The relationship between processing speed and brain network characteristics has been widely studied, yet the results remain inconsistent. While many studies have linked processing speed to the microstructure of white matter, discrepancies arise due to differences in the tasks used, behavioral measures assessed (based on raw reaction time or modeled processing speed), and specific white-matter tracts considered. To address these challenges and clarify any relationship between individual differences in speed and white-matter brain networks, we present a pre-registered analysis using a large (N = 159) dataset, incorporating state-of-the-art MRI data acquired from a high-gradient 3T Connectom scanner. We combine data from three reaction-time tasks to create composite measures of cognitive performance, mitigating the limitations of experiment-specific analyses. Alongside classic behavioral measures of mean reaction time, reaction-time variability, and accuracy, we applied the drift-diffusion model to derive the common metric of modeled processing speed, drift rate, as well as accompanying parameters of boundary separation, and non-decision time. Using general linear models, we explored the relationship between these parameters and the whole-brain and task-specific structural networks of the brain, weighted by volume-normalized streamline counts and myelin water fraction. Our results revealed negative associations between the global efficiency of streamline-weighted networks and both mean reaction time and reaction-time variability (β = -0.18/-0.21, p = 0.025/0.01 for whole-brain and β = -0.18/-0.18, p = 0.028/0.022 for the task-specific network). Effect sizes were small, consistent with other pre-registered assessments of brain-behavior correlations. These effects were not captured by decision model parameters signaling a note of caution for the assumed interpretation of these parameters. The significant association with reaction-time variability was robust to controlling for age, while age captured significant variance in the association with mean reaction time. This may imply that physiological changes associated with age would be an avenue for research to uncover mechanisms relating structure to reaction time. In sum, we attempted a state-of-the art clarification of whether structural brain organization is associated with speed in common cognitive tasks, and we found a small association with reaction-time variability and mean reaction time (and age).
Delayed-type cutaneous adverse drug reactions (CADRs) are T-cell-mediated hypersensitivity reactions that may present with variable clinical severity in children. They range from mild maculopapular exanthema (MPE) to severe, life-threatening mucocutaneous syndromes such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). Data on pediatric delayed-type CADRs remain limited. They represent an important cause of morbidity in pediatric patients and require careful diagnostic evaluation. This study aimed to describe the clinical characteristics, etiologic agents, management strategies, and outcomes of pediatric patients with delayed-type CADR followed at a tertiary pediatric center. This retrospective case series included 33 pediatric patients diagnosed with delayed-type CADR between January 2013 and December 2024. Demographic features, suspected culprit drugs, clinical manifestations, laboratory and histopathologic findings, treatment approaches, and outcomes were reviewed. RegiSCAR, EuroSCAR, and SCORTEN criteria were applied for diagnostic classification and severity assessment of DRESS, AGEP, and SJS/TEN, respectively. The median age was 9 years (range: 9 days-16 years); 17 patients were female. The most frequent diagnosis was MPE (n=18, 54.5%), followed by DRESS (n=5, 15.1%), SJS/TEN (n=3, 9.1%), AGEP/ALEP (n=3, 9.1%), erythema multiforme (n=2, 6.0%), and SDRIFE (n=2, 6.0%). Antibiotics and antiepileptic drugs were the most commonly implicated drug classes. Systemic corticosteroids were administered in moderate-to-severe cases, and intravenous immunoglobulin was used in selected patients with DRESS and SJS/TEN. Four patients died due to underlying primary diseases; no CADR-related mortality was observed. This retrospective case series describes the heterogeneous clinical spectrum of delayed-type CADRs in children in a tertiary referral setting. In our cohort, maculopapular exanthema was the most frequent phenotype, while antibiotics and antiepileptic drugs were the most commonly implicated agents. A high burden of comorbidities, including immunosuppression and polypharmacy, was notable and may have influenced the observed clinical spectrum. Severe reactions required multidisciplinary management.
