Monitoring Treatment Response Research Articles

Nano-Bio Interfaces: Pioneering Targeted Approaches for Disease Treatment and Prevention

Nanotechnology has emerged as a pivotal force in biomedical research, offering groundbreaking solutions for disease treatment and prevention through the integration of nanoscience with biology. This review explores the multifaceted applications of nano-bio interfaces in revolutionizing therapeutic interventions and public health strategies. At the forefront of innovation, nanomaterial-based drug delivery systems demonstrate unparalleled precision and efficacy in targeted drug delivery, minimizing systemic toxicity and maximizing therapeutic outcomes. Furthermore, the development of multifunctional nanoparticles capable of simultaneous drug delivery and diagnostic imaging enables real-time monitoring of treatment responses, heralding a new era of personalized medicine. Nano-bio interfaces also play a crucial role in advancing vaccine development and immunotherapies, with nanoparticle-based vaccine platforms offering enhanced antigen delivery and immune stimulation for robust and durable immune responses against infectious diseases and cancer. In the realm of disease prevention, antimicrobial nanomaterials provide effective strategies for infection control, while nanovaccines and prophylactic drug delivery systems offer tailored solutions for mitigating the spread of infectious agents. Through a comprehensive exploration of these pioneering approaches, this review, we believe, highlights the transformative potential of nano-bio interfaces in reshaping the landscape of disease treatment and prevention.

Gamma gap as a prognostic marker of treatment response in patients with multiple myeloma.

Multiple myeloma (MM) is defined by the excessive growth of cancerous plasma cells in the bone marrow, resulting in the production of an abnormal monoclonal paraprotein and signs of damage to vital organs. The diagnosis of multiple myeloma can be complex. This paper centers on the diagnosis of MM and examines the role of the gamma gap (GG) in prompting tests to assess treatment effectiveness. Sixty individuals newly diagnosed with MM were selected from medical facilities in Iraq, specifically Baghdad Hospital/Medical City and Hematological Center, between November 2022 and March 2023. Additionally, 30 healthy participants were included as a comparison group. The assessment of suspected MM patients involves confirming the presence of a monoclonal paraprotein using serum electrophoresis (SEPG) and immunofixation (SIF), as well as analyzing free light chains (FLC). Spectrophotometric methods were used to measure total serum protein and albumin levels and calculate the globulin-to-albumin ratio by subtracting serum albumin from total serum protein. In most MM cases the monoclonal immunoglobulin (as M-spike) was identified and quantified by SPEP. Based on the findings from IFE detection, the prevalence of M-spike, particularly type IgG, was observed in 45 cases (83.3%), of which 40% were type κ, 24.6% were type λ, and 19.3% were of an unknown type. Additionally, type IgA was the second most prevalent (10 cases, 16.7%), with 14.3% being type κ and 1.7% being type λ. Moreover, the results indicated a significant association between GG and M-spike, as well as a strong correlation between GG and pre- and post-treatment M-spike levels. The area under the curve was deemed acceptable (AUC = 0.735, p = 0.0001), demonstrating high diagnostic accuracy (86.2) in distinguishing MM patients before and after treatment. The evaluation of GG in the serum of MM patients demonstrated elevated levels, which were significantly associated with patients post-treatment. Therefore, our findings have significant implications for the use of GG as a prognostic indicator for monitoring treatment response in MM patients.

Histopathological insights into ovarian tumors: A case series perspective

: Ovarian cancer stands as the third most prevalent cancer among women in India and contributes to 6% of cancer-related facilities emphasizing its significant impact on mortality. Usually, it manifests with nonspecific symptoms in correlation with age, leading to a frequent oversight in early diagnosis causing more advanced stages when intervention becomes challenging.Case records of six patientsshed light on the diverse spectrum of ovarian neoplasms encountered in clinical practice, highlighting the complexity and heterogeneity within this disease entity of different age groups. In our case series, we found that the overall burden of ovarian cancer was heaviest in the age group 20–45, while the increase was the largest in the age group 50 years and above. Given their asymptomatic nature, late onset of symptoms, and lack of effective screening facilities, ovarian cancers are known as the “silent killer”. Hence, histopathological examination plays a prime role in diagnosis and for primary optimum treatment management. Tumor markers such as AFP, LDH, and beta hCG serve as supplementary tools in the initial diagnostic process, monitoring treatment response, and post-treatment surveillance. Proactive measures targeting diverse risk factors are essential for effective prevention and treatment strategies. This case series underscores the critical importance of timely diagnosis of ovarian tumors, particularly in young females. Heightened vigilance is warranted given the potential for diverse presentations, therefore precise categorization into specific histological types is crucial for clinicians to devise timely management strategies for affected patients.

