Assessment Of Therapeutic Response Research Articles

Single‐Walled Carbon Nanotube‐Based Optical Nano/Biosensors for Biomedical Applications: Role in Bioimaging, Disease Diagnosis, and Biomarkers Detection

AbstractThe convergence of advanced nanotechnology with disease diagnosis has ushered in a transformative era in healthcare, empowering early and accurate detection of diseases and paving the way for timely interventions, improved treatment outcomes, and enhanced patient well‐being. The development of novel materials is frequently the impetus behind significant advancements in sensor technology. Among them, single‐walled carbon nanotubes (SWCNTSs) have emerged as promising nanomaterials for developing biosensors. Their unique optical, electrical, and biocompatibility properties make them promising candidates for enhancing the sensitivity and real‐time monitoring capabilities of biosensors, as well as for enabling various bioimaging techniques. Recent studies have demonstrated the utility of SWCNTS‐based biosensors in the real‐time monitoring of biological analytes, such as nitric oxide and hydrogen peroxide (H2O2), with potential implications for disease understanding and therapeutic response assessment. Moreover, SWCNTSs have shown promise in bioimaging applications, including fluorescence, Raman spectroscopy, and photoluminescence imaging of biological samples. This article delves into the core principles, design strategies, and operational mechanisms that underpin SWCNTS‐bioimaging techniques‐based biosensors. It emphasizes on their unique properties and versatile functionalization of carbon nanotubes, laying the foundation for their integration into biosensor platforms and applications aimed at diagnosing a wide spectrum of diseases including infectious diseases, cancer, neurological disorders, and metabolic conditions.

A new Neu-a syngeneic model of spontaneously metastatic HER2-positive breast cancer.

Metastatic disease results from the dissemination of tumor cells beyond their organ of origin to grow in distant organs and is the primary cause of death in patients with advanced breast cancer. Preclinical murine models in which primary tumors spontaneously metastasize are valuable tools for studying metastatic progression and novel cancer treatment combinations. Here, we characterize a novel syngeneic murine breast tumor cell line that provides a model of spontaneously metastatic neu-expressing breast cancer with quicker onset of widespread metastases after orthotopic mammary implantation in immune-competent NeuN mice. The NT2.5-lung metastasis (-LM) cell line was derived from serial passaging of tumor cells that were macro-dissected from spontaneous lung metastases after orthotopic mammary implantation of parental NT2.5 cells. Within one week of NT2.5-LM implantation, metastases are observed in the lungs. Within four weeks, metastases are also observed in the bones, spleen, colon, and liver. We demonstrate that NT2.5-LM metastases are positive for NeuN-the murine equivalent of human epidermal growth factor 2 (HER2). We further demonstrate altered expression of markers of epithelial-to-mesenchymal transition (EMT), suggestive of their enhanced metastatic potential. Genomic analyses support these findings and reveal enrichment in EMT-regulating pathways. In addition, the metastases are rapidly growing, proliferative, and responsive to HER2-directed therapy. The new NT2.5-LM model provides certain advantages over the parental NT2/NT2.5 model, given its more rapid and spontaneous development of metastases. Besides investigating mechanisms of metastatic progression, this new model may be used for the rationalized development of novel therapeutic interventions and assessment of therapeutic responses.

ASSESSMENT OF THE THERAPEUTIC EFFICACY OF PROPRANOLOL FOR THE TREATMENT OF INFANTILE HEMANGIOMAS

Infantile hemangiomas (IHs) are common vascular tumors affecting pediatric populations, often necessitating medical intervention due to their potential for complications. Propranolol has emerged as a promising therapeutic option for IHs, although optimal dosing regimens and treatment outcomes remain areas of ongoing research. This prospective observational study aimed to evaluate the therapeutic efficacy, safety profile, and clinical characteristics associated with propranolol treatment in pediatric patients with IHs. Eighty infants aged one month to 1 year were included in the study, with IH occurrence and treatment initiation predominantly observed within the first 12 months of life. Propranolol was administered orally at a starting dose of 2 mg/kg/day, titrated up to 3-4 mg/kg/day as tolerated. Assessment of therapeutic response revealed significant reductions in IH size and vascularity, with 31.3% of patients demonstrating an excellent response and 37.5% showing a good response. Adverse effects were minimal, with diarrhea (22.5%) and decreased heart rate (7.5%) being the most commonly reported side effects. Anatomical distribution analysis identified the parotid region as the most common site of lesion occurrence, highlighting the heterogeneous nature of IHs. Overall, our findings support the favorable outcomes of propranolol therapy in pediatric patients with IHs, emphasizing the need for individualized treatment approaches tailored to patient-specific characteristics.

