tbuckley/cabot-search huggingface dataset:
Bacterial extracellular vesicles at the interface of gut microbiota and immunity
Authors: Inês Melo-Marques, Sandra Morais Cardoso, Nuno Empadinhas
Journal: Gut Microbes (2024)

Bacterial extracellular vesicles (BEVs) are nano-sized lipid-shielded structures released by bacteria and that play an important role in intercellular communication. Their broad taxonomic origins and varying cargo compositions suggest their active participation in significant biological mechanisms. Specifically, they are involved in directly modulating microbial ecosystems, competing with other organisms, contributing to pathogenicity, and influencing the immunity of their hosts. This review examines the mechanisms that underlie the modulatory effects of BEVs on gut dynamics and immunity. Understanding how BEVs modulate microbiota composition and functional imbalances is crucial, as gut dysbiosis is implicated not only in the pathogenesis of various gastrointestinal, metabolic, and neurological diseases, but also in reducing resistance to colonization by enteric pathogens, which is particularly concerning given the current antimicrobial resistance crisis. This review summarizes recent advancements in the field of BEVs to encourage further research into these enigmatic entities. This will facilitate a better understanding of intra- and interkingdom communication phenomena and reveal promising therapeutic approaches.
3D bioprinting of high-performance hydrogel with in-situ birth of stem cell spheroids
Authors: Shunyao Zhu, Xueyuan Liao, Yue Xu, Nazi Zhou, Yingzi Pan, Jinlin Song, Taijing Zheng, Lin Zhang, Liyun Bai, Yu Wang, Xia Zhou, Maling Gou, Jie Tao, Rui Liu
Journal: Bioactive Materials (2024)
A multicenter, randomized, non-comparative, phase II study of nivolumab ± ipilimumab for patients with metastatic sarcoma (Alliance A091401): expansion cohorts and correlative analyses
Authors: Nathan D Seligson, James L Chen, Austin C Goodrich, Brian A Van Tine, Jordan D Campbell, Allison L Richards, Cristina R Antonescu, David A Liebner, Mohammed M Milhem, Howard Streicher, William D Tap, Gary K Schwartz, Suzanne George, Sandra P D'Angelo
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background In this open-label, randomized, non-comparative, multicenter phase II study (Alliance A091401) we report on three expansion cohorts treated with nivolumab (N) with and without ipilimumab (N+I) and provide a multi-omic correlative analysis of actionable biomarkers. Methods Patients were randomized (non-comparative) to receive either N or N+I. The primary endpoint was a 6-month confirmed response rate (CRR) defined by Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included treatment-related adverse events (TRAEs), progression-free survival, and overall survival. Multi-omic correlative analyses were conducted using samples from both the primary and expansion cohorts. Results A total of 66 patients were evaluated for the primary endpoint with disease including gastrointestinal stromal tumor (GIST, n=18), undifferentiated pleomorphic sarcoma (UPS, n=24), and dedifferentiated liposarcoma (DDLPS, n=24). Neither N nor N+I achieved a complete or partial response in the GIST expansion cohort. In DDLPS and UPS, the primary response endpoint of CRR was met with N+I (both 16.6%, 2/12) but not with N alone (both 8.3%, 1/12). In the GIST cohort, TRAE was higher with N+I treatment, halting enrollment as required per protocol. In a correlative analysis of patients for the expansion cohort and the original cohort (n=86), traditional biomarkers of immunotherapy response were not correlated with response in any histological subtype. Markers of genomic instability including the presence of gene fusions and increased subclonal mutations correlated with improved clinical outcomes. Conclusions This expansion cohort reaffirms the outcomes of A091401. There remains a pressing need to determine the role of and predictive biomarkers for immunotherapy in sarcoma. Trial registration number NCT02500797 .
