Advanced Diagnostics Research Articles

Multimodal corneal imaging before refractive cataract surgery.

To prospectively review the advances in diagnostics for refractive cataract surgery, focusing on multimodal corneal analysis. The article explores the considerations related to planning refractive cataract surgery, emphasizing its potential to enhance patients' vision performance and quality of life. This review explores preoperative analysis in cataract surgery, focusing on assessing the cornea and ocular surface using multimodal diagnostics, including Placido disk-based corneal topography, Scheimpflug tomography OCT (optical coherence tomography), and biomechanical assessment. Wavefront technology, gene therapy, and artificial intelligence are also relevant in enhancing surgical precision and outcomes. It highlights the importance of preoperative thorough evaluations and technological advancements in ophthalmology. The rapid evolution and advancement of technology enable excellent refractive outcomes in most cases following cataract surgery. Consideration of appropriate preoperative factors is essential for achieving the desired postoperative outcome.

Challenges in the diagnosis and management of soft tissue tumors of the oral cavity.

Soft tissue lesions are among the most prevalent forms of tumors or tumor-like alterations within the oral cavity. They exhibit a wide spectrum of characteristics, ranging from benign, noninvasive lesions to malignant tumors, which collectively present a diagnostic challenge. A 67-year-old patient presented with an incidental finding of induration on the right cheek during dental hygiene. The intraoral examination revealed a soft, non-tender swelling measuring 20 mm in diameter. The sensitivity and percussion tests for the teeth in the fourth quadrant yielded unremarkable results. Panoramic radiography (OPG) revealed tip-ping of the premolars and an unclear apical finding in region 44. Cone-beam computed tomography (CBCT) revealed a sharply defined, lobulated hypodense lesion in the right buccal area. To clarify the diagnosis and optimize perioperative management, a 3 Tesla dental magnetic resonance imaging (MRI) scan was performed. This identified a 23×6×23 mm lipoma along the right mandibular ramus, causing detachment of the buccinator and de-pressor anguli oris muscles. A cinematic rendering reconstruction derived from the MRI data facilitated enhanced visualization for preoperative planning. The surgical excision was performed under local anesthesia, resulting in the successful removal of the neoplasm while preserving the mental nerve and submandibular gland. Histo-pathology confirmed the presence of a lobulated mature cell lipoma. The patient exhibited no complications during the removal of the sutures, with complete wound healing and no recurrence observed. This article highlights the efficacy of advanced MRI diagnostics and post-processing techniques in the management of ambiguous soft tissue neoplasms.

Distance-Based Fluorescent Immunosensor for Point-of-Care Test of Illegal Additives through the Gas-Producing Nanozyme.

The colorimetric point-of-care test (POCT) offers a rapid and efficient method for detecting specific targets in real samples. However, traditional colorimetric methods often rely on complex signal amplification techniques or electronic devices to enhance detection sensitivity, which can inadvertently increase both cost and time, thus contradicting the fundamental goals of visual detection methods. Here, we presented a distance-based fluorescent immunosensor that utilized a gas-producing nanozyme for continuous gas production reaction as a signal. Specifically, the SOM-ZIF-8@Pt nanozyme catalyzed the production of O2 from H2O2 to cause an obvious increase in the pressure within a sealed chamber, thus driving the production of H2S to quench the fluorescence of CsPbBr3 on the walls of the capillaries. Based on the competitive immunoassay, the fluorescence quenching lengths were relative with the concentration of aminopyrine in the range from 0.2 to 20 ng/L; thus, the fluorescent POCT-based homemade device was realized through the amplification of distance-based signals facilitated by the continuous gas production reaction. This strategy provides an effective way to realize POCT assays in resource-limited areas by transforming pressure variations into directly observable signals. Furthermore, distinguished by its high sensitivity, ease of operation, and portability, it also represents a significant advancement in biomedical diagnostics, particularly within home healthcare and clinical POCT.