Molecular Engineering of Activatable NIR-II Hemicyanine Reporters for Early Diagnosis and Prognostic Assessment of Inflammatory Bowel Disease.

Molecular imaging in the second near-infrared window (NIR-II) provides high-fidelity visualization of biopathological events in deep tissue. However, most NIR-II probes produce "always-on" output and demonstrate poor signal specificity toward biomarkers. Herein, we report a series of hemicyanine reporters (HBCs) with tunable emission to NIR-II window (715-1188 nm) and structurally amenable to constructing activatable probes. Such manipulation of emission wavelengths relies on rational molecular engineering by integrating benz[c,d]indolium, benzo[b]xanthonium, and thiophene moieties to a conventional hemicyanine skeleton. In particular, HBC4 and HBC5 possess bright and record long emission over 1050 nm, enabling improved tissue penetration depth and superior signal to background ratio for intestinal tract mapping than NIR-I fluorophore HC1. An activatable inflammatory reporter (AIR-PE) is further constructed for pH-triggered site-specific release in colon. Due to minimized background interference, oral gavage of AIR-PE allows clear delineation of irritated intestines and assessment of therapeutic responses in a mouse model of inflammatory bowel disease (IBD) through real-time NIRF-II imaging. Benefiting from its high fecal clearance efficiency (>90%), AIR-PE can also detect IBD and evaluate the effectiveness of colitis treatments via in vitro optical fecalysis, which outperforms typical clinical assays including fecal occult blood testing and histological examination. This study thus presents NIR-II molecular scaffolds that are not only applicable to developing versatile activatable probes for early diagnosis and prognostic monitoring of deeply seated diseases but also hold promise for future clinical translations.

Development of a haematological indices-based nomogram for prognostic prediction and immunotherapy response assessment in primary pulmonary lymphoepithelioma-like carcinoma patients.

Primary pulmonary lymphoepithelioma-like carcinoma (PPLELC) is a rare yet aggressive malignancy. This study aims to investigate a deep learning model based on hematological indices, referred to as haematological indices-based signature (HIBS), and propose multivariable predictive models for accurate prognosis prediction and assessment of therapeutic response to immunotherapy in PPLELC. This retrospective study included 117 patients with PPLELC who received immunotherapy and were randomly divided into a training (n=82) and a validation (n=35) cohort. A total of 41 hematological features were extracted from routine laboratory tests and the least absolute shrinkage and selection operator (LASSO) algorithm were utilized to establish the HIBS. Additionally, we developed a nomogram using the HIBS and clinical characteristics through multivariate Cox regression analysis. To evaluate the nomogram's predictive performance, we used calibration curves and calculated the time-dependent area under the curve (AUC). Kaplan-Meier survival analysis was performed to estimate progression-free survival (PFS) in both cohorts. The proposed HIBS comprised 14 hematological features and showed that patients who experienced disease progression had significantly higher HIBS scores compared to those who did not progress (P<0.001). Five prognostic factors, including HIBS, tumor-node-metastasis (TNM) stage, presence of bone metastasis and the specific immunotherapy regimen, were found to be independent factors and were used to construct a nomogram, which effectively categorized PPLELC patients into a high-risk and a low-risk group, with patients in the high-risk patients demonstrating worse PFS (7.0 vs. 18.0 months, P<0.001) and lower overall response rates (22.2% vs. 52.7%, P<0.001). The nomogram showed satisfactory discrimination for PFS, with AUC values of 0.837 and 0.855 in the training and validation cohorts, respectively. The HIBS-based nomogram could effectively predict the PFS and response of patients with PPLELC regarding immunotherapy and serve as a valuable tool for clinical decision making.