In this research, furochromene derivatives were synthesized using multicomponent reactions of dihydroxyacetophenone, isopropenylacetylene, aldehydes and 1,3-dicarbonyl compounds in aqueous media at room temperature in the presence of bio-Fe3O4/SiO2 magnetic nanoparticles (MNPs). The catalytic activity of the bio-Fe3O4/SiO2 was evaluated in the reduction of organic pollutants such as 4-nitrophenol (4-NP) in water under mild conditions. The results indicated that the biosynthesized Fe3O4/SiO2 MNPs exhibited high catalytic activity, enabling the removal of organic pollutants within a few seconds. To determine the antioxidant activity of the synthesized furochromenes, diphenylpicrylhydrazine (DPPH) radical scavenging assays were applied. A further evaluation of the antibacterial activity of the generated compounds was carried out in a methodical manner by employing the disk diffusion technique using two distinct strains of Gram-negative bacteria as well as Gram-positive bacteria. The synthesis approach that was applied for the development of furochromenes was marked by a confluence of good properties. One of these characteristics was the ability to recover the catalyst from the reaction environment with an external magnet. Other characteristics included faster reaction kinetics and greater product yields.
We report a very delayed paradoxical reaction presenting more than 4 years after antibiotic treatment of Buruli ulcer that settled without further antibiotic treatment. Our report aims to alert clinicians to this possibility to avoid misdiagnosis of relapsed infection and unnecessary antibiotic re-treatment which can be associated with toxicity, inconvenience and cost for the patient.
A [H]-accelerated catalytic Fenton system was developed using Pd/UiO-66(Zr)-F4 as the catalyst. This system enabled the regeneration of Fe2+ and facilitated the continuous generation of both ·OH and 1O2 through [H]-mediated electron transfer at ambient temperature and pressure. Under the conditions of 0.2 g L-1 catalyst (Pd loading 0.516 wt%), 25 μM Fe2+, 60 mL min-1 H2 flow (as the [H] source), 20 mM H2O2, and pH 3, approximately 89% of carbamazepine (initial concentration 20 mg L-1) was degraded within 3 h using trace iron. However, the catalytic activity of Pd/UiO-66(Zr)-F4 gradually declined from 89% to 53% over six reaction cycles. This decrease was likely due to loss of specific surface area caused by microstructural degradation associated with hydrogen spillover effects.
Urea is a key chemical for agriculture and industry, yet its conventional synthesis is energy-intensive and environmentally unfriendly. Electrocatalytic C-N coupling offers a sustainable alternative for urea production under mild conditions; however, significant challenges remain. Herein, density functional theory (DFT) is employed to investigate Fe- and Co-decorated defective boron nitride (BN) monolayers with mono-vacancies (VB, VN) and divacancies (VBB, VBN) as electrocatalysts. Their structural stability, activation of N2, corresponding reaction mechanism and selectivity for urea synthesis are comprehensively analyzed. Among the studied systems, Fe-VBN exhibits the lowest thermodynamic limiting potential of -0.413 V. In contrast, despite a compromised limiting potential of -0.715 V, the FeCo-VBB shows superior thermodynamic selectivity. This study provides insights into the C-N coupling mechanism on defective BN materials and may inform the rational design of electrocatalysts for urea synthesis.
We report a direct, one-pot and one-step synthesis of nanoarchitectures composed of molybdenum disulfide (MoS2) and gold nanoparticles (AuNPs), along with mechanistic insights into the reaction pathway. A spontaneous reaction between exfoliated MoS2 and aqueous solution of HAuCl4 was driven at the interface between two immiscible liquids, producing thin, transparent, homogeneous, and colorful films. By adjusting the reaction time and precursor ratios, we successfully created nanoarchitectures comprising AuNPs and a mixture of 2H- and 1T-MoS2 structures. Supported by different characterization techniques, we propose a reaction mechanism based on the partial oxidation of Mo(iv) associated with the reduction of the gold precursor to metallic gold. These materials exhibit tunable MoS2 interlayer distances and an increased density of defects, making them promising candidates for catalytic applications in the hydrogen evolution reaction. Electrochemical characterization revealed an overpotential 45% lower for MoS2/AuNPs nanoarchitectures than that observed for pristine MoS2.
