Publications by authors named "Sammeth M"

: Hemoglobin (Hb) is a crucial parameter in perioperative care due to its essential role for oxygen transport and tissue oxygenation. Accurate Hb monitoring allows for timely interventions to address perioperative anemia and, thus, prevent morbidity and mortality. Traditional Hb measurements rely on invasive blood sampling, which significantly contributes to iatrogenic anemia and poses discomfort and increased infection risks.

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Nerve injury causes neuropathic pain and multilevel nerve barrier disruption. Nerve barriers consist of perineurial, endothelial and myelin barriers. So far, it is unclear whether resealing nerve barriers fosters pain resolution and recovery.

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Spatial Transcriptomics (ST), coined as the term for parallel RNA-Seq on cell populations ordered spatially on a histological tissue section, has recently become increasingly popular, especially in experiments where microfluidics-based single-cell sequencing fails, such as assays on neurons. ST platforms, like the 10x Visium technology investigated herein, therefore produce in a single experiment simultaneously thousands of RNA readouts, captured by an array of micrometer scale spots under the histological section. Therefore, a central challenge of analyzing ST experiments consists of analyzing the gene expression morphology of all spots to delineate clusters of similar cell mixtures, which are then compared to each other to identify up- or down-regulated marker genes.

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Introduction: Fitness trackers can provide continuous monitoring of vital signs and thus have the potential to become a complementary, mobile and effective tool for early detection of patient deterioration and post-operative complications.

Methods: To evaluate potential implementations in acute care setting, we included 36 patients after moderate to major surgery in a recent randomised pilot trial to compare the performance of vital sign monitoring by three different fitness trackers (Apple Watch 7, Garmin Fenix 6pro and Withings ScanWatch) with established standard clinical monitors in post-anaesthesia care units and monitoring wards.

Results: During a cumulative period of 56 days, a total of 53,197 heart rate (HR) measurements, as well as 12,219 measurements of the peripheral blood oxygen saturation (SpO) and 28,954 respiratory rate (RR) measurements were collected by fitness trackers.

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Blood oxygen saturation is an important clinical parameter, especially in postoperative hospitalized patients, monitored in clinical practice by arterial blood gas (ABG) and/or pulse oximetry that both are not suitable for a long-term continuous monitoring of patients during the entire hospital stay, or beyond. Technological advances developed recently for consumer-grade fitness trackers could-at least in theory-help to fill in this gap, but benchmarks on the applicability and accuracy of these technologies in hospitalized patients are currently lacking. We therefore conducted at the postanaesthesia care unit under controlled settings a prospective clinical trial with 201 patients, comparing in total >1,000 oxygen blood saturation measurements by fitness trackers of three brands with the ABG gold standard and with pulse oximetry.

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Background: Over the recent years, technological advances of wrist-worn fitness trackers heralded a new era in the continuous monitoring of vital signs. So far, these devices have primarily been used for sports.

Objective: However, for using these technologies in health care, further validations of the measurement accuracy in hospitalized patients are essential but lacking to date.

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The close monitoring of blood pressure during a caesarean section performed under central neuraxial anaesthesia should be the standard of safe anaesthesia. As classical oscillometric and invasive blood pressure measuring have intrinsic disadvantages, we investigated a novel, non-invasive technique for continuous blood pressure measuring. In this monocentric, retrospective data analysis, the reliability of continuous non-invasive blood pressure measuring using ClearSight (Edwards Lifesciences Corporation) is validated in 31 women undergoing central neuraxial anaesthesia for caesarean section.

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Article Synopsis
  • Rhodnius prolixus is a significant vector for Chagas disease, and recent research sequenced its genome, improving gene annotations for 9,206 genes.
  • This study involved analyzing around 228 million RNA-Seq reads, which identified over 2,000 new genes and increased the total gene count from 15,738 to 17,864.
  • The findings reveal key gene expression changes during oogenesis, highlighting crucial factors for germline development and early embryonic processes, particularly in mature eggs where various signaling pathways are active.
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The failure to translate preclinical results to the clinical setting is the rule, not the exception. One reason that is frequently overlooked is whether the animal model reproduces distinctive features of human disease. Another is the reproducibility of the method used to measure treatment effects in preclinical studies.

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Scarce data are available on the expression of papillomavirus genome and the frequency of alternatively spliced E6E7 mRNAs in invasive cervical cancer. We carried out a comprehensive characterization of HPV expression by RNA-Seq analysis in 22 invasive cervical cancer with HPV16 or HPV18, characterizing the presence of integrated/episomal viral DNA, the integration sites in human genome and the proportion of alternative splicing products of E6 and E7 genes. The expression patterns suggested the presence of episomal and/or integrated viral DNA, with integration detected in most tumors, frequently occurring within human genes in HPV18+ and in intergenic regions in HPV16+ tumors.

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The piRNA pathway is a surveillance system that guarantees oogenesis and adult fertility in a range of animal species. The pathway is centered on PIWI clade Argonaute proteins and the associated small non-coding RNAs termed piRNAs. In this study, we set to investigate the evolutionary conservation of the piRNA pathway in the hemimetabolous insect Rhodnius prolixus.

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Motivation: Alternative splicing (AS) has been demonstrated to play a role in shaping eukaryotic gene diversity at the transcriptional level. However, the impact of AS on the proteome is still controversial. Studies that seek to explore the effect of AS at the proteomic level are hampered by technical difficulties in the cumbersome process of casting forth and back between genome, transcriptome and proteome space coordinates, and the naïve prediction of protein domains in the presence of AS suffers many redundant sequence scans that emerge from constitutively spliced regions that are shared between alternative products of a gene.