Inhibition of the NF-κB/HIF-1α signaling pathway in colorectal cancer by tyrosol: a gut microbiota-derived metabolite
Authors: Jian Guo, Fanqi Meng, Ruixue Hu, Lei Chen, Jiang Chang, Ke Zhao, Honglin Ren, Zengshan Liu, Pan Hu, Guangyi Wang, Jiandong Tai
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background The development and progression of colorectal cancer (CRC) are influenced by the gut environment, much of which is modulated by microbial-derived metabolites. Although some research has been conducted on the gut microbiota, there have been limited empirical investigations on the role of the microbial-derived metabolites in CRC. Methods In this study, we used LC-MS and 16S rRNA sequencing to identify gut microbiome-associated fecal metabolites in patients with CRC and healthy controls. Moreover, we examined the effects of Faecalibacterium prausnitzii and tyrosol on CRC by establishing orthotopic and subcutaneous tumor mouse models. Additionally, we conducted in vitro experiments to investigate the mechanism through which tyrosol inhibits tumor cell growth. Results Our study revealed changes in the gut microbiome and metabolome that are linked to CRC. We observed that Faecalibacterium prausnitzii , a bacterium known for its multiple anti-CRC properties, is significantly more abundant in the intestines of healthy individuals than in those of individuals with CRC. In mouse tumor models, our study illustrated that Faecalibacterium prausnitzii has the ability to inhibit tumor growth by reducing inflammatory responses and enhancing tumor immunity. Additionally, research investigating the relationship between CRC-associated features and microbe–metabolite interactions revealed a correlation between Faecalibacterium prausnitzii and tyrosol, both of which are less abundant in the intestines of tumor patients. Tyrosol demonstrated antitumor activity in vivo and specifically targeted CRC cells without affecting intestinal epithelial cells in cell experiments. Moreover, tyrosol treatment effectively reduced the levels of reactive oxygen species (ROS) and inflammatory cytokines in MC38 cells. Western blot analysis further revealed that tyrosol inhibited the activation of the NF-κB and HIF-1 signaling pathways. Conclusions This study investigated the relationship between CRC development and changes in the gut microbiota and microbial-derived metabolites. Specifically, the intestinal metabolite tyrosol exhibits antitumor effects by inhibiting HIF-1α/NF-κB signaling pathway activation, leading to a reduction in the levels of ROS and inflammatory factors. These findings indicate that manipulating the gut microbiota and its metabolites could be a promising approach for preventing and treating CRC and could provide insights for the development of anticancer drugs.
Phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: the desmoid tumors
Authors: Young Kwang Chae, Megan Othus, Sandip Patel, Benjamin Powers, Chung-Tsen Hsueh, Rangaswamy Govindarajan, Silvana Bucur, Hye Sung Kim, Liam Il-Young Chung, Christine McLeod, Helen X Chen, Elad Sharon, Howard Streicher, Christopher W Ryan, Charles Blanke, Razelle Kurzrock
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Dual inhibition using anti-programmed death-1 (PD-1) and anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) checkpoint inhibitors has proven effective in many cancers. However, its efficacy in rare solid cancers remains unclear. Desmoid tumors are ultrarare soft-tissue tumors, traditionally treated with surgery. This study reviews the first results of using ipilimumab and nivolumab in the desmoid tumor cohort of the SWOG S1609 Dual Anti-CTLA-4 &amp; Anti-PD-1 blockade in Rare Tumors (DART) trial. Methods DART is a prospective/open-label/multicenter (1,016 US sites)/multicohort phase II trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) that opened at 1,016 US sites. The primary endpoint included overall response rate (ORR) defined as confirmed complete (CR) and partial responses (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1. Secondary endpoints include progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR; stable disease (SD) ≥6 months plus CR and PR) and toxicity. Results Sixteen evaluable patients (median age: 37) with desmoid tumors and a median of 1.5 prior therapies (with no prior exposure to immunotherapy) were analyzed. The tumors varied in location (eight abdomen, three lower limb, two upper limb, two pelvis, and one neck). ORR was 18.8% (3/16; 3 confirmed PR): 40% regression (PFS 30+ months), 83% regression (PFS 16 months) and 71% regression (PFS 8.4 months). Seven additional patients (43.8%) had prolonged SD over 6 months (PFS: 16.5, 22.4+, 22.6, 30.1, 38.2+, 48.3+ and 60.7+ months). Overall CBR was 62.5% (10/16). Median PFS was 19.4 months, with 6-month PFS of 73% and 1-year PFS of 67%. All patients were alive at 1 year; median OS was not assessable, as 13 patients were alive at analysis. Common adverse events included fatigue, nausea and hypothyroidism, with 50% experiencing grade 3–4 events. There were no grade 5 events. Conclusion Treatment with ipilimumab and nivolumab in desmoid tumors yielded an ORR of 18.8% and a CBR of 62.5% with durable responses seen. This is the first prospective study exploring the efficacy of this combination in this rare disease. Ongoing studies aim to identify markers for response and resistance. Expanded trials are necessary. Trial registration number NCT02834013 .
