Search Results (24)

During aging, the brain vasculature undergoes significant deterioration characterized by increased arterial tortuosity, compromised blood–brain barrier integrity, and reduced cerebral blood flow, all of which contribute to various neurological disorders. Thus, understanding the mechanisms underlying aging-related cerebrovascular defects is critical for developing strategies to alleviate aging-associated neurological diseases. In this study, we investigated the role of aging-related genes in brain vascular development using zebrafish as an in vivo model. By thoroughly analyzing scRNA-seq datasets of mid- and old-aged brain vascular endothelial cells (human/mouse), we found ribosomal protein S20 (rps20) significantly down-regulated during aging. qPCR analysis and whole-mount in situ hybridization validated a high expression of rps20 during early zebrafish development, which progressively decreased in adult and aged zebrafish brains. Functional studies using the CRISPR/Cas9-mediated knockout of rps20 revealed an impaired growth of central arteries in the hindbrain and a marked increased intracranial hemorrhage incidence. Mechanistically, qPCR analysis demonstrated a significant downregulation of vegfa, cxcl12b, and cxcr4a, key signaling molecules required for hindbrain vascular development, in rps20-deficient embryos. In conclusion, our findings demonstrate that rps20 is essential for proper brain vascular development and the maintenance of vascular homeostasis in zebrafish, revealing a novel mechanism by which aging-related genes regulate brain vascular development. This study provides new insights that may aid in understanding and treating aging-associated vascular malformations and neurological pathologies. Full article

Camels have been essential to human survival and development across the arid Central Asian steppes, particularly in Kazakhstan, where the breeding of one-humped and two-humped camels is a longstanding tradition supporting the nomadic lifestyle. This study aimed to assess the genetic diversity and population structure of these camels across their distribution range in Kazakhstan. Blood samples from 100 individuals were collected from five locations, Almaty (ALA), Atyrau (ATR), Shymkent (SHK), Kyzylorda (KZL), and Taraz (TRZ), and genotyped using 17 microsatellite markers. All loci were polymorphic, with a mean observed heterozygosity of 0.707 in C. dromedarius and 0.643 in C. bactrianus. The highest expected heterozygosity (He = 0.939) was observed at VOLP67 in C. bactrianus and at VOLP03 in C. dromedarius. Genetic differentiation was low (FST = 0.021), indicating a weak population structure between the two species with substantial gene flow (Nm = 19.972). The hybrid analysis identified 31% hybrids, including F1, F2, and backcrosses, with the highest frequencies in KZL and TRZ, moderate frequencies in ATR, and lowest frequencies in SHK and ALA. These patterns, consistent with STRUCTURE clustering, reflect widespread but regionally variable hybridization. The phylogenetic analysis revealed three clades, separating Bactrian camels (ALA), dromedaries (SHK), and a hybrid group (ATR, KZL, and TRZ). These findings enhance our understanding of the genetic diversity of Kazakhstan’s camels and support effective conservation, breeding strategies, and genotyping applications in camel husbandry. Full article

Background: Aplastic anemia (AA) is a rare bone marrow failure syndrome characterized by notably short telomere length, which is associated with treatment responses. In this study, we measured telomere lengths in Korean pediatric AA patients using flow-fluorescence in situ hybridization (Flow-FISH) and explored their shortening in relation to disease characteristics, genetic conditions and patient outcomes. Methods: We analyzed peripheral blood samples from 75 AA patients and 101 healthy controls. Telomere lengths were measured using Flow-FISH, and relative telomere length (RTL) and delta RTL assessments were conducted. Genetic evaluations included karyotyping, chromosome breakage tests and clinical exome sequencing (CES) to identify inherited bone marrow failure syndrome (IBMFS)-associated genetic variants. Results: Telomere lengths in AA patients were significantly lower than those of age-adjusted healthy controls. Patients receiving immunosuppressive therapy tended to have long telomeres, as indicated by high delta RTL values. Patients with genetic abnormalities, including karyotype abnormalities (n = 2) and genetic variants (n = 11) such as carrier genes of IBMFS or variants of unclear significance, showed significantly short telomere lengths. Conclusions: This study reinforces the importance of telomere length as a biomarker in acquired AA. Utilizing Flow-FISH, we were able to accurately measure telomere lengths and establish confidence in this method as an appropriate laboratory test. We found significant reduction in telomere lengths in AA patients, and importantly, longer telomeres were correlated with better outcomes in immunosuppressive therapy. Additionally, our genetic analysis underscored the relevance of variants in IBMFS-associated genes to the pathophysiology of short telomeres. Full article

