Candida albicans in the oral cavities of pets: biofilm formation, putative virulence, antifungal resistance profiles and classification of the isolates.

The study aimed to investigate Candida albicans presence, antifungal resistance, biofilm formation, putative virulence genes, and molecular characterization in oral samples of dogs and cats. A total of 239 oral samples were collected from cats and dogs of various breeds and ages at Erciyes University, Faculty of Veterinary Medicine Clinics, between May 2017 and April 2018. Among 216 isolates obtained, 15 (6.95%) were identified as C. albicans, while 8 (3.7%) were non-albicans Candida species. Antifungal susceptibility testing revealed sensitivities to caspofungin, fluconazole, and flucytosine in varying proportions. Molecular analysis indicated the presence of fluconazole and caspofungin resistance genes in all C. albicans isolates. Additionally, virulence genes ALS1, HWP1, and HSP90 showed variable presence. Biofilm formation varied among isolates, with 46.7% strong, 33.3% moderate, and 20% weak producers. PCA analysis categorized isolates into two main clusters, with some dog isolates grouped separately. The findings underscore the significance of oral care and protective measures in pets due to C. albicans prevalence, biofilm formation, virulence factors, and antifungal resistance in their oral cavity, thereby aiding clinical diagnosis and treatment in veterinary medicine.

Optimizing single-cell RNA sequencing methods for human colon biopsies: droplet-based vs. picowell-based platforms.

Background & Aims: Single-cell RNA sequencing (scRNA) has empowered many insights into gastrointestinal microenvironments. However, profiling human biopsies using droplet-based scRNA (D-scRNA) is challenging since it requires immediate processing to minimize epithelial cell damage. In contrast, picowell-based (P-scRNA) platforms permit short-term frozen storage before sequencing. We compared P- and D-scRNA platforms on cells derived from human colon biopsies. Methods: Endoscopic rectosigmoid mucosal biopsies were obtained from two adults and conducted D-scRNA (10X Chromium) and P-scRNA (Honeycomb HIVE) in parallel using an individual's pool of single cells (> 10,000 cells/participant). Three experiments were performed to evaluate 1) P-scRNA with cells under specific storage conditions (immediately processed [fresh], vs. frozen at -20C vs. -80C [2 weeks]); 2) fresh P-scRNA versus fresh D-scRNA; and 3) P-scRNA stored at -80C with fresh D-scRNA. Results: Significant recovery of loaded cells was achieved for fresh (80.9%) and -80C (48.5%) P-scRNA and D-scRNA (76.6%), but not -20C P-scRNA (3.7%). However, D-scRNA captures more typeable cells among recovered cells (71.5% vs. 15.8% Fresh and 18.4% -80C P-scRNA), and these cells exhibit higher gene coverage at the expense of higher mitochondrial read fractions across most cell types. Cells profiled using D-scRNA demonstrated more consistent gene expression profiles among the same cell type than those profiled using P-scRNA. Significant intra-cell-type differences were observed in profiled gene classes across platforms. Conclusions: Our results highlight non-overlapping advantages of P-scRNA and D-scRNA and underscore the need for innovation to enable high-fidelity capture of colonic epithelial cells. The platform-specific variation highlights the challenges of maintaining rigor and reproducibility across studies that use different platforms.

Assessing venous invasion in stage II colon cancer: optimal elastin stains and survival analysis.

AIMS: Venous invasion (VI) in colorectal carcinoma influences treatment strategies, especially in early stages. Despite elastin staining effectiveness in detecting VI, guidelines for its routine application, including the optimal number of slides for staining, are limited. METHODS: Elastin staining was performed for VI assessment in patients with colorectal adenocarcinoma. Patients were categorised into two groups: single elastin stain group (SEG, n=248) and multiple elastin stain group (MEG, n=204). RESULTS: The average number of elastin-stained blocks was 2±1.7, increasing to 3.3±1.9 in MEG. VI detection was significantly higher in patients in MEG (50.5%) compared with SEG (37.0%) (p=0.004). VI detection rate was higher in MEG (63.7%) than in SEG (46.0%) among patients with stage III-IV disease (p=0.011), but did not significantly differ among patients with stage I-II disease. Staining two blocks improved VI detection without additional gains from more stains. Compared with elastin performed on a single block, VI detected by elastin stain on two or more blocks did not significantly impact progression-free or disease-free survival with stage II patients. CONCLUSIONS: Employing two elastin stains on separate blocks significantly enhances VI detection in colorectal carcinoma without additional benefits from more extensive staining. This study suggests that while increasing sensitivity for VI detection, staining beyond two blocks may not benefit prognostication and could be counterproductive, warranting further research. We emphasise the need for strategic use of the elastin stain and cautious interpretation of the increased detection sensitivity of multiple elastin stains.

