<p>The most widely accepted technique for the confirmation of semen presence in forensic biology is the microscopic identification of sperm cells. The process of manual microscopic examination, however, can often be time consuming, particularly where sperm numbers are low or where sperm cells are absent, particularly when in the presence of numerous non-sperm cells. The findings of this study demonstrate that automated microscopy utilising Deep Neural Network (DNN) allows for an improvement of the efficiency of examination times associated with microscopy. Additionally, the use of instrument and slide data as diagnostic tools permits rapid detection of invalid results. Metafer with Sperm Detection, using DNN v3.1.1, successfully identified sperm cells present in both high and low semen concentrations in mixed-cell substrates, often with a higher accuracy than manual microscopic examinations where very low sperm numbers were present (1\u8211?5 sperm cells on an entire slide). Whilst there were instances of false positive and false negative sperm cell classifications observed, the overall sensitivity, specificity and accuracy of automated microscopy using Metafer with Sperm Detection (DNN v3.1.1) was 0.9999, 0.9996 and 0.9999, respectively. The conversion of Metafer sperm counts to an existing sperm grading system allows compatibility with manual microscopy outcomes and allows decisions regarding sample triage and submission for specific DNA extraction protocols in routine casework to be made with confidence.</p>

Digital object identifier (DOI): 10.1016/j.scijus.2025.101370

<p>We conducted a study to validate the automated scoring of Fluorescent in Situ Hybridization (FISH) in a routine cytogenetics laboratory using selected CD138-positive cells in samples from patients with multiple myeloma. A workstation was optimized based on the manufacturer's configurations. Six commercial probes (CDKN2C/CKS1B, RB1/DLEU1/LAMP1, TP53/CEN17, FGFR3::IGH, CCND1::IGH, and IGH::MAF) were examined to detect gains, losses, and rearrangements of genes across a total of 180 slides. We used reference values proposed by the European Myeloma Network (10% for rearrangements and 20% for gains and losses) to compare the accuracy of manual, automated, and semi-automated (automated coupled with manual revision) scoring. The time spent by the biologist to perform semi-automated and manual scoring was compared. Automated scoring was not effective and lacked validation. In contrast, semi-automated scoring proved to be efficient and highly accurate for all probes and offered time-saving benefits for deletion/gain probes. These findings suggest that semi-automated iFISH scoring for multiple myeloma is feasible and could become a routine practice in cytogenetics laboratories.</p>

Digital object identifier (DOI): 10.1002/jemt.24844

<p>Small RNAs interacting with PIWI (piRNAs) play a crucial role in regulating transposable elements and translation during spermatogenesis and are essential in male germ cell development. Disruptions in the piRNA pathway typically lead to severe spermatogenic defects and thus male infertility. The HENMT1 gene is a key player in piRNAs primary biogenesis and dysfunction of HENMT1 protein in meiotic and haploid germ cells resulted in the loss of piRNA methylation, piRNA instability, and TE de-repression. Henmt1-knockout mice exhibit a severe oligo-astheno-teratozoospermia (OAT) phenotype, whereas patients with HENMT1 variants display more severe azoospermia phenotypes, ranging from meiotic arrest to hypospermatogenesis. Through whole-exome sequencing (WES) of infertile patient cohorts, we identified two new patients with variants in the HENMT1 gene presenting spermatozoa in their ejcaulate, providing us the opportunity to study spermatozoa from these patients. Investigate the spermatozoa of two patients harboring an HENMT1 variant to determine whether or not these scarce spermatozoa could be used with assisted reproductive technologies. HENMT1 variants identified by WES were validated through Sanger sequencing. Comprehensive semen analysis was conducted, and sperm cells were subjected to transmission electron microscopy for structural examination, in situ hybridization for aneuploidy assessment, and aniline blue staining for DNA compaction status. Subsequently, we assessed their suitability for in vitro fertilization using intracytoplasmic sperm injection (IVF-ICSI). Our investigations revealed a severe OAT phenotype similar to knockout mice, revealing altered sperm concentration, mobility, morphology, aneuploidy and nuclear compaction defects. Multiple IVF-ICSI attempts were also performed, but no live births were achieved. We confirm the crucial role of HENMT1 in spermatogenesis and highlight a phenotypic continuum associated with HENMT1 variants. Unfortunately, the clinical outcome of these genetic predispositions remains unfavorable, regardless of the patient's phenotype. The presence of spermatozoa is insufficient to anticipate ICSI pregnancy success in HENMT1 patients.</p>

