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International Neurourology Journal Jun 2024Bladder cancer (BCa) is the most common malignancy of the urinary system. It has a high recurrence rate and requires longterm follow-up. Significant advances in BCa...
Bladder cancer (BCa) is the most common malignancy of the urinary system. It has a high recurrence rate and requires longterm follow-up. Significant advances in BCa research have been made in recent years; however, the initial diagnosis and follow-up of BCa relies on cystoscopy, which is an invasive and expensive procedure. Over the past decade, liquid biopsies (e.g., blood and urine) have proven to be highly efficient methods for the discovery of BCa biomarkers. This noninvasive sampling method is used to analyze unique tumor components released into body fluids and enables serial sampling and longitudinal monitoring of tumor progression. Several liquid biopsy biomarkers have been studied extensively and have shown promising results in the clinical applications of BCa, including early detection, microscopic residual disease detection, recurrence prediction, and treatment response. Therefore, this review aims to provide an update on various new liquid biopsy markers and the advantages and current limitations of liquid biopsy in the diagnosis of BCa.
PubMed: 38956768
DOI: 10.5213/inj.2448198.099 -
Annals of Pediatric Endocrinology &... Jun 2024Recent advances in long-read next-generation sequencing (NGS) have enabled researchers to identify several pathogenic variants overlooked by short-read NGS, array-based...
Recent advances in long-read next-generation sequencing (NGS) have enabled researchers to identify several pathogenic variants overlooked by short-read NGS, array-based comparative genomic hybridization, and other conventional methods. Long-read NGS is particularly useful in the detection of structural variants and repeat expansions. Furthermore, it can be used for mutation screening in difficultto- sequence regions, as well as for DNA-methylation analyses and haplotype phasing. This mini-review introduces the usefulness of long-read NGS in the molecular diagnosis of pediatric endocrine disorders.
PubMed: 38956752
DOI: 10.6065/apem.2448028.014 -
Annals of Pediatric Endocrinology &... Jun 2024
PubMed: 38956750
DOI: 10.6065/apem.24224014edi03 -
BJOG : An International Journal of... Jul 2024To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies.
OBJECTIVE
To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies.
DESIGN
Cross-sectional survey.
SETTING
International.
POPULATION
Clinicians involved in the management of MCDA twin pregnancies with sFGR.
METHODS
A structured, self-administered survey.
MAIN OUTCOME MEASURES
Clinical practices and attitudes to diagnostic criteria and management strategies.
RESULTS
Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide.
CONCLUSIONS
There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.
PubMed: 38956742
DOI: 10.1111/1471-0528.17891 -
BMC Research Notes Jul 2024Bartonella are emerging bacterial zoonotic pathogens. Utilization of clotted blood samples for surveillance of these bacteria in wildlife has begun to supersede the use...
OBJECTIVE
Bartonella are emerging bacterial zoonotic pathogens. Utilization of clotted blood samples for surveillance of these bacteria in wildlife has begun to supersede the use of tissues; however, the efficacy of these samples has not been fully investigated. Our objective was to compare the efficacy of spleen and blood samples for DNA extraction and direct detection of Bartonella spp. via qPCR. In addition, we present a protocol for improved DNA extraction from clotted, pelleted (i.e., centrifuged) blood samples obtained from wild small mammals.
RESULTS
DNA concentrations from kit-extracted blood clot samples were low and A260/A280 absorbance ratios indicated high impurity. Kit-based DNA extraction of spleen samples was efficient and produced ample DNA concentrations of good quality. We developed an in-house extraction method for the blood clots which resulted in apposite DNA quality when compared to spleen samples extracted via MagMAX DNA Ultra 2.0 kit. We detected Bartonella in 9/30 (30.0%) kit-extracted spleen DNA samples and 11/30 (36.7%) in-house-extracted blood clot samples using PCR. Our results suggest that kit-based methods may be less suitable for DNA extraction from blood clots, and that blood clot samples may be superior to tissues for Bartonella detection.
Topics: Animals; Bartonella; DNA, Bacterial; Spleen; Bartonella Infections; Animals, Wild; Real-Time Polymerase Chain Reaction
PubMed: 38956715
DOI: 10.1186/s13104-024-06841-5 -
Biology Direct Jul 2024Esophageal carcinoma (EC) and gastric cardiac adenocarcinoma (GCA) have high incidence rates in the Chaoshan region of South China. Multifocal esophageal and cardiac...
BACKGROUND
Esophageal carcinoma (EC) and gastric cardiac adenocarcinoma (GCA) have high incidence rates in the Chaoshan region of South China. Multifocal esophageal and cardiac cancer (MECC) is commonly observed in this region in clinical practice. However, the genomic characteristics of MECC remains unclear.
