Narrow-window data-independent acquisition (nDIA) is emerging as a powerful technique for bottom-up proteomics. Here, we systematically benchmarked nDIA, wide-window DIA (wDIA), narrow-window data-dependent acquisition (nDDA), and wide-window DDA (wDDA) for rapid, single-shot proteomic analysis. For data processing, we introduced Tesorai Search, a new search engine leveraging a large pre-trained model and compared it with DIA-NN and FragPipe across both DIA and DDA datasets. Among 12 acquisition-analysis pipelines evaluated, nDIA combined with DIA-NN and Tesorai Search delivered the highest proteome coverage, identifying 10,255 and 10,766 protein groups from benchmark samples, respectively. Both search engines maintained rigorous false-discovery rate (FDR) control. While nDIA generally outperformed nDDA in sensitivity, FragPipe-DDA+ approach proved to be the most sensitive within the nDDA pipelines. However, entrapment analyses indicate that this sensitivity comes at the cost of less robust FDR control compared to Tesorai Search. As a proof of concept, we applied nDIA-MS to 17 cancer cell lines harboring DNA damage response (DDR) gene knockouts, successfully detecting significant downregulation of all targeted proteins and uncovering 81 DDR-related proteins modulated in at least one cell line. These results underscore nDIA-MS, together with DIA-NN and Tesorai Search, as a robust and scalable platform for high-throughput functional proteomic screening.

Circulating tumor DNA (ctDNA) is a promising biomarker for disease monitoring, yet evidence of its clinical utility in routine care remains limited. We evaluated the utility of serial ctDNA monitoring using digital PCR (ddPCR) for detecting acquired resistance (AR) and monitoring response in metastatic non-small cell lung cancer (NSCLC) and breast cancer (MBC). This real-world, longitudinal study included 48 metastatic patients (42 with EGFR-mutant NSCLC; 6 with HR+/HER2-negative MBC) treated at a Brazilian oncology reference center. Serial plasma samples were analyzed by ddPCR for activating and resistance mutations at specific time points. In the NSCLC cohort, EGFR T790M was detected in 48.4% of patients who progressed on 1st/2nd-generation TKIs. For patients on 3rd-generation TKIs, EGFR C797S was the main AR mechanism (47%), followed by PIK3CA, BRAF mutations, and ERBB2/EGFR amplifications. Longitudinal analysis anticipated radiological progression by approximately 5 months. Early molecular response, characterized by mutation clearance, preceded radiological response. In the MBC cohort, hotspot ESR1 mutations (D538G, L536R, Y537S) were identified in 50% of patients. Variations in ctDNA fractional abundance predicted disease progression up to 9 months before radiological confirmation. This study provides real-world evidence that ddPCR-based ctDNA monitoring enables early detection of resistance and predicts disease progression significantly earlier than standard imaging in both NSCLC and MBC. Despite the limited sample size, particularly in the MBC cohort, these real-world findings support liquid biopsy as a minimally invasive tool with the potential to guide therapeutic decisions and inform personalized management in precision oncology. Larger prospective studies are needed to confirm these observations.

This study aimed to evaluate the prevalence, types, and duration of diagnosed cancers among adult type 2 diabetes mellitus (T2DM) patients in a primary care setting in Türkiye and to examine associated clinical and demographic factors according to T2DM duration.

Early detection of cancer remains challenging due to the extremely low concentration of biomarkers present during initial disease stages. Dysregulation of key signaling pathways, including cyclin-dependent kinase (CDK) networks, drives uncontrolled cell proliferation and tumor progression, underscoring the need for highly sensitive, label-free biosensing technologies. Conventional analytical methods such as ELISA and PCR offer reliable detection but require complex sample preparation, fluorescent labeling, and long processing times, limiting their suitability for rapid diagnostics. This work introduces a novel label-free Biological Micro-Opto-Electro-Mechanical System (BioMEMS) platform based on an unbalanced Michelson interferometer with DBR mirrors to interrogate the minute spectral shifts induced by biomolecular interactions. A microcantilever is suspended above a silicon-on-insulator (SOI) waveguide, where the specific binding of biomarkers generates compressive surface stress, causing a downward deflection that reduces the cantilever-to-waveguide gap. This displacement modulates the effective refractive index of the sensing arm through enhanced evanescent-field coupling. The resulting phase variation is further detected through the high-sensitivity Michelson interferometric architecture, enabling ultrasensitive spectral interrogation. Numerical simulations using COMSOL Multiphysics demonstrate a narrow full width at half maximum (FWHM) of 27.6 nm, a quality factor (Q) of 53.34, and an overall sensitivity of 75.74 µm/(N/m). These results highlight the potential of the proposed platform for early cancer detection and precise monitoring of dysregulated signaling pathways.