Ovarian Cancer Diagnosis and Prognosis Based on Cell-Free DNA Methylation.

Background:Ovarian cancer stands as the deadliest malignant tumor within the female reproductive tract. As a result of the absence of effective diagnostic and monitoring markers, 75% of ovarian cancer cases are diagnosed at a late stage, leading to a mere 50% survival rate within five years. The advancement of molecular biology is essential for accurate diagnosis and treatment of ovarian cancer.Methods:A review of several randomized clinical trials, focusing on the ovarian cancer, was undertaken. The advancement of molecular biology and diagnostic methods related to accurate diagnosis and treatment of ovarian cancer were examined. Results:Liquid biopsy is an innovative method of detecting malignant tumors that has gained increasing attention over the past few years. Cell-free DNA assay-based liquid biopsies show potential in delineating tumor status heterogeneity and tracking tumor recurrence. DNA methylation influences a multitude of biological functions and diseases, especially during the initial phases of cancer. The cell-free DNA methylation profiling system has emerged as a sensitive and non-invasive technique for identifying and detecting the biological origins of cancer. It holds promise as a biomarker, enabling early screening, recurrence monitoring, and prognostic evaluation of cancer. Conclusions:This review evaluates recent advancements and challenges associated with cell-free DNA methylation analysis for the diagnosis, prognosis monitoring, and assessment of therapeutic responses in the management of ovarian cancers, aiming to offer guidance for precise diagnosis and treatment of this disease.

Inter-reader variability of imaging biomarkers for therapeutic response in pancreatic ductal adenocarcinoma.

700 Background: Indeterminate borders of pancreatic ductal adenocarcinoma (PDAC) can impair reliability of lesion annotation in imaging assessment of therapeutic response (TR) after neoadjuvant chemotherapy (NAT). Previous work showed that longitudinal image registration algorithms can track treatment-related changes and produce quantitative imaging biomarkers (QIB) for TR that predict overall (OS) and recurrence-free survival (RFS). We compare inter-reader agreements of these biomarkers against conventional RECIST and tumor volume QIB. Methods: N=30 patients enrolled in a Phase II clinical trial comparing outcomes of a NAT regimen were retrospectively analyzed. In baseline and restaging CT, whole pancreas and tumor segmentations and tumor diameters were annotated by 2 expert attending radiologists and 2 novice radiology fellows. For each reader, percent change in tumor diameter (RECIST score), percent change in tumor volume (ΔV), and difference in ratio of tumor burden to pancreas volume (ΔB) were computed as QIB for TR across the NAT interval via two approaches: image registration of the baseline tumor region of interest, and direct segmentation of the PDAC lesion in baseline and restaging images. Inter-reader agreements of RECIST, ΔV, and ΔB QIB from both approaches were compared via concordance correlation coefficient (CCC). Associations with OS and RFS were compared over 5-year follow-up via Harrell’s C-index. Results: Among expert radiologists, RECIST score CCC was 0.77 [95% CI: 0.59-0.88], whereas image registration QIB CCC values were significantly higher (ΔV: 0.95 [0.90-0.98], p=0.002; ΔB: 0.93 [0.86-0.97], p=0.014). ΔV and ΔB QIB measured by direct tumor segmentation had significantly lower CCC than by image registration (p&lt;0.001). Among novice readers, image registration QIB (ΔV: 0.83 [0.67-0.91], ΔB: 0.70 [0.48-0.84]) produced higher agreement than RECIST (0.26 [-0.17-0.61]; p=0.002 and p=0.035), with CCC more similar to expert readers. While image registration QIB did not differ from RECIST in association with RFS, registration-based QIB predicted OS with significantly higher C-index (ΔV: 0.58 [0.56-0.60], p&lt;0.001; ΔB: 0.64 [0.62-0.66], p&lt;0.001) than RECIST (0.50 [0.45-0.55]) among experts. Conclusions: Longitudinal registration of the pancreas yields more consistent QIB for PDAC TR with stronger association to OS outcomes than RECIST. These registration-based QIB aim to advance PDAC management by improving patient-specific discrimination of TR after NAT. [Table: see text]

Nuclear medicine imaging for bone metastases assessment: what else besides bone scintigraphy in the era of personalized medicine?

