High Sensitivity Research Articles

The role of HOTAIR in the modulation of resistance to anticancer therapy.

Leading anti-tumour therapeutic strategies typically involve surgery and radiotherapy for locally advanced (non-metastatic) cancers, while hormone therapy, chemotherapy, and molecular targeted therapy are the current treatment options for metastatic cancer. Despite the initially high sensitivity rate to anticancer therapies, a large number of patients develop resistance, leading to a poor prognosis. The mechanisms related to drug resistance are highly complex, and long non-coding RNAs appear to play a crucial role in these processes. Among these, the lncRNA homeobox transcript antisense intergenic RNA (HOTAIR), widely implicated in cancer initiation and progression, likewise plays a significant role in anticancer drug resistance. It can modulate cell activities such as proliferation, apoptosis, hypoxia, autophagy, as well as epithelial-mesenchymal transition, thereby contributing to the development of resistant tumour cells. In this manuscript, we describe different mechanisms of antitumor drug resistance in which HOTAIR is involved and suggest its potential as a therapeutic predictive biomarker for the management of cancer patients.

Sensitivity, robustness, and reproducibility of U-shaped delamination test for evaluation of candidate ultra-high molecular weight polyethylene materials for joint replacements.

The delamination of ultra-high molecular weight polyethylene (UHMWPE) in artificial joints is a major cause limiting the long-term clinical results of arthroplasty. However, the conventional test method using simple reciprocation to evaluate the delamination resistance of UHMWPE materials has insufficient detection sensitivity. To reproduce delamination, the unconformity contact must be maintained throughout the test so that the maximum stress is generated below the surface. Therefore, a test method that applies a U-shaped motion comprising two long-linear and one short linear sliding motion was developed. The sensitivity, robustness, and reproducibility of the U-shaped delamination test were investigated and compared with the traditional test method. The traditional test method could reproduce delamination only in materials that had degraded considerably, whereas the U-shaped delamination test could reproduce delamination in a wide range of materials, demonstrating its superior sensitivity. Additionally, using a higher load helped accelerate the test without affecting the test results. The optimal length of the short linear sliding motion was confirmed to be 1 mm. Finally, the inter-laboratory reproducibility of the U-shaped delamination test was confirmed using the round-robin test. The U-shaped delamination test demonstrates high sensitivity, robustness, and reproducibility and contributes to the selection and development of UHMWPE materials and artificial joints with a lower risk of delamination.

Sensitive Detection of Perfluoroalkyl Substances Using MXene-AgNP-Based Electrochemical Sensors.

Per- and polyfluoroalkyl substances (PFAS) pose a significant threat to the environment due to their persistence, ability to bioaccumulate, and harmful effects. Methods to quantify PFAS rapidly and effectively are essential to analyze and track contamination, but measuring PFAS down to the ultralow regulatory levels is extremely challenging. Here, we describe the development of a low-cost sensor that can measure a representative PFAS, perfluorooctanesulfonic acid (PFOS), at the parts per quadrillion (ppq) level within 5 min. The method combines the ability of PFOS to bind to silver nanoparticles (AgNPs) embedded within a fluorine-rich Ti3C2-based multilayered MXene, which provides a large surface area and accessible binding sites for direct impedimetric detection. Fundamentally, we show that MXene-AgNPs are capable of binding PFOS and other long-chain PFAS compounds, though the synergistic action of AgNPs and MXenes via electrostatic and F-F interactions. This binding induced concentration-dependent changes in the charge-transfer resistance, enabling rapid and direct quantification with extremely high sensitivity and no response to interferences. The sensor displayed a linear range from 50 ppq to 1.6 ppt (parts per trillion) with an impressively low limit of detection of 33 ppq and a limit of quantification of 99 ppq, making this sensor a promising candidate for low-cost screening of the PFAS content in water samples, using a simple and inexpensive procedure.

The Influence of Microstructure on TCR for Inkjet-Printed Resistive Temperature Detectors Fabricated Using AgNO3/Ethylene-Glycol-Based Inks.