Applications of Artificial Intelligence for Pediatric Cancer Imaging.

Artificial intelligence (AI) is transforming the medical imaging of adult patients. However, its utilization in pediatric oncology imaging remains constrained, in part due to the inherent scarcity of data associated with childhood cancers. Pediatric cancers are rare, and imaging technologies are evolving rapidly, leading to insufficient data of a particular type to effectively train these algorithms. The small market size of pediatric patients compared with adult patients could also contribute to this challenge, as market size is a driver of commercialization. This review provides an overview of the current state of AI applications for pediatric cancer imaging, including applications for medical image acquisition, processing, reconstruction, segmentation, diagnosis, staging, and treatment response monitoring. Although current developments are promising, impediments due to the diverse anatomies of growing children and nonstandardized imaging protocols have led to limited clinical translation thus far. Opportunities include leveraging reconstruction algorithms to achieve accelerated low-dose imaging and automating the generation of metric-based staging and treatment monitoring scores. Transfer learning of adult-based AI models to pediatric cancers, multiinstitutional data sharing, and ethical data privacy practices for pediatric patients with rare cancers will be keys to unlocking the full potential of AI for clinical translation and improving outcomes for these young patients.

Oral enzyme-responsive nanoprobes for targeted theranostics of inflammatory bowel disease

BackgroundInflammatory bowel disease (IBD) is a progressive and debilitating inflammatory disease of the gastrointestinal tract (GIT). Despite recent advances, precise treatment and noninvasive monitoring remain challenging.MethodsHerein, we developed orally-administered, colitis-targeting and hyaluronic acid (HA)-modified, core-shell curcumin (Cur)- and cerium oxide (CeO2)-loaded nanoprobes (Cur@PC-HA/CeO2 NPs) for computed tomography (CT) imaging-guided treatment and monitoring of IBD in living mice.ResultsFollowing oral administration, high-molecular-weight HA maintains integrity with little absorption in the upper GIT, and then actively accumulates at local colitis sites owing to its colitis-targeting ability, leading to specific CT enhancement lasting for 24 h. The retained NPs are further degraded by hyaluronidase in the colon to release Cur and CeO2, thereby exerting anti-inflammatory and antioxidant effects. Combined with the ability of NPs to regulate intestinal flora, the oral NPs result in substantial relief in symptoms. Following multiple treatments, the gradually decreasing range of the colon with high CT attenuation correlates with the change in the clinical biomarkers, indicating the feasibility of treatment response and remission.ConclusionThis study provides a proof-of-concept for the design of a novel theranostic integration strategy for concomitant IBD treatment and the real-time monitoring of treatment responses.

Imaging Enigma in Mastitis: A Comprehensive study of Multifaceted Causes, Clinical and Radiological Presentations

Mastitis is an inflammatory condition of the breast which represents an array of underlying etiologies encompassing both infectious and non-infectious causes. Exacerbating factors include endemic infections, lack of awareness and suboptimal breastfeeding practices. Neglected cases lead to prolonged morbidity, recurrent episodes, and complications such as abscess or sinus formation, resulting in permanent breast disfigurement. Its overlapping clinical presentation with breast cancer necessitates an integrated multidisciplinary approach for diagnosis and treatment. The primary aim was to investigate demographic, radiological, and histopathological characteristics of mastitis. Objectives included correlating radiological and histopathological findings, classifying mastitis by etiology, identifying the clinical and imaging patterns across diverse clinical settings to enhance the understanding of mastitis. This is a retrospective observational study, analysing the clinical, radiological, and histopathological data from 65 patients with mastitis between February 2023 and February 2024. The study included 65 patients, aged 18 to 65 years, with breast pain as the most prevalent clinical presentation. Cases were classified as infectious (47.6%) and non-infectious (52%). Acute puerperal mastitis (26.15%) and granulomatous mastitis (30%) were the most common subtypes. The commonest mammographic finding was focal asymmetry. On ultrasound, infectious mastitis showed oedema with other inflammatory changes, including diffuse skin thickening and collections; while non-infectious mastitis typically presented as solitary or multiple breast masses (p < 0.001). Surprisingly, idiopathic granulomatous mastitis constituted the largest percentage amongst various histopathological causes of mastitis in our study. An integrated multidisciplinary approach with understanding of the pathogenesis is imperative for prompt diagnosis and optimizing treatment strategies, thereby improving patient outcome. Radiological imaging is critical for diagnosis, evaluating disease extent, conducting guided interventions, and monitoring treatment response.