Digital object identifier (DOI): 10.1111/andr.13730

<p>Tuberculosis (TB) remains a global health challenge, with timely and accurate diagnosis being critical for effective disease management and control. Recent advancements in the field of TB diagnostics have focused on the identification and utilization of blood-based biomarkers, offering a non-invasive, rapid, and scalable approach to disease detection. This review provides a comprehensive overview of the latest progress in blood-based biomarkers for TB, highlighting their potential to revolutionize diagnostic strategies. Furthermore, we explore emerging technologies such as NGS, PET-CT, Xpert and line probe assays, which have enhanced the sensitivity, specificity, and accessibility of biomarker-based diagnostics. The integration of artificial intelligence (AI) and machine learning (ML) in biomarker analysis is also examined, showcasing its potential to improve diagnostic accuracy and predictive capabilities. This review underscores the need for multidisciplinary collaboration and continued innovation to translate these promising technologies into practical, point-of-care solutions. By addressing these challenges, blood-based biomarkers and emerging technologies hold the potential to significantly improve TB diagnosis, ultimately contributing to global efforts to eradicate this devastating disease.</p>

Digital object identifier (DOI): 10.3389/fcimb.2025.1567592

<p>Potable water contain various chemicals, compounds and disinfection by-products. The presence of these substances can result in mutagenic risk to the public, highlighting the need for surveillance. This study evaluated the mutagenic potential of source water and drinking water from two South African drinking water treatment plants. The study also investigated the high-throughput scoring of the <em>Salmonella typhimurium</em> Ames mutagenicity assay with frameshift and base-pair mutations. Two different scoring approaches were used including visual manual scoring and using the automatic image scanning platform. No mutagenic risk was detected for both TA98 and TA100 bacteria regardless of metabolic activation. Grab sampling may have missed any transient mutagenic events. Despite the limitations, automatic scanning of the microtiter plates ensured consistent, reliable and accurate results that can be reviewed. The outcomes of the study show effective mitigation of mutagenic risk by the treatment plants and deliver public reassurance of drinking water. The advantageous combination of automated scoring technologies, as demonstrated in this study, provides a scalable and standardized monitoring programme for mutagenic risk. Regulatory frameworks would benefit from a mutagenic risk monitoring programme, given the myriad health risks involved in exposure to environmental mutagens.</p>

Digital object identifier (DOI): 10.21203/rs.3.rs-7883227/v1

<p>Dicentric chromosome analysis (DCA) has limitations in its use for the evaluation of the radiation dose upon the development of medical radiation equipment due to its time/labour-consuming procedure and the requirement of highly trained experts. Therefore, we aimed to construct a dose–response curve using a semi-automatic cytokinesis-block micronucleus (CBMN) analysis method that can be easily analysed and utilised by anyone. CHO-K1 cells were exposed to gamma rays at various doses (0–4 Gy). For the CBMN assay, the bi-nucleated cells were selected and captured, and micronuclei (MN) scoring was automatically performed using the Metafer4 system. The MN scores were manually confirmed and corrected by analysts. Using the frequency distributions of MN according to the radiation dose, the dose–response calibration curve was generated using Dose Estimate v5.2 software. The equation of dose–response calibration curve is Y = 0.0299 (±0.0057) + 0.1502 (±0.0151) × D + 0.0111 (±0.0048) × D2. The goodness-of-fit parameters were also calculated (chi-squared [χ 2] = 39.45, degrees of freedom = 5, p = 0.0000). The semi-automated CBMN assay consist of two steps: the automated MN capture/scoring step and the manual confirmation/correction step. Using an established dose–response calibration curve and the procedure of the semi-automated CBMN assay, the dose-estimation of gamma-irradiated (0.5 or 2 Gy) CHO-K1 cells were performed by two analysts individually, and it was inter-compared to verify the accuracy, the results showed that the estimated doses were a good fit the applied doses of radiation. The CBMN assay using CHO-K1 cells can be easily used as a biodosimetry tool for dose assessment of medical radiation equipment due to the advantage of being simple, easy, and quick to measure the dose.</p>

