Intraoperative pneumatic tourniquet application reduces soft-tissue microcirculation, but without affecting wound healing in calcaneal fractures.

BACKGROUND: Wound healing complications are a major challenge following the extended lateral approach in calcaneal fractures. Soft-tissue microcirculation plays an important role via the delivery of oxygen, nutrients, and the regulation of a local milieu. The aim of this clinical study was to examine the effect of intraoperative pneumatic tourniquet application on skin and subcutaneous microcirculation, and its impact on wound healing progression. METHODS: Patients with calcaneal fractures were randomly assigned to two groups defined by a surgery conducted either with use or without use of a tourniquet. Blood flow (BF [AU]), tissue oxygen saturation (SO2[%]) and the relative amount of haemoglobin (rHb[AU]) were intraoperatively measured at two depths (2 and 8 mm) non-invasively by spectrophotometry (Micro-Lightguide O2C®, LEA Medizintechnik, Giessen, Germany). Time points were before and after inflation of the pneumatic tourniquet and also at the end of surgery before deflation. A linear mixed model (LMM) was fitted for statistical analysis. RESULTS: Thirty-four patients (3 women and 31 men) with 37 calcaneal fractures were included. In 22 of them, the surgery was conducted with a tourniquet and in the other 15 without its use. A significant decrease of microcirculation, characterized by decreases in blood flow (p = 0.011) and tissue oxygenation (p = 0.023) was measured in 8 mm depth after inflating the tourniquet. However, these changes did not influence the time of postoperative wound healing. CONCLUSION: The use of a pneumatic tourniquet reduces deep microcirculation without affecting postoperative wound healing. Trial registration The study was registered in www. CLINICALTRIALS: gov (NCT01264146).

Maintaining the Balance: Regulation of NK Cell Activity.

Natural Killer (NK) cells, integral components of the innate immune system, play a crucial role in the protection against intracellular threats. Their cytotoxic power requires that activation is tightly controlled, and in this, they take a unique position within the immune system. Rather than depending on the engagement of a single activating receptor, their activation involves a delicate balance between inhibitory and activating signals mediated through an array of surface molecules. Only when this cumulative balance surpasses a specific threshold do NK cells initiate their activity. Remarkably, the activation threshold of NK cells remains robust even when cells express vastly different repertoires of inhibitory and activating receptors. These threshold values seem to be influenced by NK cell interactions with their environment during development and after release from the bone marrow. Understanding how NK cells integrate this intricate pattern of stimuli is an ongoing area of research, particularly relevant for cellular therapies seeking to harness the anti-cancer potential of these cells by modifying surface receptor expression. In this review, we will explore some of the current dogmas regarding NK cell activation and discuss recent literature addressing advances in our understanding of this field.

Structural insights into the human P2X1 receptor and ligand interactions.

The P2X1 receptor is a trimeric ligand-gated ion channel that plays an important role in urogenital and immune functions, offering the potential for new drug treatments. However, progress in this area has been hindered by limited structural information and a lack of well-characterised tool compounds. In this study, we employ cryogenic electron microscopy (cryo-EM) to elucidate the structures of the P2X1 receptor in an ATP-bound desensitised state and an NF449-bound closed state. NF449, a potent P2X1 receptor antagonist, engages the receptor distinctively, while ATP, the endogenous ligand, binds in a manner consistent with other P2X receptors. To explore the molecular basis of receptor inhibition, activation, and ligand interactions, key residues involved in ligand and metal ion binding were mutated. Radioligand binding assays with [3H]-α,ß-methylene ATP and intracellular calcium ion influx assays were used to evaluate the effects of these mutations. These experiments validate key ligand-receptor interactions and identify conserved and non-conserved residues critical for ligand binding or receptor modulation. This research expands our understanding of the P2X1 receptor structure at a molecular level and opens new avenues for in silico drug design targeting the P2X1 receptor.

Cancer Care Terminology in African Languages.