Accurate detection and reliable assessment of therapeutic responses in bone metastases are imperative for guiding treatment decisions, preserving quality of life, and ultimately enhancing overall survival. Nuclear imaging has historically played a pivotal role in this realm, offering a diverse range of radiotracers and imaging modalities. While the conventional bone scan using 99mTc marked bisphosphonates has remained widely utilized, its diagnostic performance is hindered by certain limitations. Positron emission tomography, particularly when coupled with computed tomography, provides improved spatial resolution and diagnostic performance with various pathology-specific radiotracers. This review aims to evaluate the performance of different nuclear imaging modalities in clinical practice for detecting and monitoring the therapeutic responses in bone metastases of diverse origins, addressing their limitations and implications for image interpretation.

Decoding polymyalgia rheumatica, the role of Nuclear Medicine Imaging

Polymyalgia rheumatica (PMR) is an inflammatory joint disease that presents in patients older than 50 years with prolonged morning pain and stiffness in the shoulder and hip joints and neck. The lack of specific clinical findings, laboratory signs, biomarkers and established imaging methods makes it difficult to diagnose patients with this disease. 18F-FDG PET/CT is a functional imaging technique that is an established tool in oncology and has also proven useful in the field of inflammatory diseases. The aim of this paper is to present literature evidence on the use of molecular imaging methods such as PET/CT for early diagnosis, assessment of disease activity and therapeutic response in PMR. At the same time, the advantages, disadvantages and contraindications of other methods are considered.

Metabolic Interplay in the Tumor Microenvironment: Implications for Immune Function and Anticancer Response.

Malignant tumors exhibit rapid growth and high metabolic rates, similar to embryonic stem cells, and depend on aerobic glycolysis, known as the "Warburg effect". This understanding has enabled the use of radiolabeled glucose analogs in tumor staging and therapeutic response assessment via PET scans. Traditional treatments like chemotherapy and radiotherapy target rapidly dividing cells, causing significant toxicity. Despite immunotherapy's impact on solid tumor treatment, gaps remain, leading to research on cancer cell evasion of immune response and immune tolerance induction via interactions with the tumor microenvironment (TME). The TME, consisting of immune cells, fibroblasts, vessels, and the extracellular matrix, regulates tumor progression and therapy responses. TME-targeted therapies aim to transform this environment from supporting tumor growth to impeding it and fostering an effective immune response. This review examines the metabolic disparities between immune cells and cancer cells, their impact on immune function and therapeutic targeting, the TME components, and the complex interplay between cancer cells and nontumoral cells. The success of TME-targeted therapies highlights their potential to achieve better cancer control or even a cure.

Desenmascarando la polimialgia reumática, papel de la Medicina Nuclear

Polymyalgia rheumatica (PMR) is an inflammatory joint disease that presents in patients older than 50 years with prolonged morning pain and stiffness in the shoulder and hip joints and neck. The lack of specific clinical findings, laboratory signs, biomarkers and established imaging methods makes it difficult to diagnose patients with this disease. 18F-FDG PET/CT is a functional imaging technique that is an established tool in oncology and has also proven useful in the field of inflammatory diseases. The aim of this paper is to present literature evidence on the use of molecular imaging methods such as PET/CT for early diagnosis, assessment of disease activity and therapeutic response in PMR. At the same time, the advantages, disadvantages and contraindications of other methods are considered.

Imaging for assessment of cancer treatment response to immune checkpoint inhibitors can be complementary in identifying hypophysitis.