Background. Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia defined by the presence of a genetic abnormality, namely the PML::RARA gene fusion, as the result of a reciprocal balanced translocation between chromosome 17 and chromosome 15. APL is a veritable emergency in hematology due to the risk of early death and coagulopathy if left untreated; thus, a rapid diagnosis is needed in this hematological malignancy. Needless to say, cytogenetic and molecular biology techniques, i.e., fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR), are essential in the diagnosis and management of patients diagnosed with APL. In recent years, the use of artificial intelligence (AI) and its brances, machine learning (ML), and deep learning (DL) in the field of medicine, including hematology, has brought to light new avenues for research in the fields of blood cancers. However, to our knowledge, there is no comprehensive evaluation of the potential applications of AI, ML, and DL in APL. Thus, the aim of the current publication was to evaluate the prospective uses of these novel technologies in APL. Methods. We conducted a comprehensive literature search in PubMed/MEDLINE, SCOPUS, and Web of Science and identified 20 manuscripts eligible for the qualitative analysis. Results. The included publications highlight the potential applications of ML, DL, and other AI branches in the diagnosis, evaluation, and management of APL. The examined AI models were based on the use of routine biological parameters, cytomorphology, flow-cytometry and/or OMICS, and demonstrated excellent performance metrics: sensitivity, specificity, accuracy, AUROC, and others. Conclusions. AI can emerge as a relevant tool in the evaluation of APL cases and potentially contribute to more rapid screening and identification of this hematological emergency. Full article

Hepatitis, most importantly hepatitis B and hepatitis C, is a significant global health concern, requiring an accurate and early diagnosis to prevent severe liver damage and ensure effective treatment. The currently employed diagnostic methods, while effective, are often limited in their sensitivity, specificity, and rapidity, and the quest for improved diagnostic tools is ongoing. This review explores the innovative application of Raman spectroscopy combined with a chemometric analysis as a powerful diagnostic tool for hepatitis. Raman spectroscopy offers a non-invasive, rapid, and detailed molecular fingerprint of biological samples, while chemometric techniques enhance the interpretation of complex spectral data, enabling precise differentiation between healthy and diseased states and moreover the severity/stage of disease. This review aims to provide a comprehensive overview of the current research, foster greater understanding, and stimulate further innovations in this burgeoning field. The Raman spectrum of blood plasma or serum provides fingerprints of biochemical changes in the blood profile and the occurrence of disease simultaneously, while Raman analyses of polymerase chain reaction/hybridization chain reaction (PCR/HCR)-amplified nucleic acids and extracted DNA/RNA as the test samples provide more accurate differentiation between healthy and diseased states. Chemometric tools enhance the diagnostic efficiency and allow for quantification of the viral loads, indicating the stage of disease. The incorporation of different methodologies like surface enhancement and centrifugal filtration using membranes provides the ability to target biochemical changes directly linked with the disease. Immunoassays and biosensors based on Raman spectroscopy offer accurate quantitative detection of viral antigens or the immune response in the body (antibodies). Microfluidic devices enhance the speed of detection through the continuous testing of flowing samples. Raman diagnostic studies with massive sample sizes of up to 1000 and multiple reports of achieving a greater than 90% differentiation accuracy, sensitivity, and specificity using advanced multivariate data analysis tools indicate that Raman spectroscopy is a promising tool for hepatitis detection. Its reproducibility and the identification of unique reference spectral features for each hepatic disease are still challenges in the translation of Raman spectroscopy as a clinical tool, however. The development of databases for automated comparison and the incorporation of automated chemometric processors into Raman diagnostic tools could pave the way for their clinical translation in the near future. Full article