I-Biomarker CaDx: A circulating miRNA-based multi-cancer detection test with generative and explainable AI for colorectal cancer.

64 Background: Colorectal cancer (CRC), the second most deadly cancer, underscores the critical need for early detection to significantly improve treatment outcomes and survival rates. Colonoscopy, flexible sigmoidoscopy, and the fecal immunochemical tests (FIT), often fail to capture early disease, significantly decreasing the survival chance. Circulating miRNA is a promising non-invasive biomarker for various cancers, including CRC. The i-Biomarker CaDx (patent pending) is an innovative multi-cancer early detection and diagnosis platform, covering 32 cancer types with an impressive accuracy rate of 99-100%. This study focuses on the effectiveness of i-Biomarker CaDx for CRC, employing significant data collection and leveraging insights from Generative AI (GenAI) and Explainable Artificial Intelligence (XAI). Methods: We collected various available datasets (e.g. GSE106817, etc.) encompassing 305 colorectal cancer patients and a matching number of healthy controls. Microarray was employed to profile circulating miRNAs. We used various classification paradigms, e.g., decision trees, neural networks, etc. Hyperparameter optimization was conducted, and the best-performing classifiers were amalgamated in the final model, weighted by their respective efficacies. We assessed i-Biomarker CaDx's performance through cross-validation and independent test sets. The XAI provided detailed insights into miRNA variations associated with personalized diagnostic. GenAI integrated the test into the screening and early detection best practice workflows and performs Functional Analysis. Results: i-Biomarker CaDx shows exceptional diagnostic accuracy of 99-100%, surpassing conventional colorectal cancer diagnostic methods like colonoscopy, flexible sigmoidoscopy, and FIT. It can also be used for personalized treatment response monitoring. I-Biomarker effectively deciphers intricate miRNA relationships relevant to colorectal cancer using XAI. Thus, our analyses shed light on miRNA patterns and their associations with colorectal cancer, enhancing the understanding of the underlying molecular complexities of the disease. It goes further by explaining the personalized cellular and molecular mechanisms involved, and it will be integrated into the corresponding medical workflows. Conclusions: Our AI-powered multi-cancer early diagnostic platform demonstrates outstanding performance in detecting CRC, surpassing traditional diagnostic methods like colonoscopy, flexible sigmoidoscopy, and FIT. XAI allows for in-depth exploration of miRNA alterations and their impact on CRC, enriching our interpretations at both the population and individual levels. These findings underscore the substantial potential of i-Biomarker CaDx as a transformative, non-invasive diagnostic tool for CRC.

Recent Technologies towards Diagnostic and Therapeutic Applications of Circulating Nucleic Acids in Colorectal Cancers.

Liquid biopsy has emerged as a promising noninvasive approach for colorectal cancer (CRC) management. This review focuses on technologies detecting circulating nucleic acids, specifically circulating tumor DNA (ctDNA) and circulating RNA (cfRNA), as CRC biomarkers. Recent advancements in molecular technologies have enabled sensitive and specific detection of tumor-derived genetic material in bodily fluids. These include quantitative real-time PCR, digital PCR, next-generation sequencing (NGS), and emerging nanotechnology-based methods. For ctDNA analysis, techniques such as BEAMing and droplet digital PCR offer high sensitivity in detecting rare mutant alleles, while NGS approaches provide comprehensive genomic profiling. cfRNA detection primarily utilizes qRT-PCR arrays, microarray platforms, and RNA sequencing for profiling circulating microRNAs and discovering novel RNA biomarkers. These technologies show potential in early CRC detection, treatment response monitoring, minimal residual disease assessment, and tumor evolution tracking. However, challenges remain in standardizing procedures, optimizing detection limits, and establishing clinical utility across disease stages. This review summarizes current circulating nucleic acid detection technologies, their CRC applications, and discusses future directions for clinical implementation.