Pertussis on the territory of Serbia in 2024 - challenges and opportunities for the future

Abstract Introduction Surveillance of pertussis in Serbia is passive surveillance and every 3 to 4 years an increased number of positive cases are registered in the population. The last quarter of 2023 and the first quarter of 2024 are characterized by an increased number of pertussis cases. Methods Descriptive study of cases with confirmed pertussis in the territory of the Republic of Serbia based on the evidence by the Public Health Service System of the Institute of Public Health of Serbia Results According to data from the Public Health Service System in the Republic of Serbia, a total of 1348 confirmed cases of pertussis were registered by the end of April 2024 (incidence rate 20.2 per 100,000 inhabitants). Conclusions The largest number of cases was registered in the age groups of people older than 20 years, that is, aged 10 to 14 years, while the highest age-specific incidence rate was recorded in the age group of infants younger than 12 months and in children aged 10 to 14 years. Of the total number of reported cases, 120 (8.9%) were hospitalized, with the largest number of those hospitalized being in the age group younger than 12 months (85, ie 70.8% of hospitalized cases). As for the territorial distribution, the largest number of pertussis cases in relation to the place of residence was reported from the territory of two districts, Južnobački District and the City of Belgrade, where the highest incidence rates were also registered. The postponement of timely vaccination against pertussis and the impossibility of vaccinating newborns up to 2 months of age have influenced the increase in the number of infected persons. Also, advanced PCR diagnostics during Covid and the possibility of applying PCR diagnostics in pertussis helped the timely diagnosis of pertussis. The introduction of vaccination with another dose of acellular pertussis vaccine and vaccination of pregnant women would be a desirable public health intervention to prevent pertussis infection. Key messages • Protection of the target population before starting school and at the age of 14 will contribute to stopping the occurrence of new cases of pertussis. These are public health challenges. • PCR diagnosis of pertussis influenced the timely diagnosis of this infection and the possibility of its adequate and timely treatment.

Investigation of IDO1 and TDO2 expression in breast tumors by immunohistochemistry and real-time polymerase chain reaction methods

Although diagnostic and therapeutic advances have been made in the treatment of breast cancer, the challenge of effectively controlling tumor progression persists. The objective of this study was to determine the relationship between IDO1 and TDO2 expression in breast cancer by immunohistochemistry and real-time polymerase chain reaction, hormone receptor status, Ki67 proliferation index, molecular classification, metastasis, and to investigate whether IDO1 and TDO2 expression can be used in combination with targeted therapy or as a marker to increase treatment efficacy in selected cases. The study included 74 cases of breast cancer and 14 cases of normal breast tissue as controls. All cases were analyzed for IDO1 and TDO2 by both immunohistochemistry and real-time polymerase chain reaction. The immunohistochemical analysis revealed that IDO1 immunoreactivity was significantly higher in tumor tissue compared to normal breast tissue. A statistically significant correlation was observed between IDO1 immunoreactivity and histologic subtypes. Furthermore, IDO1 gene expression was correlated with IDO1 immunoreactivity. TDO2 immune reactivity did not differ between tumor and non-tumor tissues and no correlation was found between histological subtypes. There was no correlation between TDO2 immunoreactivity and gene expression. The significant increase in IDO1 levels in tumor tissue and high positivity in age, HER2 positive and triple negative cases compared to other cases suggest that IDO1 inhibitors may be suitable for the target patient group in treatment selection.

Advances in Plant Disease Diagnostics and Surveillance- A review

Plant diseases pose a significant threat to global food security, leading to substantial yield losses and economic impacts. Early detection and effective monitoring are crucial for managing plant diseases, yet traditional diagnostic methods such as visual inspections, serological tests, and molecular assays face limitations in sensitivity, specificity, and scalability. In recent years, advancements in diagnostic and surveillance technologies have revolutionized plant health management. Next-Generation Sequencing (NGS) enables comprehensive pathogen profiling, while CRISPR-based diagnostics offer rapid and highly specific detection. Similarly, biosensors and portable devices provide on-site diagnostics, and machine learning and AI applications enhance the analysis of complex datasets, supporting automated disease identification and predictive modeling. Concurrently, advances in disease surveillance through remote sensing technologies, including satellites and Unmanned Aerial Vehicles (UAVs), enable large-scale, real-time monitoring of crop health, detecting disease outbreaks and facilitating targeted interventions. Integrating these diverse technologies into multi-platform systems offers a holistic approach to plant disease management, combining molecular diagnostics, environmental monitoring, and digital platforms to support data-driven decision-making. Several challenges remain, including high costs, technical complexities, and the need for standardized data integration. Addressing these barriers is essential to ensure that these technologies are accessible and effective across various agricultural systems, particularly in resource-limited settings. Future research should focus on enhancing the robustness, affordability, and scalability of these tools while promoting interdisciplinary collaborations.