Importance: Effective communication between patients and health care teams is essential in the health care setting for delivering optimal cancer care and increasing cancer awareness. While the significance of communication in health care is widely acknowledged, the topic is largely understudied within African settings. Objective: To assess how the medical language of cancer and oncology translates into African languages and what these translations mean within their cultural context. Design, Setting, and Participants: In this multinational survey study in Africa, health professionals, community health workers, researchers, and scientists involved in cancer care and research and traditional healers were invited to participate in an online survey on a voluntary basis through online platforms. The survey provided 16 cancer and oncologic terms used in cancer diagnosis and treatment (eg, cancer, radiotherapy) to participants, mostly health care workers, who were asked to provide these terms in their local languages (if the terms existed) followed by a direct or close translation of the meaning in English. The survey was open from February to April 2023. Main Outcomes and Measures: Patterns of meaning that recurred across languages were identified using thematic analysis of 16 English-translated terms categorized into 5 themes (neutral, negative, positive, phonetic or borrowed, and unknown). Results: A total of 107 responses (response rate was unavailable given the open and widespread distribution strategy) were collected from 32 countries spanning 44 African languages, with most participants (63 [59%]) aged 18 to 40 years; 54 (50%) were female. Translations for cancer were classified as phonetic or borrowed (34 [32%]), unknown (30 [28%]), neutral (24 [22%]), and negative (19 [18%]), with the latter category including universal connotations of fear, tragedy, incurability, and fatality. Similar elements connoting fear or tragedy were found in translations of terms such as malignant, chronic, and radiotherapy. The term radiotherapy yielded a high percentage of negative connotations (24 [22%]), with a prevailing theme of describing the treatment as being burned or burning with fire, heat, or electricity, which may potentially hinder treatment. Conclusions and Relevance: In this survey study of cancer communication and the translation of oncology terminology in African languages, the findings suggest that the terminology may contribute to fear, health disparities, and barriers to care and pose communication difficulties for health professionals. The results reinforce the need for culturally sensitive cancer terminology for improving cancer awareness and communication.

The immunology of sickness metabolism.

Everyone knows that an infection can make you feel sick. Although we perceive infection-induced changes in metabolism as a pathology, they are a part of a carefully regulated process that depends on tissue-specific interactions between the immune system and organs involved in the regulation of systemic homeostasis. Immune-mediated changes in homeostatic parameters lead to altered production and uptake of nutrients in circulation, which modifies the metabolic rate of key organs. This is what we experience as being sick. The purpose of sickness metabolism is to generate a metabolic environment in which the body is optimally able to fight infection while denying vital nutrients for the replication of pathogens. Sickness metabolism depends on tissue-specific immune cells, which mediate responses tailored to the nature and magnitude of the threat. As an infection increases in severity, so do the number and type of immune cells involved and the level to which organs are affected, which dictates the degree to which we feel sick. Interestingly, many alterations associated with metabolic disease appear to overlap with immune-mediated changes observed following infection. Targeting processes involving tissue-specific interactions between activated immune cells and metabolic organs therefore holds great potential for treating both people with severe infection and those with metabolic disease. In this review, we will discuss how the immune system communicates in situ with organs involved in the regulation of homeostasis and how this communication is impacted by infection.

Characterization of Mild Traumatic Brain Injury Cohort With Photophobia From the Defense and Veterans Eye Injury and Vision Registry.