Digital object identifier (DOI): 10.14293/genint.15.1.003

<p>The dicentric chromosome assay is a well-established biodosimetric method used to assess absorbed ionizing radiation doses by detecting dicentric chromosomal aberrations. Here, we present a detailed, reproducible protocol for applying the dicentric chromosome assay for in vitro evaluation of radioprotective agents, including novel piperazine derivatives compared with amifostine and its active metabolite WR-1065. The protocol covers all key steps—blood sample preparation, in vitro irradiation, lymphocyte culture, metaphase preparation, and scoring of dicentric chromosomes. It highlights critical stages that affect data quality and reproducibility. Integrating manual scoring with automated analysis using the Metafer system ensures accurate and efficient assessment. Thus, this protocol bridges the fields of biological dosimetry and preclinical screening of radioprotective agents, providing a reliable framework for emergency radiation dose estimation and the development of new radiation medical countermeasures.</p>

Digital object identifier (DOI): 10.1093/biomethods/bpaf058

<p>This article shows the development of a dose–effect calibration curve for X-ray exposures ranging from 0 to 4 Gy using the cytokinesis-block micronucleus assay and automated analysis—the first effort of its kind reported in Latin America. This work establishes a regional benchmark for high-throughput methodologies in cytogenetic biodosimetry, highlighting their potential to improve operational efficiency and reduce response times in radiological emergencies. Methods: Blood samples from six healthy donors were irradiated with X-rays at seven dose levels (0–4 Gy) using a calibrated 6 MV linear accelerator. Two blind samples (1.5 and 3 Gy) were included for validation. The CBMN assay was performed following IAEA protocols, DAPI-stained slides were analyzed using a AxioImager.Z2 automated microscope integrated with MetaSystems Metafer4 and the MNScoreX classifier software. A negative binomial regression model (NB1) was used for model fitting, accounting for overdispersion in micronucleus (MN) frequency. Results: Automated scoring of binucleated lymphocytes showed a dose-dependent increase in MN frequency. The fitted model followed a linear–quadratic relationship: Y = 0.0545 + 0.0448·D + 0.0145·D², with all coefficients statistically significant (p &lt; 0.001). Dose estimates for blinded samples (1.5 and 3 Gy) matched the true doses within 95% confidence intervals, with all z-scores &lt; |3|. Conclusions: The resulting linear–quadratic dose–response curve enabled accurate estimation of blinded sample doses, with all z-scores falling within acceptable fitness-for-purpose thresholds. These results underscore the value of combining automated microscopy with robust statistical modeling to achieve reliable dose assessment, particularly in high-throughput settings and radiological emergency scenarios.</p>

Digital object identifier (DOI): 10.15392/2319-0612.2025.2908

<p>Several fusion oncogenes showing a higher incidence in pediatric acute myeloid leukemia (AML) are associated with heterogeneous megakaryoblastic and other myeloid features. Here we addressed how developmental mechanisms influence human leukemogenesis by ETO2::GLIS2, associated with dismal prognosis. We created novel ETO2::GLIS2 models of leukemogenesis through lentiviral transduction and CRISPR-Cas9 gene editing of human fetal and post-natal hematopoietic stem/progenitor cells (HSPCs), performed in-depth characterization of ETO2::GLIS2 transformed cells through multiple omics and compared them to patient samples. This led to a preclinical assay using patient-derived-xenograft models to test a combination of two clinically-relevant molecules. We showed that ETO2::GLIS2 expression in primary human fetal CD34 hematopoietic cells led to more efficient in vivo leukemia development than expression in post-natal cells. Moreover, cord blood-derived leukemogenesis has a major dependency on the presence of human cytokines, including IL3 and SCF. Single cell transcriptomes revealed that this cytokine environment controlled two ETO2::GLIS2-transformed states that were also observed in primary patient cells. Importantly, this cytokine sensitivity may be therapeutically-exploited as combined MEK and BCL2 inhibition showed higher efficiency than individual molecules to reduce leukemia progression in vivo. Our study uncovers an interplay between the cytokine milieu and transcriptional programs that extends a developmental window of permissiveness to transformation by the ETO2::GLIS2 AML fusion oncogene, controls the intratumoral cellular heterogeneity, and offers a ground-breaking therapeutical opportunity by a targeted combination strategy.</p>