Catalytic hydrogenolysis is considered as a promising process for the chemical upcycling of polyethylene under mild conditions providing a homogeneous mixture of n-alkanes. This work highlights the potential of hydrogenolysis to effectively convert high molecular weight polyethylene-based polymers (LDPE and HDPE) and real plastic consumer products under mild reaction conditions using highly dispersed ruthenium catalysts supported on high surface area micro/mesoporous activated carbons (AC). The effect of the reaction conditions (temperature, time, hydrogen gas pressure, catalyst-to-feed ratio) and catalyst (metal typeRu, Pt, Reand loading, carbon support) was investigated using n-octane as a solvent/substrate and a high molecular weight (M w ∼ 110000 g/mol) low-density polyethylene (LDPE). Under the optimized conditions of 250 °C, 3 h, 50 bar H2, and a catalyst-to-feed ratio (C/F) = 0.1 with 5%Ru/AC, complete conversion of pure LDPE was achieved toward 78 wt % liquid alkanes with C5-C30 carbon number distribution. More intense conditions (i.e., higher temperature or prolonged reaction time) favored further hydrogenolysis of initially formed higher molecular weight alkanes toward smaller alkanes. The hydrogenolysis of high-density polyethylene (HDPE, M w ∼ 95000 g/mol) exhibited higher liquid alkane yields compared to LDPE (up to 91 wt % at 67-99 wt % conversion), owing to its higher melt flow index that facilitated solubility and depolymerization. The composition of the liquid products in terms of carbon number and established refinery fractions (i.e., naphtha, diesel, kerosene, heavy/lubricants) from both LDPE and HDPE was determined and correlated to reaction conditions, feedstock type, and catalyst properties. When real consumer LDPE- or HDPE-based plastics were used as feedstocks, the conversion was 67-98 wt % and the liquid alkanes yielded up to 91 wt %, similar to pristine polymers. The negative effect of inorganic additives in the real plastics was also identified, with CaCO3 and TiO2 reducing the hydrogenolysis reactivity and shifting selectivity toward larger alkane fractions. Overall, the ruthenium-based catalysts supported on high surface area micro/mesoporous activated carbons exhibited high activity in the hydrogenolysis of high molecular weight polyethylene-based plastics, exhibiting also high stability and reusability for at least three successive catalytic cycles without intermediate regeneration.
A persistent C-phosphonio boratavinyl anion 1 has been successfully synthesized. This boron-containing vinyl-lithium 1, featuring a vinyl carbon with a negative charge (-1.59), considerably higher than that of carbon analogue 7 (-0.76), exhibits strongly nucleophilic and basic properties, as demonstrated by the results of rapid reactions with H2 (10 bar, 15 min or 1 bar, 2 h at RT) and C6F6 (1 equiv., 15 min at -80°C). The reactions of boratavinyl anion 1 with electrophiles offer a convenient route for the introduction of a borata-alkene-based bulky and σ,π-double-donating substituent, enabling to efficiently stabilize reactive intermediates such as halogenogermylenes. Furthermore, the reaction with CO2 takes place at the borata-alkene moiety, rather than at the P-ylide function, resulting in the double insertion of CO2 into the B─C bond to afford a unique cyclic P-ylide 13.