Anti-metabolite chemotherapy increases LAG-3 expressing tumor-infiltrating lymphocytes which can be targeted by combination immune checkpoint blockade
Authors: Nicola Principe, Amber-Lee Phung, Kofi L P Stevens, Omar Elaskalani, Ben Wylie, Caitlin M Tilsed, Fezaan Sheikh, M Lizeth Orozco Morales, Joel Kidman, Elly Marcq, Scott A Fisher, Anna K Nowak, Alison M McDonnell, W Joost Lesterhuis, Jonathan Chee
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein/ligand 1 (PD-1/PD-L1) are approved for treatment of multiple cancer types. Chemotherapy is often administered with immune checkpoint blockade (ICB) therapies that target CTLA-4 and/or PD-(L)1. ICB targeting other immune checkpoints such as lymphocyte activating gene-3 (LAG-3) has the potential to improve antitumor responses when combined with chemotherapy. Response to anti-PD-1 ICB is dependent on progenitor exhausted CD8 + T cells (T PEX ) in the tumor, but it is unclear how chemotherapy alters T PEX proportions and phenotype. Methods Here we investigated whether sequential chemotherapy altered T PEX frequency and immune checkpoint expression in multiple murine tumor models. Results Two doses of two different anti-metabolite chemotherapies increased tumor infiltrating CD4 + , and CD8 + T PEX expressing LAG-3 in multiple mouse models, which was not restricted to tumor antigen specific CD8 + T cells. To determine if LAG-3 + tumor infiltrating lymphocytes (TILs) could be targeted to improve tumor control, we administered anti-LAG-3 and anti-PD-1 ICB after two doses of chemotherapy and found combination therapy generated robust antitumor responses compared with each agent alone. Both anti-LAG-3 and anti-PD-1 ICB with chemotherapy were required for the complete tumor regression observed. Conclusions Changes in immune checkpoint expression on TILs during chemotherapy administration informs selection of ICB therapies to combine with.
PSMA and Sigma-1 receptor dual-targeted peptide mediates superior radionuclide imaging and therapy of prostate cancer
Authors: Zhenyuan Huangfu, Jiangtao Yang, Juan Sun, Bin Xu, Lei Tao, Jiang Wu, Feng Wang, Guanglin Wang, Fenghua Meng, Zhiyuan Zhong
Journal: Journal of Controlled Release (2024)
Efficacy and Safety of Finerenone Across the Ejection Fraction Spectrum in Heart Failure with Mildly Reduced and Preserved Ejection Fraction: a Prespecified Analysis of The FINEARTS-HF Trial
Authors: Kieran F. Docherty, Alasdair D. Henderson, Pardeep S. Jhund, Brian L. Claggett, Akshay S. Desai, Katharina Mueller, Prabhakar Viswanathan, Andrea Scalise, Carolyn S.P. Lam, Michele Senni, Sanjiv J. Shah, Adriaan A. Voors, Faiez Zannad, Bertram Pitt, Muthiah Vaduganathan, Scott D. Solomon, John JV.. McMurray
Journal: Circulation (2024)

Background: The effect of treatments for heart failure may vary among patients according to left ventricular ejection fraction (LVEF). In the FINEARTS-HF, the nonsteroidal MRA finerenone reduced the risk of cardiovascular death and total worsening heart failure events in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). We examined the effect of finerenone according to LVEF in FINEARTS-HF. Methods: FINEARTS-HF was a randomized, placebo-controlled trial examining the efficacy and safety of finerenone in patients with heart failure and LVEF &amp;#x226540%. The treatment effect of finerenone was examined in prespecified analyses according to LVEF categories (&lt;50%, ≥50 to &lt;60%, and ≥60%) and with LVEF as a continuous variable. The primary outcome was a composite of total (first and recurrent) worsening HF events and cardiovascular death. Results: Baseline LVEF data were available for 5993 of the 6001 participants in FINEARTS-HF. Mean and median LVEF were 53 ± 8% and 53% (IQR 46% -58%), respectively. LVEF was &lt;50% in 2172 (36), between 