Digital object identifier (DOI): 10.1186/s12943-024-02110-y

<p>Human exposure to radiofrequency electromagnetic fields (RF-EMF) is restricted to prevent thermal effects in the tissue. However, at very low intensity exposure "non-thermal" biological effects, like oxidative stress, DNA or chromosomal aberrations, etc. collectively termed genomic-instability can occur after few hours. Little is known about chronic (years long) exposure with non-thermal RF-EMF. We identified two neighboring housing estates in a rural region with residents exposed to either relatively low (control-group) or relatively high (exposed-group) RF-EMF emitted from nearby mobile phone base stations (MPBS). 24 healthy adults that lived in their homes at least for 5 years volunteered. The homes were surveyed for common types of EMF, blood samples were tested for oxidative status, transient DNA alterations, permanent chromosomal damage, and specific cancer related genetic markers, like MLL gene rearrangements. We documented possible confounders, like age, sex, nutrition, life-exposure to ionizing radiation (X-rays), occupational exposures, etc. The groups matched well, age, sex, lifestyle and occupational risk factors were similar. The years long exposure had no measurable effect on MLL gene rearrangements and c-Abl-gene transcription modification. Associated with higher exposure, we found higher levels of lipid oxidation and oxidative DNA-lesions, though not statistically significant. DNA double strand breaks, micronuclei, ring chromosomes, and acentric chromosomes were not significantly different between the groups. Chromosomal aberrations like dicentric chromosomes (p=0.007), chromatid gaps (p=0.019), chromosomal fragments (p&lt;0.001) and the total of chromosomal aberrations (p&lt;0.001) were significantly higher in the exposed group. No potential confounder interfered with these findings. Increased rates of chromosomal aberrations as linked to excess exposure with ionizing radiation may also occur with non-ionizing radiation exposure. Biological endpoints can be informative for designing exposure limitation strategies. Further research is warranted to investigate the dose-effect-relationship between both, exposure intensity and exposure time, to account for endpoint accumulations after years of exposure. As established for ionizing radiation, chromosomal aberrations could contribute to the definition of protection thresholds, as their rate reflects exposure intensity and exposure time.</p>

Digital object identifier (DOI): 10.1016/j.ecoenv.2024.116486

<p>Astronauts travelling in space will be exposed to mixed beams of particle radiation and photons. Exposure limits that correspond to defined cancer risk are calculated by multiplying absorbed doses by a radiation-type specific quality factor that reflects the biological effectiveness of the particle without considering possible interaction with photons. We have shown previously that alpha radiation and X-rays may interact resulting in synergistic DNA damage responses in human peripheral blood lymphocytes but the level of intra-individual variability was high. In order to assess the variability and validate the synergism, blood from two male donors was drawn at 9 time points during 3 seasons of the year and exposed to 0-2 Gy of X-rays, alpha particles or 1:1 mixture of both (half the dose each). DNA damage response was quantified by chromosomal aberrations and by mRNA levels of 3 radiation-responsive genes FDXR, CDKN1A and MDM2 measured 24 h post exposure. The quality of response in terms of differential expression of alternative transcripts was assessed by using two primer pairs per gene. A consistently higher than expected effect of mixed beams was found in both donors for chromosomal aberrations and gene expression with some seasonal variability for the latter. No synergy was detected for alternative transcription.</p>

