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Emerging Opportunity and Destiny of mcr-1- and tet(X4)-Coharboring Plasmids in Escherichia coli.

The emergence of the plasmid-mediated colistin resistance gene mcr-1 and the plasmid-mediated tigecycline resistance gene tet(X4) represents a significant threat to public health. Although mcr-1 and tet(X4) have been reported to coexist in the same isolate, there are no reports on the emergence of plasmids coharboring mcr-1 and tet(X4). In this study, we aimed to investigate the opportunities for the emergence of mcr-1- and tet(X4)-coharboring plasmids and their destiny in Escherichia coli. Two plasmids carrying both mcr-1 and tet(X4) were constructed through conjugation assays and confirmed b

Nanopore long-read metabarcoding for comprehensive characterisation of parasitic nematodes in humans and animals: a development and diagnostic validation study.

BACKGROUND: Parasitic nematodes of vertebrates impose a substantial burden on human and animal health; however, advanced diagnostic tools for the accurate characterisation of these parasites are scarce. One promising but nascent approach is metabarcoding, which enables the simultaneous characterisation of all parasitic nematodes in a sample, termed the nemabiome. However, earlier iterations of this approach could not detect socioeconomically important nematodes such as those in the genera Strongyloides and Trichuris. Therefore, we aimed to develop a novel nemabiome method capable of detecting

Third generation sequencing analysis detects significant differences in duodenal microbiome composition between functional dyspepsia patients and control subjects.

BACKGROUND: Functional dyspepsia (FD) is a multifactorial disorder as its development may be based on several different pathophysiological mechanisms. Interaction of gut microbiome with the host has been proposed as a potential mechanism involved in the disease's pathogenesis. AIM/METHODS: We aimed to characterize microbiome profiling on duodenal luminal content (DLC) of FD patients and compare it to that of controls (CG) and patients with irritable bowel syndrome (IBS). Outpatients fulfilling Rome IV criteria for FD, IBS, and control group (CG) underwent upper gastrointestinal endoscopy and

Genomic phylogeny, taxonomic classification, genetic landscape, and antibiotic resistance of clinical Stenotrophomonas isolates.

BACKGROUND: Stenotrophomonas spp. are increasingly recognized opportunistic pathogens characterized by intrinsic multidrug resistance. Despite recent taxonomic reclassification and the delineation of new species within the S. maltophilia complex (Smc), routine diagnostics often misidentify these species, and their distinctive antibiotic resistance traits and genetic makeup remain underexplored. We aimed to characterize the phylogenomic diversity, genotypic and phenotypic antibiotic resistance traits, virulence markers and horizontally transferrable elements in a large national cohort of clinic

Dynamics of subclinical pneumonia in male dairy calves in relation to antimicrobial therapy and production outcomes.

Quick thoracic ultrasonography (qTUS) is increasingly used as an on-farm method to diagnose clinical and subclinical pneumonia in dairy calv … became more clinical, and treatment with amoxicillin resulted in a cure risk of 52.7%. Culture and nanopore sequencing diagnostics on nonendoscopic broncho-alveolar lavage (nBAL) samples identified bovine respiratory syncytial virus and Mycoplasma bovis as the dominant agents in the first outbreak. The isolated M. bovis strain showed mutations associated with macrol …

Application of Next Generation Sequencing in Laboratory Medicine.

The rapid development of next-generation sequencing (NGS) technology, including advances in sequencing chemistry, sequencing technologies, bioinformatics, and data interpretation, has facilitated its wide clinical application in precision medicine. This review describes current sequencing technologies, including short- and long-read sequencing technologies, and highlights the clinical application of NGS in inherited diseases, oncology, and infectious diseases. We review NGS approaches and clinical diagnosis for constitutional disorders; summarize the application of U.S. Food and Drug Administr

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… Not only can Nanopore sequence DNA, it can also directly sequence RNA and protein [ 48 ]. This technology also has the advantages of short turnaround time and no GC bias. … Nanopore sequencing, which is as fast, or faster than standard approaches, has been used to identify pathogens, as well as antibiotic resistance markers [ 211 , 212 ]. …

Emerging therapeutic strategies in glioblastsoma: drug repurposing, mechanisms of resistance, precision medicine, and technological innovations.

Glioblastoma (GBM) is an aggressive Grade IV brain tumor with a poor prognosis. It results from genetic mutations, epigenetic changes, and factors within the tumor microenvironment (TME). Traditional treatments like surgery, radiotherapy, and chemotherapy provide limited survival benefits due to the tumor's heterogeneity and resistance mechanisms. This review examines novel approaches for treating GBM, focusing on repurposing existing medications such as antipsychotics, antidepressants, and statins for their potential anti-GBM effects. Advances in molecular profiling, including next-generation

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… Techniques like PacBio’s SMRT sequencing and nanopore sequencing offer real-time sequencing with less need for extensive sample preparation [ 37 ]. … In particular, nanopore sequencing uses an electric field to pull single-stranded DNA or RNA through tiny pores, converting the resulting electrical signals into sequence data [ 21 ]. …

Искусственный интеллект основывается на достижениях в области наномедицины для лечения мозговых расстройств: обновленный обзор повествования.