The effectiveness factor (EF) concept is extended for non-catalytic pyrolysis reactions involving no gaseous reactant. A fully transient, non-isothermal model is formulated for a single biomass pellet by incorporating structural evolution, porosity variation, and temperature-dependent properties. The study presented a theoretical analysis of EF for different values of Lewis number (L e), heat of reaction (G factor), Arrhenius number (Ē), Thiele modulus (ϕ), and heating rate (γ). The model was solved using two approaches (i) a numerical solution and (ii) an approximate solution based on the Quantized Method (QM). Good agreement was observed between the numerical and QM solutions for pellet conversion within the investigated thermicity factor range of -0.25 ≤ β ≤ 0.225, while the effectiveness factors predicted by the two approaches differed by a maximum of 7.14%. Furthermore, analytical asymptotic limits show that EF approaches unity for homogeneous behavior, while it drops to as low as 0.005 (200-fold reduction in reaction rate) under shrinking-core conditions. For practical applications in fixed-bed gasifiers, a pellet diameter of 4 mm is recommended under the investigated conditions (L e = 0.25, G = -6), providing a favorable balance between heat and hydrodynamic constraints. The developed EF correlations enable rapid estimation of effective pyrolysis rates without detailed multiscale modeling, offering a computationally efficient tool for reactor design and optimization in biomass gasification systems.
Microwave (MW)-assisted catalytic pyrolysis offers a promising pathway for efficient plastic upcycling. This work develops an integrated modeling framework combining dynamic data reconciliation, a temperature-dependent rate model, and a yield model to represent the time-varying production rate of components in MW-assisted LDPE pyrolysis conducted in a batch reactor. An Arrhenius-type rate model with a temperature-dependent reaction order is developed. A biexponential correlation is proposed for the yield of gaseous products that enables to capture the evolving product formation behavior during conversion. In the yield correlation, one term is used to represent the initial increase in yield, reflecting the rapid formation of intermediate or primary products at the early stages of the reaction when a larger fraction of the reactant remains available. As conversion progresses, the influence of this term gradually diminishes. The other term accounts for the subsequent decrease in the predicted yield, representing secondary reactions such as further cracking or coke formation that reduce the concentration of certain products at higher conversion. The model is found to accurately represent reconciled experimental flow rate profiles from an in-house MW-assisted catalytic batch reactor for major products, including ethylene, ethane, 1-butene, and benzene, across 250-350 °C. Ethylene remains the dominant product but decreases from about 41.95% at 250 °C to 30.14% at 350 °C, while heavier products increase significantly, with 1-butene rising to nearly 8.37% and benzene reaching 2.17% at intermediate temperatures. The model shows that the ethylene production rate can be maximized at around 270 °C. The models developed in this work can be utilized for process optimization, reactor design and scale-up of microwave-assisted plastic conversion technologies, and economic analysis.
Chronic non-specific low back pain (CNLBP) is a common musculoskeletal disease that troubles adults worldwide. Adverse reactions associated with drug therapy are unavoidable, so non-pharmacological treatments have gained attention. Acupuncture can effectively relieves pain, improve function, and avoid adverse drug reactions. However, existing guidelines for low back pain have a broad scope, and the evidence assessment of acupuncture for CNLBP is not comprehensive. In addition, there are various types of acupuncture, and there is still a lack of consensus on diverse acupuncture treatment protocols. Therefore, the formulation of this guideline will fill the gap and meet the clinical needs. The main steps for the formulation of this guideline will include: (1) Establishing a guideline development group; (2) Managing conflicts of interest; (3) Researching and identifying clinical questions; (4) Searching and assessing evidence; (5) Assessing and grading the quality of evidence; (6) Developing decision tables for recommendations; (7) Reaching consensus and making decisions on recommendations; (8) Formulating treatment protocols; (9) Drafting the guideline document; (10) Conducting peer review. This guideline is the first to focus its scope on CNLBP. It systematically synthesizes research evidence on acupuncture treatment, combines experts' clinical experience with patients' preferences, and develops clinically applicable recommendations and treatment plans. We incorporated the GRADE approach for evidence grading and a Delphi process for expert consensus. This process enhanced the scientific rigor and practical applicability of the recommendations. This guideline aims to provide clinicians with standardized and operable acupuncture treatment plans, and promote the standardization of acupuncture in the management of CNLBP. http://www.guidelines-registry.cn/, identifier [PREPARE-2024CN071].