Aphakia treatment with sutureless scleral fixation or retropupillary iris-claw intraocular lens implantation: visual acuity, anterior segment and keratometry outcomes.

PURPOSE: Evaluation of anterior segment parameters using the Scheimpflug corneal topography 1 year after surgery in patients who underwent sutureless scleral fixation intraocular lens (SFIOL) implantation using the modified Yamane technique and retropupillary iris-claw intraocular lens (RPIOL) implantation. METHODS: A total of 60 eyes from 57 patients who underwent sutureless SFIOL implantation and 57 eyes from 52 patients who underwent RPIOL implantation were included. Anterior chamber depth (ACD), anterior chamber angle (ACA), anterior chamber volume (ACV), anterior-posterior corneal astigmatism, and keratometric values were assessed using the Scheimpflug corneal topography (Pentacam HR, Germany). RESULTS: There was no statistically significant difference in postoperative UCVA and BCVA between the sutureless SFIOL and the RPIOL group (p = 0.236, p = 0.293, respectively). While there was no statistically significant difference in postoperative IOP between the two groups (p = 0.223), a statistically significant decrease in IOP was observed in both groups (p < 0.001). While there was no statistical difference between the sutureless SFIOL group and the RPIOL group in terms of spherical value (p = 0.441) and spherical equivalence (p = 0.237), there was a statistically significant difference in cylindrical value (p < 0.001). While there was a statistical difference in anterior astigmatism (p < 0.001), there was no statistical difference in posterior astigmatism (p = 0.405). There was no statistical difference in terms of ACV, ACD, and ACA between the sutureless SFIOL and the RPIOL group (p = 0.812, p = 0.770, p = 0.401, respectively). CONCLUSION: In this study, although there was a statistical difference in cylindrical value and anterior corneal astigmatism between the sutureless SFIOL and RPIOL groups, vision was not affected. According to this study, sutureless SFIOL and RPIOL are two successful methods in terms of visual acuity, anterior segment, and keratometry outcomes in aphakic patients after phacoemulsification.

ß2-microglobulin expression is associated with aggressive histology, activated tumor immune milieu, and outcome in colon carcinoma.

OBJECTIVES: We sought to assess the expression of human leukocyte antigen (HLA) proteins and ß2-microglobulin (B2M) in tumor cells and the relationship with immune microenvironment and outcome in colorectal cancer (CRC). METHODS: A total of 953 CRC cases were evaluated by immunohistochemistry for HLA class I, HLA class II, and B2M. The expression level of these biomarkers was correlated with clinicopathologic information, BRAF V600E and mismatch repair (MMR) proteins, and the quantitated expression levels of immune cells (CD8 and CD163) and immune regulatory proteins (FoxP3, programmed cell death 1 ligand 1 [PD-L1], and LAG3). RESULTS: We found that B2M-low tumors were statistically correlated with aggressive histologic features, including higher stage, higher grade, extramural venous invasion, perineural invasion, and distant metastasis. Expression of B2M was positively correlated (R2 = 0.3) and significantly associated with MMR-deficient tumors (P < .001); B2M-low tumors were also associated with an "immune cold"' microenvironment, including a reduced number of immune cells (CD8 and CD163), reduced expression of immune regulatory proteins by immune cells (PD-L1, FoxP3, and LAG3), and reduced tumor cell expression of PD-L1. These B2M-low tumors correlated with lower disease-specific survival (P = .018), a finding that maintained significance only for the proficient MMR cohort (P = .037). CONCLUSIONS: Our findings suggest that B2M expression may support predictive models for both outcome and checkpoint inhibitor therapy treatment response for colorectal adenocarcinoma.

SOX17 enables immune evasion of early colorectal adenomas and cancers.