Assessment of minimal residual disease (MRD) is the most powerful predictor of outcome in B-type acute lymphoblastic leukemia (B-ALL). MRD, defined as the presence of leukemic cells in the blood or bone marrow, is used for the evaluation of therapy efficacy. We report on a microfluidic-based MRD (MF-MRD) assay that allows for frequent evaluation of blood for the presence of circulating leukemia cells (CLCs). The microfluidic chip affinity selects B-lineage cells, including CLCs using anti-CD19 antibodies poised on the wall of the microfluidic chip. Affinity-selected cells are released from the capture surface and can be subjected to immunophenotyping to enumerate the CLCs, perform fluorescence in situ hybridization (FISH), and/or molecular analysis of the CLCs’ mRNA/gDNA. During longitudinal testing of 20 patients throughout induction and consolidation therapy, the MF-MRD performed 116 tests, while only 41 were completed with multiparameter flow cytometry (MFC-MRD) using a bone marrow aspirate, as standard-of-care. Overall, 57% MF-MRD tests were MRD(+) as defined by CLC numbers exceeding a threshold of 5 × 10⁻⁴%, which was determined to be the limit of quantitation. Above a threshold of 0.01%, MFC-MRD was positive in 34% of patients. The MF offered the advantage of the opportunity for efficiently processing small volumes of blood (2 mL), which is important in the care of pediatric patients, especially infants. The minimally invasive means of blood collection are of high value when treating patients whose MRD is typically tested using an invasive bone marrow biopsy. MF-MRD detection can be useful for stratification of patients into risk groups and monitoring of patient well-being after completion of treatment for early recognition of potential impending disease recurrence. Full article

Background: Sutton–Kadir syndrome describes a rare pathology that commonly includes an aneurysm of the inferior pancreaticoduodenal artery in combination with a celiac trunk stenosis or occlusion, often caused by median arcuate ligament compression. Several therapeutic approaches exist including open surgical, endovascular, and hybrid treatments. Other combinations of visceral artery aneurysms and upstream stenoses exist but the cumulative body of evidence on these combinations is weak due to their rarity. Methods: A retrospective analysis of patient data from a single center was carried out. Electronic patient records were filtered for keywords including “visceral aneurysm”, “Sutton–Kadir”, and “median arcuate ligament”. Imaging studies were re-examined by two blinded vascular surgeons with a third vascular surgeon as a referee in case of diverging results. Results: Sixteen patients had a visceral artery aneurysm with an upstream stenosis. All cases had a celiac trunk obstruction while one patient also had a concomitant superior mesenteric artery stenosis. Both median arcuate ligament compression and atherosclerotic lesions were identified. The location of the aneurysms varied even though the inferior pancreaticoduodenal artery was most frequently affected. A classification system based on the different combinations of stenoses and aneurysms is presented and introduced as a new pathologic entity: visceral artery aneurysm in the presence of upstream stenosis (VAPUS). Conclusions: The concomitant presence of visceral artery aneurysms, especially in the pancreaticoduodenal arteries, and blood flow impairment of the celiac axis or superior mesenteric artery is a rare pathology. The proposed VAPUS classification system offers an accessible and transparent route to the precise localization of the affected vessels. Full article

The adsorption kinetics of human serum albumin (HSA) on bare and poly-L-arginine (PARG)-modified silica substrates were investigated using reflectometry and atomic force microscopy (AFM). Measurements were carried out at various pHs, flow rates and albumin concentrations in the 10 and 150 mM NaCl solutions. The mass transfer rate constants and the maximum protein coverages were determined for the bare silica at pH 4.0 and theoretically interpreted in terms of the hybrid random sequential adsorption model. These results were used as reference data for the analysis of adsorption kinetics at larger pHs. It was shown that the adsorption on bare silica rapidly decreased with pH and became negligible at pH 7.4. The albumin adsorption on PARG-functionalized silica showed an opposite trend, i.e., it was negligible at pH 4 and attained maximum values at pH 7.4 and 150 mM NaCl, the conditions corresponding to the blood serum environment. These results were interpreted as the evidence of a significant role of electrostatic interactions in the albumin adsorption on the bare and PARG-modified silica. It was also argued that our results can serve as useful reference data enabling a proper interpretation of protein adsorption on substrates functionalized by polyelectrolytes. Full article