MATERIALS AND METHODS
In this study, a total of 2123 clinical samples of EC and GCA were analyzed to determine the frequency of multifocal tumors, as well as their occurrence sites and pathological types. Cox proportional hazards regression was used to model the relationship between age, sex, and tumor state concerning survival in our analysis of the cohort of 541 patients with available follow-up data. We performed whole-genome sequencing on 20 tumor foci and 10 normal samples from 10 MECC patients to infer clonal structure on 6 MECC patients to explore genome characteristics.
RESULT
The MECC rate of EC and GCA was 5.65% (121 of 2123). Age and sex were potential factors that may influence the risk of MECC (p < 0.001). Furthermore, MECC patients showed worse survival compared with single tumor patients. We found that 12 foci from 6 patients were multicentric origin model (MC), which exhibited significant heterogeneity of variations in paired foci and had an increased number of germline mutations in immune genes compared to metastatic model. In MC cases, different lesions in the same patient were driven by distinct mutation and copy number variation (CNV) events. Although TP53 and other driver mutation genes have a high frequency in the samples, their mutation sites show significant heterogeneity in paired tumor specimens. On the other hand, CNV genes exhibited higher concordance in paired samples, especially in the amplification of oncogenes and the deletion of tumor suppressor genes.
CONCLUSIONS
The extent of inter-tumor heterogeneity suggests both monoclonal and polyclonal origins of MECC, which could provide insight into the genome diversity of MECC and guide clinical implementation.
Topics: Humans; Esophageal Neoplasms; Male; Female; Stomach Neoplasms; Middle Aged; Aged; Genomics; Whole Genome Sequencing; China; Adenocarcinoma; Adult
PubMed: 38956687
DOI: 10.1186/s13062-024-00493-y -
Radiation Oncology (London, England) Jul 2024Radiotherapy is essential in the treatment of prostate cancer. An alternative to conventional photon radiotherapy is the application of carbon ions, which provide a...
BACKGROUND
Radiotherapy is essential in the treatment of prostate cancer. An alternative to conventional photon radiotherapy is the application of carbon ions, which provide a superior intratumoral dose distribution and less induced damage to adjacent healthy tissue. A common characteristic of prostate cancer cells is their dependence on androgens which is exploited therapeutically by androgen deprivation therapy in the advanced prostate cancer stage. Here, we aimed to analyze the transcriptomic response of prostate cancer cells to irradiation by photons in comparison to carbon ions, focusing on DNA damage, DNA repair and androgen receptor signaling.
METHODS
Prostate cancer cell lines LNCaP (functional TP53 and androgen receptor signaling) and DU145 (dysfunctional TP53 and androgen receptor signaling) were irradiated by photons or carbon ions and the subsequent DNA damage was assessed by immuno-cytofluorescence. Furthermore, the cells were treated with an androgen-receptor agonist. The effects of irradiation and androgen treatment on the gene regulation and the transcriptome were investigated by RT-qPCR and RNA sequencing, followed by bioinformatic analysis.
RESULTS
Following photon or carbon ion irradiation, both LNCaP and DU145 cells showed a dose-dependent amount of visible DNA damage that decreased over time, indicating occurring DNA repair. In terms of gene regulation, mRNAs involved in the TP53-dependent DNA damage response were significantly upregulated by photons and carbon ions in LNCaP but not in DU145 cells, which generally showed low levels of gene regulation after irradiation. Both LNCaP and DU145 cells responded to photons and carbon ions by downregulation of genes involved in DNA repair and cell cycle, partially resembling the transcriptome response to the applied androgen receptor agonist. Neither photons nor carbon ions significantly affected canonical androgen receptor-dependent gene regulation. Furthermore, certain genes that were specifically regulated by either photon or carbon ion irradiation were identified.
CONCLUSION
Photon and carbon ion irradiation showed a significant congruence in terms of induced signaling pathways and transcriptomic responses. These responses were strongly impacted by the TP53 status. Nevertheless, irradiation mode-dependent distinct gene regulations with undefined implication for radiotherapy outcome were revealed. Androgen receptor signaling and irradiations shared regulation of certain genes with respect to DNA-repair and cell-cycle.
Topics: Humans; Male; Prostatic Neoplasms; Receptors, Androgen; Tumor Suppressor Protein p53; Photons; Transcriptome; Signal Transduction; DNA Damage; Heavy Ion Radiotherapy; DNA Repair; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Carbon
PubMed: 38956684
DOI: 10.1186/s13014-024-02480-z -
Acta Veterinaria Scandinavica Jul 2024Heterakis gallinarum (H. gallinarum) is a common poultry parasite that can be found in the ceca of many gallinaceous bird species, causing minor pathology and reduced...