Acute kidney injury (AKI) remains a critical clinical condition with high morbidity and mortality, underscoring the urgent need for early and accurate diagnostic tools. Traditional biomarkers such as serum creatinine (Cr) and blood urea nitrogen (BUN) suffer from delayed response and lack of specificity, limiting their utility in early-stage AKI detection. This study presents an innovative nanotechnology-enabled platform combining isothermal nucleic acid amplification with surface-enhanced Raman spectroscopy (SERS) for the direct and ultrasensitive detection of urinary microRNA-21 (miR-21), a promising early biomarker for AKI. The platform leverages a cascade signal amplification strategy: (1) a polymerase/endonuclease-mediated isothermal amplification system for target recognition and primer generation, (2) a hybridization chain reaction (HCR) to self-assemble DNA nanostructures conjugated with gold nanostars core with silver shell and 4-aminothiophenol (AuNS/Ag@4-ATP) SERS nanoprobes, and (3) a polyadenine-functionalized SERS substrate for robust signal capture. This integrated approach achieves a remarkable detection limit of 8.4 femtomolar (fM), surpassing conventional methods like quantitative reverse transcription polymerase chain reaction (qRT-PCR) in sensitivity while eliminating the need for RNA extraction or thermocycling. Clinical validation using patient urine samples demonstrated the platform's ability to detect miR-21 elevations 24-48 h earlier than traditional biomarkers, with exceptional specificity and reproducibility (relative standard deviation (RSD) < 5.7%). The modular design and direct urine compatibility highlight its potential for point-of-care applications, offering a rapid (<2 h) and equipment-minimized solution for early AKI diagnosis. This work not only advances AKI biomarker detection but also provides an adaptable framework for other disease-related nucleic acid analyses, bridging nanotechnology with clinical diagnostics.
The Rh blood group system is recognized for its complexity and its clinical importance in transfusion medicine. Antibodies against Rh antigens are associated with hemolytic transfusion reactions, autoimmune hemolytic anemia, and hemolytic disease of the fetus and newborn. The present study aims to characterize D antigens and assess their allele frequencies at the molecular level. Molecular characterization of RHD variants was performed on blood donors from the Brazilian Central-West who presented atypical D typing results. Serological profiles of all identified RHD variant alleles were also analyzed using different anti-D clones. Among the D-positive samples, 1.25% exhibited weak or discrepant agglutination during serological D typing. Most samples (67/103; 65%) were classified within the RHD*weak partial 4 cluster, followed by RHD*weak D type 3 (17/103; 16%). Lower frequencies were observed for RHD*weak D type 1 (2/103; 1.9%) and RHD*weak D type 2 (6/103; 5.8%). Furthermore, the rare RHD*weak D type 38 and RHD*weak D type 145 variants were identified. Analysis with different anti-D reagents showed that 52% of the samples had agglutination scores below 2+. Notably, 27% were classified as inconclusive, and 21% exhibited RhD serological discrepancies. Atypical reactions in RhD serological testing indicate the presence of variant D antigens. The RHD*weak partial 4 allele was the most prevalent RHD variant in the Brazilian Central-West population. However, the identification of rare RHD*weak D variants, such as types 38 and 145, highlight the genetic diversity reflective of the region's multiracial composition. Understanding the distribution of RHD variants can improve transfusion support and inform future RHD genotyping strategies.