50 to &lt;60% in 2674 (45%), and ≥60% in 1147 (19%). Patients with a higher LVEF were older, more commonly female, were less likely to have a history of coronary artery disease, and more frequently had a history of hypertension and chronic kidney disease compared to those with a lower LVEF. Finerenone reduced the risk of cardiovascular death and total heart failure events consistently across LVEF categories: LVEF &lt;50% rate ratio (RR) = 0.84 (95% CI 0.68, 1.03), LVEF ≥50 to &lt;60% RR = 0.80 (0.66, 0.97) and LVEF ≥60% RR = 0.94 (0.70, 1.25); p interaction = 0.70. There was no modification of the benefit of finerenone across the range of LVEF when analyzed as a continuous variable (p interaction = 0.28). There was a similar consistent effect of finerenone on reducing the total number of worsening heart failure events (continuous p interaction = 0.26). Conclusions: In patients with HFmrEF/HFpEF, finerenone reduced the risk of cardiovascular death and worsening heart failure events, irrespective of LVEF.
The effect of dupilumab on caregiver- and patient-reported outcomes in young children with moderate-to-severe atopic dermatitis: results from a placebo-controlled, phase 3 study
Authors: Amy S Paller, Jonathan I Silverberg, Eric L Simpson, Michael J Cork, Peter D Arkwright, Zhen Chen, Ashish Bansal, Randy Prescilla, Zhixiao Wang, Ainara R Marco
Journal: Journal of the American Academy of Dermatology (2024)
Stereotactic Radiosurgery for 1-10 Brain Metastases to avoid Whole-Brain Radiotherapy - Results of the CYBER-SPACE Randomized Phase 2 Trial
Authors: Rami A El Shafie, Denise Bernhardt, Thomas Welzel, Annabella Schiele, Daniela Schmitt, Paul Thalmann, Sinem Erdem, Angela Paul, Simon Höne, Kristin Lang, Laila König, Fabian Weykamp, Sebastian Adeberg, Adriane Lentz-Hommertgen, Cornelia Jäkel, Farastuk Bozorgmehr, Ursula Nestle, Michael Thomas, Anja Sander, Meinhard Kieser, Jürgen Debus, Stefan Rieken
Journal: Neuro-Oncology (2024)

Abstract Background Stereotactic radiosurgery (SRS) is an emerging alternative to whole-brain radiotherapy (WBRT) for treating multiple brain metastases (BM), reducing toxicity, and improving tumor control. The CYBER-SPACE trial compared SRS based on either SPACE or MPRAGE MRI sequence for avoiding or delaying WBRT in patients with 1–10 BM. Methods Patients with 1–10 untreated BM were randomized 1:1 to receive SRS of all lesions based on either SPACE or MPRAGE MRI sequences. If subsequently new BM occurred, SRS was repeated. WBRT was indicated upon occurrence of &amp;gt;10 new BM, leptomeningeal disease, or exhausted SRS-radiotolerance. The primary outcome was freedom from WBRT indication (WBRTi). Secondary outcomes included overall survival (OS), safety, and quality of life. Results A total of 202 patients were randomized; SPACE n = 99, MPRAGE n = 103. Twelve-month WBRTi-free survival was 77.1% (95% CI: 69.5%–83.1%) overall, 78.5% (95% CI: 66.7%–86.5%) for SPACE, and 76.0% (95% CI: 65.2%–83.9%) for MPRAGE (hazard ratio [HR] = 0.84, 95% CI: 0.43–1.63, P = .590). Patients with 5–10 BM had shorter WBRTi-free survival (HR = 3.13, 95% CI: 1.53–6.40, P = .002). Median OS was 13.1 months overall, 10.5 months for SPACE, and 15.2 months for MPRAGE (HR = 1.10, 95% CI: 0.78–1.56, P = .585). Neurologic death rate was 10.1%. Predictors for longer OS included Karnofsky Performance Status &amp;gt;80% (HR = 0.51, 95% CI: 0.33–0.77, P = .002) and concurrent immunotherapy (HR = 0.34, 95% CI: 0.23–0.52, P &amp;lt; .001). Conclusions The more sensitive SPACE sequence did not improve outcomes over MPRAGE. SRS with thorough monitoring and immediate re-treatment for new lesions decreases the need for WBRT and achieves low neurologic death rates. SRS should be considered a favorable alternative to WBRT for patients with 1–10 BM.