Identification of a Novel Signature Based on Ferritinophagy-Related Genes to Predict Prognosis in Lung Adenocarcinoma: Focus on AHNAK2

Background: Lung adenocarcinoma (LUAD) accounts for over 40% of all non-small cell lung cancer (NSCLC) cases and continues to be difficult to treat despite advancements in diagnostics and therapies. Ferritinophagy, a newly recognized autophagy process linked to ferroptosis, has been associated with LUAD development. Recent studies have shown a dysregulation of genes related to ferritinophagy in LUAD, indicating its potential as a therapeutic target. Methods: We constructed a predictive model using seven genes associated with ferritinophagy. The model’s accuracy was evaluated across three independent gene expression datasets. We analyzed the biological functions, immune environment, mutations, and drug sensitivities in groups with high and low risk. Utilizing a single-cell sequencing (scRNA-seq) dataset, we confirmed the expression of the model genes and identified a subtype of epithelial cells expressing AHNAK2. We further investigated the impact of the ferritinophagy-related gene AHNAK2 on LUAD cell proliferation, invasion, migration, and ferroptosis in vitro. Results: Our prediction model, comprising seven genes (AHNAK2, ARNTL2, CD27, LTB, SLC15A1, SLC2A1, and SYT1), has shown potential in predicting the prognosis of individuals diagnosed with LUAD. Notably, AHNAK2 impedes ferroptosis, promoting LUAD progression in vitro. Conclusions: Our research suggests that ferritinophagy-associated genes are promising prognostic markers for LUAD and lay the groundwork for further exploration of ferritinophagy’s role in LUAD. Furthermore, we present AHNAK2 as a novel regulator of ferroptosis, which requires further investigation to understand its mechanism.

Advancements in LAMP-Based Diagnostics: Emerging Techniques and Applications in Viral Detection with a Focus on Herpesviruses in Transplant Patient Management

Loop-mediated isothermal amplification (LAMP) is a highly effective molecular diagnostic technique, particularly advantageous for point-of-care (POC) settings. In recent years, LAMP has expanded to include various adaptations such as DARQ-LAMP, QUASR, FLOS-LAMP, displacement probes and molecular beacons. These methods enable multiplex detection of multiple targets in a single reaction, enhancing cost-effectiveness and diagnostic efficiency. Consequently, LAMP has gained significant traction in diagnosing diverse viruses, notably during the COVID-19 pandemic. However, its application for detecting Herpesviridae remains relatively unexplored. This group of viruses is of particular interest due to their latency and potential reactivation, crucial for immunocompromised patients, including organ and hematopoietic stem cell transplant recipients. This review highlights recent advancements in LAMP for virus diagnosis and explores current research trends and future prospects, emphasizing the detection challenges posed by Herpesviridae.

Smartphone-driven centrifugal microfluidics for diagnostics in resource limited settings

The broad availability of smartphones has provided new opportunities to develop less expensive, portable, and integrated point-of-care (POC) platforms. Here, a platform that consists of three main components is introduced: a portable housing, a centrifugal microfluidic disc, and a mobile phone. The mobile phone supplies the electrical power and serves as an analysing system. The low-cost housing made from cardboard serves as a platform to conduct tests. The electrical energy stored in mobile phones was demonstrated to be adequate for spinning a centrifugal disc up to 3000 revolutions per minute (RPM), a rotation speed suitable for majority of centrifugal microfluidics-based assays. For controlling the rotational speed, a combination of magnetic and acoustic tachometry using embedded sensors of the mobile phone was used. Experimentally, the smartphone-based tachometry was proven to be comparable with a standard laser-based tachometer. As a proof of concept, two applications were demonstrated using the portable platform: a colorimetric sandwich immunoassay to detect interleukin-2 (IL-2) having a limit of detection (LOD) of 65.17 ng/mL and a fully automated measurement of hematocrit level integrating blood-plasma separation, imaging, and image analysis that takes less than 5 mins to complete. The low-cost platform weighing less than 150 g and operated by a mobile phone has the potential to meet the REASSURED criteria for advanced diagnostics in resource limited settings.