Evaluation of e-Lung automated quantitative CT biomarkers in idiopathic pulmonary fibrosis

BackgroundIn patients with idiopathic pulmonary fibrosis (IPF), there is a need to identify biomarkers that i) are associated with increased risk of adverse outcome and ii) can be used to monitor treatment response or identify disease progression over time.MethodsTwo consecutive cohorts of patients with IPF were accessed from the Open Source Imaging Consortium database. Automated CT biomarkers of disease severity incorporating fibrotic and pulmonary vascular features (the reticulovascular score and weighted reticulovascular score (WRVS)), were studied. Relationships between imaging biomarkers, lung function and survival were analysed.ResultsIn separate test and validation cohorts, 168 and 176 patients with IPF respectively (median survival 2.6 years) were studied. A threshold of WRVS ≥15% at baseline CT was most strongly associated with transplant free survival (HR 3.00, 95% CI 1.47, 6.10, p=0.002) when adjusted for baseline FVC and age. In patients with 12 month follow up CT and lung function tests (n=89) an increase in 3% of WRVS (the minimal clinically important difference) was also significantly associated with reduced survival independent of FVC, and outperformed visual evaluation of progressive fibrosis.ConclusionsWRVS is an automated CT biomarker which can identify patients with IPF at increased risk of progression and is able to reliably capture disease progression over time.

Role and potential of 18F-fluorodeoxyglucose-positron emission tomography-computed tomography in large-vessel vasculitis: a comprehensive review.

Large-vessel vasculitis (LVV) is a group of diseases characterized by inflammation of the aorta and its main branches, which includes giant cell arteritis (GCA), polymyalgia rheumatica (PMR), and Takayasu's arteritis (TAK). These conditions pose significant diagnostic and management challenges due to their diverse clinical presentations and potential for serious complications. 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET-CT) has emerged as a valuable imaging modality for the diagnosis and monitoring of LVV, offering insights into disease activity, extent, and response to treatment. 18F-FDG-PET-CT plays a crucial role in the diagnosis and management of LVV by allowing to visualize vessel involvement, assess disease activity, and guide treatment decisions. Studies have demonstrated the utility of 18F-FDG-PET-CT in distinguishing between LVV subtypes, evaluating disease distribution, and detecting extracranial involvement in patients with cranial GCA or PMR phenotypes. Additionally, 18F-FDG-PET-CT has shown promising utility in predicting clinical outcomes and assessing treatment response, based on the correlation between reductions in FDG uptake and improved disease control. Future research should focus on further refining PET-CT techniques, exploring their utility in monitoring treatment response, and investigating novel imaging modalities such as PET-MRI for enhanced diagnostic accuracy in LVV. Overall, 18F-FDG-PET-CT represents a valuable tool in the multidisciplinary management of LVV, facilitating timely diagnosis and personalized treatment strategies to improve patient outcomes.

Study protocol: perinatal mood treatment study

Perinatal depression (PND) affects up to 20% of women and is associated with significant impairment and disability in affected women. In addition, perinatal depression is associated with broader public health and multigenerational consequences. Innovative approaches are needed to reduce the burden of perinatal depression through identification, tracking, and treatment of depressive symptoms during the perinatal period. This study is a randomized clinical trial comparing the relative efficacy of a multi-tiered system of care, Screening and Treatment of Anxiety and Depression (STAND) to perinatal care delivered by a reproductive psychiatrist in reducing symptoms of depression and anxiety. A sample of 167 individuals was randomized between week 28 of pregnancy and 6 months postpartum. A secondary aim compares the original online therapy intervention used in the first half of the study to a newer online therapy program used in the second half of the study for individuals assigned to the STAND treatment. The study measures, intervention groups, and analysis methods are described, as well as expected implications. The findings from this study may improve the methods for tracking symptom changes over time, monitoring treatment response, and providing personalized care for individuals with PND. As such, this study may improve the lives of patients with PND and their families and lower the related health care costs to society.Trial registration NCT: 9/24/2021NCT direct link: https://www.clinicaltrials.gov/study/NCT05056454?term=NCT05056454&rank=1&a=1.

18F-FDG PET/CT imaging and curative effect evaluation of multiple muscular tuberculosis.