Наномедицина - это наномасштабные, биосопоставимые материалы, которые предлагают перспективные альтернативы традиционным методам лечения расстройств мозга. Технологические достижения в области искусственного интеллекта (АИ), в частности машинного обучения (МЛ) и глубокого обучения (ДЛ), трансформируют область наномедицины путем совершенствования диагностики заболеваний, биомаркировки, прогнозирования и мониторинга заболеваний, целевых поставок наркотиков и терапевтического вмешательства, а также содействия расчетным и методологическим разработкам. Эти успехи могут быть достигнуты за счет анали

The Potential of Nuclear Pore Complexes in Cancer Therapy.

Nuclear pore complexes (NPCs) play a critical role in regulating transport-dependent gene expression, influencing various stages of cancer development and progression. Dysregulation of nucleocytoplasmic transport has profound implications, particularly in the context of cancer-associated protein mislocalization. This review provides specific information about the relationship between nuclear pore complexes, key regulatory proteins, and their impact on cancer biology. Highlighting the influence of tumor-suppressor proteins as well as the potential of gold nanoparticles and intelligent nanosyste

Clinical and Genomic Epidemiology of Carbapenem-Nonsusceptible Citrobacter spp. at a Tertiary Health Care Center over 2 Decades.

Carbapenem-nonsusceptible Citrobacter spp. (CNSC) are increasingly recognized as health care-associated pathogens. Information regarding their clinical epidemiology, genetic diversity, and mechanisms of carbapenem resistance is lacking. We examined microbiology records of adult patients at the University of Pittsburgh Medical Center (UMPC) Presbyterian Hospital (PUH) from 2000 to 2018 for CNSC, as defined by ertapenem nonsusceptibility. Over this time frame, the proportion of CNSC increased from 4% to 10% (P = 0.03), as did daily defined carbapenem doses/1,000 patient days (6.52 to 34.5; R2 =

Clinical, molecular, and in vitro evidence of artemisinin partial resistance in Ethiopian Plasmodium falciparum: a prospective, multisite, surveillance study.

BACKGROUND: Artemisinin partial resistance (ART-R) has been confirmed in four sub-Saharan African countries since 2020, but evidence from Et … temether-lumefantrine according to bodyweight (six doses during 3 days). Pfkelch13 was genotyped by Nanopore sequencing and Pfhrp2/Pfhrp3 deletions were assessed by quantitative PCR. The RSA0-3 h was performed on culture-adapted field isolates. Follow-up occurred on days 0 and 3. The main outcome was day-3 parasite positivity rate (defined as microscopically detectab …

IDH Mutations in Glioma: Molecular, Cellular, Diagnostic, and Clinical Implications.

In 2021, the World Health Organization classified isocitrate dehydrogenase (IDH) mutant gliomas as a distinct subgroup of tumors with genetic changes sufficient to enable a complete diagnosis. Patients with an IDH mutant glioma have improved survival which has been further enhanced by the advent of targeted therapies. IDH enzymes contribute to cellular metabolism, and mutations to specific catalytic residues result in the neomorphic production of D-2-hydroxyglutarate (D-2-HG). The accumulation of D-2-HG results in epigenetic alterations, oncogenesis and impacts the tumor microenvironment via i

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… Methylation status has been interrogated using Nanopore sequencing [ 173 , 176 ] and methylation profiling arrays [ 170 , 171 , 172 , 173 ] and can be performed using snap frozen or FFPE tissue. … Nanopore sequencing for the determination of methylation status is particularly advantageous because it does not require a precursor bisulfite treatment, which is associated with DNA degradation [ 177 ] and is rapid enough to adapt for intraoperative use [ 176 ]. …

5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation.

Developing accurate, clinically convenient, and non-invasive methods for early cancer detection, monitoring, and prognosis assessment is essential for improving patient survival rates, enhancing quality of life, and reducing the socioeconomic burden associated with cancer. This goal is critical in precision oncology. Genetic and epigenetic alterations in circulating cell-free DNA (cfDNA) have emerged as transformative tools for advancing early cancer detection, monitoring, and improving patient outcomes. Among these, 5-hydroxymethylcytosine (5hmC) modifications in circulating cfDNA stand out a

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… Wang Y Zhao Y Bollas A Wang Y Au KF Nanopore sequencing technology, bioinformatics and applications Nat Biotechnol 2021 39 11 1348 1365 10.1038/s41587-021-01108-x 34750572 PMC8988251 Wang Y, Zhao Y, Bollas A, Wang Y, Au KF. Nanopore sequencing technology, bioinformatics and applications. … Nanopore sequencing technology and tools for genome assembly: computational analysis of the current state, bottlenecks and future directions. Brief Bioinform. 2019;20(4):1542–59. 29617724 10.1093/bib/bby017 PMC6781587 42. Jia H, Tan S, Zhang YE. …

Геномический диагноз детских расстройств: революция и эволюция.