INTRODUCTION: Photophobia is a common visual symptom following mild traumatic brain injury (mTBI), which can adversely affect the military readiness and performance of service members (SMs). We employed the Defense and Veterans Eye Injury and Vision Registry (DVEIVR) to identify and describe a cohort of SMs diagnosed with photophobia post-mTBI. The objective of this study was to characterize comorbid conditions and symptoms in an mTBI cohort with photophobia, to assess their co-occurrence, to describe the persistence of photophobia, and to assess the effectiveness of utilization of currently available International Statistical Classification of Diseases and Related Health Problems (ICD) codes in reporting photophobia in this cohort. MATERIALS AND METHODS: The DVEIVR database was searched to identify a cohort of SMs experiencing photophobia after mTBI. Photophobia and other potentially related conditions and symptoms, both coded and descriptive, which were abstracted directly from the medical records of SMs, were found within DVEIVR. The presence of the conditions and symptoms comorbid with photophobia was characterized on both patient and encounter levels. Analysis of co-occurrence of photophobia with these conditions or symptoms was performed on the encounter level using co-occur package in the statistical program R. Persistence of photophobia up to 1 year since the injury was assessed. The utilization of currently available ICD codes for photophobia was analyzed. RESULTS: A total of 639 SMs exhibiting photophobia after mTBI were identified in DVEIVR. Headaches, including migraines, were the most frequently experienced comorbidity affecting 92% of the SMs in the cohort. The second most frequent complaint was dizziness and/or vertigo (53%) followed by nausea (42%), blurry vision (31%), and irritation and discomfort in the eye (17%). In all, 20% of encounters with photophobia had a complaint of headaches, followed by 8.3% of photophobia encounters co-occurring with dizziness and vertigo, 5.7%-with nausea, 4.5%-with blurred vision, and 2.1%-with subjective sensations in the eye. All comorbidities co-occurred with photophobia at probabilities higher than by chance alone. The percentage of mTBI SMs experiencing photophobia declined to 20% at 30 days after the injury, 17% at 3 months, 12% at 6 months, and 7% at 12 months post-injury, respectively. The use of currently available ICD codes for photophobia was very low-only 27.1% of the cohort had at least 1 ICD code recorded in their medical records. CONCLUSIONS: The results of this study support the idea that there is a strong relationship between photophobia and headache after an mTBI. Additional research is warranted to better understand this relationship and its causes so that clinical management improves. The results of this study show a precipitous decline in the numbers of cases of photophobia after mTBI over the first 30 days and a longer-term persistence up to a year in a minority of cases, which is consistent with other research in this field. Various ICD codes, which are currently used to code for photophobia, along with other vision conditions, were not widely used to document photophobia symptoms. It is important to adopt a dedicated ICD code for photophobia to improve the surveillance, data collection, and analysis of this condition.

Structure-Based Design of Bicyclic Helical Peptides That Target the Oncogene ß-Catenin.

The inhibition of intracellular protein-protein interactions is challenging, in particular, when involved interfaces lack pronounced cavities. The transcriptional co-activator protein and oncogene ß­catenin is a prime example of such a challenging target. Despite extensive targeting efforts, available high-affinity binders comprise only large molecular weight Inhibitors. This hampers the further development of therapeutically useful compounds. Herein, we report the design of a considerably smaller peptidomimetic scaffold derived from the α-helical ß­catenin-binding motif of Axin. Sequence maturation and bicyclization provided a stitched peptide with an unprecedented crosslink architecture. The binding mode and site were confirmed by a crystal structure. Further derivatization yielded a ß-catenin inhibitor with single-digit micromolar activity in a cell-based assay. This study sheds a light on how to design helix mimetics with reduced molecular weight thereby improving their biological activity.

Reconsideration of the alar base cinch suture technique involving the perinasal musculature: an in-depth review.

Orthognathic surgery affects both function and aesthetics. An important aesthetic complication is the nasal alteration that can result from Le Fort I osteotomy. A common method for countering this complication is the alar base cinch suture technique. Although the method for this suture has been standardized, the results vary and are inconsistent; further improvements are therefore required. The objective of this study was to review the literature data on the alar base cinch suture technique and associated results. In this review, the PubMed, Ovid, and Ichushi-Web electronic databases were searched using logical combinations of keywords related to the perinasal musculature and alar base cinch suture technique. Following screening of the results, 42 publications were included. The review findings prompted several conclusions. The anatomy of the myrtiformis muscle and depressor septi nasalis may differ between ethnicities, and it is essential to take certain factors related to ethnicity into account when implementing the alar base cinch suture technique. It is also important to consider factors such as the patient's aesthetic preferences.

Inhibiting the NADase CD38 improves cytomegalovirus-specific CD8+ T cell functionality and metabolism.

Cytomegalovirus (CMV) is one of the most common and relevant opportunistic pathogens in people who are immunocompromised, such as kidney transplant recipients (KTRs). The exact mechanisms underlying the disability of cytotoxic T cells to provide sufficient protection against CMV in people who are immunosuppressed have not been identified yet. Here, we performed in-depth metabolic profiling of CMV-specific CD8+ T cells in patients who are immunocompromised and show the development of metabolic dysregulation at the transcriptional, protein, and functional level of CMV-specific CD8+ T cells in KTRs with noncontrolled CMV infection. These dysregulations comprise impaired glycolysis and increased mitochondrial stress, which is associated with an intensified expression of the nicotinamide adenine dinucleotide nucleotidase (NADase) CD38. Inhibiting NADase activity of CD38 reinvigorated the metabolism and improved cytokine production of CMV-specific CD8+ T cells. These findings were corroborated in a mouse model of CMV infection under conditions of immunosuppression. Thus, dysregulated metabolic states of CD8+ T cells could be targeted by inhibiting CD38 to reverse hyporesponsiveness in individuals who fail to control chronic viral infection.