Tuberculosis continues to be a significant global health concern, impacting various parts of the body aside from the lungs. Muscular tuberculosis (MT), while rare, poses diagnostic hurdles due to its nonspecific imaging features. Presenting a case of a 66-year-old man with multiple MT lesions, we underscore the vital contribution of positron emission tomography/computed tomography (PET/CT) in both diagnosis and treatment assessment. Fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT imaging revealed hypermetabolism in bilateral chest and back muscles, facilitating accurate diagnosis and monitoring treatment response. This highlights the pivotal role of 18F-FDG PET/CT in managing MT, especially in cases with multiple lesions.

Imaging timing after surgery for glioblastoma: an evaluation of practice in Great Britain and Ireland (INTERVAL-GB)- a multi-centre, cohort study

PurposePost-operative MRI is used to assess extent of resection, monitor treatment response and detect progression in high-grade glioma. However, compliance with accepted guidelines for follow-up MRI, and impact on management/outcomes is unclear.MethodsMulti-center, retrospective observational cohort study of patients with confirmed WHO grade 4 glioma (August 2018-February 2019) receiving oncological treatment. Primary objective: investigate follow-up MRI surveillance practice and compliance with recommendations from NICE (Post-operative scan < 72h, MRI every 3–6 months) and EANO (Post-operative scan < 48h, MRI every 3 months).ResultsThere were 754 patients from 26 neuro-oncology centers with a median age of 63 years (IQR 54–70), yielding 10,100 (median, 12.5/person, IQR 5.2–19.4) person-months of follow-up. Of patients receiving debulking surgery, most patients had post-operative MRI within 72 h of surgery (78.0%, N = 407/522), and within 48 h of surgery (64.2%, N = 335/522). The median number of subsequent follow-up MRI scans was 1 (IQR 0–4). Compliance with NICE and EANO recommendations for follow-up MRI was 52.8% (N = 398/754) and 24.9% (N = 188/754), respectively. On multivariable Cox regression analysis, increased time spent in recommended follow-up according to NICE guidelines was associated with longer OS (HR 0.56, 95% CI 0.46–0.66, P < 0.001), but not PFS (HR 0.93, 95% CI 0.79–1.10, P = 0.349). Increased time spent in recommended follow-up according to EANO guidelines was associated with longer OS (HR 0.54, 95% CI 0.45–0.63, P < 0.001) but not PFS (HR 0.99, 95% CI 0.84–1.16, P = 0.874).ConclusionRegular surveillance follow-up for glioblastoma is associated with longer OS. Prospective trials are needed to determine whether regular or symptom-directed MRI influences outcomes.Graphical

Monkeypox-related ophthalmic disease (MPXROD): Monitoring the antiviral effect of tecovirimat with monkeypox virus detection in tear samples.

Although monkeypox-related ophthalmic disease (MPXROD) is rare, visual impairing complications have been reported. At present, tecovirimat is the standard-of-care antiviral treatment. In this MPXROD case, the effect of tecovirimat was assessed with PCR analysis of tear samples and concurrent monitoring of inflammation with laser flare photometry (LFP). The patient presented with a palpebral lesion and a corneal ulcer in his right eye, with complete absence of the corneal epithelium, high intraocular pressure and anterior uveitis. MPXV-DNA was detected in tear samples with real-time PCR (RT-PCR). A total volume of 0.5 ml tear-wash was aspirated from the inferior fornix, following instillation of saline onto the ocular surface. In addition, LFP was used to quantify inflammation in both eyes. Viral load in tear samples was detected prior to treatment initiation. In the left eye, tear samples tested negative for MPXV-DNA one week post-treatment while MPXV-DNA was still detected in the right eye, before reaching undetectable levels four weeks post-treatment. Objective quantification of anterior chamber inflammation through LFP demonstrated gradual decrease that was more pronounced in the affected right eye and coincided with the clinical improvement of the corneal ulcer. This case of Mpox related corneal ulcer with associated uveitis manifests the feasibility of monitoring the antiviral effect of tecovirimat with virus detection in tear samples and LFP. Our observations indicate that tecovirimat resulted in viral load reduction in both eyes. RT-PCR MPXV detection in tear samples and LFP represent noninvasive tools that could assist with treatment response monitoring.

Association of VEGFA polymorphisms with the risk of oesophageal cancer in Punjab, India: A case-control study.

