Molecular testing

OBJECTIVES: Skeletal muscles mitochondrial dysfunction is the main cause of sarcopenia. Both electroacupuncture (EA) and sulforaphane (SFN) have been shown to improve oxidative stress and inflammation levels to maintain mitochondrial function, but the effects and mechanisms of their combination on sarcopenia are unclear. This study aimed to investigate the regulatory effects of EA combined with SFN on sarcopenia. MATERIALS AND METHODS: SAMP8 mice were used and intervened with EA or SFN, respectively, and Masson and HE staining were used to observe pathological changes in skeletal muscle tissue...

BACKGROUND: Fosfomycin treatment of urinary tract infections is increasingly attractive due to escalating antibiotic resistance rates among urinary pathogens. Standard antibiotic susceptibility testing methods perform poorly for fosfomycin as there is poor correlation between susceptibility results and clinical outcomes in urinary pathogens other than Escherichia coli . OBJECTIVE: We evaluated the performance of fosfomycin susceptibility testing in E. coli and Klebsiella pneumoniae to determine whether fosfomycin susceptibility is associated with molecular resistance mechanisms...

PURPOSE: To report a rare clinical finding of preretinal granules associated with atypical familial exudative vitreoretinopathy (FEVR) and perform a review of the literature. OBSERVATIONS: An asymptomatic 18-year-old male was referred for unilateral peripheral avascular retina evaluation in association with presumed FEVR. He was first noted to have white preretinal granules on fundus examination at five years of age. The lesions remained unchanged over the subsequent years...

BACKGROUND: Respiratory syncytial virus (RSV) is a common cause of upper and lower respiratory tract infections. This study aimed to explore the prevalence of respiratory syncytial virus (RSV) and other respiratory viruses in Bulgaria, characterize the genetic diversity of RSV strains, and perform amino acid sequence analyses of RSV surface and internal proteins. METHODS: Clinical and epidemiological data and nasopharyngeal swabs were prospectively collected from patients with acute respiratory infections between October 2020 and May 2023...

A series of 1-(4-sulfamoylbenzoyl)piperidine-4-carboxamides deriving from substituted piperazines/benzylamines was designed, synthesized, and tested on human carbonic anhydrase (hCA). The inhibitory activity of the new sulfonamides was analyzed using acetazolamide (AAZ) as a standard inhibitor against hCA I, II, IX, and XII. Several sulfonamides showed both inhibitory activity at low nanomolar concentrations and selectivity against the cytosolic hCA II isoform, and the same trend was observed on the tumor-associated hCA IX and XII...

The gut microbiota is associated with GC; however, the causal association between the gut microbiota and GC remains to be determined. The aim of the present study was to investigate the causal association between gut microbiota and gastric cancer (GC) from the perspective of Mendelian randomization (MR). The present study performed MR analysis using summary statistics from a genome-wide association study of the gut microbiome and GC. Inverse-variance weighted, MR-Egger and weighted median methods were used to investigate the causal relationship between gut microbiota and GC...

The diagnostics of colorectal cancer (CRC) and precancerous lesions in the colon is one of the most urgent matters to be considered for the modern protocols of complex examination, recommended for use from the age of 45 years, and including both instrumental and laboratory methods of research: Colonoscopy, CT colonography, flexible sigmoidoscopy, fecal occult blood test, fecal immunohistochemistry test and stool DNA test Nevertheless, the removal of those precancerous lesions does not solve the issue, and, apart from the regular endoscopic monitoring of patients who are at a high risk of developing CRC, the pharmacological treatment of certain key pathogenic mechanisms leading to the development of CRC is required...

Cellular therapies for the treatment of human diseases, such as chimeric antigen receptor (CAR) T and NK cells have shown remarkable clinical efficacy in treating hematological malignancies, however current methods mainly utilize viral vectors which are limited by their cargo size capacities, high cost, and long timelines for production of clinical reagent. Delivery of genetic cargo via DNA transposon engineering is a more timely and cost-effective approach, yet has been held back by less efficient integration rates...

The latest breakthroughs in spatially resolved transcriptomics technology offer comprehensive opportunities to delve into gene expression patterns within the tissue microenvironment. However, the precise identification of spatial domains within tissues remains challenging. In this study, we introduce AttentionVGAE (AVGN), which integrates slice images, spatial information and raw gene expression while calibrating low-quality gene expression. By combining the variational graph autoencoder with multi-head attention blocks (MHA blocks), AVGN captures spatial relationships in tissue gene expression, adaptively focusing on key features and alleviating the need for prior knowledge of cluster numbers, thereby achieving superior clustering performance...

Most of the Escherichia coli turned into serious pathogens or developed antibiotic resistance, mainly due to their ability to show different phenotypic traits. In order to overcome the resistance to these antibiotics, the use of essential oils (EOs) is of great significance against highly pathogenic microorganisms. This study has been made to compare the in vitro antibacterial activity and further validated the same through the molecular docking study of 13 antibiotics such as ciprofloxacin, chloramphenicol, erythromycin, ampicillin, cefotaxime, rifampicin, kanamycin, vancomycin, streptomycin, penicillin, nalidixic acid, trimethoprim, and polymyxin, and 10 EOs such as garlic, tulsi, neem, clove, thyme, peppermint, coriander, tea, lavender, and eucalyptus against the target protein (DNA gyrase) of E...