How to talk about dying? The development of an evidence-based model for communication with patients in their last days of life and their family caregivers.

Objective: To help healthcare professionals (HCP) act with more confidence when communicating about approaching death, we sought to develop a communication model for HCP to facilitate conversations with dying patients and family caregivers (FC) in nonemergency situations. Methods: We used a four-phase integrative approach: (1) creation of a preliminary model based on a systematic literature review and expert knowledge, (2) review of the model draft by international palliative care experts, (3) review by key stakeholders, and (4) final appraisal by communication experts. Results: After the clinical recognition of dying, the communication model provides a structure and practical communication aids for navigating the conversation based on three phases. It describes the content and relational level as core dimensions of effective conversations about approaching death and highlights the importance of HCP self-awareness and self-care when caring for the dying. Conclusion: Based on systematic involvement of key stakeholders, the model supports clinicians navigating challenging conversations about approaching death with dying patients and their FC successfully and with more confidence. Innovation: This study expands the theoretical basis for communication about approaching death and offers a pragmatic model for educational interventions and clinical use.

Historical control data of rare events: Issues, chronological patterns and their relevance for toxicological evaluations.

Historical control data (HCD) give context for a measurement by providing a biological reference frame. HCD are used in the evaluation of toxicological bioassays for quality and performance control, informal statistical false discovery rate mitigation, and to estimate the biological relevance of observed potentially adverse findings. The current commentary shortly highlights 5 points that should be considered when working with HCD of rare events: 1) HCD database (HCDB) size, 2) the issue of rare events, 3) potential chronological patterns, 4) using point estimates to summarize HCD and 5) independence from treatment bias, i.e., HCD are mostly informative for primary toxicity. It is argued to use exploratory data analysis and to apply ad hoc time windows for assessment based on an HCDB that is as large as possible to monitor for potential structure and systemic bias in the data.

An 8000 years old genome reveals the Neolithic origin of the zoonosis Brucella melitensis.

Brucella melitensis is a major livestock bacterial pathogen and zoonosis, causing disease and infection-related abortions in small ruminants and humans. A considerable burden to animal-based economies today, the presence of Brucella in Neolithic pastoral communities has been hypothesised but we lack direct genomic evidence thus far. We report a 3.45X B. melitensis genome preserved in an ~8000 year old sheep specimen from Mentese Höyük, Northwest Türkiye, demonstrating that the pathogen had evolved and was circulating in Neolithic livestock. The genome is basal with respect to all known B. melitensis and allows the calibration of the B. melitensis speciation time from the primarily cattle-infecting B. abortus to approximately 9800 years Before Present (BP), coinciding with a period of consolidation and dispersal of livestock economies. We use the basal genome to timestamp evolutionary events in B. melitensis, including pseudogenization events linked to erythritol response, the supposed determinant of the pathogen's placental tropism in goats and sheep. Our data suggest that the development of herd management and multi-species livestock economies in the 11th-9th millennium BP drove speciation and host adaptation of this zoonotic pathogen.

The Use of 18F-Fluoride Positron Emission Tomography/Computed Tomography Scanning to Identify Sources of Pain after Posterior Lumbar Interbody Fusion-An Analysis in Patients with and without Symptoms.

BACKGROUND: Identifying the cause of recurrent or persisting pain after posterior lumbar interbody fusion (PLIF) is essential for establishing optimal treatment. In this study, we evaluate patients after PLIF surgery by 18F-fluoride PET/CT scans and patient-reported outcome measures (PROMs). METHODS: A total of 36 PLIF patients were included. Sixty minutes after intravenous injection of 18F-fluoride, PET/CT scanning was performed. Bone graft ingrowth, subsidence, screw loosening and damage of facet joints were scored by quantifying the level of bone metabolism of the vertebral endplates in the disc spaces, around screws and around the facet joints on the PET scans. RESULTS: In contrast to asymptomatic patients, symptomatic patients showed abnormal PET values around pedicle screws and/or facet joints and at the lower endplates of the disc spaces, identifying a possible source of pain. On CT, no significant differences between these two groups were found. CONCLUSION: The PET/CT findings appeared to correlate better with symptoms on PROMs compared to CT findings alone. When interpreting 18F-fluoride PET/CT findings after PLIF surgery, one should realize bone metabolism in the disc spaces of the operated segments and around pedicle screws or facet joint changes during follow-up, reflecting natural recovery.