Background & objectives Vascular endothelial growth factor (VEGF) is one of the most important angiogenic factors which stimulates tumour progression induction of endothelial cell migration and division, inhibition of the apoptosis of endothelial cells, induction of serine protease activity and enhancement of vascular permeability. This study aimed to investigate the correlation of VEGF+405G/C,-7C/T and+936C/T polymorphisms with oesophageal cancer risk. Methods DNA samples of 464 subjects (231 sporadic oesophageal cancer affected individuals and 233 controls) were genotyped forVEGF+936C/T,+405G/C and-7C/T polymorphisms. VEGF+936C/T and +405G/C polymorphisms were genotyped by PCR-RFLP method whereas VEGF-7C/T polymorphism was genotyped using Amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results CT genotype of VEGF-7C/T polymorphism was significantly associated with reduced risk of oesophageal cancer. VEGF-7C/T polymorphism was significantly associated with reduced risk of oesophageal cancer underdominant, co-dominant, over dominant and log-additive genetic models in total patients and in the female group. C+936G+405T-7 haplotype was significantly associated with decreased risk (P=0.01)of oesophageal cancer in total patients and also in the male group (P=0.02). Interpretation & conclusions In future, replication of the findings of the present study in a larger sample from different ethnic groups, along with functional analysis, may be insightful for the role of VEGFA polymorphisms in the pathogenesis of oesophageal cancer. Identification of the correlation of VEGF variants with specific therapy in oesophageal cancer may help in better selection of patients and monitoring treatment response in VEGF-therapy.

Fe-Gallic acid metal organic framework-encapsulated cellulose polymer thin film for fluorescent immunoassay of prostate-specific antigen

A novel, highly sensitive, and cost-effective biosensor for prostate-specific antigen (PSA) detection has been developed using bioengineered nanotechnology. This biosensor integrates a Fe(III)-Gallic acid metal organic framework (Fe-GA MOF) embedded in a carboxymethyl cellulose polymer thin film, coupled with a PSA monoclonal antibody for capture. The resulting sensor demonstrates exceptional performance in detecting PSA levels within a wide concentration range (0.1–170 ng/mL), with a remarkable limit of detection of 0.06 ng/mL. This advanced technology surpasses conventional methods by providing enhanced sensitivity, stability, and reduced interference. The biosensor holds immense potential for early prostate cancer diagnosis, monitoring treatment response, and detecting recurrence. Moreover, its applicability may extend to other cancers characterized by elevated PSA levels, ultimately improving patient outcomes through timely intervention and optimized care.

Rapid response to selpercatinib in RET fusion positive pancreatic neuroendocrine carcinoma confirmed by smartwatch

This case report describes the efficacy of selpercatinib, a selective RET inhibitor, in an unusual case of large-cell neuroendocrine pancreatic carcinoma (LCNEPAC) harboring a CCDC6::RET fusion. A 56-year-old male with a history of multiple lines of systemic therapies exhibited marked clinical amelioration shortly after initiating selpercatinib within the LOXO-RET-17001 study (ClinicalTrials.gov ID: NCT03157128, first posted: 2017-05-17). Data from the patient’s smartwatch suggested early efficacy before conventional methods, such as serum tumor markers and CT imaging confirmed the antitumor activity. This case not only underscores the efficacy of selpercatinib in treating RET fusion-positive rare tumors but also highlights the potential of wearable technology in cancer care. In conclusion, the standard readings from commercially available wearable devices can be useful for the monitoring of treatment response to targeted therapy and may serve as digital biomarkers in clinical trials. This approach marks a significant advancement in patient-centric healthcare, leveraging technology to enhance the effectiveness and precision of treatment evaluation.

Employing Siamese Networks as Quantitative Biomarker for Assessing the Effect of Dolphin-Assisted Therapy on Pediatric Cerebral Palsy.

