tbuckley/cabot-search huggingface dataset:
Combined uterine and colorectal screening: A call for action.
Authors: Ruolin Lorraine Jiang, Caitlin Ruth Johnson, Alex Andrea Francoeur, Amandeep Kaur Mann-Grewal, Daniel Stuart Kapp, John K Chan
Journal: Journal of Clinical Oncology (2024)

5615 Background: Colon cancer is currently one of the top three malignancies in the US with routine screening guidelines in place. With the current rise in uterine cancer incidence and mortality, there is currently no screening for uterine cancer. We propose to evaluate the demographics and trends in uterine and colorectal cancer incidences among women in the United States. Methods: Uterine and colorectal cancer incidence data among U.S. women were collected from the United States Cancer Statistics (USCS) database from 2001-2019. Annual estimated uterine and colon cancer incidence data among women was obtained from the American Cancer Society (ACS) from 2015-2024. SEER*Stat 8.3.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate cancer incidences and trends per 100,000. Average annual percentage change (AAPC) was used to describe trends. Age-adjusted incidences were adjusted by the U.S. 2000 standard population. SAS Enterprise Guide v 7.1 was employed to analyze estimated cancer incidences. Results: From 2001-2019, 904,032 incident uterine cases were identified from USCS. Regarding race, 76.5% identified as non-Hispanic White, 10.5% as non-Hispanic Black, 8.38% as Hispanic, and 3.42% as non-Hispanic Asian/Pacific Islander. Of the 1,337,470 incident colorectal cancer cases obtained from USCS, 76.4% identified as White, 12.1% as Black, 7.10% as Hispanic, and 3.23% as Asian. Using ACS data from 2015-2024, the estimated number of annual incident uterine cancer cases increased from 54,870 to 67,880 while colorectal cancer incidence changed from 63,610 to 71,270 cases over the past 10 years (p&lt;0.0001). Using a projection model, we predict that the incidence of uterine cancer will surpass colon cancer by 2025 at 40.17 and 37.07/100,000 respectively (Table). Given that Black women have a high rate of increasing uterine cancer incidence (AAPC 2.88%; p&lt;0.0001), we predict that uterine cancer incidence among Black populations will surpass their rate of colon cancer by 2025 (42.97 vs 35.10/100,000). Conclusions: These findings suggest that uterine cancer incidence is increasing at a concerning rate and will likely surpass colon cancer by 2025. The impact of health disparities on Black women calls for research on the need for screening and novel therapies. [Table: see text]
Evaluation of a novel extracellular vesicle (EV) based ovarian cancer (OC) screening test in asymptomatic postmenopausal women.
Authors: Brendan Manning, Sanchari Banerjee, Laura T Bortolin, Emily S. Winn-Deen, Bilal Hamzeh, Brittany Grimes, Timothy Santos-Heiman, Delaney M. Byrne, Troy B Hawkins, MacKenzie Sadie King, Daniel P. Salem, Michael Smith, Sophia Apostolidou, Aleksandra Gentry-Maharaj, Christine D. Berg, Steven Skates, David Ransohoff, Toumy Guettouche, Dawn R Mattoon, Usha Menon
Journal: Journal of Clinical Oncology (2024)