To address the issues of low activity, inadequate stability, and susceptibility to deactivation in ammonia-containing alkaline water electrolysis catalysts, Ni9S8@Fe-NiP-O2 bifunctional electrocatalysts with a fractional core-shell structure were effectively synthesised using a phosphating oxidation coupling strategy. The Ni9S8@N3Fe-PBA precursor underwent structural transformation to form porous cubic-like particles, exhibiting significant electronic interaction between the Ni9S8 core and the Fe-NiP-O2 shell, which effectively modulated the surface electronic structure. Electrochemical assessments indicate that in a 1 M KOH solution, the oxygen evolution reaction (OER) overpotential of Ni9S8@Fe-NiP-O2 is at 235.6 mV at 20 mA cm-2, while the hydrogen evolution reaction (HER) overpotential is as low as 125.4 mV. The Tafel slope and charge transfer resistance are markedly superior to those of Ni(OH)2, Ni9S8, and other comparison samples, exhibiting the highest electrochemical double layer capacitance (C dl) and electrochemical active surface area (ECSA). In a 25% ammonia aqueous solution, the catalyst exhibits exceptional catalytic activity for both OER and HER, with superior overpotential, kinetics, and mass transfer characteristics. The comprehensive water electrolysis assessment indicates that Ni9S8@Fe-NiP-O2 demonstrates great efficiency and stability in water electrolysis across alkaline systems, ammonia aqueous solutions, and membrane electrode assemblies (MEAs). The current density in the MEA system can attain 950 mA cm-2 at 60 °C. The results show that the core-shell synergistic effect, multi-stage porous structure and multi-component electronic regulation jointly endow the catalyst with excellent bifunctional catalytic activity and ammonia resistance.
In the present work, a facile hydrothermal route was employed to synthesize the nanocomposite MgFe2O4/MoS2, which acted as a heterogeneous photo-Fenton catalyst for the degradation of a synthetic diazo dye, Acid Blue 113 (AB113). The nanocatalyst produced underwent analysis using multiple characterization techniques. The parameters influencing the oxidative reaction were statistically modeled and optimized using response surface methodology. Optimal degradation efficiency for AB113 (94.92%) was attained at pH 8.79 using 10 mg of MgFe2O4/MoS2 nanocatalyst, 1.6 mL of H2O2, and a reaction duration of 27 min. The synergistic effect resulting from the formation of electron-hole pairs renders the combined photocatalysis and Fenton process a more efficient treatment approach. The kinetic study data indicate that the photo-Fenton process follows the pseudo-first-order model. The nanocatalyst fabricated demonstrated exceptional stability, maintaining a high degradation performance after seven consecutive photo-Fenton cycles. The results obtained indicate that the MgFe2O4.MoS2/H2O2/Vis system is an effective method for treating wastewaters containing organic contaminants.
To compare the effects of dexmedetomidine and propofol on early postoperative cognitive function and safety in patients undergoing short-term surgical sedation. This retrospective cohort study included 295 adult patients who received intravenous sedation during non-cardiac surgery (January 2023-January 2025). Patients were divided into dexmedetomidine (n = 150) and propofol (n = 145) groups. Postoperative day 1 outcomes included explicit memory (RAVLT delayed recall) and processing speed (picture naming reaction time). Perioperative hemodynamics, recovery time, and adverse events were recorded. On postoperative day 1, the dexmedetomidine group showed higher RAVLT delayed recall scores (8.08 ± 3.06 vs. 7.24 ± 2.82, p = 0.015) but longer picture naming reaction time (881.42 ± 125.34 ms vs. 847.53 ± 118.76 ms, p = 0.037) compared to propofol. Median recovery time was longer with dexmedetomidine (18.00 vs. 14.00 min, p < 0.001). Dexmedetomidine was associated with more bradycardia requiring intervention (p = 0.034), while propofol had more injection pain (p < 0.001). No significant differences were found in hypoxemia or hypotension (p > 0.05). Multivariate analysis identified dexmedetomidine use as an independent factor for higher postoperative RAVLT scores (p = 0.007). In this short-term sedation cohort, dexmedetomidine was associated with better explicit memory but slower processing speed and longer recovery versus propofol, with distinct safety profiles. The clinical significance of these small cognitive differences remains uncertain, and prospective validation is needed.
2-Deoxy-d-glucose (2-DG), an inhibitor of key enzymes in the glycolytic pathway, has broad therapeutic potential and is a part of various natural products. Its 3,6-anhydro backbones are also present in bioactive natural sauropunols. A short and linear synthesis of 2-DG and sauropunols (A-D, F, and H) reported herein, involves conversion of d-glucose-derived 3,5,6-tri-O-benzoyl-1,2-isopropylidene-α-d-glucofuranose to alkyl-3,5,6-tri-O-benzoyl-d-glucofuranosides as the key intermediates through acid-catalyzed glycosylation reaction using three alcohols, followed by Barton-McCombie deoxygenation, cyclization, and appropriate deprotection reactions with excellent functional group tolerance and high yields.