This study explores the potential of using a Siamese Network as a biomarker for assessing the effectiveness of Dolphin-Assisted Therapy (DAT) in children with Spastic Cerebral Palsy (SCP). The problem statement revolves around the need for objective measures to evaluate the impact of DAT on patients with SCP, considering the subjective nature of traditional assessment methods. The methodology involves training a Siamese network, a type of neural network designed to compare similarities between inputs, using data collected from SCP patients undergoing DAT sessions. The study employed Event-Related Potential (ERP) and Fast Fourier Transform (FFT) analyses to examine cerebral activity and brain rhythms, proposing the use of SNN to compare electroencephalographic (EEG) signals of children with cerebral palsy before and after Dolphin-Assisted Therapy. Testing on samples from four children yielded a high average similarity index of 0.9150, indicating consistent similarity metrics before and after therapy. The network is trained to learn patterns and similarities between pre- and post-therapy evaluations, in order to identify biomarkers indicative of therapy effectiveness. Notably, the Siamese Network's architecture ensures that comparisons are made within the same feature space, allowing for more accurate assessments. The results of the study demonstrate promising findings, indicating different patterns in the output of the Siamese Network that correlate with improvements in symptoms of SCP post-DAT. Confirming these observations will require large, longitudinal studies but such findings would suggest that the Siamese Network could have utility as a biomarker in monitoring treatment responses for children with SCP who undergo DAT and offer them more objective as well as quantifiable manners of assessing therapeutic interventions. Great discrepancies in neuronal voltage perturbations, 7.9825 dB on average at the specific samples compared to the whole dataset (6.2838 dB), imply a noted deviation from resting activity. These findings indicate that Dolphin-Assisted Therapy activates particular brain regions specifically during the intervention.

Imaging and Monitoring HER2 Expression in Tumors during HER2 Antibody-Drug Conjugate Therapy Utilizing a Radiolabeled Site-Specific Single-Domain Antibody Probe: 68Ga-NODAGA-SNA004-GSC.

The overexpression of HER2 is pivotal in the initiation and progression of breast cancer. Developing HER2-targeted radiotracers is crucial for noninvasive assessment of HER2 expression, patient selection for HER2-targeted therapy, monitoring treatment response, and identifying resistance. Here, we reported a nonsite-specific coupled radiotracer, 68Ga-NOTA-SNA004-His6, and a site-specific coupled radiotracer, 68Ga-NODAGA-SNA004-GSC, based on a novel HER2 nanobody, SNA004. Both radiotracers exhibited high affinity, specific targeting, and rapid clearance in vitro and in vivo. Additionally, these tracers and trastuzumab showed noncompetitive binding to HER2. Compared to 68Ga-NOTA-SNA004-His6, 68Ga-NODAGA-SNA004-GSC demonstrated significantly reduced renal and liver uptake. PET/CT imaging with 68Ga-NODAGA-SNA004-GSC sensitively detected the responsiveness of various tumor models to trastuzumab and its antibody-drug conjugates (ADCs). Overall, the site-specific coupled radiotracer 68Ga-NODAGA-SNA004-GSC offered significant advantages in biodistribution and signal-to-noise ratio, making it a valuable tool for monitoring HER2 expression levels before, during, and after trastuzumab and ADC treatment.

In vivo Metabolic Sensing of Hyperpolarized [1‐13C]Pyruvate in Mice Using a Recyclable Perfluorinated Iridium Signal Amplification by Reversible Exchange Catalyst

AbstractReal‐time visualization of metabolic processes in vivo provides crucial insights into conditions like cancer and metabolic disorders. Metabolic magnetic resonance imaging (MRI), by amplifying the signal of pyruvate molecules through hyperpolarization, enables non‐invasive monitoring of metabolic fluxes, aiding in understanding disease progression and treatment response. Signal Amplification By Reversible Exchange (SABRE) presents a simpler, cost‐effective alternative to dissolution dynamic nuclear polarization, eliminating the need for expensive equipment and complex procedures. We present the first in vivo demonstration of metabolic sensing in a human pancreatic cancer xenograft model compared to healthy mice. A novel perfluorinated Iridium SABRE catalyst in a fluorinated solvent and methanol blend facilitated this breakthrough with a 1.2‐fold increase in [1‐13C]pyruvate SABRE hyperpolarization. The perfluorinated moiety allowed easy separation of the heavy‐metal‐containing catalyst from the hyperpolarized [1‐13C]pyruvate target. The perfluorinated catalyst exhibited recyclability, maintaining SABRE‐SHEATH activity through subsequent hyperpolarization cycles with minimal activity loss after the initial two cycles. Remarkably, the catalyst retained activity for at least 10 cycles, with a 3.3‐fold decrease in hyperpolarization potency. This proof‐of‐concept study encourages wider adoption of SABRE hyperpolarized [1‐13C]pyruvate MR for studying in vivo metabolism, aiding in diagnosing stages and monitoring treatment responses in cancer and other diseases.