A hallmark of cancer is the avoidance of immune destruction. This process has been primarily investigated in locally advanced or metastatic cancer1-3; however, much less is known about how pre-malignant or early invasive tumours evade immune detection. Here, to understand this process in early colorectal cancers (CRCs), we investigated how naive colon cancer organoids that were engineered in vitro to harbour Apc-null, KrasG12D and Trp53-null (AKP) mutations adapted to the in vivo native colonic environment. Comprehensive transcriptomic and chromatin analyses revealed that the endoderm-specifying transcription factor SOX17 became strongly upregulated in vivo. Notably, whereas SOX17 loss did not affect AKP organoid propagation in vitro, its loss markedly reduced the ability of AKP tumours to persist in vivo. The small fraction of SOX17-null tumours that grew displayed notable interferon-γ (IFNγ)-producing effector-like CD8+ T cell infiltrates in contrast to the immune-suppressive microenvironment in wild-type counterparts. Mechanistically, in both endogenous Apc-null pre-malignant adenomas and transplanted organoid-derived AKP CRCs, SOX17 suppresses the ability of tumour cells to sense and respond to IFNγ, preventing anti-tumour T cell responses. Finally, SOX17 engages a fetal intestinal programme that drives differentiation away from LGR5+ tumour cells to produce immune-evasive LGR5- tumour cells with lower expression of major histocompatibility complex class I (MHC-I). We propose that SOX17 is a transcription factor that is engaged during the early steps of colon cancer to orchestrate an immune-evasive programme that permits CRC initiation and progression.

Lymphoglandular Complex-Like Colorectal Carcinoma-A Series of 20 Colorectal Cases, Including Newly Reported Features of Malignant Behavior.

Distinguishing colon carcinoma that is surrounded by well-circumscribed lymphoid tissue from adenomas involving lymphoglandular complexes can be difficult. We assessed a multi-institutional international cohort of 20 colorectal carcinomas with associated prominent lymphoid infiltrates, which we referred to as lymphoglandular complex-like carcinoma (LGCC). We collected clinical and endoscopic features, including lesion size, endoscopic appearance, location, procedure, follow-up, AJCC stage, and mismatch repair status. We recorded the presence of the following histologic features: haphazard gland distribution, gland angulation, gland fusion, solid nest formation, single-cell formation, stromal desmoplasia, presence of lymphovascular invasion and perineural invasion, presence of lamina propria, cytologic atypia as low- or high-grade, presence of goblet cells in the invasive component, and the presence of a surface lesion. Most cases (9 of 13) were described endoscopically as sessile polyps with an average size of 1.56 cm. Most cases (90%) were associated with a surface lesion, of which the majority were tubular adenomas, though a subset was associated with sessile serrated lesions with dysplasia (3 of 18). All cases of LGCC demonstrated haphazard gland distribution and either gland angulation, fusion, or solid nest formation. A portion of cases demonstrated single-cell infiltration (35%) and desmoplasia (50%), and rarely lymphovascular invasion was present (5%). A subset (10%) of cases invaded beyond the submucosa. Deficient mismatch repair was present in 22% (2 of 9) of cases for which it was performed. In cases of colectomy or completion colectomy, nodal metastasis was present in 38% (3 of 8). No cases demonstrated disease recurrence or disease-specific mortality. Overall, LGCC represents an enigmatic subset of carcinomas that is important to distinguish from adenomas involving lymphoglandular complexes due to its varying prognostic outcomes.

Does corneal tattooing affect the conjunctival microbiota?

PURPOSE: This study aimed to investigate the effects of commercial tattoo inks used in corneal tattooing on conjunctival microbiota. METHOD: This prospective case control study consisted of 125 participants divided in the following three groups: 35 patients with corneal tattoos, 40 patients with corneal leukoma, and 50 healthy subjects. Corneal tattooing was performed in all the cases in this study using a tattoo pen machine and commercial tattoo ink. A total of 500 cultures were taken from 250 eyes of 125 individuals on chocolate and sheep blood agar. Bacteriological samples were taken from the inferior eyelid conjunctiva using a sterile cotton swab. Without any contact elsewhere, the swabs were smeared on bedside chocolate agars and 5% sheep blood agar. RESULTS: In tattooed eyes, bacterial growth was detected in 42.9% of the chocolate and sheep blood agar samples. In other healthy eyes of patients with corneal tattoos, 54.5% bacterial growth on chocolate agar and 57.1% on sheep blood agar were detected. No statistical difference was detected in the conjunctival microbiota of chocolate and sheep blood agar (p = 0.254, p = 0.134, respectively) in the tattooed eyes compared to the other eye of the individual. No statistically significant difference was found in terms of bacterial growth in tattooed, leukoma, or healthy eyes on chocolate and sheep blood agar (p = 0.408, p = 0.349). The growth rate of Staphylococcus epidermidis decreased by 33.3% (from 12 to 8) on chocolate agar in 35 tattooed eyes, and it decreased by 28.5% (from 14 to 10) on sheep blood agar, while gram-negative bacteria Brevundimonas diminuta, Acinetobacter lwoffii, and Psychrobacter faecalis were detected in three patients. CONCLUSION: Corneal tattooing using commercial dye does not affect conjunctival microbiota. In the past 3 years, 120 patients have been tattooed with commercial tattoo ink in Istanbul Medeniyet University Göztepe Training and Research Hospital. No complications related to infection were found in the 3-year follow-up. The gram-negative bacteria detected in the healthy control group and tattooed eyes were bacteria found on normal skin or in the respiratory tract. Although some gram-negative bacteria do not cause infection, careful eye examination, follow-up, and culture are required in suspicious cases.