5553 Background: Screening for OC that relies on CA125 and imaging lacks early-stage sensitivity, highlighting the need for a more effective test. EVs in blood may provide increased sensitivity from vesicles released in abundance and increased specificity from assessing multiple cancer-related markers colocalized on a vesicle surface. We report performance of an EV based OC Test in samples from asymptomatic postmenopausal women in the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Methods: The OC Test (biomarkers, classifier, cutoff) was locked following a training study, after which we observed consistent assay performance in an independent cohort. Here we evaluated the OC Test in a blinded case-control study nested within the no screening (NS) and annual ultrasound screening (USS) arms of UKCTOCS. Cases were all women with a diagnosis (Dx) of high-grade serous carcinoma (HGSC) within 36 months following sample donation and were matched 10:1 by age at collection to women who had no OC detected before or within the trial follow up period (controls). In addition, samples drawn within 6 months prior to a false positive (FP) transvaginal ultrasound from women who underwent surgery for benign findings in the USS arm were evaluated. OC Test and research use CA125 test at previously established 98% specificity cutoff, were determined blinded to case-control status, with unblinding done by UCL only after all tests were completed. Results: We assessed 129 samples from women with HGSC, 1310 controls and 100 USS FP samples. Data from 160 samples were excluded due to operator error, low sample volume or quality issues. In healthy controls, we observed a 97.7% specificity for the OC Test, and 95.5% for CA125, P = 0.006 McNemar test. We observed a sensitivity of 82% for the OC Test in samples drawn 0-12 months prior to Dx, and 63% for CA125, P = 0.016 McNemar test. Additionally, only 2.3% (2/86, 95% CI 0.3-8.1) women who underwent surgery for false positive USS results were positive for the OC Test vs 10.4% (9/86, 95% CI 4.9-18.9) for CA125. Conclusions: The OC Test is capable of highly sensitive and specific detection of HGSC in asymptomatic postmenopausal women one year prior to Dx and can detect HGSC up to three years prior to Dx with superior sensitivity and specificity compared to CA125. The data supports further evaluation of the OC Test for OC screening. [Table: see text]
Characterization of <i>ESR1</i> mutations in endometrial and ovarian cancers.
Authors: Stephanie Gaillard, Asnakech Bayable, Sachin Kumar Deshmukh, Utthara Nayar, Joanne Xiu, Lishann Ingram, Gretchen Hubbard, George W. Sledge, Thomas J. Herzog, Premal H. Thaker, Sharon Wu
Journal: Journal of Clinical Oncology (2024)

5598 Background: Low-grade ovarian (OC) and endometrial (EC) cancers frequently express estrogen receptor (ERα, encoded by ESR1), and are considered hormonally responsive tumors. The use of endocrine therapy in the advanced and recurrent disease setting is common. In breast cancer, ESR1 mutations ( ESR1mt) convey resistance to endocrine therapy. Mechanisms for endocrine failure in gynecologic cancers are not well understood. In this study, we aim to evaluate the prevalence of ESR1mt, and associated characteristics, in EC and OC. Methods: 17,666 EC and 21,879 OC samples were analyzed by NGS of DNA (NextSeq, 592 genes and NovaSeq, WES) and RNA (NovaSeq, WTS) (Caris Life Sciences, Phx, AZ). Tumor mutational burden (TMB) totaled all somatic mutations (mt) per tumor (TMB-H: &gt; 10 mt/MB). Statistical significance determined using chi-square and Mann-Whitney U test and adjusted for multiple comparisons (q&lt;0.05). Real-world overall survival (rwOS) and time on treat (ToT) obtained from insurance claims data and calculated from first treatment to last contact or last