This study investigated the influence of microstructure on the performance of Ag inkjet-printed, resistive temperature detectors (RTDs) fabricated using particle-free inks based on a silver nitrate (AgNO3) precursor and ethylene glycol as the ink solvent. Specifically, the temperature coefficient of resistance (TCR) and sensitivity for sensors printed using inks that use monoethylene glycol (mono-EG), diethylene glycol (di-EG), and triethylene glycol (tri-EG) and subjected to a low-pressure argon (Ar) plasma after printing were investigated. Scanning electron microscopy (SEM) confirmed previous findings that microstructure is strongly influenced by the ink solvent, with mono-EG inks producing dense structures, while di- and tri-EG inks produce porous structures, with tri-EG inks yielding the most porous structures. RTD testing revealed that sensors printed using mono-EG ink exhibited the highest TCR (1.7 × 10-3/°C), followed by di-EG ink (8.2 × 10-4/°C) and tri-EG ink (7.2 × 10-4/°C). These findings indicate that porosity exhibits a strong negative influence on TCR. Sensitivity was not strongly influenced by microstructure but rather by the resistance of RTD. The highest sensitivity (0.84 Ω/°C) was observed for an RTD printed using mono-EG ink but not under plasma exposure conditions that yield the highest TCR.

Polarity-sensitive fluorescent probe based on coumarin derivatives for imaging lipid droplets and diagnosis of non-alcoholic fatty liver

Aberrant alterations in the polarity of lipid droplets (LDs) are closely linked to disorders of lipid metabolism, which can result in LDs dysfunction and the onset of various diseases, including non-alcoholic fatty liver disease (NAFLD) and specific types of cancer. Therefore, it is imperative to comprehensively comprehend and accurately diagnose associated diseases by monitoring changes in LDs polarity in real time. In this paper, we designed and synthesized four novel fluorescent probes XOT1-XOT4 by using coumarin as a polarity-sensitive group and incorporate various triphenylamine derivatives as electron-donating groups, enabling specific targeting of LDs. All four probes possess high sensitivity towards minute polarity changes. Among them, XOT3 exhibited excellent photophysical properties and demonstrated a linear fluorescence change (R2 = 0.98596) within the polarity range of Δf = 0.023496 ∼ 0.047464. Moreover, probe XOT3 could be effectively utilized for visualizing intracellular LDs by precisely targeting them without requiring any washing steps. Importantly, probe XOT3 has been successfully utilized to monitor alterations in the polarity of LDs during apoptosis and ferroptosis as well as the quantity, size, and fluorescence intensity of LDs stimulated by oleic acid. Furthermore, probe XOT3 was capable of effectively visualizing LDs in tissues and organs in mouse models of non-alcoholic fatty liver disease (NAFLD), which provides a powerful tool for the early diagnosis of NAFLD.

Bimetal−organic framework-integrated electrochemical sensor for on-chip detection of H2S and H2O2 in cancer tissues

Studies on the interaction between hydrogen sulfide (H2S) and hydrogen peroxide (H2O2) in redox signaling motivate the development of a sensitive sensing platform for their discriminatory and dynamic detection. Herein, we present a fully integrated microfluidic on-chip electrochemical sensor for the online and simultaneous monitoring of H2S and H2O2 secreted by different biological samples. The sensor utilizes a cicada-wing-like RuCu bimetal−organic framework with uniform nanorods architecture that grows on a flexible carbon fiber microelectrode. Owing to the optimized electronic structural merits and satisfactory electrocatalytic properties, the resultant microelectrode shows remarkable electrochemical sensing performance for sensitive and selective detection of H2S and H2O2 at the same time. The result exhibits low detection limits of 0.5 μM for H2S and 0.1 μM for H2O2, with high sensitivities of 61.93 μA cm−2 mM−1 for H2S, and 75.96 μA cm−2 mM−1 for H2O2. The integration of this biocompatible microelectrode into a custom wireless microfluidic chip enables the construction of a miniature intelligent system for in situ monitoring of H2S and H2O2 released from different living cells to differentiate between cancerous and normal cells. When applied for real-time tracking of H2S and H2O2 secreted by colorectal cancer tissues, it allows the evaluation of their chemotherapeutic efficacy. These findings hold paramount implications for disease diagnosis and therapy.