Chronic metabolic stress drives developmental programs and loss of tissue functions in non-transformed liver that mirror tumor states and stratify survival.

Under chronic stress, cells must balance competing demands between cellular survival and tissue function. In metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH), hepatocytes cooperate with structural and immune cells to perform crucial metabolic, synthetic, and detoxification functions despite nutrient imbalances. While prior work has emphasized stress-induced drivers of cell death, the dynamic adaptations of surviving cells and their functional repercussions remain unclear. Namely, we do not know which pathways and programs define cellular responses, what regulatory factors mediate (mal)adaptations, and how this aberrant activity connects to tissue-scale dysfunction and long-term disease outcomes. Here, by applying longitudinal single-cell multi -omics to a mouse model of chronic metabolic stress and extending to human cohorts, we show that stress drives survival-linked tradeoffs and metabolic rewiring, manifesting as shifts towards development-associated states in non-transformed hepatocytes with accompanying decreases in their professional functionality. Diet-induced adaptations occur significantly prior to tumorigenesis but parallel tumorigenesis-induced phenotypes and predict worsened human cancer survival. Through the development of a multi -omic computational gene regulatory inference framework and human in vitro and mouse in vivo genetic perturbations, we validate transcriptional (RELB, SOX4) and metabolic (HMGCS2) mediators that co-regulate and couple the balance between developmental state and hepatocyte functional identity programming. Our work defines cellular features of liver adaptation to chronic stress as well as their links to long-term disease outcomes and cancer hallmarks, unifying diverse axes of cellular dysfunction around core causal mechanisms.

Beta-Hydroxybutyrate Augments Oxaliplatin-Induced Cytotoxicity by Altering Energy Metabolism in Colorectal Cancer Organoids.

Deregulation of cellular metabolism has recently emerged as a notable cancer characteristic. This reprogramming of key metabolic pathways supports tumor growth. Targeting cancer metabolism demonstrates the potential for managing colorectal cancer. Beta-hydroxybutyrate (BOHB) acts as an acetyl-CoA source for the tricarboxylic acid (TCA) cycle, possibly redirecting energy metabolic pathways towards the TCA cycle that could enhance sensitivity to oxaliplatin, through the generation of reactive oxygen species (ROS). This study explores the potential of BOHB to enhance oxaliplatin's cytotoxic effect by altering the energy metabolism in colorectal cancer. The study employed advanced in vitro organoid technology, which successfully emulates in vivo physiology. The combination treatment efficacy of BOHB and oxaliplatin was evaluated via cell viability assay. The levels of key proteins involved in energy metabolism, apoptotic pathways, DNA damage markers, and histone acetylation were analyzed via Western Blot. ROS levels were evaluated via flow cytometer. Non-toxic doses of BOHB with oxaliplatin significantly amplified cytotoxicity in colorectal cancer organoids. Treatment with BOHB and/or melatonin resulted in significantly decreased lactate dehydrogenase A and increased mitochondrial carrier protein 2 levels, indicating inhibited aerobic glycolysis and an increased oxidative phosphorylation rate. This metabolic shift induced apoptotic cell death mediated by oxaliplatin, owing to high levels of ROS. Melatonin counteracted this effect by protecting cancer cells from high oxidative stress conditions. BOHB may enhance the efficacy of chemotherapeutics with a similar mechanism of action to oxaliplatin in colorectal cancer treatment. These innovative combinations could improve treatment outcomes for colorectal cancer patients.

A NEW ARTIFICIAL INTELLIGENCE-BASED CLINICAL DECISION SUPPORT SYSTEM FOR DIAGNOSIS OF MAJOR PSYCHIATRIC DISEASES BASED ON VOICE ANALYSIS.

