more extensive and detailed than the previous edition published 20 years ago. The new edition is based on data regarding newly described tumor entities and the behavior and prognosis of the previously classified tumors. The distinct morphologic features of monomorphic adenomas justify their separation for purposes of identification. Among the carcinomas, various types were distinguished for purposes of recognition, prognosis, and treatment. The term tumor was replaced by carcinoma in the following two entities: acinic cell carcinoma and mucoepidermoid carcinoma. The tumor-like lesions were described in more detail.

Adenoma↗
PubMed1991

Longitudinal spin-order-based pulse sequence for lactate editing.

A new pulse sequence which edits proton spectra of lactate with full signal return and gives good suppression of water and fat signals is described. This sequence exploits longitudinal spin-order from lactate to edit lactate from fat. Experimental results from phantoms and excised pig heart are presented.

Animals↗
PubMed1993

A highly sensitive lactate editing technique for surface coil spectroscopic imaging in vivo.

A lactate editing sequence based on the use of spin-locking pulses with surface coils is described. The sequence retains more than 90% of the available lactate magnetization and suppresses at least 95% of the lipid signal in a single scan and ca. 99.5% after a simple two step cycle. The technique allows simultaneous observation of lactate and uncoupled metabolites in the range 2 to 3 ppm. The sequence was combined with two-dimensional spectroscopic imaging to obtain a lactate map of an ischemic rat brain in vivo.

Animals↗
PubMed1998

Spectral editing technique for the in vitro and in vivo detection of taurine.

In vivo 1H NMR spectroscopy has proven to be a useful noninvasive tool for the investigation of numerous metabolic and physiological states. Taurine is potentially a useful indicator in neonate development and is involved in a number of physiological processes. However, it could not previously be observed in the in vivo 1H spectrum because of overlap with adjacent resonances. We have developed a spectral editing technique based upon double quantum filtration which allows the taurine resonances to be resolved from adjacent peaks. The experiment is demonstrated both on perchloric acid rodent brain extract and on rodent brain homogenate.

Algorithms↗
PubMed1993

A fast algorithm for the optimal alignment of three strings.

Ukkonen's (pair-wise) string alignment technique is extended to the problem of finding an optimal alignment for three strings. The resulting algorithm has worst-case time-complexity O(nd2) and space-complexity O(d3), where the string lengths are ñ and d is the three-way edit-distance based on tree-costs. In practice, the algorithm usually runs in O(n + d3) time. The algorithm is particularly fast when the strings are similar, in which case, d << n. Three-way alignment is an important special case in string alignment. Each internal node in an unrooted, binary evolutionary-tree has three neighbours. The algorithm presented can be used as an iterative step in a heuristic multiple-alignment program for more than three strings.

Algorithms↗
PubMed2005

Shift in absorbed dose for megavoltage photons when changing to TRS-398 in Australia.

Australian primary standards of air kerma and absorbed dose are realized in 60Co gamma rays. To calibrate the megavoltage photon beams from linear accelerators, radiotherapy centres have their ionization chamber calibrated in a 60Co beam and then use a protocol to transfer this calibration to the higher energy. The radiotherapy community is in the process of changing from the ACPSEM Protocol (Second Edition 1998) based on an air kerma calibration to the IAEA's TRS-398 Code of Practice, based on an absorbed dose to water calibration. To evaluate the shift in absorbed dose resulting from the new protocol, the absorbed dose should be determined using both protocols and compared. We present a formula for this shift which can be used to check the result. To use this formula the centre needs to measure a displacement correction and know the ratio of the air kerma to absorbed dose to water calibration factors at 60Co. We calculate the change they should expect by using the average ratio of the air kerma and absorbed dose to water calibration factors for NE2571 and NE2561 chambers, based on Australian standards, and by estimating the displacement correction from published depth dose data. We find the absorbed dose in a megavoltage photon beam to increase by between 0.1 and 0.6% for NE2571 chambers and between 0.7 and 1.1% for NE2561 chambers, for beams up to 35 MV. The dose measured using TRS-398 is always higher.

Australia↗
PubMed2026

The mighty microproteins: from versatile cellular regulators to precision medicine therapeutics.