Helicobacter pylori VacA-induced mitochondrial damage in the gastric pit cells of the antrum and therapeutic rescue
Authors: Ye Seul Son, Yong Hwan Kwon, Moo-Seung Lee, Ohman Kwon, Yu-Jin Jeong, Seon Ju Mun, Sojeong Jeon, Ji Hye Park, Man-Hoon Han, Jae-Sung Bae, Keun Hur, Ah-Ra Jang, Jong-Hwan Park, Hyun-Soo Cho, Cho-Rok Jung, Choong-Min Ryu, Myung Jin Son, Doo-Sang Park, Mi-Young Son
Journal: Biomaterials (2024)
Massive detection of cryptic recessive genetic defects in dairy cattle mining millions of life histories
Authors: Florian Besnard, Ana Guintard, Cécile Grohs, Laurence Guzylack-Piriou, Margarita Cano, Clémentine Escouflaire, Chris Hozé, Hélène Leclerc, Thierry Buronfosse, Lucie Dutheil, Jeanlin Jourdain, Anne Barbat, Sébastien Fritz, Marie-Christine Deloche, Aude Remot, Blandine Gaussères, Adèle Clément, Marion Bouchier, Elise Contat, Anne Relun, Vincent Plassard, Julie Rivière, Christine Péchoux, Marthe Vilotte, Camille Eche, Claire Kuchly, Mathieu Charles, Arnaud Boulling, Guillaume Viard, Stéphanie Minéry, Sarah Barbey, Clément Birbes, Coralie Danchin-Burge, Frédéric Launay, Sophie Mattalia, Aurélie Allais-Bonnet, Bérangère Ravary, Yves Millemann, Raphaël Guatteo, Christophe Klopp, Christine Gaspin, Carole Iampietro, Cécile Donnadieu, Denis Milan, Marie-Anne Arcangioli, Mekki Boussaha, Gilles Foucras, Didier Boichard, Aurélien Capitan
Journal: Genome biology (2024)

niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.
Correction: SMARCA4 controls state plasticity in small cell lung cancer through regulation of neuroendocrine transcription factors and REST splicing
Authors: Esther Redin, Harsha Sridhar, Yingqian A Zhan, Barbara Pereira Mello, Hong Zhong, Vidushi Durani, Amin Sabet, Parvathy Manoj, Irina Linkov, Juan Qiu, Richard P Koche, Elisa de Stanchina, Maider Astorkia, Doron Betel, Álvaro Quintanal-Villalonga, Charles M Rudin
Journal: Journal of Hematology & Oncology (2024)
Blending space and time to talk about cancer in extended reality
Authors: Tamsin J Robb, Yinan Liu, Braden Woodhouse, Charlotta Windahl, Daniel Hurley, Grant McArthur, Stephen B Fox, Lisa Brown, Parry Guilford, Alice Minhinnick, Christopher Jackson, Cherie Blenkiron, Kate Parker, Kimiora Henare, Rose McColl, Bianca Haux, Nick Young, Veronica Boyle, Laird Cameron, Sanjeev Deva, Jane Reeve, Cristin G Print, Michael Davis, Uwe Rieger, Ben Lawrence
Journal: npj Digital Medicine (2024)

We introduce a proof-of-concept extended reality (XR) environment for discussing cancer, presenting genomic information from multiple tumour sites in the context of 3D tumour models generated from CT scans. This tool enhances multidisciplinary discussions. Clinicians and cancer researchers explored its use in oncology, sharing perspectives on XR's potential for use in molecular tumour boards, clinician-patient communication, and education. XR serves as a universal language, fostering collaborative decision-making in oncology.