Higher mortality from cervical cancer and lower cervical screening attendance in England are both associated with social deprivation. Linkage of 2012 data showed 4.9% percentage points between coverage in the upper and lower quintile of social deprivation. To investigate whether this inequality has changed in the last decade, general practice-level coverage data from 2024 were linked to area-level index of multiple deprivation. Cervical screening coverage was estimated to be 73.5% among those in the most affluent areas decreasing to 66.1% in the most deprived areas, a gap of 7.4%. Coverage has decreased over the last decade and the inequality in coverage between least and most deprived is wider than it was 12 years ago. The 2026 National Cancer Plan includes ambitious targets to reduce inequalities in accessing screening. Routinely linking coverage data to deprivation indices is essential to evaluate whether they are met.

Fruquintinib (FRU) is a vascular endothelial growth factor receptor (VEGFR)-1, 2, 3 tyrosine kinase inhibitor (TKI) approved for metastatic colorectal cancer. While hypertension, fatigue, and hand-foot syndrome are common adverse events, severe proteinuria and nephrotic syndrome are rare and has not been reported in clinical trials. A woman in her 60s with recurrent rectal cancer began fruquintinib at 5 mg/d as a 4th-line treatment. She had a history of hypertension and was taking amlodipine. On day 8 of the first cycle, she developed hypertension (grade 2) . On day 22, proteinuria (grade 3) was detected and hypertension had worsened (grade 3) . Since these changes occurred during the off-treatment period, observation was selected. However, on day 23, the patient presented with fatigue, generalized edema, and dyspnea. Laboratory tests revealed a urine protein/creatinine ratio of 10.3 g/gCr and elevated serum creatinine (grade 1), leading to hospitalization. Post-admission, hypermagnesemia (grade 3) was also noted. loxoprofen and magnesium oxide were discontinued and furosemide was initiated. By day 6 of hospitalization, 24-h urine protein quantification had decreased to 2.1 g/d. By day 9, edema and hypertension had both improved, and the patient was discharged. The Naranjo score were 7 for fruquintinib, 6 for loxoprofen and bevacizumab, and 5 for trifluridine/tipiracil hydrochloride, suggesting probable adverse drug reaction. VEGFR-TKIs are presumed to impair glomerular structure and function, leading to proteinuria. Although renal biopsy was not performed, thrombocytopenia and elevated lactate dehydrogenase suggested thrombotic microangiopathy. Earlier monitoring could have enabled faster detection and prevention of severe symptoms.

Serrated polyposis syndrome (SPS) is the most common polyposis syndrome, yet SPS often goes unrecognized. SPS diagnosis is based on clinical criteria established by the World Health Organization and includes the size, cumulative lifetime number, and location of serrated polyps throughout the colon. Individuals with SPS have an increased risk of prevalent and incident colorectal cancer (CRC). Meticulous inspection, clearing of the colon and frequent surveillance colonoscopy is recommended to decrease incident CRC. Colorectal surgery is indicated for individuals diagnosed with cancer or whose polyp burden cannot be managed endoscopically by expert endoscopists. There is no common germline pathogenic variant associated with SPS. Germline genetic testing is indicated only in individuals who meet criteria for a known hereditary syndrome in the appropriate clinical setting. First-degree relatives of patients with SPS are at heightened risk of CRC and should undergo colonoscopic screening.