Hypophysitis is reported in 8.5%-14% of patients receiving combination immune checkpoint inhibition (cICI) but can be a diagnostic challenge. This study aimed to assess the role of routine diagnostic imaging performed during therapeutic monitoring of combination anti-CTLA-4/anti-PD-1 treatment in the identification of hypophysitis and the relationship of imaging findings to clinical diagnostic criteria. This retrospective cohort study identified patients treated with cICI between January 2016 and January 2019 at a quaternary melanoma service. Medical records were reviewed to identify patients with a documented diagnosis of hypophysitis based on clinical criteria. Available structural brain imaging with magnetic resonance imaging (MRI) or computed tomography (CT) of the brain and 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography with computed tomography (FDG-PET/CT) were assessed retrospectively. The main radiological outcome measures were a relative change in pituitary size or FDG uptake temporally attributed to cICI. There were 162 patients (median age 60 years, 30% female) included. A total of 100 and 134 had serial CT/MRI of the brain and FDG-PET/CT, respectively. There were 31 patients who had a documented diagnosis of hypophysitis and an additional 20 who had isolated pituitary imaging findings. The pituitary gland enlargement was mild, and the largest absolute gland size was 13 mm, with a relative increase of 7 mm from baseline. There were no cases of optic chiasm compression. Pituitary enlargement and increased FDG uptake were universally transient. High-dose glucocorticoid treatment for concurrent irAEs prevented assessment of the pituitary-adrenal axis in 90% of patients with isolated imaging findings. Careful review of changes in pituitary characteristics on imaging performed for assessment of therapeutic response to iICI may lead to increased identification and more prompt management of cICI-induced hypophysitis.

Blood-Based Diagnostic Assay for λ Light Chain Amyloidosis through Quantification of an Amyloidogenicity-Indicating Neo-Epitope

Light chain amyloidosis (AL) is a rare, progressive, and often fatal protein misfolding disease. AL is caused by aberrant clonal plasma cell proliferation, where excess amounts of amyloidogenic monoclonal Free Light Chain (FLC) are produced, secreted into the circulation, misfolded and deposted as amyloid fibrils in various vital organs, such as the heart, kidney, liver, and nerves. The involed lambda (λ) FLC accounts for ~75% of all AL cases. Amyloidogenic FLCs (aFLCs) are believed to be the toxic species contributing to AL disease pathology. Specific quantification of aFLCs can provide critical guidance in clinical practice but has been hampered by the LCs sequence diversity as well as the lack of tests that are able to differentiate between circulating normal polyclonal FLCs and aFLCs. Contrary to non-amyloidogenic, aFLCs are kinetically and oftentimes thermodynamically unstable. aFLCs are prone to misfolding and formation of pathogenic conformations such as non-native structures, proteolytic fragments, soluble aggregates, and amyloid fibrils. We exploited such characteristics of aFLCs by applying limited proteolysis using Proteinase K, where less stable λ aFLC proteins readily yield a 23KDa fragment composed of the homodimeric LC constant domain (dLCCD) linked by a disulfide bond. Formation of the dLCCD fragment reveals a highly conserved, novel, cryptic epitope at the N-terminus of the fragment. We have generated monoclonal antibodies (mAbs) that explicitly bind to such novel epitope and developed immunoassays for the specific detection and sensitive quantification of λ aFLCs in biological samples. Western blot or Meso Scale Discovery (MSD) analyses were employed to detect and quantify dLCCD signal using the dLCCD mAbs on plasma samples from randomly selected, treatment naïve and λ-restricted cases with biopsy-proven AL amyloidosis before and after exposure to optimized proteolytic conditions. Tissue amyloid deposits of λ-type were confirmed in most AL cases. Informed consent for data and plasma sample collections were obtained from the Institutional Review Boards and in accordance with the Declaration of Helsinki. Multiple myeloma (MM) plasma samples of unknown LC restriction type, treatment or amyloid deposits status and normal volunteer control samples were purchased from BioIVT (USA). A set of representative results based on three runs are shown in Fig. 1. As little as 2 µL of biofluid was used for each assay. Upon limited proteolysis, dLCCD signal was detected in 32 of 35 AL plasmas, including two samples from patients with AL-associated IgM lymphoplasmacytic lymphoma (LPL). Of the three dLCCD negative AL samples, one presented with monoclonal IgAλ, and two cases were bi-clonal on serum immunofixation electrophoresis. dLCCD signal was not detected in 18 of 19 MM plasma samples. Similarly, dLCCD signal was undetectable in 23 normal plasmas. Overall, the dLCCD signals detected in AL plasmas were 10x-200x above that of normal control and most MM samples (Fig. 1). The low limit of quantification of the MSD assay was ~0.4 ng/dL (1.4 pM), with &amp;gt;500x dynamic range, enabling sensitive and robust quantification of λ aFLCs in biosamples. Analysis of Proteinase K recognition potential of the cleavage site of 389 λ LC sequences from the AL-Base, a database of amyloidogenic LC sequences (https://wwwapp.bumc.bu.edu/BEDAC_ALBase/) predicted that the dLCCD assay can detect λ aFLCs in up to 99% of λ AL patients, irrespective of the FLC sequences. This was confirmed with the 100% detection rate of the dLCCD signal in a validation cohort of 35 additional monoclonal λ-restricted AL samples. In summary, we have developed a quantitative blood-based immunoassay that is sensitive and highly specific for λ aFLC irrespective of the protein sequences. The preliminary data demonstrates the potential of our assay for AL diagnostics. Additional clinical applications for future exploration will include (i) monitoring and early detection of AL amyloidosis in plasma cell dyscrasias (monoclonal gammopathy of unknown significance, MM, and smoldering MM) and lymphoproliferative disorders, including LPL; and (ii) clinical management of patients with AL amyloidosis via the assessment and monitoring of minimal residual disease and therapeutic responses. The utility of the dLCCD assay in the quantification of λ aFLCs in bi-clonal AL cases warrants further investigation.