BACKGROUND
Heterakis gallinarum (H. gallinarum) is a common poultry parasite that can be found in the ceca of many gallinaceous bird species, causing minor pathology and reduced weight gain. Most infections go unnoticed in commercial flocks due to the dependence on fecal egg counts, which are prone to false-negative diagnoses. Furthermore, there is a lack of research on gastrointestinal nematodes that use molecular identification methods, which could be essential for rapid diagnosis and developing efficient control approaches. As a result, the study aimed to look at the cause of mortality in layer chickens induced by H. gallinarum in Egyptian poultry farms using morphological, ultrastructural, and molecular characterization. Histopathological, immunohistochemical, and cell-mediated immune responses from damaged cecal tissues were also examined.
RESULTS
Seventy bird samples from ten-layer flocks of different breeds (Native, white, and brown layers) suffering from diarrhea, decreased egg output, and emaciation were collected. Cecal samples were collected from affected and non-affected birds and were examined for parasitic diseases using light and a scanning electron microscope. The mitochondrial cytochrome oxidase 1 (COX1) gene was used to characterize H. gallinarum. Our results showed that the collected nematodal worms were identified as H. gallinarum (male and female), further confirmed by COX1 gene amplification and sequence alignment. Gene expression analysis of the inflammatory markers in infected tissues showed a significant up-regulation of IL-2, IFN-γ, TLR-4, and IL-1β and a significant down-regulation of the anti-inflammatory IL-10. The mRNA level of the apoptotic cas-3 revealed apoptotic activity among the H. gallinarum samples compared to the control group.
CONCLUSIONS
Our results implemented the use of molecular methods for the diagnosis of Heterakis, and this is the first report showing the tissue immune response following infection in layers: upregulation of IL-1β, IFN-γ, Il-2, and TLR-4, while down-regulation of anti-inflammatory IL-10 in cecal tissue, Cas-3 apoptotic activity and Nuclear factor-κB (NF-κB)activity with immunophenotyping of T-cells in Heterakis infected tissue.
Topics: Animals; Poultry Diseases; Chickens; Typhlitis; Cecum; Female; Immunity, Cellular; Ascaridida Infections; Ascaridoidea; Egypt
PubMed: 38956671
DOI: 10.1186/s13028-024-00748-8 -
Acta Neuropathologica Communications Jul 2024The genetic architecture of Parkinson's disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here...
The genetic architecture of Parkinson's disease (PD) is complex and multiple brain cell subtypes are involved in the neuropathological progression of the disease. Here we aimed to advance our understanding of PD genetic complexity at a cell subtype precision level. Using parallel single-nucleus (sn)RNA-seq and snATAC-seq analyses we simultaneously profiled the transcriptomic and chromatin accessibility landscapes in temporal cortex tissues from 12 PD compared to 12 control subjects at a granular single cell resolution. An integrative bioinformatic pipeline was developed and applied for the analyses of these snMulti-omics datasets. The results identified a subpopulation of cortical glutamatergic excitatory neurons with remarkably altered gene expression in PD, including differentially-expressed genes within PD risk loci identified in genome-wide association studies (GWAS). This was the only neuronal subtype showing significant and robust overexpression of SNCA. Further characterization of this neuronal-subpopulation showed upregulation of specific pathways related to axon guidance, neurite outgrowth and post-synaptic structure, and downregulated pathways involved in presynaptic organization and calcium response. Additionally, we characterized the roles of three molecular mechanisms in governing PD-associated cell subtype-specific dysregulation of gene expression: (1) changes in cis-regulatory element accessibility to transcriptional machinery; (2) changes in the abundance of master transcriptional regulators, including YY1, SP3, and KLF16; (3) candidate regulatory variants in high linkage disequilibrium with PD-GWAS genomic variants impacting transcription factor binding affinities. To our knowledge, this study is the first and the most comprehensive interrogation of the multi-omics landscape of PD at a cell-subtype resolution. Our findings provide new insights into a precise glutamatergic neuronal cell subtype, causal genes, and non-coding regulatory variants underlying the neuropathological progression of PD, paving the way for the development of cell- and gene-targeted therapeutics to halt disease progression as well as genetic biomarkers for early preclinical diagnosis.
Topics: Humans; Parkinson Disease; Neurons; Gene Regulatory Networks; Male; Female; alpha-Synuclein; Aged; YY1 Transcription Factor; Genome-Wide Association Study; Transcriptome; Single-Cell Analysis; Temporal Lobe; Middle Aged; Gene Expression Regulation; Multiomics
PubMed: 38956662
DOI: 10.1186/s40478-024-01803-1 -
Acta Neuropathologica Communications Jul 2024
PubMed: 38956659
DOI: 10.1186/s40478-024-01816-w