Evaluating Visual Dependence in Postural Stability Using Smartphone and Stroboscopic Glasses

This study explores the efficacy of integrating stroboscopic glasses with smartphone-based applications to evaluate postural control, offering a cost-effective alternative to traditional forceplate technology. Athletes, particularly those with visual and visuo-oculomotor enhancements due to sports, often suffer from injuries that necessitate reliance on visual inputs for balance—conditions that can be simulated and studied using visual perturbation methods such as stroboscopic glasses. These glasses intermittently occlude vision, mimicking visual impairments that are crucial in assessing dependency on visual information for postural stability. Participants performed these tasks under three visual conditions: full vision, partial vision occlusion via stroboscopic glasses, and no vision (eyes closed), on foam surfaces to induce postural instability. The use of a smartphone app to measure postural sway was validated against traditional force plate measurements, providing a comparative analysis of both tools under varied sensory conditions. We investigated postural parameters like anterior–posterior and medial–lateral sway ranges, root mean square values, 95% confidence ellipse area, and sway velocity and median dominant sway frequency from both the smartphone and the force plates. Our findings indicate that force plates exhibit high sensitivity to various visual conditions, as evidenced by significant differences observed in certain postural parameters, which were not detected by smartphone-based measurements. Overall, our findings indicate that smartphones show promise as a cost-effective alternative to force plate measurements for routine monitoring of postural control in sports, although they may not achieve the same level of accuracy as force plates. The integration of stroboscopic glasses further refined the assessment by effectively simulating visual impairments, thereby allowing precise evaluation of an individual’s ability to maintain balance under visually perturbed conditions.

A concave octahedral hollow SnO2 nanocage for enhancing typical electrolyte (EMC) leakage gas sensing performance in lithium-ion batteries

The safety issues caused by lithium-ion battery (LIB) failures are the pain points that constrain the development of LIB. Developing a high sensitivity and low-cost gas sensor targeting trace electrolyte vapors, such as methyl ethyl carbonate (EMC), can help achieve early warning in accidents. Tin dioxide (SnO2) has always been one of the most widely used gas sensitive materials. Herein, the concave octahedral hollow SnO2 nanocages (SnO2-Hoc) are quickly prepared by template-engaged coordinating etching. The response value of its sensor to 10 ppm EMC is 7.24 at 140℃ and it shows sufficient sensitivity in LIB leakage simulation tests. The hollow concave octahedral structure promotes the EMC diffusion, and the lower energy barrier of EMC cleavage is the key to selective response. Overall, this work synthesized SnO2-Hoc sensor to directly detect trace EMC, which is expected to provide new guarantees for the LIB safe application.

Detection of miR-203 expression using a nanofluorescent probe to study the neuroprotective effect of sevoflurane in a neuroinflammatory injury rat model

Ischemic cerebrovascular disease has high disability and mortality rates that can result in related sequelae if not treated promptly and properly. Nanofluorescent probes are useful in the early diagnosis of the disease due to their high sensitivity and specificity, thus facilitating early therapeutic measures and observation of disease progression. Here, a novel nanostructure probe was designed to detect the expression of miR-203 in a cerebral ischemia-reperfusion injury (CIRI) model after sevoflurane treatment, and the effects of sevoflurane and neuroinflammatory injury were discussed. A CIRI rat model was established to study miR-203 expression, nerve injury, oxidative stress, and inflammatory factors in the brain tissue of rats treated with sevoflurane. The nanofluorescent probe showed high specificity and sensitivity for miR-203 detection. miR-203 was over-expressed in CIRI rats, which was decreased by sevoflurane treatment. In addition, sevoflurane treatment significantly improved neurological function, learning, and memory in CIRI rats; decreased malondialdehyde, lactate dehydrogenase, and superoxide dismutase levels; and inhibited the expression of tumor necrosis factor α and interleukins 1 and 6. Moreover, an inverse correlation was determined between miR-203 expression and the degree of neuroinflammation. This study demonstrated that miR-203 may be a useful diagnostic and prognostic index for neuroinflammatory injury.