Visualizing Macrophage Phenotypes and Polarization in Diseases: From Biomarkers to Molecular Probes.

Macrophage is a kind of immune cell and performs multiple functions including pathogen phagocytosis, antigen presentation and tissue remodeling. To fulfill their functionally distinct roles, macrophages undergo polarization towards a spectrum of phenotypes, particularly the classically activated (M1) and alternatively activated(M2) subtypes. However, the binary M1/M2 phenotype fails to capture the complexity of macrophages subpopulations in vivo. Hence, it is crucial to employ spatiotemporal imaging techniques to visualize macrophage phenotypes and polarization, enabling the monitoring of disease progression and assessment of therapeutic responses to drug candidates. This review begins by discussing the origin, function and diversity of macrophage under physiological and pathological conditions. Subsequently, we summarize the identified macrophage phenotypes and their specific biomarkers. In addition, we present the imaging probes locating the lesions by visualizing macrophages with specific phenotype in vivo. Finally, we discuss the challenges and prospects associated with monitoring immune microenvironment and disease progression through imaging of macrophage phenotypes.

Diagnostic Value of Multi Detector Computed Tomography in Evaluation of Abdominopelvic Extra-nodal Lymphoma with Assessment of Therapeutic Response

Diagnostic Value of Multi Detector Computed Tomography in Evaluation of Abdominopelvic Extra-nodal Lymphoma with Assessment of Therapeutic Response

A signature based on neutrophil extracellular trap-related genes for the assessment of prognosis, immunoinfiltration, mutation and therapeutic response in hepatocellular carcinoma.

Liver cancer is a highly lethal and aggressive form of cancer that poses a significant threat to patient survival. Within this category, liver hepatocellular carcinoma (LIHC) represents the most common subtype of liver cancer. Despite decades of research and treatment, the overall survival rate for LIHC has not significantly improved. Improved models are necessary to differentiate high-risk cases and predict possible treatment options for LIHC patients. Recent studies have identified a set of genes associated with neutrophil extracellular traps (NETs) that may contribute to tumor growth and metastasis; however, their prognostic value in LIHC has yet to be established. This study aims to construct a prognostic signature based on a set of NET-related genes (NRGs) for patients diagnosed with LIHC. The transcriptomic data and clinical information concerning LIHC patients were procured from the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium LIHC (ICLIHC) databases, respectively. To determine the NRG subtypes, the k-means algorithm was employed, along with consensus clustering. The aforementioned analysis aided the construction of a prognostic signature utilizing the last absolute shrinkage and selection operator Cox analysis. To validate the prognostic model, an external dataset, receiver operating characteristic curve, and principal component analysis were utilized. Moreover, the immune microenvironment and the proportion of immune cells between high- and low-risk cases were scrutinized by ESTIMATE and CIBERSORT algorithms. Finally, gene set enrichment analysis was executed to investigate the potential mechanism of NRGs in the pathogenesis and prognosis of LIHC. Two molecular subtypes of LIHC were identified based on the expression patterns of differentially expressed NRGs (DE-NRGs). The two subtypes demonstrated significant differences in survival rates and immune cell expression levels. The study results demonstrated the role of NRGs in antigen presentation, which led to the promotion of tumor immune escape. A risk model was developed and validated with strong overall survival prediction ability. The model, comprising 34 NRGs, showed a strong ability to predict prognosis. We built a dependable prognostic signature based on NRGs for LIHC. We identified that NRGs could have a significant interaction in LIHC's immune microenvironment and therapeutic response. This finding offers insight into the molecular mechanisms and targeted therapy for LIHC.