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Spliced leader dependent trans-splicing (SLTS) has been described as an important RNA regulatory process that occurs in different organisms, including the trematode Schistosoma mansoni. We identified more than seven thousand putative SLTS sites in the parasite, comprising genes with a wide spectrum of functional classes, which underlines the SLTS as a ubiquitous mechanism in the parasite. Also, SLTS gene expression levels span several orders of magnitude, showing that SLTS frequency is not determined by the expression level of the target gene, but by the presence of particular gene features facilitating or hindering the trans-splicing mechanism.

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Article Synopsis
  • Post-mortem tissue samples are valuable for studying gene expression, but the time since death (PMI) can significantly affect RNA levels.
  • Research utilizing GTEx project data shows that gene expression changes in a tissue-specific manner during post-mortem intervals, but these effects can be minimized with the right analytical adjustments.
  • The study reveals that the process of dying triggers specific transcriptional changes rather than random mRNA degradation, and a predictive model for estimating the time since death was created based on this analysis.
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Genomes can be compared at different levels of divergence, either between species or within species. Within species genomes can be compared between different subpopulations, such as human subpopulations from different continents. Investigating the genomic differences between different human subpopulations is important when studying complex diseases that are affected by many genetic variants, as the variants involved can differ between populations.

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Since the pioneering studies of Thomas Hunt Morgan and coworkers at the dawn of the twentieth century, Drosophila melanogaster and its sister species have tremendously contributed to unveil the rules underlying animal genetics, development, behavior, evolution, and human disease. Recent advances in DNA sequencing technologies launched Drosophila into the post-genomic era and paved the way for unprecedented comparative genomics investigations. The complete sequencing and systematic comparison of the genomes from 12 Drosophila species represents a milestone achievement in modern biology, which allowed a plethora of different studies ranging from the annotation of known and novel genomic features to the evolution of chromosomes and, ultimately, of entire genomes.

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Recent advances in the cost-efficiency of sequencing technologies enabled the combined DNA- and RNA-sequencing of human individuals at the population-scale, making genome-wide investigations of the inter-individual genetic impact on gene expression viable. Employing mRNA-sequencing data from the Geuvadis Project and genome sequencing data from the 1000 Genomes Project we show that the computational analysis of DNA sequences around splice sites and poly-A signals is able to explain several observations in the phenotype data. In contrast to widespread assessments of statistically significant associations between DNA polymorphisms and quantitative traits, we developed a computational tool to pinpoint the molecular mechanisms by which genetic markers drive variation in RNA-processing, cataloguing and classifying alleles that change the affinity of core RNA elements to their recognizing factors.

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Accurate prediction of the functional effect of genetic variation is critical for clinical genome interpretation. We systematically characterized the transcriptome effects of protein-truncating variants, a class of variants expected to have profound effects on gene function, using data from the Genotype-Tissue Expression (GTEx) and Geuvadis projects. We quantitated tissue-specific and positional effects on nonsense-mediated transcript decay and present an improved predictive model for this decay.

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Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples.

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Alternative splicing (AS) is a eukaryotic principle to derive more than one RNA product from transcribed genes by removing distinct subsets of introns from a premature polymer. We know today that this process is highly regulated and makes up a large part of the differences between species, cell types, and states. The key to compare AS across different genes or organisms is to tokenize the AS phenomenon into atomary units, so-called AS events.

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Alternative splicing (AS) is a fundamental mechanism for the regulation of gene expression. It affects more than 90% of human genes but its role in the regulation of pancreatic beta cells, the producers of insulin, remains unknown. Our recently published data indicated that the 'neuron-specific' Nova1 splicing factor is expressed in pancreatic beta cells.

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Article Synopsis
  • Lichtheimia corymbifera is a significant cause of mucormycosis in Europe, and its genome, which contains 12,379 protein-coding genes, was sequenced and compared with the genome of Rhizopus oryzae, the leading cause of the disease worldwide.
  • Key differences were identified between the two genomes, including higher gene duplications in L. corymbifera, a lower frequency of alternative splicing, a low content of repetitive elements, and its haploid nature.
  • Additionally, novel virulence factors related to iron adaptation were discovered, including unique transcription factors and a greater number of secreted proteases in L. corymbifera compared to R.
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  • The study investigates how saturated fatty acids, specifically palmitate, lead to pancreatic β-cell dysfunction and death, which are key factors in the development of type 2 diabetes (T2D).
  • RNA sequencing was used to analyze gene expression changes in human islet cells treated with palmitate, revealing 1,325 modified genes linked to fatty acid metabolism and endoplasmic reticulum stress.
  • The findings highlight the role of palmitate in disrupting transcription factors that maintain β-cell function, linking metabolic stress to T2D candidate genes and uncovering mechanisms of β-cell lipotoxicity.
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  • RNA sequencing is gaining popularity for analyzing gene expression, but there's still limited understanding of variations between different labs.
  • The GEUVADIS consortium conducted a study with 465 individuals across seven labs, finding that lab-related differences were less significant than biological differences.
  • They identified specific technical variations and proposed guidelines to help standardize RNA sequencing practices, making it feasible to conduct experiments in multiple labs.
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