Comparison and review of abrasive bronchial brushing versus non-abrasive aspiration, lavage and washing – Higher sensitivity but with risk of over-diagnosis for bronchial brushing

Bronchial exfoliative cytology is classified as non-abrasive (washing, aspiration and bronchoalveolar lavage) and abrasive (brushing). Brush abrasion dislodges epithelial cells but can induce bleeding and cytomorphologic artifacts. In this study, the largest cohort to date of bronchial cytology specimens were referenced against bronchial biopsy as the reference standard. Findings in the study will be useful for selecting biopsy modality and reducing necessary procedural risks. All consecutive bronchial cytology and bronchial biopsy from 1995 to 2022 were retrieved. The diagnoses were reviewed and categorized into five-tiered diagnostic categories to compare diagnostic agreement and concordance. Review of 14,148 specimens yielded 3963 non-abrasive, 2378 abrasive cytology specimens matched to biopsy, with 4355 matches between non-abrasive and abrasive cytology specimens. Agreement between non-abrasive and abrasive cytology was moderate (κ = 0.580), and similar when referenced against biopsy (κ = 0.456 (non-abrasive), κ = 0.498 (abrasive)). Abrasive bronchial cytology showed a higher percentage of malignant diagnosis (20.95 % vs. 12.63 %, p < 0.001) and over-diagnosis rate (36.40 % vs. 29.79 %, p < 0.001), but higher sensitivity (0.747 vs. 0.572, p = 0.002). For subgroup analysis of transbronchial biopsies, matched abrasive cytology showed higher discordant rates (p < 0.05) and lower accuracy (0.907 vs. 0.873, p = 0.020). With the added bleeding risk associated with brushing, abrasive techniques may only be preferable in cases with clinical or bronchoscopic suspicion of malignancy, in particular endobronchial mucosal lesions. For routine bronchoscopy, non-abrasive bronchial cytology appears to be adequate.

Handheld echocardiography for the screening and diagnosis of rheumatic heart disease: a systematic review to inform WHO guidelines

Early detection and diagnosis of acute rheumatic fever and rheumatic heart disease are key to preventing progression, and echocardiography has an important diagnostic role. Standard echocardiography might not be feasible in high-prevalence regions due to its high cost, complexity, and time requirement. Handheld echocardiography might be an easy-to-use, low-cost alternative, but its performance in screening for and diagnosing acute rheumatic fever and rheumatic heart disease needs further investigation. In this systematic review and meta-analysis, we searched Embase, MEDLINE, LILACS, and Conference Proceedings Citation Index-Science up to Feb 9, 2024, for studies on the screening and diagnosis of acute rheumatic fever and rheumatic heart disease using handheld echocardiography (index test) or standard echocardiography or auscultation (reference tests) in high-prevalence areas. We included all studies with useable data in which the diagnostic performance of the index test was assessed against a reference test. Data on test accuracy in diagnosing rheumatic heart disease, acute rheumatic fever, or carditis with acute rheumatic fever (primary outcomes) were extracted from published articles or calculated, with authors contacted as necessary. Quality of evidence was appraised using GRADE and QUADAS-2 criteria. We summarised diagnostic accuracy statistics (including sensitivity and specificity) and estimated 95% CIs using a bivariate random-effects model (or univariate random-effects models for analyses including three or fewer studies). Area under the curve (AUC) was calculated from summary receiver operating characteristic curves. Heterogeneity was assessed by visual inspection of plots. This study was registered with PROSPERO (CRD42022344081). Out of 4868 records we identified 11 studies, and two additional reports, comprising 15 578 unique participants. Pooled data showed that handheld echocardiography had high sensitivity (0·87 [95% CI 0·76-0·93]), specificity (0·98 [0·71-1·00]), and overall high accuracy (AUC 0·94 [0·84-1·00]) for diagnosing rheumatic heart disease when compared with standard echocardiography (two studies; moderate certainty of evidence), with better performance for diagnosing definite compared with borderline rheumatic heart disease. High sensitivity (0·79 [0·73-0·84]), specificity (0·85 [0·80-0·89]), and overall accuracy (AUC 0·90 [0·85-0·94]) for screening rheumatic heart disease was observed when pooling data of handheld echocardiography versus standard echocardiography (seven studies; high certainty of evidence). Most studies had a low risk of bias overall. Some heterogeneity was observed for sensitivity and specificity across studies, possibly driven by differences in the prevalence and severity of rheumatic heart disease, and level of training or expertise of non-expert operators. Handheld echocardiography has a high accuracy and diagnostic performance when compared with standard echocardiography for diagnosing and screening of rheumatic heart disease in high-prevalence areas. World Health Organization. For the Chinese, French, Italian, Persian, Portuguese, Spanish and Urdu translations of the abstract see Supplementary Materials section.