of treatment, respectively. Results: L536, Y537, and D538 were the most common ESR1 hotspot mutations. ESR1mt (EC: 2.38%, OC: 0.22%) were more prevalent in endometrioid EC tumors (4.2%) compared to other EC histologies (1.7%)(p&lt;0.05). Compared to high-grade serous (HGS) OC tumors (0.07%), ESR1mtmore prevalent in in low-grade serous (1.08%) and endometrioid (1.48%) (p&lt;0.05). ESR1mt was associated with higher ESR1 RNA expression (EC: 1.19-fc, OC: 1-.28-fc), ER+ (EC: 94.1% vs 63%, OC: 80.9% vs 49.3%), and PR+ (EC: 90.8% vs 46.7%, OC: 36% vs 24.5%) (q&lt;0.05). ESR1mt were associated with decreased TP53 mt (EC: 10.7% vs 50.9%, OC: 16.7% vs 78.3%), but increased PI3K pathway alterations (EC: PTEN mt: 70.4% vs 40%, PIK3R1 mt: 34.1% vs 19.6%, PIK3CA mt: 47.9% vs 36.6%, AKT1 mt: 11% vs 2.8%; OC: PTEN mt: 36.2% vs 4.%, PIK3CA mt: 32.7% vs 8.97%, AKT1 mt: 8.33% vs 0.62%), CTNNB1 mt (EC: 52.5% vs 13.9%; OC: 39.6% vs 3.09%), ARID1A mt (EC: 56% vs 32.2%; OC:28.6% vs 8.04%) and TGFBR1 mt (EC: 55.6% vs 9.16%) (q&lt;0.05). ESR1mt was associated with TMB high (30.7% vs 21.6%) and high median IFN score (EC: -0.42 vs -0.35, OC: -0.48 vs -0.27) (q&lt;0.05). ESR1mt enriched in patients with prior AI treatment (EC: 6.38% vs 2.65%, q=0.02; OC: 1.26% vs 0.18%), especially in EOC (14.7% vs 3.37%) (q&lt;0.05). Conclusions: ESR1mt were more common in EC and were enriched in the endometrioid subtype, and in general associated with increased molecular alterations but a more cold immune microenvironment. Hotspot mutations known to confer endocrine resistance were most common and enrichment was observed in cases previously exposed to AIs, suggesting this may be a mechanism of resistance to endocrine therapy for some gynecologic malignancies.
Pediatric Leukemia Roadmaps Are a Guide for Positive Metastatic Bone Sarcoma Trials
Authors: Damon R. Reed, Asmin Tulpule, Jonathan Metts, Matteo Trucco, Mark Robertson-Tessi, Tara J. O'Donohue, Fiorella Iglesias-Cardenas, Michael S. Isakoff, Audrey Mauguen, Neerav Shukla, Filemon S. Dela Cruz, William Tap, Alex Kentsis, Carol D. Morris, Meera Hameed, Joshua N. Honeyman, Gerald G. Behr, Maria Luisa Sulis, Michael V. Ortiz, Emily Slotkin
Journal: Journal of Clinical Oncology (2024)

ALL cures require many MRD therapies. This strategy should drive experiments and trials in metastatic bone sarcomas.
Molecular and immune characterization of squamous cell ovarian cancers for identification of therapeutic targets.
Authors: Jessie Hollingsworth, Sharon Wu, Anusha Adkoli, Alex Patrick Farrell, Kurt Hodges, Matthew James Oberley, Anthony Karnezis, Premal H. Thaker, Eugenia Girda
Journal: Journal of Clinical Oncology (2024)

5584 Background: Squamous cell carcinoma (SCC) represents &lt;1% of all Ovarian cancers (OC) and is associated with poor prognosis. This study seeks to identify prognostic factors and molecular markers associated with OSCC compared to Endometrioid OC (EOC), Clear Cell OC (CCOC), HPV16/18-negative vulvar SCC (VSCC) and HPV16/18-negative cervical SCC (CSCC). Methods: 812 EOC, 846 CCOC, 32 OSCC, 15 malignant BT, 500 HPV16/18- CSCC, and 472 HPV16/18- VSC were analyzed using next-generation sequencing of DNA (NextSeq, 592 genes and NovaSeq, WES) and RNA (NovaSeq, WTS) (Caris Life Sciences, Phx, AZ). Tumor mutational burden (TMB) was measured by totaling all somatic mutations (mt) per tumor (TMB-H: &gt; 10 mt/MB). PD-L1 IHC positivity was determined by a cut-off of &gt;1% CPS (22c3, Agilent) and &gt;2|5% (SP142, Spring Biosciences). HPV status determined by WES for HPV16 and 18. Statistical significance determined using chi-square and Mann-Whitney U test and adjusted for multiple comparisons (q&lt;0.05). UMAP was used to visualize differences or similarities in transcriptomic profiles. Real-world overall survival (rwOS) obtained from insurance claims data and calculated from first treatment to last contact. Hazard ratio (HR) was calculated by Cox proportional hazards, with p-value calculated using log-rank test. Results: OSCC had the highest rate of TP53-mt and CDKN2A-mt compared to BT, EOC, CCOC, and CSCC (TP53-mt: 71.9%, 33.3%, 25.1%, 11.6% and 27.1%, CDKN2A-mt: 25%, 0%, 1.49%, 0.48%, and 4.45%) but lower than VSCC (TP53-mt: 80%, CDKN2A-mt: 38.9%). OSCC had lower mt of Chromatin Remodeling (CR) genes ARID1A (3.13%) compared to EOC (39.3%) and CCOC (58.2%) but higher mt of CR gene KMT2D (19.4%) compared to CCOC (3.62%) (q&lt;0.05). OSCC had increased TMB-H than EOC, CCOC and VSCC (41.9% vs 13.6% vs 5.7% vs 8.84%) and PD-L1 IHC (all q&lt;0.05). There was no ER/PR staining in OSCC. Median interferon (IFN) score was higher in OSCC compared to EOC, CCOC and BT (-0.24 vs -0.44 vs -0.46 vs -0.51, q&lt;0.05) but similar to CSCC (-0.29) and VSCC (-0.17). Pathway analysis showed enrichment of IFNγ Response, Inflammatory Response, EMT and TNFα Signaling (NES: 1.53-2.05, FDR&lt;0.25) in OSCC compared to EOC and CCOC. UMAP showed OSCC clustering more closely with CSCC and VSCC compared to EOC and CCOC. OSCC had worse post-Carboplatin survival (19.6 mo) compared to EOC (71.6 mo, p&lt;0.01) and CCOC (46.9 mo, p&lt;0.01), similar post-Carbo survival to TP53-mt CSCC (22.5 mo; p=0.80) but improved post-Carbo survival compared to TP53-mt VSCC (9.05 mo; p=0.01). Conclusions: The molecular and transcriptomic profile of OSCC is distinct from EOC, CCOC, and BT but similar to CSCC and VSCC. OSCC demonstrated a more immune hot phenotype. Further studies are needed to investigate the potential use of immunotherapy in OSCC.
Efficacy of niraparib in patients with advanced ovarian cancer: A meta-analysis of randomized controlled trials.
Authors: Alice Marinho, Eduardo Lambert Fossen, Maria Carolina Caldeira de Freitas, Gabriela Coelho Itaya, Larissa Maria Da Costa, Yasmin Dias, Davi Said Gonçalves Celso, Marcela Bonalumi Dos Santos, Mariana De Souza, Maysa Vilbert
Journal: Journal of Clinical Oncology (2024)

5587 Background: Niraparib is a poly-adenosine diphosphate-ribose polymerase (PARP) inhibitor that has shown clinical benefits as a maintenance therapy for patients with advanced ovarian cancer. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy of niraparib as maintenance therapy after platinum-based chemotherapy for patients with advanced ovarian cancer. PubMed, Embase, and Cochrane Central Register of Controlled Trials databases were searched for RCTs published up to January 17, 2024. Hazard ratios (HR) and Odds ratio (OR) with 95% confidence intervals (CI) were pooled using a random-effects model. The endpoints of interest were time to first subsequent therapy (TFST) and progression-free survival (PFS). We performed subgroup analyses for BRCA-mutation, HRD-positive, HRD-negative, response to platinum therapy, and newly diagnosed disease. Results: Four RCTs were included, comprising a total of 1,935 patients of whom 1,291 received niraparib and 644 received placebo. Niraparib significantly improved PFS in the overall