Digital object identifier (DOI): 10.1038/s41598-024-62313-7

<p>This study aimed to validate Metasystems' automated acid-fast bacilli (AFB) smear microscopy scanning and deep-learning-based image analysis module (Neon Metafer) with assistance on respiratory and pleural samples, compared to conventional manual fluorescence microscopy (MM). Analytical parameters were assessed first, followed by a retrospective validation study. In all, 320 archived auramine-O-stained slides selected non-consecutively [85 originally reported as AFB-smear-positive, 235 AFB-smear-negative slides; with an overall mycobacterial culture positivity rate of 24.1% (77/320)] underwent whole-slide imaging and were analyzed by the Metafer Neon AFB Module (version 4.3.130) using a predetermined probability threshold (PT) for AFB detection of 96%. Digital slides were then examined by a trained reviewer blinded to previous AFB smear and culture results, for the final interpretation of assisted digital microscopy (a-DM). Paired results from both microscopic methods were compared to mycobacterial culture. A scanning failure rate of 10.6% (34/320) was observed, leaving 286 slides for analysis. After discrepant analysis, concordance, positive and negative agreements were 95.5% (95%CI, 92.4%-97.6%), 96.2% (95%CI, 89.2%-99.2%), and 95.2% (95%CI, 91.3%-97.7%), respectively. Using mycobacterial culture as reference standard, a-DM and MM had comparable sensitivities: 90.7% (95%CI, 81.7%-96.2%) versus 92.0% (95%CI, 83.4%-97.0%) ( -value = 1.00); while their specificities differed 91.9% (95%CI, 87.4%-95.2%) versus 95.7% (95%CI, 92.1%-98.0%), respectively ( -value = 0.03). Using a PT of 96%, MetaSystems' platform shows acceptable performance. With a national laboratory staff shortage and a local low mycobacterial infection rate, this instrument when combined with culture, can reliably triage-negative AFB-smear respiratory slides and identify positive slides requiring manual confirmation and semi-quantification. This manuscript presents a full validation of MetaSystems' automated acid-fast bacilli (AFB) smear microscopy scanning and deep-learning-based image analysis module using a probability threshold of 96% including accuracy, precision studies, and evaluation of limit of AFB detection on respiratory samples when the technology is used with assistance. This study is complementary to the conversation started by Tomasello et al. on the use of image analysis artificial intelligence software in routine mycobacterial diagnostic activities within the context of high-throughput laboratories with low incidence of tuberculosis.</p>

Digital object identifier (DOI): 10.1128/jcm.01069-23

<p>This study aims to evaluate the effectiveness and reliability of the utilization for clinical reporting of the evaluation of digital images of bone marrow aspirates by morphologists and their comparability with the classic microscopic morphological evaluation. We scanned 180 consecutive bone marrow needle aspirates smears using the "Metafer4 VSlide" whole slide imaging (WSI) digital scanning system. We evaluated the statistical comparability and the risk of bias of the microscopic readings with those performed on the screen on the digitized medullary images. The evaluation of cellularity on the screen was equivalent, with a higher frequency of "normal" than the analysis of digital preparations. The means and medians of the percentage values obtained on the different cell populations with the microscopic and digital reading were comparable as the main categories are concerned, with an average difference equal to 0 for the neutrophilic and eosinophilic granulocytic series, at -0.2% for the total myeloid cells, at 1.2% for the erythroid series, at -0.4% for the lymphocytes and at -0.4% for the blasts. Dysplastic features were consistently identified in 69/71 cell lineages. Our study demonstrated that screen evaluation of digitized bone marrow needle aspirates provides quantitative and qualitative results comparable to traditional microscopic analysis of the corresponding slide smears. Digital images offer significant benefits in reducing the workload of experienced operators, reproducibility and sharing of observations, and image preservation. Even in routine diagnostic activities, their use does not alter the quality of the results obtained in evaluating bone marrow needle aspirates.</p>

Digital object identifier (DOI): 10.1111/ijlh.14238

<p>The diagnosis and treatment of bacterial infections in the medical and public health field in the 21st century remain significantly challenging. Artificial Intelligence (AI) has emerged as a powerful new tool in diagnosing and treating bacterial infections. AI is rapidly revolutionizing epidemiological studies of infectious diseases, providing effective early warning, prevention, and control of outbreaks. Machine learning models provide a highly flexible way to simulate and predict the complex mechanisms of pathogen-host interactions, which is crucial for a comprehensive understanding of the nature of diseases. Machine learning-based pathogen identification technology and antimicrobial drug susceptibility testing break through the limitations of traditional methods, significantly shorten the time from sample collection to the determination of result, and greatly improve the speed and accuracy of laboratory testing. In addition, AI technology application in treating bacterial infections, particularly in the research and development of drugs and vaccines, and the application of innovative therapies such as bacteriophage, provides new strategies for improving therapy and curbing bacterial resistance. Although AI has a broad application prospect in diagnosing and treating bacterial infections, significant challenges remain in data quality and quantity, model interpretability, clinical integration, and patient privacy protection. To overcome these challenges and, realize widespread application in clinical practice, interdisciplinary cooperation, technology innovation, and policy support are essential components of the joint efforts required. In summary, with continuous advancements and in-depth application of AI technology, AI will enable doctors to more effectivelyaddress the challenge of bacterial infection, promoting the development of medical practice toward precision, efficiency, and personalization; optimizing the best nursing and treatment plans for patients; and providing strong support for public health safety.</p>