In this current work, we assume the mathematical modelling of non-Newtonian time-dependent hybrid nanoparticles via a cylindrical stenosis artery. In this work, blood is used as a base fluid, and the nanoparticles (copper and aluminum oxide) of cylindrical shape are inserted inside the artery to combine with blood to form hybrid nanofluid (HNF). The homotopy analysis method (HAM) is deployed for the solution of nonlinear resulting equations. For the validation of this current work, the results of the existing work have been compared with our proposed model results. A comparison of key profiles like velocity, temperature, wall shear stress, and flow rate is also performed at a specific critical height of the stenosis. It is also observed that the thermal conductance of hybrid nanofluids is greater than that of nanofluids. Including the hybrid nanoparticles (copper and aluminum oxide) inside the blood enhances the blood axial velocity. These simulations are applicable to the magnetic targeting treatment of stenosed artery disorders and the diffusion of nanodrugs. Full article

Atherosclerosis, a disease of the large arteries, is the primary cause of heart disease and stroke. It often begins with the formation of fatty streaks (FS). The FS consists of subendothelial accumulations of cholesterol-engorged macrophages, called ‘foam cells’. For this to happen, there needs to be a significant change in the permeability of the endothelial layer. Considering the established influence of mechanical stresses on endothelial properties, shear stress can increase the permeability of the endothelial layer. This study employs a hybrid approach, combining computational fluid dynamics (CFD) simulation with numerical analysis, on a simplified model of the aorta to Investigate Endothelial Shear Stress (ESS) changes in the FS. Our findings reveal that the presence of FS leads to quantitative changes in ESS. Further numerical analysis in MATLAB 9.14 suggests a pattern that metaphorically resembles a dam, potentially trapping ‘foam cells’. In an additional aspect of this study, our findings suggest that an increase in blood flow could potentially counteract the permeability increase, thus acting as a preventative measure against atherosclerosis progression. These results underscore the importance of early intervention strategies to mitigate atherosclerosis progression. Full article

The present research examines the unsteady sensitivity analysis and entropy generation of blood-based silver–titanium dioxide flow in a tilted cylindrical W-shape symmetric stenosis artery. The study considers various factors such as the electric field, joule heating, viscous dissipation, and heat source, while taking into account a two-dimensional pulsatile blood flow and periodic body acceleration. The finite difference method is employed to solve the governing equations due to the highly nonlinear nature of the flow equations, which requires a robust numerical technique. The utilization of the response surface methodology is commonly observed in optimization procedures. Drawing inspiration from drug delivery techniques used in cardiovascular therapies, it has been proposed to infuse blood with a uniform distribution of biocompatible nanoparticles. The figures depict the effects of significant parameters on the flow field, such as the electric field, Hartmann number, nanoparticle volume fraction, body acceleration amplitude, Reynolds number, Grashof number, and thermal radiation, on velocity, temperature (nondimensional), entropy generation, flow rate, resistance to flow, wall shear stress, and Nusselt number. The velocity and temperature profiles improve with higher values of the wall slip parameter. The flow rate profiles increase with an increment in wall velocity but decrease with the Womersley number. Increasing the intensity of radiation and decreasing magnetic fields both result in a decrease in the rate of heat transfer. The blood temperature is higher with the inclusion of hybrid nanoparticles than the unitary nanoparticles. The total entropy generation profiles increase for higher values of the Brickman number and temperature difference parameters. Unitary nanoparticles exhibit a slightly higher total entropy generation than hybrid nanoparticles, particularly when positioned slightly away from the center of the artery. The total entropy production decreases by 17.97% when the thermal radiation is increased from absence to 3. In contrast, increasing the amplitude of body acceleration from 0.5 to 2 results in a significant enhancement of 76.14% in the total entropy production. Full article