'Great Masquerader': a history of diagnosing pheochromocytoma.

Pheochromocytoma is a unique tumour with a variety of clinical presentations. Coined as 'the great masquerader', it can present with the classical triad of headache, sweating and tachycardia and sometimes in an acute hypertensive crisis. This paper describes the evolutionary history of the diagnosis of this condition. A literature review was conducted using Medline Database from 1900 to 2023 outlining the methods of diagnosis for pheochromocytoma. There have been diagnostic dilemmas and localization challenges of pheochromocytoma over the last century. From the first description of pheochromocytoma in 1886 to the first successful resection in 1926, there was poor recognition of its atypical symptoms and lack of reliable diagnostic tests. Over the next few decades, there were significant advances in screening and biochemical tests. Further understanding of catecholamine release and metabolic pathways led to the development of tests to identify end products of catecholamine metabolism in plasma and urine. Computed imaging however heralded significant improvement in surgical planning and management. The evolution of histopathological diagnosis with the use of immunostains and genetic testing has further contributed to the identification of malignant pheochromocytomas and an understanding of their behaviours. Significant advances in the biochemical and imaging have shaped our understanding of pathophysiology and management. These diagnostic advances have enabled early and accurate detection and localization of pheochromocytomas to enable prompt surgical management.

MUCM-Net: a Mamba powered UCM-Net for skin lesion segmentation

Aim: Skin lesion segmentation is critical for early skin cancer detection. Challenges in automatic segmentation from dermoscopic images include variations in color, texture, and artifacts of indistinct lesion boundaries. This study aims to develop and evaluate MUCM-Net, a lightweight and efficient model for skin lesion segmentation, leveraging Mamba state-space models integrated with UCM-Net architecture optimized for mobile deployment and early skin cancer detection. Methods: MUCM-Net combines Convolutional Neural Networks (CNNs), multi-layer perceptions (MLPs), and Mamba elements into a hybrid feature learning module. Results: The model was trained and tested on the International Skin Imaging Collaboration (ISIC) 2017 and ISIC2018 datasets, consisting of 2,000 and 2,594 dermoscopic images, respectively. Critical metrics for evaluation included Dice Similarity Coefficient (DSC), sensitivity (SE), specificity (SP), and accuracy (ACC). The model’s computational efficiency was also assessed by measuring Giga Floating-point Operations Per Second (GFLOPS) and the number of parameters. MUCM-Net demonstrated superior performance in skin lesion segmentation with an average DSC of 0.91 on the ISIC2017 dataset and 0.89 on the ISIC2018 dataset, outperforming existing models. It achieved high SE (0.93), SP (0.95), and ACC (0.92) with low computational demands (0.055–0.064 GFLOPS). Conclusions: The model’s innovative Mamba-UCM layer significantly enhanced feature learning while maintaining efficiency that is suitable for mobile devices. MUCM-Net establishes a new standard in lightweight skin lesion segmentation, balancing exceptional ACC with efficient computational performance. Its ability to perform well on mobile devices makes it a scalable tool for early skin cancer detection in resource-limited settings. The open-source availability of MUCM-Net supports further research and collaboration, promoting advances in mobile health diagnostics and the fight against skin cancer. MUCM-Net source code will be posted on https://github.com/chunyuyuan/MUCM-Net.

CFTrack: Advanced Diagnostic, Monitoring, and Tracking Device for Cystic Fibrosis Care.