Digital object identifier (DOI): 10.3389/fmicb.2024.1449844

Digital object identifier (DOI): 10.1016/j.htct.2022.01.016

<p>Sensitivity to ionizing radiation differs between individuals, but there is a limited understanding of the biological mechanisms that account for these variations. One example of such mechanisms are the mutations in the ATM (mutated ataxia telangiectasia) gene, that cause the rare recessively inherited disease Ataxia telangiectasia (AT). Hallmark features include chromosomal instability and increased sensitivity to ionizing radiation (IR). To deepen the molecular understanding of radiosensitivity and to identify potential new markers to predict it, human ATM-mutated and proficient cells were compared on a proteomic level. In this study, we analyzed 3 cell lines from AT patients, with varying radiosensitivity, and 2 cell lines from healthy volunteers, 24 hours and 72 hours post-10 Gy irradiation. We used label-free mass spectrometry to identify differences in signaling pathways after irradiation in normal and radiosensitive individuals. Cell viability was initially determined by water soluble tetrazolium (WST) assay and DNA damage response was analyzed with 53BP1 repair foci formation along with KRAB-associated protein 1 (KAP1) phosphorylation. Proteomic analysis identified 4028 proteins, which were used in subsequent in silico pathway enrichment analysis to predict affected biological pathways post-IR. In AT cells, networks were heterogeneous at both time points with no common pathway identified. Mitotic cell cycle progress was the most prominent pathway altered after IR in cells from healthy donors. In particular, components of the chromosome passenger complex (INCENP and CDCA8) were significantly downregulated after 72 hours. This could also be verified at the mRNA level. Altogether, the most striking result was that proteins forming the chromosome passenger complex were downregulated after radiation exposure in healthy normosensitive control cells, but not in radiosensitive ATM-deficient cells. Thus, mitosis-associated proteins form an interesting compound to gain insights into the development and prediction of radiosensitivity.</p>

Digital object identifier (DOI): 10.1177/11772719241274017

<p>GBS read coverage analysis identified a Robertsonian chromosome from two Thinopyrum subgenomes in wheat, conferring leaf and stripe rust resistance, drought tolerance, and maintaining yield stability. Agropyron glael (GLAEL), a Thinopyrum intermedium\u8201?\u215?\u8201?Th. ponticum hybrid, serves as a valuable genetic resource for wheat improvement. Despite its potential, limited knowledge of its chromosome structure and homoeologous relationships with hexaploid wheat (Triticum aestivum) has restricted the full exploitation of GLAEL's genetic diversity in breeding programs. Here, we present the development of a 44-chromosome wheat/GLAEL addition line (GLA7). Multicolor genomic in situ hybridization identified one chromosome arm from the St subgenome of Th. intermedium, while the other arm remained unclassified. Genotyping-by-sequencing (GBS) read coverage analysis revealed a unique Robertsonian translocation between two distinct Thinopyrum subgenomes, identified as 4StS\u183?1J (vs)S. The GLA7 line demonstrated strong adult plant resistance to both leaf rust and stripe rust under natural and artificial infection conditions. Automated phenotyping of shoot morphological parameters together with leaf relative water content and yield components showed that the GLA7 line exhibited elevated drought tolerance compared to parental wheat genotypes. Three years of field trials showed that GLA7 exhibits similar agronomic performance and yield components to the wheat parents. This unique addition line holds promise for enhancing wheat's tolerance to multiple stresses through the introduction of new resistance genes, as well as its ability to mitigate the effects of temporary water limitation during flowering, all without negatively impacting wheat performance.</p>