Autologous platelet concentrates as adjuvant in the surgical management of medication‐related osteonecrosis of the jaw
Authors: Francesco Bennardo, Selene Barone, Alessandro Antonelli, Amerigo Giudice
Journal: Periodontology 2000 (2024)

Abstract Medication‐related osteonecrosis of the jaw (MRONJ) is an infectious side effect associated with bisphosphonates and monoclonal antibodies (denosumab, immune modulators, and antiangiogenic medications). Adjunctive therapies for the surgical management of MRONJ include autologous platelet concentrates (APCs). These APCs serve as a source of various cells and growth factors that aid tissue healing and regeneration. This review evaluated the use of platelet‐rich plasma (PRP), plasma‐rich in growth factors (PRGF), and leukocyte‐ and platelet‐rich fibrin (L‐PRF) as adjuvant therapies for the surgical management of MRONJ by conducting analyses on the results of 58 articles. Compared to surgical treatment alone, the application of PRP and L‐PRF after surgery appears to increase healing in the management of patients with MRONJ. No studies have reported unhealed lesions as a result of surgical treatment of MRONJ with PRGF application or compared it with surgical treatment alone. The overall results of this review have shown favorable healing rates of MRONJ lesions managed with the application of APCs after surgical treatment; however, significant methodological limitations may limit the scientific evidence supporting their use. Further randomized controlled trials with strict criteria are needed to establish the extent to which APCs can improve wound healing and quality of life in patients with MRONJ requiring surgical treatment.
Early detection of ovarian cancer using cell-free DNA fragmentomes and protein biomarkers
Authors: Jamie E. Medina, Akshaya V. Annapragada, Pien Lof, Sarah Short, Adrianna L. Bartolomucci, Dimitrios Mathios, Shashikant Koul, Noushin Niknafs, Michael Noe, Zachariah H. Foda, Daniel C. Bruhm, Carolyn Hruban, Nicholas A. Vulpescu, Euihye Jung, Renu Dua, Jenna V. Canzoniero, Stephen Cristiano, Vilmos Adleff, Heather Symecko, Daan van den Broek, Lori J. Sokoll, Stephen B. Baylin, Michael F. Press, Dennis J. Slamon, Gottfried E. Konecny, Christina Therkildsen, Beatriz Carvalho, Gerrit A. Meijer, Claus Lindbjerg. Andersen, Susan M. Domchek, Ronny Drapkin, Robert B. Scharpf, Jillian Phallen, Christine A.R. Lok, Victor E. Velculescu
Journal: Cancer Discovery (2024)

Abstract Ovarian cancer is a leading cause of death for women worldwide, in part due to ineffective screening methods. In this study, we used whole-genome cell-free DNA (cfDNA) fragmentome and protein biomarker [cancer antigen 125 (CA-125) and human epididymis protein 4 (HE4)] analyses to evaluate 591 women with ovarian cancer, with benign adnexal masses, or without ovarian lesions. Using a machine learning model with the combined features, we detected ovarian cancer with specificity &amp;gt;99% and sensitivities of 72%, 69%, 87%, and 100% for stages I to IV, respectively. At the same specificity, CA-125 alone detected 34%, 62%, 63%, and 100%, and HE4 alone detected 28%, 27%, 67%, and 100% of ovarian cancers for stages I to IV, respectively. Our approach differentiated benign masses from ovarian cancers with high accuracy (AUC = 0.88, 95% confidence interval, 0.83–0.92). These results were validated in an independent population. These findings show that integrated cfDNA fragmentome and protein analyses detect ovarian cancers with high performance, enabling a new accessible approach for noninvasive ovarian cancer screening and diagnostic evaluation. Significance: There is an unmet need for effective ovarian cancer screening and diagnostic approaches that enable earlier-stage cancer detection and increased overall survival. We have developed a high-performing accessible approach that evaluates cfDNA fragmentomes and protein biomarkers to detect ovarian cancer.