Mesoporous Au-CuO substrate with dual super-hydrophilicity and efficient chemical enhancement for 4-aminothiophenol SERS detection

aminothiophenol (4-ATP) residues and accumulation in aquaculture/animal husbandry are becoming a serious threat to food safety. Development of highly sensitive metal-semiconductor surface-enhanced Raman scattering (SERS) substrates for the detection of 4-ATP is urgently needed. In this work, mesoporous Au-CuO substrate with dual super-hydrophilicity and efficient chemical enhancement is constructed for high-sensitivity SERS detection of 4-ATP. Mesoporous Au-CuO substrate is prepared by thermal decomposition. The super-hydrophilic substrate could mitigate droplet-induced "coffee ring" effect, thereby promoting rapid diffusion and uniform distribution of target molecules. Meanwhile, hybridizing gold nanoparticles (Au NPs) and CuO could enhance analyte polarization rate in that multi-channel photon-induced charge transfer between the target molecule and Au-CuO substrate. Mesoporous Au-CuO exhibited high sensitivity (10-8M) and reproducibility (Relative standard deviation (RSD=6.06%, n=11)) for crystal violet (CV) probe. The as-prepared substrate demonstrated reliable assay ability for 4-ATP with a detection limit of 10-7M and a good reproducibility with RSD=3.33% (n=11). Additionally, the substrate was not impacted by heavy metal ions in actual water environment. Trace residues of 4-ATP were still detected at concentrations as low as 10-7M. Au-CuO substrate is expected to be a favorable candidate for the detection of 4-ATP residues in complex matrices.

3D printed microfluidic chip integrated with nanointerferometer for multiplex detection of foodborne pathogens

The current foodborne pathogen detection methods, such as culture-based methods, polymerase chain reaction, and optical and electrochemical biosensors with nucleic acid, have high sensitivity and selectivity. However, they are slow, expensive, and require well-trained operators. In this study, we utilized a 3D printer to develop a novel chip with an aptamer-based nanointerferometer capable of identifying four distinct foodborne pathogens: Listeria monocytogenes, Escherichia coli, Salmonella typhimurium, and Staphylococcus aureus. The aptamer sensor on the chip achieved a limit-of-detection of 10 colony forming unit (CFU)/ml. With its high sensitivity and specificity, this chip offers a cost-effective platform for distinguishing and screening different foodborne pathogens.

A novel AgNFs/MOF/CFC substrate-based flexible SERS sensor for high-sensitive detection of dye molecules

Metal–organic framework (MOF) materials have been increasingly used owing to their high porosity, chemical stability, and semiconducting properties. With the help of MOF materials, MOF-based SERS substrates can exhibit high sensitivity. Herein, we proposed a flower-like Ag nanoparticles (AgNFs)/metal–organic framework (MOF)/ carbon fiber cloth (CFC) substrate-based surface-enhanced Raman scattering (SERS) sensor for the high-sensitive detection of dye molecules. MOF is used as a signal amplifier to accelerate the approach of dye molecules near AgNFs on the MOF surface and anchor AgNFs on the substrate surface. The detection occurred on the AgNFs/MOF/CFC SERS substrate, providing an enhancement factor (EF) of 5.53 × 107. Benefitting from the signal amplification function of AgNFs/MOF/CFC and the superiority of SERS, this sensor represented high sensitivity performance and a wide detection range. Importantly, the combination of Co elements with silver in the AgNFs/MOF/CFC composite substrate enhances the resistance of Ag to oxidation by atmospheric moisture resulting in excellent stability (the substrate maintained good SERS activity after 45 days of exposure to air) of the SERS substrate. The basic performance of the substrate was evaluated using rhodamine 6 G (R6G). (Detection limit reached 10−12 M) The detection limit of TC was 0.1 ppm. This method provides a potential and cost-effective strategy to develop advanced SERS sensing devices to effectively monitor pollutants in environmental waters.