BACKGROUND: Speech features are essential components of psychiatric examinations, serving as important markers in the recognition and monitoring of mental illnesses. This study aims to develop a new clinical decision support system based on artificial intelligence, utilizing speech signals to distinguish between bipolar, depressive, anxiety and schizophrenia spectrum disorders. SUBJECTS AND METHODS: A total of 79 patients, who were admitted to the psychiatry clinic between 2020-2021, including 15 with schizophrenia spectrum disorders, 24 with anxiety disorders, 25 with depressive disorders, and 15 with bipolar affective disorder, alongside with 25 healthy individuals were included in the study. The speech signal dataset was created by recording participants' readings of two texts determined by the Russell emotion model. The number of speech samples was increased by using random sampling in speech signals. The sample audio signals were decomposed into time-frequency coefficients using Wavelet Packet Transform (WPT). Feature extraction was performed using each coefficient obtained from both Mel-Frequency Cepstral Coefficients (MFCC) and Gammatone Cepstral Coefficient (GTCC) methods. The disorder classification was carried out using k-Nearest Neighbor (kNN) and Support Vector Machine (SVM) classifiers. RESULTS: The success rate of the developed model in distinguishing the disorders was 96.943%. While the kNN model exhibited the highest performance in diagnosing bipolar disorder, it performed the least effectively in detecting depressive disorders. Whereas, the SVM model demonstrated close and high performance in detecting anxiety and psychosis, but its performance was low in identifying bipolar disorder. The findings support the utilization of speech analysis for distinguishing major psychiatric disorders. In this regard, the future development of artificial intelligence-based systems has the potential to enhance the psychiatric diagnosis process.

Randomised, placebo-controlled, phase 3 trial of the effect of the omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) on colorectal cancer recurrence and survival after surgery for resectable liver metastases: EPA for Metastasis Trial 2 (EMT2) study protocol.

INTRODUCTION: There remains an unmet need for safe and cost-effective adjunctive treatment of advanced colorectal cancer (CRC). The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) is safe, well-tolerated and has anti-inflammatory as well as antineoplastic properties. A phase 2 randomised trial of preoperative EPA free fatty acid 2 g daily in patients undergoing surgery for CRC liver metastasis showed no difference in the primary endpoint (histological tumour proliferation index) compared with placebo. However, the trial demonstrated possible benefit for the prespecified exploratory endpoint of postoperative disease-free survival. Therefore, we tested the hypothesis that EPA treatment, started before liver resection surgery (and continued postoperatively), improves CRC outcomes in patients with CRC liver metastasis. METHODS AND ANALYSIS: The EPA for Metastasis Trial 2 trial is a randomised, double-blind, placebo-controlled, phase 3 trial of 4 g EPA ethyl ester (icosapent ethyl (IPE; Vascepa)) daily in patients undergoing liver resection surgery for CRC liver metastasis with curative intent. Trial treatment continues for a minimum of 2 years and maximum of 4 years, with 6 monthly assessments, including quality of life outcomes, as well as annual clinical record review after the trial intervention. The primary endpoint is CRC progression-free survival. Key secondary endpoints are overall survival, as well as the safety and tolerability of IPE. A minimum 388 participants are estimated to provide 247 CRC progression events during minimum 2-year follow-up, allowing detection of an HR of 0.7 in favour of IPE, with a power of 80% at the 5% (two sided) level of significance, assuming drop-out of 15%. ETHICS AND DISSEMINATION: Ethical and health research authority approval was obtained in January 2018. All data will be collected by 2025. Full trial results will be published in 2026. Secondary analyses of health economic data, biomarker studies and other translational work will be published subsequently. TRIAL REGISTRATION NUMBER: NCT03428477.

Evaluation of the effect of unilateral and bilateral inferior oblique myectomy on fundus torsion in primary and secondary inferior oblique overaction.