Cystic fibrosis (CF) is a genetic disorder that primarily affects the respiratory, digestive, and reproductive systems. In the United States, approximately 32,000 individuals, spanning both children and adults, suffer from CF, and roughly 1,000 new cases are diagnosed annually. The current gold standard for CF diagnosis is the sweat test, yet this method is plagued by issues such as being time-consuming, expensive, challenging to replicate, and lacking treatment monitoring capabilities. In contrast, the emerging field of wearable sweat biosensors has gained significant attention due to their potential for noninvasive health monitoring. Despite this, there remains a conspicuous absence of a wearable sweat biosensor tailored specifically for CF diagnosis and monitoring. Here, this study introduces a flexible wearable sweat biosensor, named CFTrack, designed to address the unique challenges associated with CF. This proposed CFTrack biosensor not only facilitates CF diagnosis but also enables the monitoring of medication treatment effectiveness and tracks therapy activities. In addition, it operates in a self-powered and customized manner, ensuring seamless integration into the daily lives of individuals with CF. Given that sweat tests and fitness routines are the predominant methods for diagnosing and treating cystic fibrosis patients, respectively, the proposed CFTrack biosensor leverages ion concentration in sweat for diagnostic purposes. Additionally, it incorporates a motion-tracking function to monitor physical activity, providing a comprehensive approach to CF management. To evaluate the feasibility of the proposed CFTrack biosensor, a comprehensive evaluation has been performed including numerical simulations, theoretical analyses, and experimental tests. The results demonstrate the efficacy of the proposed CFTrack biosensor in diagnosing and monitoring CF conditions while also showcasing its ability to effectively track the progress of patients undergoing physical therapy. The proposed CFTrack biosensor resolves key issues associated with existing sweat sensors including high energy consumption, intricate fabrication procedures, and the absence of continuous monitoring capabilities. By addressing these challenges, the proposed sweat biosensor aims to revolutionize CF diagnosis and monitoring, offering a more efficient and user-friendly alternative to current methods.

Hematological Cancer and Viral Infection

Hematological cancer patients are particularly vulnerable to the morbidity and death caused by viral infections. But, it is not well known how common viral infections are or what effects they have on patients undergoing traditional nontransplant treatment. How severe and how long T-cell-mediated immune suppression is determines the variation in viral infection incidence and prognosis between patient groups. Topics covered in this mini-review article include late CMV infection, new viral pathogens (human herpesvirus-6, BK virus, adenovirus, and human metapneumovirus), advancements in molecular diagnostics, and the possibility of novel agents for viral prophylaxis (maribavir) or preemptive therapy (valganciclovir). The infections caused by these viruses have been extensively studied. If we want to understand the range of these viral diseases and come up with effective ways to prevent and cure them, we need well-designed prospective trials. Patients undergoing nontransplant treatment for hematological malignancies are at greater risk for viral infections; this is especially important given the rising use of drugs like alemtuzumab, which cause significant T-cell depletion.

Traumatic brain injury (TBI): Is there anything we can do? A review

Introduction Traumatic brain injury (TBI) is considered a global health crisis. It results in injury to the brain from an external impact leading to severe disability, with higher incidence statistics recently observed in young adults and elderly individuals. Purpose The review aims to analyze current research findings explaining the prevalence, incidence, and demographics of such injuries stressing the need for enhanced prevention and management techniques. The pathophysiology involves a complex cascade of biochemical and cellular events, which results in necrotic-apoptotic neuronal cell death. Method The review synthesizes current research on TBI, highlighting epidemiological data, advanced diagnostics, and effective rehabilitation strategies like physical and cognitive therapy. Findings Traumatic Brain Injury is an important public health issue with high morbidity and mortality rates causing extreme damage to a person, such as comas, catatonic states for various years, or lifelong injury or demolition. Early diagnostic imaging techniques include CT, MRI, advanced neuroimaging methods, and blood-based biomarkers. In the acute setting, initial management is directed toward stabilizing and preventing secondary injuries and early mobilization. The goals of rehabilitation are to promote the highest level of functional independence and physical function, cognitive functions, and social integration. Conclusion This review highlights that the use of new rehabilitation technologies, such as VR-based and robot-assisted therapies, might lead to improved recovery. Long-term supportive care combined with community integration is mandatory for enhancing quality of life. A systematic multidisciplinary team approach and family support are needed for traumatic brain injury survivors.