Feline herpesvirus-1 (FHV-1) is a major pathogen responsible for feline upper respiratory tract disease (URTD), with a global distribution that poses significant threats to both the health of domestic cat and the conservation of wild felids. Thus, the development of a rapid and specific diagnostic method is crucial for controlling FHV-1 infection. In this study, we established a visual detection assay for FHV-1 by combining loop-mediated isothermal amplification (LAMP) with lateral flow dipstick (LFD). The assay utilized six of primers targeting the highly conserved TK gene of FHV-1. The LAMP amplification was performed using biotin-labeled H-FIP and 6-FAM-labeled H-LF, followed by visual detection using LFD. After optimizing the reaction conditions, the LAMP-LFD assay was established and systematically evaluated for its specificity, sensitivity, and repeatability. Furthermore, the performance of this assay was assessed using nasal swabs from 87 cats suspected with feline URTD. The optimal reaction conditions were determined as follows: 0.2 μM each of outer primers, 1.2 μM each of inner primers, and 0.6 μM each of loop primers, with amplification at 63 °C for 40 min. The assay showed no cross-reactivity with other pathogens caused feline URTD, demonstrating high specificity. The detection limit was 102 copies/μL for recombinant plasmid and 101.5 TCID50/mL for FHV-1 viral culture. Good repeatability was also confirmed. Clinical testing of 87 nasal swabs revealed positive rates of 49.43% (43/87). Compared to qPCR, the assay exhibited a specificity of 97.56%, sensitivity of 91.30%, and an overall agreement of 94.25%, with a kappa value of 0.89, indicating almost perfect concordance between the two methods. The LAMP-LFD assay developed in this study is highly sensitive, specific, simple, independent of specialized equipment and easy to perform with results visualized by the naked eye, making it well-suited for point-of-care testing of FHV-1 in primary veterinary hospitals and field setting.
Treatment resistance has become increasingly common in patients with chronic myeloid leukemia. Lack of response to tyrosine kinase inhibitors is associated with mutations in the BCR::ABL1 kinase domain. This study aims to report the frequency and types of BCR::ABL1 kinase domain mutations in Pakistani chronic myeloid leukemia patients. This prospective study was conducted from January to June 2025 at the Armed Forces Institute of Pathology in Pakistan. It included adult patients with chronic myeloid leukemia who were non-responsive to treatment based on molecular, hematological, and clinical criteria. Allele-specific real-time polymerase chain reaction was performed to detect four kinase domain mutations: T315I, E255V, E255K and Y253H. Data was analyzed using IBM SPSS v23. The mean age of the 133 treatment-resistant chronic myeloid leukemia patients included in the study was 47.3 ± 13.6 years. The majority of cases (62.4%) were male and 79 (59.4%) patients were currently on imatinib therapy. The median BCR::ABL1 level, as measured by quantitative polymerase chain reaction, was 30.73% (range: 1.17-100%) International Scale. BCR::ABL1 kinase domain mutations were detected in 57 (42.9%) patients. E255K was the most common mutation detected in 45 (33.8%) cases, followed by E255V in 11 (8.3%), T315I in 1 (0.8%) and the Y253H mutation in 1 (0.8%) patient. The presence of kinase domain mutations was significantly associated with higher total leucocyte count (p = 0.002), while the E255K mutation was significantly associated with blast crisis (p = 0.048). This study revealed a high prevalence of BCR::ABL1 kinase domain mutations in Pakistani chronic myeloid leukemia patients. E255K, the most frequently detected mutation, was significantly associated with blast crisis. These findings underscore the significance of molecular testing for personalized treatment.