OBJECTIVE: This article evaluates the effects of unilateral and bilateral inferior oblique myectomy (IOM) on fundus torsion in primary and secondary inferior oblique overaction (IOOA). METHODS: This study analyzed 230 OCT images of 53 eyes of 32 patients who had undergone IOM by a single surgeon in the last two years. The disc-foveal angle (DFA) was calculated by digitally measuring the angle between the horizontal line passing through the geometric center of the optic disc and the curved line connecting the fovea to the geometric center of the optic disc. DFA was classified into intorsion, normal torsion, and extortion. The DFA was measured from the OCT images before the operation in the first week, first month, third month, and sixth month. RESULTS: When all the patients in our study were evaluated together, IOM statistically reduced the mean DFA in the third month (p=0.00). The DFA was higher in the secondary IOOA group than in the primary IOOA group (p=0.24). Bilateral IOM statistically significantly reduced DFA in the third month (p=0.00) and decreased the DFA difference between the two eyes in the third month (p=0.583). Unilateral IOM increased the DFA, rather than decreasing it, in the first week in operated eyes (p=0594) and increased the DFA difference between the two eyes after surgery (p=0.477). When we evaluated the localization of the macula as an intorsion, normal intorsion, or extortion, the extortion decreased from 36 to nine in the third month after bilateral IOM, and intorsion was seen in only two. Unilateral surgery did not significantly change fundus torsion in primary IOOA, and it caused intorsion in 3 of 6 (50%) operated eyes in secondary IOOA. CONCLUSION: Although unilateral IOM provides a clinical improvement in secondary IOOA, it increases the difference in DFA between both eyes and causes intorsion in 50% of patients. Masked IOOA was detected in 3 of 11 (27.3%) patients who underwent unilateral IOM. When deciding on unilateral surgery, the possibility of increased DFA difference between both eyes, intorsion in the operated eye, and masked IOOA in the other eye should be considered.

Bacterial contamination of multi-use tear drops, gels, and ointments.

PURPOSE: This study aimed to investigate the bacterial contamination of multi-use tear drops, gels, and ointments that patients use at home. METHOD: A total of 271 multi-use containers used by 168 patients were examined. Conjunctival culture samples were obtained from patients who used tear drops, gels, and ointments that were found to be contaminated. RESULTS: Bacterial contamination was detected in 33 (12.2 %) out of the 271 containers. The contamination rate was 7.9 % in tear drops, 11.7 % in gels, and 32 % in ointments. A statistically significant difference was found between the drops, gels, and ointment groups (P = 0.04). Bacterial contamination was detected in 25 (18.9 %) out of 132 collapsible tubes and 8 (5.8 %) out of 139 plastic bottles (P = 0.01). Important bacteria, including Pseudomonas stutzeri, Pseudomonas aeruginosa, Bacillus licheniformis, Paenibacillus pabuli, Proteus mirabilis, Pantoea agglomerans, Morganella morganii, Serratia marcescens, and Serratia liquefaciens, were detected. Mucorales spp. fungus was seen in a gel. Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus, and M. morganii were found in the conjunctival microbiota of three patients. CONCLUSION: The overall contamination rate of ocular lubricants was low (12.2%); however, a significant difference was found between the drops, gels, and ointments. The contamination rate was higher in gels and ointments than that in drops. The contamination rate was found to be increased in the collapsible tube. The use of ocular lubricants is safe; however, patients must be cautious when using multi-use tear drops, gels, and ointments to avoid contamination. Whenever possible, bottles should be preferred instead of collapsible tubes.

Ultrasensitive Detection of Circulating LINE-1 ORF1p as a Specific Multicancer Biomarker.

Improved biomarkers are needed for early cancer detection, risk stratification, treatment selection, and monitoring treatment response. Although proteins can be useful blood-based biomarkers, many have limited sensitivity or specificity for these applications. Long INterspersed Element-1 (LINE-1) open reading frame 1 protein (ORF1p) is a transposable element protein overexpressed in carcinomas and high-risk precursors during carcinogenesis with negligible expression in normal tissues, suggesting ORF1p could be a highly specific cancer biomarker. To explore ORF1p as a blood-based biomarker, we engineered ultrasensitive digital immunoassays that detect mid-attomolar (10-17 mol/L) ORF1p concentrations in plasma across multiple cancers with high specificity. Plasma ORF1p shows promise for early detection of ovarian cancer, improves diagnostic performance in a multianalyte panel, provides early therapeutic response monitoring in gastroesophageal cancers, and is prognostic for overall survival in gastroesophageal and colorectal cancers. Together, these observations nominate ORF1p as a multicancer biomarker with potential utility for disease detection and monitoring. SIGNIFICANCE: The LINE-1 ORF1p transposon protein is pervasively expressed in many cancers and is a highly specific biomarker of multiple common, lethal carcinomas and their high-risk precursors in tissue and blood. Ultrasensitive ORF1p assays from as little as 25 µL plasma are novel, rapid, cost-effective tools in cancer detection and monitoring. See related commentary by Doucet and Cristofari, p. 2502. This article is featured in Selected Articles from This Issue, p. 2489.