population (HR 0.45; 95% CI 0.31-0.66; p &lt; 0.0001; I2= 82%), in patients with BRCA mutation (HR 0.32; 95% CI 0.25-0.43; p &lt; 0.00001; I2= 21%), HRD positivity (HR 0.39; 95% CI 0.30-0.51; p &lt; 0.00001; I2= 40%), HRD negativity (HR 0.45; 95% CI 0.36-0,57; p &lt; 0.00001; I2= 0%), and newly diagnosed cancer (HR 0.59; 95% CI 0.39-0.73; p &lt; 0.0001; I2= 68%). The TFST was longer in the niraparib group (HR 0.48; 95% CI 0.33-0.68; p &lt; 0.0001; I2= 80%). There was no statistical difference between complete and partial response to platinum therapy (OR 1.00; 95% CI 0.87-0.1.16; p = 0.98; I2= 0%). Conclusions: Niraparib improves PFS and lowers the time to first subsequent therapy in patients with advanced ovarian cancer. Outcomes and results by studies. [Table: see text]
Deep learning models for thyroid nodules diagnosis of fine-needle aspiration biopsy: a retrospective, prospective, multicentre study in China
Authors: Jue Wang, Nafen Zheng, Huan Wan, Qinyue Yao, Shijun Jia, Xin Zhang, Sha Fu, Jingliang Ruan, Gui He, Xulin Chen, Suiping Li, Rui Chen, Boan Lai, Jin Wang, Qingping Jiang, Nengtai Ouyang, Yin Zhang
Journal: The Lancet Digital Health (2024)
Burr-hole drainage with or without irrigation for chronic subdural haematoma (FINISH): a Finnish, nationwide, parallel-group, multicentre, randomised, controlled, non-inferiority trial
Authors: Rahul Raj, Pihla Tommiska, Timo Koivisto, Ville Leinonen, Nils Danner, Jussi P Posti, Dan Laukka, Teemu Luoto, Minna Rauhala, Sami Tetri, Tommi K Korhonen, Jarno Satopää, Riku Kivisaari, Teemu Luostarinen, Christoph Schwartz, Tomasz Czuba, Simo Taimela, Kimmo Lönnrot, Teppo L N Järvinen, Abdirisak Ahmed, Tarmo Areda, Jiri Jr Bartek, Tomasz Czuba, Nils Danner, Antti-Pekka Elomaa, Janek Frantzén, Ilkka Haapala, Joonas Haapasalo, Juuso Heikkilä, Minttu Hellman, Henna Henttonen, Nora Huuska, Teppo LN Järvinen, Henna-Kaisa Jyrkkänen, Aku Kaipainen, Olli-Pekka Kämäräinen, Hanna Kämppi, Milla Kelahaara, Riku Kivisaari, Nikolai Klimko, Oula A Knuutinen, Timo Koivisto, Tommi Korhonen, Janne Koskimäki, Anselmi Kovalainen, Xenia Kuparinen, Dan Laukka, Martin Lehecka, Kai Lehtimäki, Ville Leinonen, Kimmo Lönnrot, Antti Luikku, Teemu Luostarinen, Teemu Luoto, Janne Luotonen, Lauriina Lustig-Tammi, Henna-Riikka Maanpää, Jenni Määttä, Timo Möttönen, Eliisa Netti, Laura Nevaharju-Sarantis, Mika Niemelä, Tero Niskakangas, Mette Nissinen, Ville Nurminen, Minna Oinas, Teemu Ollonen, Anna Östberg, Elias Oulasvirta, Krista Pantzar, Katri Piilonen, Anni Pohjola, Markus Polvivaara, Jussi P Posti, Rahul Raj, Linnea Rajala, Jonas Ranstam, Minna Rauhala, Behnam Rezai Jahromi, Miika Roiha, Ilkka Saarenpää, Antti Sajanti, Henrikki Salmi, Jarno Satopää, Christoph Schwartz, Niina Shemeikka, Pia Sorto, Simo Taimela, Sami Tetri, Tuomo Thesleff, Pihla Tommiska, Maarit Tuomisto, Nuutti Vartiainen, Ville Vasankari, Jyri Virta, Mikko Visuri, Paula Walle, Frederick A Zeiler
Journal: The Lancet (2024)
Unlocking Transplant Tolerance with Biomaterials
Authors: John‐Paul A. Pham, María M. Coronel
Journal: Advanced Healthcare Materials (2024)