Performance evaluation of iterative PET reconstruction with resolution recovery incorporating Gallium-68 positron range correction.

BACKGROUND: The distance traveled by the positron before annihilation with an electron, the so-called positron range, negatively effects the positron emission tomography (PET) image quality for radionuclides emitting high-energy positrons such as Gallium-68 (68Ga). PURPOSE: In this study, the effect of a tissue-independent positron range correction for Gallium-68 (68Ga-PRC) was investigated based on phantom measurements. The effect of the 68Ga-PRC was also explored in four patients. METHODS: The positron range distribution profile of 68Ga in water was generated via Monte Carlo simulation. That profile was mapped to a spatially invariant 3D convolution kernel which was incorporated in the OSEM and Q.Clear reconstruction algorithms to perform the 68Ga-PRC. In addition, each reconstruction method included point spread function (PSF) modeling and time-of-flight information. For both Fluorine-18 (18F) and 68Ga, the NEMA IQ phantom was filled with a sphere-to-background ratio of 10:1 and scanned with the GE Discovery MI 5R PET/CT system. Standard non-positron range correction (PRC) reconstructions were performed for both radionuclides, while also PRC reconstructions were performed for 68Ga. Reconstructions parameters (OSEM: number of updates, Q.Clear: beta value) were adapted to achieve similar noise levels between the corresponding reconstructions. The effect of 68Ga-PRC was assessed for both OSEM and Q.Clear reconstructions and compared to non-PRC reconstructions for 68Ga and 18F in terms of image contrast, noise, recovery coefficient (RC), and spatial resolution. For the clinical validation, 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) and 68Ga-DOTATOC PET scans were included of two patients each. For each PET scan, patients were injected with 1.5 MBq/kg of 68Ga-PSMA or 68Ga-DOTATOC and the contrast-to-noise ratio (CNR) was calculated and compared to the non-PRC reconstructions. RESULTS: For OSEM reconstructions, including the 68Ga-PRC improved the RC by 9.4% (3.7%-19.3%) and spatial resolution by 21.7% (4.6 mm vs. 3.6 mm) for similar noise levels. For Q.Clear reconstructions, 68Ga-PRC modeling improved the RC by 6.7% (2.8%-10.5%) and spatial resolution by 15.3% (5.9 mm vs. 5.0 mm) while obtaining similar noise levels. In the patient data, the use of 68Ga-PRC enhanced the CNR by 13.2%. CONCLUSIONS: Including 68Ga-PRC in the PET reconstruction enhanced the image quality of 68Ga PET data compared to the standard non-PRC reconstructions for similar noise levels. Limited patient results also supported this improvement.

The database makes the poison: How the selection of datasets in QSAR models impacts toxicant prediction of higher tier endpoints.

As the United States and the European Union continue their steady march towards the acceptance of new approach methodologies (NAMs), we need to ensure that the available tools are fit for purpose. Critics will be well-positioned to caution against NAMs acceptance and adoption if the tools turn out to be inadequate. In this paper, we focus on Quantitative Structure Activity-Relationship (QSAR) models and highlight how the training database affects quality and performance of these models. Our analysis goes to the point of asking, "are the endpoints extracted from the experimental studies in the database trustworthy, or are they false negatives/positives themselves?" We also discuss the impacts of chemistry on QSAR models, including issues with 2-D structure analyses when dealing with isomers, metabolism, and toxicokinetics. We close our analysis with a discussion of challenges associated with translational toxicology, specifically the lack of adverse outcome pathways/adverse outcome pathway networks (AOPs/AOPNs) for many higher tier endpoints. We recognize that it takes a collaborate effort to build better and higher quality QSAR models especially for higher tier toxicological endpoints. Hence, it is critical to bring toxicologists, statisticians, and machine learning specialists together to discuss and solve these challenges to get relevant predictions.

Limited Additional Value of a Chest CT in Whole-Body Staging with PET-MRI: A Retrospective Cohort Study.