Morphometry-based radiomics for predicting therapeutic response in patients with gliomas following radiotherapy.

Gliomas are still considered as challenging in oncologic management despite the developments in treatment approaches. The complete elimination of a glioma might not be possible even after a treatment and assessment of therapeutic response is important to determine the future course of actions for patients with such cancers. In the recent years radiomics has emerged as a promising solution with potential applications including prediction of therapeutic response. Hence, this study was focused on investigating whether morphometry-based radiomics signature could be used to predict therapeutic response in patients with gliomas following radiotherapy. 105 magnetic resonance (MR) images including segmented and non-segmented images were used to extract morphometric features and develop a morphometry-based radiomics signature. After determining the appropriate machine learning algorithm, a prediction model was developed to predict the therapeutic response eliminating the highly correlated features as well as without eliminating the highly correlated features. Then the model performance was evaluated. Tumor grade had the highest contribution to develop the morphometry-based signature. Random forest provided the highest accuracy to train the prediction model derived from the morphometry-based radiomics signature. An accuracy of 86% and area under the curve (AUC) value of 0.91 were achieved for the prediction model evaluated without eliminating the highly correlated features whereas accuracy and AUC value were 84% and 0.92 respectively for the prediction model evaluated after eliminating the highly correlated features. Nonetheless, the developed morphometry-based radiomics signature could be utilized as a noninvasive biomarker for therapeutic response in patients with gliomas following radiotherapy.

An MMP-2 Responsive Nanotheranostic Probe Enabled Synergistic Therapy of Rheumatoid Arthritis and MR/CT Assessment of Therapeutic Response In Situ.

This study reports a facile and green synthesis of a new multifunctional nanotheranostic probe for the synergistic therapy of rheumatoid arthritis (RA) and in situ assessment of therapeutic response. The probe is synthesized through a one-step self-assembly of two exquisitely designed peptide-amphiphilic block copolymers (PEG-DTIPA-KGPLGVRK-MTX and Pal-GGGGHHHHD-TCZ) under mild conditions, requiring minimal energy input. The resultant probe demonstrates excellent biocompatibility, water solubility, and colloidal stability. It exhibits a strong IL-6R targeting ability toward inflamed joints, and releases drugs in an MMP-2-responsive manner. The co-loading of methotrexate(MTX) and tocilizumab (TCZ) into the probe enables synergistic RA therapy with improved efficacy by simultaneously decreasing the activity of adenosine synthetase and interfering with the binding of IL-6 to its receptor. In addition, the resultant probe exhibits a high r1 relaxation rate (7.00 mm-1 s-1 ) and X-ray absorption capability (69.04 Hu mm-1 ), enabling sensitive MR and CT dual-modal imaging for simultaneous evaluation of synovial thickness and bone erosion. Both in vitro experiments using lipopolysaccharide-treated RAW264.7 cells and in vivo experiments using collagen-induced arthritis mice demonstrate the probe's high effectiveness in synergistically inhibiting inflammation. This study provides new insights into RA theranostics, therapeutic monitoring, the design of multifunctional theranostic probes, and beyond.

Prospective study to assess treatment response and predict patient prognosis by a blood-based multi-omics assay in lymphoma patients.