Microproteins, are tiny proteins encoded by small open reading frame (sORF), translation of these non-canonical open reading frames (ncORFs) has been implicated in diverse biological processes and diseases. This review summarizes recent developments in the discovery, biogenesis, and functional characterization of microproteins, and their involvement in various disease, with special focus on their roles in cancer, cardiovascular, metabolic, neurodegenerative and immune-related disorders. We emphasize the regulation of key cellular pathways by microproteins, including mitochondrial homeostasis, apoptosis, metabolic reprogramming, and immune signaling, all of which affect disease initiation and progression. Emerging evidence also supports their potential as disease biomarkers and therapeutic candidates for precision medicine. Finally, the review critically discusses the current challenges including discrepancies in microprotein annotation, the limitations of ribosome profiling and proteogenomic approaches, the gap between computationally predicted and experimentally validated microproteins, and the need for rigorous orthogonal validation by means of CRISPR-based genome editing, ribosome release assays, mutational analysis, high-resolution mass spectrometry, and functional studies. Finally, we review recent development of AI-assisted ORF prediction, single-cell translatomics, spatial proteomics, and integrated multi-omics as emerging technologies reshaping. Microprotein discovery and functional annotation. Finally, we discuss the translational potential of microproteins and highlight the remaining challenges to clinical application, including peptide stability, pharmacokinetics, tissue-specific delivery, immunogenicity, and the need for rigorous preclinical and clinical validation. Together, this review provides an updated and critical overview of the rapidly evolving microprotein field and highlights future research priorities for translating these molecules into clinically useful biomarkers and precision therapeutics.

Microproteins↗
PubMed1996

Parametric genome rearrangement.

Algorithms inspired by comparative genomics calculate an edit distance between two linear orders based on elementary edit operations such as inversion, transposition and reciprocal translocation. All operations are generally assigned the same weight, simply by default, because no systematic empirical studies exist verifying whether algorithmic outputs involve realistic proportion of each. Nor do we have data on how weights should vary with the length of the inverted or transposed segment of the chromosome. In this paper, we present a rapid algorithm that allows each operation to take on a range of weights, producing an relatively tight upper bound on the distance between single-chromosome genomes, by means of a greedy search with look-ahead. The efficiency of this algorithm allows us to test random genomes for each parameter setting, to detect gene order similarity and to infer the parameter values most appropriate to the phylogenetic domain under study. We apply this method to genome segments in which the same gene order is conserved in Escherichia coli and Bacillus subtilis, as well as to the gene order in human versus Drosophila mitochondrial genomes. In both cases, we conclude that it is most appropriate to assign somewhat more than twice the weight to transpositions and inverted transpositions than to inversions. We also explore segment-length weighting for fungal mitochondrial gene orders.

Algorithms↗
PubMed2002

Pairwise sequence alignment using a PROSITE pattern-derived similarity score.

Existing methods for alignments are based on edition costs computed additionally position by position, according to a fixed substitution matrix: a substitution always has the same weight regardless of the position. Nevertheless the biologist favours a similarity according to his knowledge of the structure or the function of the sequences considered. In the particular case of proteins, we present a method consisting in integrating other information, such as patterns of the PROSITE databank, in the classical dynamic programming algorithm. The method consists in making an alignment by dynamic programming taking a decision not only letter by letter as in the Smith & Waterman algorithm but also by giving a reward when aligning patterns.

Algorithms↗
PubMed2002

Determinants of DNA mismatch recognition within the polymerase domain of the Klenow fragment.