Deep analysis of total serum N-glycome suggests glyco-signatures for phospholipase A2 receptor 1-related idiopathic membranous nephropathy diagnosis

Idiopathic membranous nephropathy (IMN) is an antibody-mediated and kidney-specific autoimmune disease, with the antigen phospholipase A2 receptor 1 (PLA2R1) accounting for approximately 70% of IMN cases. Although a variety of new podocyte target antigens and their autoantibodies have been identified, they are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. N-glycans play vital roles in renal system and their pathobiological relevance has become increasingly recognized in many kidney diseases, but not fully explored in IMN. To find possible glyco-signatures for PLA2R1-related IMN diagnosis, we herein established a comprehensive workflow for total serum N-glycome analysis based on our recently developed mass spectrometry (MS)-based N-glycan purification method, named Ultrafast Glycoprotein Immobilization for Glycan extraction (UltraGIG). A total of 191 N-glycans were identified from IMN patients, representing the largest N-glycome dataset in IMN. Compared to healthy controls, up-regulation of sialylation and core-fucosylation as well as down-regulation of galactosylation were observed in PLA2R1-positive IMN patients, and up-regulation of hyper-galactosylation was specific for PLA2R1-negative IMN patients. A six-glycan marker panel consisting of H4N3S1, H4N3F1, H6N4S2, H6H5F1S2, H6N5 and H6N6F1S1, was proposed to aid in the accurate diagnosis of PLA2R1-related IMN, which provided new insights into IMN biomarker study. SignificancePLA2R1-related IMN is a kidney-specific autoimmune disease with a high risk of developing end-stage renal disease (ESRD) and even kidney failure. Current biomarkers are still of limited diagnostic and therapeutic value due to lack of high specificity and sensitivity. An in-depth MS analysis of total serum N-glycome of PLA2R1-related IMN patients was conducted for the first time. We generated the largest dataset of serum N-glycome for IMN to date, and proposed a novel six-glycan marker panel that may help the accurate diagnosis of PLA2R1-related IMN.

The SURVIVE study: Liquid biopsy guided surveillance after intermediate- to high-risk early breast cancer.

TPS620 Background: Current guidelines limit routine breast cancer (BC) follow-up to clinical examinations and breast imaging. This is based on the results of two large cohort studies conducted in the 1980s that showed no improvement in overall survival (OS) by an intensified screening for distant metastases. Thus, imaging for distant metastases should currently only be performed in patients with specific symptoms. To detect distant relapse in a pre-symptomatic stage, we suggest the evaluation of a liquid biopsy-guided intensified surveillance, analyzing tumor markers (CA 27.29, CA 125 and CEA), circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Methods: Funded by the German Federal Ministry of Education and Research, the SURVIVE study is the first large, randomized BC surveillance trial to investigate the potential survival benefit of a liquid biopsy guided follow-up care in intermediate- to high-risk early breast cancer patients. The trial is a German multicenter, controlled phase 3 superiority study, in which 3500 patients are randomized in a 1:1 ratio to standard vs. liquid biopsy guided intensified follow-up care. Eligible patients are adults with confirmed primary invasive intermediate to high-risk early BC, defined as an indication for (neo-)adjuvant chemotherapy, and/or large tumor size (&gt; 50 mm), and/or positive lymph nodes (≥ pN1mi), and/or high grade (≥ G3). Primary anti-tumor therapy (surgery, adjuvant chemo- or radiotherapy) must have been completed previously. Patient enrollment during adjuvant endocrine, antibody- or targeted therapy is allowed. The total study duration is 144 months. Stratification factors are study site as well as HR-, HER2- and nodal status at surgery.Both study arms receive standard follow-up according to national guidelines, and the intensified surveillance arm will be tested for standard tumor markers, CTCs and ctDNA via tumor-informed approach (RaDaR assay). Pre-specified abnormal findings of any of the liquid biopsy markers indicative of minimal residual disease trigger complete staging. In the event of confirmed disease recurrence, guideline-based treatment follows, otherwise, liquid biopsy testing continues. If applicable, study participants may enter interventional trials. Statistics:The two primary objectives are to determine whether intensified, liquid biopsy-guided surveillance leads to better OS or an overall lead-time effect, compared to standard surveillance. OS will be analyzed in the ITT population using Kaplan Meier methods and cox regression models, the overall lead time effect is a purely descriptive composite measure. Secondary objectives include IDFS, DDFS, DRFS, BCSS and quality of life (QoL). Aims: We propose a liquid biopsy guided follow-up method, with high sensitivity and specificity for the earlier detection of distant (oligo-)metastases, to enable earlier initiation of therapy. Clinical trial information: NCT05658172 .