Recent Updates on Diverse Nanoparticles and Nanostructures in Therapeutic and Diagnostic Applications with Special Focus on Smart Protein Nanoparticles: A Review.

Nanomedicine enables advanced therapeutics, diagnostics, and predictive analysis, enhancing treatment outcomes and patient care. The choices and development of high-quality organic nanoparticles with relatively lower toxicity are important for achieving advanced medical goals. Among organic molecules, proteins have been prospected as smart candidates to revolutionize nanomedicine due to their inherent fascinating features. The advent of protein nanoarchitectures, which explore the biomolecular corona, offers new insights into their efficient tissue penetration and therapeutic potential. This review examines various animal- and plant-based protein nanoparticles, highlighting their source, activity, products, and unique biomedical applications in regenerative medicine, targeted therapies, gene and drug delivery, antimicrobial activity, bioimaging, immunological adjuvants, etc. It provides an extensive discussion on recent applications of protein nanoparticles across diverse biomedical fields as well as the evolving landscape of other nanoproducts and nanodevices for sensitive medical procedures. Furthermore, this review introduces different preparation technologies of protein nanoparticles, emphasizing how their design and construction significantly influence loading capacity, stability, and targeting effects. Additionally, we delve into the construction of different user-friendly multifunctional modular bioarchitectures by the assembly of protein nanoparticles (PNPs), marking a significant breakthrough in therapies. This review also considers the challenges of synthetic nanomaterials and the emergence of natural alternatives, which provides insights into protein nanoparticle research.

Mucormycosis: Current Perspectives on Treatment, Diagnosis, and Advancements

Objective: This review study examines mucormycosis treatment challenges, gaps in medicines, and COVID-19-related effects. This paper examines diagnostic and drug development advances while addressing safety and specificity. Methods: This review study searches PubMed, Web Science, and Scopus for relevant material. Keywords associated with mucormycosis, therapy, diagnosis, medication advancement, and COVID- 19 are used to identify pertinent articles. Data extraction summarizes therapeutic obstacles, diagnostic advances, and innovative drug options. Results: This review article covers mucormycosis therapy, diagnostics, and drug development. It reveals limitations in present medicines, such as selectivity, safety, and resistance mechanisms. Diagnostic advances and mucormycosis in COVID-19 have also been explored. Conclusion: This review emphasizes the need for more secure, specific mucormycosis therapies. It discusses therapy obstacles, diagnostic advances, and new drug techniques. Overall, this research emphasizes improving mucormycosis therapy to enhance patient outcomes.

Rare presentations of glioblastoma multiforme in the septum pellucidum: illustrative case.

Glioblastoma multiforme (GBM), a high-grade primary brain tumor, presents a formidable challenge in neuro-oncology because of its aggressive nature, infiltrative growth, and limited response to treatment. The septum pellucidum represents an uncommon and unexpected location for GBM, adding complexity to the diagnosis and management of this rare intracranial malignancy. A 69-year-old male with a previous history of prostate carcinoma presented to an outside hospital with a 2-week history of a "trance-like state" and cognitive decline. Initial head computed tomography showed prominent ventricles without distinct mass lesions. Upon admission, magnetic resonance imaging demonstrated a mass within the inferior septum pellucidum extending to the third and both lateral ventricles. Biopsy findings indicated a GBM, World Health Organization central nervous system tumor grade 4, with immunopositivity for glial fibrillary acidic protein and a Ki-67 labeling index of 60%-70%. Identifying only 5 cases in more than 60 years of literature, this systematic review illustrates the diverse clinical presentations, diagnostic advancements, and management approaches for septum pellucidum GBM. https://thejns.org/doi/10.3171/CASE23770.