BACKGROUND: Carbapenem-resistant Escherichia coli (CREC) has been considered as WHO priority pathogens, causing a great public health concern globally. While CREC from patients has been thoroughly investigated, the prevalence and underlying risks of CREC in healthy populations have been overlooked. Systematic research on the prevalence of CREC in healthy individuals was conducted here. We aimed to characterize CREC collected from healthy populations in China between 2020 and 2022 and to compare the genomes of CREC isolates isolated from healthy individuals and clinical patients...

Trisomy 20 has been shown to be one of the most frequent rare autosomal trisomies in patients that undergo genome-wide noninvasive prenatal testing. Here, we describe the clinical outcomes of cases that screened positive for trisomy 20 following prenatal genome-wide cell-free (cf.) DNA screening. These cases are part of a larger cohort of previously published cases. Members of the Global Expanded NIPT Consortium were invited to submit details on their cases with a single rare autosomal aneuploidy following genome-wide cfDNA screening for retrospective analysis...

OBJECTIVE: Branchio-oto-renal syndrome (BOR, OMIM#113,650) is a rare autosomal dominant disorder that presents with a variety of symptoms, including hearing loss (sensorineural, conductive, or mixed), structural abnormalities affecting the outer, middle, and inner ear, branchial fistulas or cysts, as well as renal abnormalities.This study aims to identify the pathogenic variants by performing genetic testing on a family with Branchio-oto-renal /Branchio-otic (BO, OMIM#602,588) syndrome using whole-exome sequencing, and to explore possible pathogenic mechanisms...

BACKGROUND: The incidence of gastric cancer ranks the first among digestive tract tumors in China. However, there are no specific symptoms in the early stage of the tumor and the diagnosis process is complex, so more effective detection methods are very needed. In this study, a novel long noncoding RNA (lncRNA) was introduced as a diagnostic biomarker for gastric cancer, which brought new thinking to the exploration of its pathological mechanism and clinical prediction. METHODS: The level of lncRNA EPB41L4A-AS1 (EPB41L4A-AS1) in gastric cancer serum and cells was verified via real-time quantitative polymerase chain reaction (RT-qPCR)...

Circadian clocks temporally coordinate daily organismal biology over the 24-h cycle. Their molecular design, preserved between fungi and animals, is based on a core-oscillator composed of a one-step transcriptional-translational-negative-feedback-loop (TTFL). To test whether this evolutionarily conserved TTFL architecture is the only plausible way for achieving a functional circadian clock, we adopted a transcriptional rewiring approach, artificially co-opting regulators of the circadian output pathways into the core-oscillator...

Cancer of unknown primary (CUP) site poses diagnostic challenges due to its elusive nature. Many cases of CUP manifest as pleural and peritoneal serous effusions. Leveraging cytological images from 57,220 cases at four tertiary hospitals, we developed a deep-learning method for tumor origin differentiation using cytological histology (TORCH) that can identify malignancy and predict tumor origin in both hydrothorax and ascites. We examined its performance on three internal (n = 12,799) and two external (n = 14,538) testing sets...

This study explores how machine-learning can be used to predict chromatographic retention times (RT) for the analysis of small molecules, with the objective of identifying a machine-learning framework with the robustness required to support a chemical synthesis production platform. We used internally generated data from high-throughput parallel synthesis in context of pharmaceutical drug discovery projects. We tested machine-learning models from the following frameworks: XGBoost, ChemProp, and DeepChem, using a dataset of 7552 small molecules...

The heterogeneity inherent in today's biotherapeutics, especially as a result of heavy glycosylation, can affect a molecule's safety and efficacy. Characterizing this heterogeneity is crucial for drug development and quality assessment, but existing methods are limited in their ability to analyze intact glycoproteins or other heterogeneous biotherapeutics. Here, we present an approach to the molecular assessment of biotherapeutics that uses proton-transfer charge-reduction with gas-phase fractionation to analyze intact heterogeneous and/or glycosylated proteins by mass spectrometry...

The emerging monkeypox virus (MPXV) has raised global health concern, thereby highlighting the need for rapid, sensitive, and easy-to-use diagnostics. Here, we develop a single-step CRISPR-based diagnostic platform, termed SCOPE (Streamlined CRISPR On Pod Evaluation platform), for field-deployable ultrasensitive detection of MPXV in resource-limited settings. The viral nucleic acids are rapidly released from the rash fluid swab, oral swab, saliva, and urine samples in 2 min via a streamlined viral lysis protocol, followed by a 10-min single-step recombinase polymerase amplification (RPA)-CRISPR/Cas13a reaction...

OBJECTIVES: To build self-supervised foundation models for multicontrast MRI of the whole brain and evaluate their efficacy in assisting diagnosis of brain tumors. METHODS: In this retrospective study, foundation models were developed using 57,621 enhanced head MRI scans through self-supervised learning with a pretext task of cross-contrast context restoration with two different content dropout schemes. Downstream classifiers were constructed based on the pretrained foundation models and fine-tuned for brain tumor detection, discrimination, and molecular status prediction...