Digital object identifier (DOI): 10.1007/s00122-024-04791-x

<p>The measurement of micronucleus (MN) in the cytokinesis-block arrested binucleated cells has been extensively used as a biomarker in many radiation biology applications in specific biodosimetry. Following radiation casualties, medical management of exposed individuals begins with triage and biological dosimetry. The cytokinesis blocked micronucleus (CBMN) assay is the alternate for the gold standard dicentric chromosome assay in radiation dose assessment. In recent years, the CBMN assay has become well-validated and emerged as a method of choice for evaluating occupational and accidental exposures scenario. It is feasible due to its cost-effective, simple, and rapid dose assessment rather than a conventional chromosome aberration assay. PubMed search tool was used with keywords of MN, biodosimetry, radiotherapy and restricted to human samples. Since Fenech and Morely developed the assay, it has undergone many technical and technological reforms as a biomarker of various applications. In this review, we have abridged recent developments of the CBMN assay in radiation triage and biodosimetry, focusing on (a) the influence of variables on dose estimation, (b) the importance of baseline frequency and reported dose-response coefficient values among different laboratories, (c) inter-laboratory comparison and (d) its limitations and means to overcome them.</p>

Digital object identifier (DOI): 10.1016/j.jgeb.2024.100409

<p>Exposure to indoor air pollutants (IAP) has increased recently, with people spending more time indoors (i.e. homes, offices, schools and transportation). Increased exposures of IAP on a healthy population are poorly understood, and those with allergic respiratory conditions even less so. The objective of this study, therefore, was to implement a well-characterised in vitro model of the human alveolar epithelial barrier (A549 + PMA differentiated THP-1 incubated with and without IL-13, IL-5 and IL-4) to determine the effects of a standardised indoor particulate (NIST 2583) on both a healthy lung model and one modelling a type-II (stimulated with IL-13, IL-5 and IL-4) inflammatory response (such as asthma).Using concentrations from the literature, and an environmentally appropriate exposure we investigated 232, 464 and 608ng/cm² of NIST 2583 respectively. Membrane integrity (blue dextran), viability (trypan blue), genotoxicity (micronucleus (Mn) assay) and (pro-)/(anti-)inflammatory effects (IL-6, IL-8, IL-33, IL-10) were then assessed 24 h post exposure to both models. Models were exposed using a physiologically relevant aerosolisation method (VitroCell Cloud 12 exposure system).No changes in Mn frequency or membrane integrity in either model were noted when exposed to any of the tested concentrations of NIST 2583. A significant decrease (p &lt; 0.05) in cell viability at the highest concentration was observed in the healthy model. Whilst cell viability in the "inflamed" model was decreased at the lower concentrations (significantly (p &lt; 0.05) after 464ng/cm²). A significant reduction (p &lt; 0.05) in IL-10 and a significant increase in IL-33 was seen after 24 h exposure to NIST 2583 (464, 608ng/cm²) in the "inflamed" model.Collectively, the results indicate the potential for IAP to cause the onset of a type II response as well as exacerbating pre-existing allergic conditions. Furthermore, the data imposes the importance of considering unhealthy individuals when investigating the potential health effects of IAP. It also highlights that even in a healthy population these particles have the potential to induce this type II response and initiate an immune response following exposure to IAP.</p>

Digital object identifier (DOI): 10.1186/s12989-024-00584-8

<p>The blood enzyme glutamate-oxaloacetate transaminase (GOT) has been postulated as an effective therapeutic to protect the brain during stroke. To demonstrate its potential clinical utility, a new human recombinant form of GOT (rGOT) was produced for medical use. We tested the pharmacokinetics and evaluated the protective efficacy of rGOT in rodent and non-human primate models that reflected clinical stroke conditions. We found that continuous intravenous administration of rGOT within the first 8 h after ischemic onset significantly reduced the infarct size in both severe (30%) and mild lesions (48%). Cerebrospinal fluid and proteomics analysis, in combination with positron emission tomography imaging, indicated that rGOT can reach the brain and induce cytoprotective autophagy and induce local protection by alleviating neuronal apoptosis. Our results suggest that rGOT can be safely used immediately in patients suspected of having a stroke. This study requires further validation in clinical stroke populations.</p>

Digital object identifier (DOI): 10.1016/j.isci.2024.111108