Hybrid PET-MRI systems are being used more frequently. One of the drawbacks of PET-MRI imaging is its inferiority in detecting lung nodules, so it is often combined with a computed tomography (CT) of the chest. However, chest CT often detects additional, indeterminate lung nodules. The objective of this study was to assess the sensitivity of detecting metastatic versus indeterminate nodules with PET-MRI compared to chest CT. A total of 328 patients were included. All patients had a PET/MRI whole-body scan for (re)staging of cancer combined with an unenhanced chest CT performed at our center between 2014 and 2020. Patients had at least a two-year follow-up. Six percent of the patients had lung metastases at initial staging. The sensitivity and specificity of PET-MRI for detecting lung metastases were 85% and 100%, respectively. The incidence of indeterminate lung nodules on chest CT was 30%. The sensitivity of PET-MRI to detect indeterminate lung nodules was poor (23.0%). The average size of the indeterminate lung nodules detected on PET-MRI was 7 ± 4 mm, and the missed indeterminate nodules on PET-MRI were 4 ± 1 mm (p < 0.001). The detection of metastatic lung nodules is fairly good with PET-MRI, whereas the sensitivity of PET-MRI for detecting indeterminate lung nodules is size-dependent. This may be an advantage, limiting unnecessary follow-up of small, indeterminate lung nodules while adequately detecting metastases.

Understanding Aß Peptide Binding to Lipid Membranes: A Biophysical Perspective.

Aß peptides are known to bind neural plasma membranes in a process leading to the deposit of Aß-enriched plaques. These extracellular structures are characteristic of Alzheimer's disease, the major cause of late-age dementia. The mechanisms of Aß plaque formation and deposition are far from being understood. A vast number of studies in the literature describe the efforts to analyze those mechanisms using a variety of tools. The present review focuses on biophysical studies mostly carried out with model membranes or with computational tools. This review starts by describing basic physical aspects of lipid phases and commonly used model membranes (monolayers and bilayers). This is followed by a discussion of the biophysical techniques applied to these systems, mainly but not exclusively Langmuir monolayers, isothermal calorimetry, density-gradient ultracentrifugation, and molecular dynamics. The Methodological Section is followed by the core of the review, which includes a summary of important results obtained with each technique. The last section is devoted to an overall reflection and an effort to understand Aß-bilayer binding. Concepts such as Aß peptide membrane binding, adsorption, and insertion are defined and differentiated. The roles of membrane lipid order, nanodomain formation, and electrostatic forces in Aß-membrane interaction are separately identified and discussed.

In Vivo Polymer Mechanochemistry with Polynucleotides.

Polymer mechanochemistry utilizes mechanical force to activate latent functionalities in macromolecules and widely relies on ultrasonication techniques. Fundamental constraints of frequency and power intensity have prohibited the application of the polymer mechanochemistry principles in a biomedical context up to now, although medical ultrasound is a clinically established modality. Here, a universal polynucleotide framework is presented that allows the binding and release of therapeutic oligonucleotides, both DNA- and RNA-based, as cargo by biocompatible medical imaging ultrasound. It is shown that the high molar mass, colloidal assembly, and a distinct mechanochemical mechanism enable the force-induced release of cargo and subsequent activation of biological function in vitro and in vivo. Thereby, this work introduces a platform for the exploration of biological questions and therapeutics development steered by mechanical force.

Grading of glioma tumors using digital holographic microscopy.

Gliomas are the most common type of cerebral tumors; they occur with increasing incidence in the last decade and have a high rate of mortality. For efficient treatment, fast accurate diagnostic and grading of tumors are imperative. Presently, the grading of tumors is established by histopathological evaluation, which is a time-consuming procedure and relies on the pathologists' experience. Here we propose a supervised machine learning procedure for tumor grading which uses quantitative phase images of unstained tissue samples acquired by digital holographic microscopy. The algorithm is using an extensive set of statistical and texture parameters computed from these images. The procedure has been able to classify six classes of images (normal tissue and five glioma subtypes) and to distinguish between gliomas types from grades II to IV (with the highest sensitivity and specificity for grade II astrocytoma and grade III oligodendroglioma and very good scores in recognizing grade III anaplastic astrocytoma and grade IV glioblastoma). The procedure bolsters clinical diagnostic accuracy, offering a swift and reliable means of tumor characterization and grading, ultimately the enhancing treatment decision-making process.