Implementation of a comprehensive genomic profiling (CGP) panel for precision oncology at a cancer center in Brazil.

e23520 Background: Assessing molecular alterations in solid tumors is essential for providing the best care in precision oncology. CGP tests utilize next-generation sequencing (NGS) to detect clinically relevant alterations and molecular signatures that are increasingly utilized in cancer careand can be performed in-house, which decreases test turnaround time (TAT) and costs. A paucity of studies have documented the experience of in-house testing at academic centers in Brazil. Methods: The TruSight Oncology (TSO) 500 assay/TSO 500 HRD are research use only (RUO) CGP assays that were validated for the detection of small variants (SVs), copy number variants (CNVs), microsatellite instability (MSI), tumor mutation burden (TMB) and genomic instability score (GIS) in DNA and gene fusions/splice variants in RNA in the NextSeq 500 system. Secondary analysis was performed with Illumina Connected Analytics. Tertiary analysis was performed with Illumina Connected Insights (ICI) and Sophia DDM. TMB ≥ 10mut/Mb was defined as TMB-High and GIS ≥ 42 was homologous recombination deficient (HRD). Results: We performed CGP on 40 FFPE samples (16 with HRD) with variable quality and block age most of which had known alterations detected by other genomics/molecular tests: 17 TNBC (16 paired DNA and RNA, 1 DNA only), 18 lung cancer (13 paired DNA and RNA, 5 DNA only), 1 endometrium cancer (DNA only, POLE mutated, 4 replicates), 1 colorectal cancer (DNA only, MSI unstable) and 11 sarcomas (RNA only). 84%, 84%, 90% and 89% of samples with DNA integrity number (DIN) &gt; 2.5 were qualified for analysis of SVs/TMB, MSI, CNVs, and GIS, respectively, while for samples with DIN &lt; 2.5 these values felt to 47%, 74%, 68% and 43%, respectively. RNA isolated from blocks dated up to 5 y.o. were qualified in 90% of cases while from older blocks only 6%. The 4 replicate (single sample) analysis showed 82% and 83% overall variant concordance in the ICI and Sophia DDM software, respectively. All previously known oncogenic alterations (SVs ≥5% VAF, fusions/splice, MSI, TMB) were detected (qualified samples) and with similar performance in ICI and Sophia, respectively: concordance 0.91/p &lt; 0.0001 vs 0.94/p &lt; 0.0001; sensitivity 100% vs 100%; specificity 98% vs 100%. TMB had 100% concordance with previous TMB results. Of note, 73% (8/11) TNBC samples analyzed for GIS were HRD and 75% (6/8) explained by BRCA1 germline mutation (25%) and BRCA1or RAD51C somatic promoter methylation (75%). Conclusions: This study demonstrates the utility of CGP and HRD testing in identifying multiple molecular alterations in FFPE tissue samples with high sensitivity and specificity. Pre-analytical variables directly impact data generation. BRCA1/RAD51C promoter methylation showed to be a potential biomarker for selecting metastatic TNBC patients for PARP inhibitor therapies. Offering CGP can potentially bring precision oncology to more patients with cancer in Brazil.

The use of radiomic analysis of magnetic resonance imaging findings in predicting features of early osteoarthritis of the knee-a systematic review and meta-analysis.