The Klenow fragment of Escherichia coli DNA polymerase I catalyzes template-directed synthesis of DNA and uses a separate 3'-5' exonuclease activity to edit misincorporated bases. The polymerase and exonuclease activities are contained in separate structural domains. In this study, nine Klenow fragment derivatives containing mutations within the polymerase domain were examined for their interaction with model primer-template duplexes. The partitioning of the DNA primer terminus between the polymerase and 3'-5' exonuclease active sites of the mutant proteins was assessed by time-resolved fluorescence anisotropy, utilizing a dansyl fluorophore attached to the DNA. Mutation of N845 or R668 disrupted favorable interactions between the Klenow fragment and a duplex containing a matched terminal base pair but had little effect when the terminus was mismatched. Thus, N845 and R668 are required for recognition of correct terminal base pairs in the DNA substrate. Mutation of N675, R835, R836, or R841 resulted in tighter polymerase site binding of DNA, suggesting that the side chains of these residues induce strain in the DNA and/or protein backbone. A double mutant (N675A/R841A) showed an even greater polymerase site partitioning than was displayed by either single mutation, indicating that such strain is additive. In both groups of mutant proteins, the ability to discriminate between duplexes containing matched or mismatched base pairs was impaired. In contrast, mutation of K758 or Q849 had no effect on partitioning relative to wild type, regardless of DNA mismatch character. These results demonstrate that DNA mismatch recognition is dependent on specific amino acid residues within the polymerase domain and is not governed solely by thermodynamic differences between correct and mismatched base pairs. Moreover, this study suggests a mechanism whereby the Klenow fragment is able to recognize polymerase errors following a misincorporation event, leading to their eventual removal by the 3'-5' exonuclease activity.

Amino Acid Substitution↗
PubMed2025

Integrated epigenetic and genetic programming of primary human T cells.

Targeted epigenetic engineering of gene expression in cell therapies would allow programming of desirable phenotypes without many of the challenges and safety risks associated with double-strand break-based genetic editing approaches. Here, we develop an all-RNA platform for efficient, durable and multiplexed epigenetic programming in primary human T cells, stably turning endogenous genes off or on using CRISPRoff and CRISPRon epigenetic editors. We achieve epigenetic programming of diverse targeted genomic elements without the need for sustained expression of CRISPR systems. CRISPRoff-mediated gene silencing is maintained through numerous cell divisions, T cell stimulations and in vivo adoptive transfer, avoiding cytotoxicity or chromosomal abnormalities inherent to multiplexed Cas9-mediated genome editing. Lastly, we successfully combined genetic and epigenetic engineering using orthogonal CRISPR Cas12a-dCas9 systems for targeted chimeric antigen receptor (CAR) knock-in and CRISPRoff silencing of therapeutically relevant genes to improve preclinical CAR-T cell-mediated in vivo tumor control and survival.

Humans↗
PubMed2000

[The new German resuscitation guidelines in the context of international recommendations].

The German Guidelines for Cardiopulmonary Resuscitation were adapted to match the revised International Guidelines. The revised German edition was based both on the guidelines issued by the American Heart Association (AHA) in 1992 and on those of the European Resuscitation Council (ERC) of 1998, as well as on those released by the International Liaison Committee on Resuscitation (ILCOR) in 1997. Due to the diverging instructions for action the emergency physicians felt considerably unsafe as to what they should really do to achieve maximum results. Only 10.3 per cent of the german emergency physicians followed the recommendations given by the German Federal Chamber of Physicians. Innovations in respect of the basic checkup concern the time for controlling the respiration and circulation (ten seconds). Contrary to the international recommendations the "diagnostic block" is performed in Germany without interspersing basic reanimation. In artificial respiration the tidal volume has been reduced to 600 ml in accordance to the ERC and ILCOR guidelines. The search for the pressure point for cardiac pressure massage has also been adapted to the international recommendations. Also in accordance with the international recommendations defibrillation in case of ventricular fibrillation is now being performed only thrice in series without interspersed basic reanimation. There is some uncertainty with regard to choosing the requisite energy: 16.6% of the emergency physicians opt for less than 200 joule in primary defibrillation whereas 13% are in favour of more than 200 joule. Contrary to the international recommendations which prescribe peripheral venous access as application site for reanimation by drugs, the german guidelines favour the endobronchial path, which is already being practised by 57.4% of the emergency physicians. Hence, emergency medication can be effected in Germany 4 minutes earlier than in other countries. After three unsuccessful applications of 1 mg each of adrenalin the dosage is increased to 5 mg, and in agreement with the AHA guidelines escalating doses are also possible. Sodium bicarbonate is recommended only after more than 20 minutes of reanimation and if so, only in a reduced dose of 0.5 mval/kg body weight. In accordance with the international recommendations there is now a universal algorithm that decides on application only between ventricular fibrillation and nonfibrillation. The new german recommendations have adapted the reanimation procedure in agreement with ERC to national usage without abandoning any principles of the international guidelines.

Cardiopulmonary Resuscitation↗