ASSESSMENT OF METHODS OF DIAGNOSIS AND TREATMENT OF PANCREATIC CYSTS

Abstract. The frequency of formation of pancreatic cysts in acute and chronic pancreatitis is 5-30%, and in destructive forms it increases to 60-70%. Persons of working age from 30 to 60 years old are mainly prone to the disease, which confirms the social significance of this problem. The aim: increase the effectiveness of surgical treatment of pancreatic cysts by using advanced diagnostics and methods of external and internal drainage. Materials and methods: the study is based on the analysis of the results of surgical treatment of patients with pancreatic cysts who were treated at VRCH n.a. M.I. Pirogov in the period from 01.01.2018 to 01.06.2024. A total of 65 patients were observed. The results: infection of the postoperative wound was observed in 6.15% of patients. 1.54% of patients developed adhesions, which were treated conservatively. The average time for removing drains with laparoscopic drainage is 21.2±1.5 days. There were no fatal consequences. Conclusions: the use of advanced diagnostics followed by differential selection of the treatment method significantly reduces the number of complications, reduces mortality and the length of stay of patients in the hospital.

Guanine nucleotide exchange factors and colon neoplasia

Despite many diagnostic and therapeutic advances, colorectal cancer (CRC) remains the second leading cause of cancer death for men and women in the United States. Alarmingly, for reasons currently unknown, the demographics of this disease have shifted towards a younger population. Hence, understanding the molecular mechanisms underlying CRC initiation and progression and leveraging these findings for therapeutic purposes remains a priority. Here, we review critically the evidence that canonical and noncanonical actions of guanine nucleotide exchange factors (GEFs) play important roles in CRC evolution. Rho GEF GTPases, which switch between inactive GDP-bound and active GTP-bound states, are commonly overexpressed and activated in a variety of cancers, including CRC, and may be tractable therapeutic targets. In addition to comprehensively reviewing this field, we focus on Rho/Rac GEFs that are involved in regulating key functions of normal and neoplastic cells like cell polarity, vesicle trafficking, cell cycle regulation, and transcriptional dynamics. Prime examples of such Rho/Rac GEFs include βPak-interacting exchange factor (βPix), a Rho family GEF for Cdc42/Rac1, Tiam1, GEF-H1, RGNEF, and other GEFs implicated in CRC development and progression. Throughout this analysis, we explore how these findings fill key gaps in knowledge regarding the molecular basis of colon carcinogenesis and how they may be leveraged to treat advanced CRC. Lastly, we address potential future directions for research into the role of GEFs as CRC biomarkers and therapeutic targets. In this regard, leveraging the noncanonical actions of GEFs appears to provide a relatively unexplored opportunity requiring further investigation.

Is the combination of two automated rapid assays for diagnosis of heparin-induced thrombocytopenia necessary?

Heparin-induced thrombocytopenia (HIT) is an immune-mediated condition characterized by a decrease in platelet count and an increased thrombotic risk. HIT event is caused by antiplatelet factor/heparin (PF4/H) antibodies that can activate the platelets. The diagnosis of HIT is based on a clinical evaluation and laboratory results. Aim of our study was to evaluate whether the combined use of two rapid assays for diagnosis of HIT provides a diagnostic advantage over the use of a single automate assay. We extracted from the laboratory informatic system all the determinations requested for the detection of antibodies against heparin/PF4 complexes from July 2020 to June 2024 (n. 229). In our laboratory, total antibodies against heparin/PF4 complex [HemosIL HIT-Ab-(PF4-H), Instrumentation Laboratory] and IgG Ab (HemosIL AcuStar HIT-IgG, Instrumentation Laboratory) are measured simultaneously with two different instruments. Two hundred six samples tested negative for both methods, 23 samples tested positive for at least one method and nine samples tested positive for both methods. The grade of concordance between the two assays shows a weighted Kappa of 0.536 (moderate agreement). No sample tested positive only for IgG-Ab. The sensitivity of HIT-Ab-(PF4-H) was 1, whereas the specificity was 0.95. For the HIT-IgG (PF4-H) method, sensibility and specificity were 0.77 and 1, respectively. Our results suggest that performing these two tests simultaneously does not provide additional useful information in patients with suspicion of HIT. The total Ab assay seems to be sufficient, as it shows higher sensitivity although at the expense of lower specificity.