116 Background: Lymphoma represents a diverse group of cancer that arises from clonal proliferation of lymphocytes. Clinical existing imaging and biomarkers do not reliably predict treatment response across diverse lymphoma subtypes and treatment regimens. Only rare data show circulating tumor DNA (ctDNA) testing may perform as a good predictive biomarker for assessment of therapeutic response. We conducted a prospective study to assess treatment response and predict patient prognosis via our multi-omics assay (SeekInClarity) in lymphoma patients. Methods: SeekInClarity assay utilized common 7 protein tumor markers (PTMs) and cancer genomic hallmarks: copy number aberration (CNA) and fragment size (FS), which were analyzed by shallow whole genome sequencing, to calculate the molecular tumor burden (MTB) score. 8ml peripheral blood samples were collected from patients before and after every 2 cycles of treatment respectively, meanwhile, samples from a part of patients after 1 cycle of treatment were also collected. Results: Before treatment, 95 out of 133 patients (71.4%) were succeeded in detecting cancer signals with higher MTB scores (defined as baseline+). The proportion of patients with baseline+ was higher in patients with higher tumor stages. After 2 cycles of treatment, 39 out of 112 patients had a higher MTB score (defined as MRD+). The proportion of patients with progression in MRD+ group was significantly higher than that in MRD- group (p&lt;0.001). Meanwhile, MRD+ patients had a worse PFS than MRD- patients (p &lt;0.0001, HR: 26.4, 95% CI:8.7~80.3), regardless of tumor stages, lymphoma subtypes and treatment regimens. Among baseline+ patients, after 2 cycles of treatment the patients with MTB score decrease had a better PFS than that with MTB score increase (P&lt;0.001, HR: 7.5 95% CI:0.7~76.7). Among the baseline- group, patients who remained negative after treatment had extremely well PFS (100% PFS). As for the patients after 1 cycle of treatment, MTB value has a good concordance with that after 2 cycles of treatment which demonstrated a lead time in monitoring treatment response. 54 patients with longitudinal monitoring samples, 9(16.7%) patients were always MRD- during the treatment, who had the best PFS (100% PFS), regardless of baseline status. 11 out of 54 patients with always MRD+ had the worst PFS (p &lt; 0.05). Conclusions: This study demonstrates the clinical utility of multidimensional blood-based SeekInClarity assay in pan-cancer/pan-indication treatment response assessment and patient prognosis. After treatment, the dynamic change of MTB score and MRD status were independently associated with patient’s PFS, which indicated both could be used as biomarkers to predict the effectiveness of treatment. Compared with clinical image evaluation after 2 cycles of treatment, SeekInClarity test after 1 cycle of treatment is sufficient to assess treatment response.

Study Based on the Alliance Between Serum Magnesium Levels and Preterm Labor: An Inclusive Review.

Preterm labor, regarded as the onset of labor before 37 weeks of gestation, is a highly prevalent issue in obstetrics with repercussions for neonatal health. This review article presents an in-depth analysis of the alliance between serum magnesium levels and preterm labor. The review explores the physiological roles of magnesium right through pregnancy, including its significance for energy metabolism, smooth muscle contraction, deoxyribonucleic acid (DNA), and protein synthesis. It addresses cellular transport and the homeostasis of magnesium. The pathophysiological processes encompassing inflammation, oxidative stress, calcium regulation, smooth muscle contractility, and neuroendocrine pathways are investigated. The review evaluates epidemiological studies investigating the alliance between serum magnesium levels and preterm labor. The review incorporates an assortment of study varieties, such as observational studies, case-control studies, prospective cohort studies, and meta-analyses. In the course of reviewing the prognostic relevance of serum magnesium levels in premature labor, therapeutic implications involving diagnostic precision, prognostic significance, and therapeutic response assessment have additionally been addressed. Therapeutic interventions targeting magnesium levels, such as magnesium supplementation, tocolytic therapy, and the role of magnesium in antenatal corticosteroid administration, are explored. This review provides an in-depth evaluation of the correlation between serum magnesium levels and preterm labor, stressing its therapeutic significance and repercussions for future research and treatment strategies.