Establishing a robust pre-operational radiological baseline is essential for distinguishing pre-existing environmental variability from changes associated with future nuclear medicine operations. This study characterizes the ambient gamma-radiation field at a proposed medical cyclotron facility in South Cikarang, West Java, Indonesia. Nineteen monitoring locations were designated across heterogeneous terrain, with direct measurements obtained at 18 locations because Point B was unavailable. Ambient dose equivalent rates, H*(10), were measured at the ground surface and 1 m above ground level using complementary Geiger-Müller (GM) and NaI(Tl) detectors, with ten replicate measurements per configuration. Across all detector systems and measurement heights, H*(10) ranged from 0.030 to 0.120 µSv h-1, and median surface-to-1 m reductions were 11.8% for GM and 14.2% for NaI(Tl). Inter-detector agreement was strong, with Pearson r = 0.958 at the surface and 0.919 at 1 m. Ordinary Kriging identified spatial dependence over approximately 100 m, with higher values associated with engineered sand and crushed-stone fill and lower values generally associated with natural clay-dominated and vegetated ground. Screening-level annual external dose estimates ranged from 0.052 to 0.172 mSv y-1 and excess lifetime cancer risk from 1.76 × 10-4 to 5.86 × 10-4. The findings establish a site-specific pre-operational radiological baseline and demonstrate a transferable framework integrating measurement validation, uncertainty analysis, and spatial modelling for environmental surveillance around planned radiological facilities.

CRISPR-based, amplification-free colorimetric sensing has emerged as a powerful approach for exosomal miRNA (Exo-miR) analysis, offering high specificity, simple operation, and direct visual readout suitable for point-of-care diagnostics. However, the sensitivity of existing systems is limited because conventional colorimetric probes generate inherently weak signals, making the reliable detection of ultralow-abundance Exo-miRs difficult without amplification. Here, we firstly report an amplification-free colorimetric biosensor based on a horseradish peroxidase (HRP)/gold nanoparticle (Au)/molybdenum disulfide (MoS2) nanobiohybrid catalyst (HRP/Au/MoS2) that generates intense chromogenic signals via synergistic catalytic interactions. In this nanoparticle, MoS2 provides a high-surface-area scaffold with intrinsic peroxidase-like activity, Au nanoparticles facilitate efficient electron transfer, and HRP contributes to high catalytic turnover. Together, these features markedly enhance the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) and the resulting blue coloration. Using this signal-amplifying HRP/Au/MoS2, a magnet-based sensing system was constructed by immobilizing the HRP/Au/MoS2 onto magnetic nanobeads (MNBs) through biotinylated single-stranded RNA linkers (MNB-ssRNA-HRP/Au/MoS2). This construction was then integrated into a CRISPR/Cas13a assay, in which the target miR-155 activates Cas13a, which cleaves the ssRNA linkers, releasing the HRP/Au/MoS2 into solution for colorimetric readout. The resulting biosensor exhibits a detection range of 1 fM-1 nM (LOD = 0.82 fM), and single-nucleotide specificity without nucleic acid amplification. Furthermore, our system enables detection of Exo-miR-155 in both cell-derived exosomes and clinical samples, distinguishing cancer patients from healthy donors. Therefore, this platform represents a promising approach for highly sensitive, selective, simple, and time-efficient detection of Exo-miR, which can be used for liquid biopsy-based early cancer detection.

Serrated polyposis syndrome (SPS) is the most common polyposis syndrome, yet SPS often goes unrecognized. SPS diagnosis is based on clinical criteria established by the World Health Organization and includes the size, cumulative lifetime number, and location of serrated polyps throughout the colon. Individuals with SPS have an increased risk of prevalent and incident colorectal cancer (CRC). Meticulous inspection, clearing of the colon and frequent surveillance colonoscopy is recommended to decrease incident CRC. Colorectal surgery is indicated for individuals diagnosed with cancer or whose polyp burden cannot be managed endoscopically by expert endoscopists. There is no common germline pathogenic variant associated with SPS. Germline genetic testing is indicated only in individuals who meet criteria for a known hereditary syndrome in the appropriate clinical setting. First-degree relatives of patients with SPS are at heightened risk of CRC and should undergo colonoscopic screening.