The primary aim of this study was to systematically review current literature evaluating the use of radiomics in establishing the role of magnetic resonance imaging (MRI) findings in native knees in predicting features of osteoarthritis (OA).A systematic review was performed with respect to PRISMA guidelines in search of studies reporting radiomic analysis of magnetic resonance imaging (MRI) to analyse patients with native knee OA. Sensitivity and specificity of radiomic analyses were included for meta-analysis.Following our initial literature search of 1271 studies, only 5 studies met our inclusion criteria. This included 1730 patients (71.5% females) with a mean age of 55.4 ± 15.6years (range 24-66). The mean RQS of included studies was 16.6 (11-21). Meta-analysis demonstrated the pooled sensitivity and specificity for MRI in predicting features of OA in patients with native knees were 0.74 (95% CI 0.71, 0.78) and 0.85 (95% CI 0.83, 0.87), respectively.The results of this systematic review suggest that the high sensitivities and specificity of MRI-based radiomics may represent potential biomarker in the early identification and classification of native knee OA. Such analysis may inform surgeons to facilitate earlier non-operative management of knee OA in the select pre-symptomatic patients, prior to clinical or radiological evidence of degenerative change.

Utility of perioperative ultrasonography and fine-needle aspiration cytology in differentiation between benign and malignant cervical lymphadenopathy: a retrospective cohort study

Background: The preoperative differentiation of benign form malignant cervical lymphadenopathy (CLA) is crucial in determining the need for surgical intervention. This study aims to assess the diagnostic performance of ultrasonography (US), fine-needle aspiration cytology (FNAC), and their combination with the postoperative histopathological diagnoses of CLA. Method: In a retrospective study between April 2021 and May 2023, 214 patients with CLA were assessed with preoperative US and FNAC. The morphological parameters, including tissue margins, vascularity, and fatty hilum echogenicity, were collected and analyzed retrospectively. The diagnostic efficacies of US, FNAC, and their combined use were compared to the postoperative histopathological findings. Result: In the final histopathological examination, 185 cases (86.4%) were found to be benign, while 29 cases (13.6%) were determined to be malignant. The US features of fatty hilum, echogenicity, and vascularity pattern had the highest diagnostic accuracy in characterizing CLA patterns, with values of 88.3%, 85.5%, and 85.0%, respectively. The receiver operating characteristic (ROC) curve showed a significantly higher area under the curve (AUC) value of 0.883 (95% CI: 0.832–0.923; P&lt;0.0001) for the combined use of all US parameters with better sensitivity (93.10%) and specificity (68.65%) than individual parameters. The overall sensitivity, specificity, and accuracy of FNAC were 97.3%, 82.8%, and 95.3%, respectively. Additionally, US parameters and FNAC together showed a significantly higher AUC value of 0.924 (95% CI: 0.880–0.956; P&lt;0.0001) and achieved a sensitivity of 86.21% and specificity of 88.65%. Conclusions: The combined use of US and FNAC provides high sensitivity, specificity, and diagnostic accuracy in characterizing CLA patterns. In limited-resources settings, this approach is feasible, less invasive, and cost-effective, thereby enabling clear management strategies and avoiding additional surgical interventions.

Manganese carbonate superparticles as DNA- and pH-responsive magnetic resonance imaging contrast agents

Manganese carbonate nanoparticles (NPs) have been developed as pH-triggered responsive magnetic resonance imaging (MRI) contrast agents for tumor diagnosis, but the signal amplification of MRI is still limited due to the lack of response to other pathological parameters of tumors. Here, random single-stranded deoxyribonucleic acid (ssDNA) was explored as a biomimetic template to prepare manganese carbonate superparticles (MnCO3 SPs) assembled from ultrasmall particles. We focused on the degradation ability of DNA-MnCO3 SPs triggered by DNA and its trigger mechanism. The results show that different sequences of DNA could trigger the disassembly of these DNA-MnCO3 SPs and result in MR signal amplification. Further investigations show the DNA-MnCO3 SPs possess good physiological stability, but increased degradation sensitivity under dual triggering of DNA and low pH. In vivo MR and FL dual-modal imaging for tumor region display T1-signal rapid amplification, suggesting rapid responsiveness of DNA-MnCO3 SPs to DNA. Therefore, the design of DNA- and pH-triggered DNA-MnCO3 SPs may provide a new idea for the construction of next-generation activatable contrast agents with high specificity and high sensitivity.