Мощные, последние достижения в технологиях анализа генома оказали глубокое воздействие на практику медицинской генетики как в лаборатории, так и в клинике. Более широкое использование общегеномных тестов, таких, как анализ хромосомных микроарра и последовательность экзомов, привело к переходу к "генотипному" подходу. В настоящее время имеются многочисленные методы диагностики конкретного синдрома или фенотипа, и, хотя традиционные методы остаются эффективными инструментами в некоторых ситуациях, технологии с более высокой производительностью фактически стали лабораторным инструментом диагности

Next generation sequencing: new tools in immunology and hematology.

One of the hallmarks of the adaptive immune system is the specificity of B and T cell receptors. Thanks to somatic recombination, a large repertoire of receptors can be generated within an individual that guarantee the recognition of a vast number of antigens. Monoclonal antibodies have limited applicability, given the high degree of diversity among these receptors, in BCR and TCR monitoring. Furthermore, with regard to cancer, better characterization of complex genomes and the ability to monitor tumor-specific cryptic mutations or translocations are needed to develop better tailored therapies

DNA Methylation Cancer Biomarkers: Translation to the Clinic.

Carcinogenesis is accompanied by widespread DNA methylation changes within the cell. These changes are characterized by a globally hypomethylated genome with focal hypermethylation of numerous 5'-cytosine-phosphate-guanine-3' (CpG) islands, often spanning gene promoters and first exons. Many of these epigenetic changes occur early in tumorigenesis and are highly pervasive across a tumor type. This allows DNA methylation cancer biomarkers to be suitable for early detection and also to have utility across a range of areas relevant to cancer detection and treatment. Such tests are also simple in

Взаимодействие с Мозгом: Как нанотехнология может способствовать.

Соединение искусственных устройств с человеческим мозгом является главной целью нейротехнологий. Однако наше воображение часто ограничивается существующими парадигмами и технологиями. Со временем, наряду с имеющейся технологией, изменились предложения в отношении интерфейсов мозга и автомата. Механические рычаги и кабельные лебедки использовались для перемещения частей мозга в механическую эпоху. Сложное электронное проводка и дистанционное управление возникли в эпоху электронной связи, что в конечном счете привело к созданию компьютерных интерфейсов. Тем не менее, наши мозги настолько сложны,

Современные методы диагностики медицинских паразитов и артроподов

Обычные методы, такие, как микроскопия, используются для диагностики паразитических заболеваний и медицинских заболеваний, связанных с артроподами, на протяжении многих лет. Некоторые методы считаются золотыми. Однако их ограниченная чувствительность, специфичность и точность, а также потребность в дорогостоящих реагентах и высококвалифицированных технических специалистах являются критическими проблемами. В этой связи постоянно разрабатываются новые инструменты для уменьшения числа проблем. Недавно three Возникли самые современные методы: штрих-кодирование ДНК, геометрические морфометры и иску

Митохондриальная ДНК (mtDNA) в качестве жидкого биомаркера в нейродегенеративных расстройствах: систематический обзор.

ИСТОРИЯ ВОПРОСА: В ряде исследований была проведена оценка периферийных и цереброспинных жидкостей (CSF) mtDNA как предполагаемого биомаркера нейродегенеративных заболеваний, что зачастую приводит к непоследовательным выводам. Мы систематически анализировали текущие данные, позволяющие оценить уровни крови и CSF mtDNA и возможное бремя в болезни Паркинсона (PD), болезни Альцгеймера (ALS) и амиотропическом боковом склерозе (ALS). Множественный склероз (MS) был также включен в качестве парадигмы хронического нейроинфламмации под воздействием нейродегенерации. МЕТОДЫ: Медлин, Эмбаза, Скопус и веб

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… sequencing and DNA methylation analysis mtDNA methylation ↓ in PRKN‐PD vs. … PINK1/PRKN‐NMC (joint cohort) (AUC =0.83) 47 PINK1 het asymp. 47 62.1 ± 11.6 ‐ Nanopore sequencing Large scale deletions (ND4/ND1 ratio) ↑ of mtDNA heteroplasmic variants in PINK1/PRKN‐PD (joint cohort) vs. iPD 54 PRKN‐PD 46 59.7 ± 16.9 22.8 mtDNA transcription/replication initiation (7S DNA/ND1 ratio …

Next-Generation Sequencing in Oncology: Genetic Diagnosis, Risk Prediction and Cancer Classification.

Next-generation sequencing (NGS) technology has expanded in the last decades with significant improvements in the reliability, sequencing chemistry, pipeline analyses, data interpretation and costs. Such advances make the use of NGS feasible in clinical practice today. This review describes the recent technological developments in NGS applied to the field of oncology. A number of clinical applications are reviewed, i.e., mutation detection in inherited cancer syndromes based on DNA-sequencing, detection of spliceogenic variants based on RNA-sequencing, DNA-sequencing to identify risk modifiers