One of the most effective vital signs of health conditions is blood pressure. It has such an impact that changes your state from completely relaxed to extremely unpleasant, which makes the task of blood pressure monitoring a main procedure that almost everyone undergoes whenever there is something wrong or suspicious with his/her health condition. The most popular and accurate ways to measure blood pressure are cuff-based, inconvenient, and pricey, but on the bright side, many experimental studies prove that changes in the color intensities of the RGB channels represent variation in the blood that flows beneath the skin, which is strongly related to blood pressure; hence, we present a novel approach to blood pressure estimation based on the analysis of human face video using hybrid deep learning models. We deeply analyzed proposed approaches and methods to develop combinations of state-of-the-art models that were validated by their testing results on the Vision for Vitals (V4V) dataset compared to the performance of other available proposed models. Additionally, we came up with a new metric to evaluate the performance of our models using Pearson’s correlation coefficient between the predicted blood pressure of the subjects and their respiratory rate at each minute, which is provided by our own dataset that includes 60 videos of operators working on personal computers for almost 20 min in each video. Our method provides a cuff-less, fast, and comfortable way to estimate blood pressure with no need for any equipment except the camera of your smartphone. Full article

According to FAO reports, the global mule population counts about 9 million mules. This hybrid cross of a male donkey and a female horse is mainly used for draft purposes because they are thought to be strong and hardy animals. Most consider mules to be less susceptible to disease and fatigue compared to horses. Therefore, the aim of this study was to investigate the effects of fieldwork on biochemical variables and serum amyloid A in working mules. Blood samples were collected from 10 healthy, female, working mules before and after 8 h of fieldwork. According to statistical analysis, a significant influence (p < 0.05) of fieldwork was found on mules’ electrolyte profile with increased levels of sodium, chloride, and calcium, as well as on blood urea nitrogen and creatinine. After a day of fieldwork, serum sodium, chloride, calcium, urea, and creatinine concentrations were increased, supporting decreases in body water and renal blood flow. However, without comparison to a group of mules that were not exercised yet maintained under similar ambient conditions, it is uncertain whether these changes can be attributed to exercise. Further, no change in SAA concentration was found after exercise, indicating that the work performed did not result in systemic inflammation. Full article

Curved veins and arteries make up the human cardiovascular system, and the peristalsis process underlies the blood flowing in these ducts. The blood flow in the presence of hybrid nanoparticles through a tapered complex wavy curved channel is numerically investigated. The behavior of the blood is characterized by the Casson fluid model while the physical properties of iron (Fe₃O₄) and copper (Cu) are used in the analysis. The fundamental laws of mass, momentum and energy give rise the system of nonlinear coupled partial differential equations which are normalized using the variables, and the resulting set of governing relations are simplified in view of a smaller Reynolds model approach. The numerical simulations are performed using the computational software Mathematica’s built-in ND scheme. It is noted that the velocity of the blood is abated by the nanoparticles’ concentration and assisted in the non-uniform channel core. Furthermore, the nanoparticles’ volume fraction and the dimensionless curvature of the channel reduce the temperature profile. Full article

Flow cytometric (FC) immunophenotyping is critical but time-consuming in diagnosing minimal residual disease (MRD). We evaluated whether human-in-the-loop artificial intelligence (AI) could improve the efficiency of clinical laboratories in detecting MRD in chronic lymphocytic leukemia (CLL). We developed deep neural networks (DNN) that were trained on a 10-color CLL MRD panel from treated CLL patients, including DNN trained on the full cohort of 202 patients (F-DNN) and DNN trained on 138 patients with low-event cases (MRD < 1000 events) (L-DNN). A hybrid DNN approach was utilized, with F-DNN and L-DNN applied sequentially to cases. “Ground truth” classification of CLL MRD was confirmed by expert analysis. The hybrid DNN approach demonstrated an overall accuracy of 97.1% (95% CI: 84.7–99.9%) in an independent cohort of 34 unknown samples. When CLL cells were reported as a percentage of total white blood cells, there was excellent correlation between the DNN and expert analysis [r > 0.999; Passing–Bablok slope = 0.997 (95% CI: 0.988–0.999) and intercept = 0.001 (95% CI: 0.000–0.001)]. Gating time was dramatically reduced to 12 s/case by DNN from 15 min/case by the manual process. The proposed DNN demonstrated high accuracy in CLL MRD detection and significantly improved workflow efficiency. Additional clinical validation is needed before it can be fully integrated into the existing clinical laboratory practice. Full article