For patients suffering from organ failure due to injury or autoimmune disease, allogeneic organ transplantation with chronic immunosuppression is considered the god standard in terms of clinical treatment. However, the true "holy grail" of transplant immunology is operational tolerance, in which the recipient exhibits a sustained lack of alloreactivity toward unencountered antigen presented by the donor graft. This outcome is resultant from critical changes to the phenotype and genotype of the immune repertoire predicated by the activation of specific signaling pathways responsive to soluble and mechanosensitive cues. Biomaterials have emerged as a medium for interfacing with and reprogramming these endogenous pathways toward tolerance in precise, minimally invasive, and spatiotemporally defined manners. By viewing seminal and contemporary breakthroughs in transplant tolerance induction through the lens of biomaterials-mediated immunomodulation strategies-which include intrinsic material immunogenicity, the depot effect, graft coatings, induction and delivery of tolerogenic immune cells, biomimicry of tolerogenic immune cells, and in situ reprogramming-this review emphasizes the stunning diversity of approaches in the field and spotlights exciting future directions for research to come.
Osimertinib Will Be New Standard for Some NSCLCs
Authors: Suzanne Rose
Journal: Cancer Discovery (2024)

In the international phase III LAURA trial, patients with inoperable EGFR-stage III non–small cell lung cancer that doesn't worsen during or soon after chemoradiotherapy derived a significant progression-free survival (PFS) benefit with the EGFR-directed therapy osimertinib compared with a placebo. Median PFS was 39.1 months and 5.6 months, respectively, and median duration of response was 36.9 months and 6.5 months, respectively.
Microbial metabolite butyrate modulates granzyme B in tolerogenic IL-10 producing Th1 cells to regulate intestinal inflammation
Authors: Wenjing Yang, Tianming Yu, Xia Liu, Suxia Yao, Kamil Khanipov, George Golovko, Danyvid Olivares-Villagómez, Yingzi Cong
Journal: Gut Microbes (2024)

CD4+ T cells play a critical role in regulating autoimmune diseases, and intestinal microbial metabolites control various immune responses. Granzyme B (GzmB)-producing CD4+ T cells have been recently reported to participate in the pathogenesis of autoimmune diseases. Here, we found that GzmbB-deficient CD4+ T cells induced more severe colitis in Rag1−/− mice than wild-type (WT) CD4+ T cells. Germ-free (GF) mice exhibited a lower expression of GzmB in intestinal CD4+ T cells compared to specific pathogen-free (SPF) mice. Intestinal microbial metabolite butyrate increased GzmB expression in CD4+ T cells, especially in IL-10-producing Th1 cells, through HDAC inhibition and GPR43, but not GPR41 and GPR109a. Butyrate-treated GzmB-deficient CD4+ T cells demonstrated more severe colitis compared to butyrate-treated WT CD4+ T cells in the T cell transfer model. Butyrate altered intestinal microbiota composition, but altered microbiota did not mediate butyrate induction of intestinal CD4+ T cell expression of GzmB in mice. Blimp1 was involved in the butyrate induction of GzmB in IL-10-producing Th1 cells. Glucose metabolism, including glycolysis and pyruvate oxidation, mediated butyrate induction of GzmB in Th1 cells. In addition, we found that IKZF3 and NR2F6 regulated GzmB expression induced by butyrate. Together, our studies underscored the critical role of GzmB in mediating gut bacterial metabolite butyrate regulation of T cell tolerance at the mucosal surface.
Enhancing social behavior in an autism spectrum disorder mouse model: investigating the underlying mechanisms of <i>Lactiplantibacillus plantarum</i> intervention
Authors: Chih-Ming Chen, Chien-Chen Wu, Yebeen Kim, Wei-Yu Hsu, Ying-Chieh Tsai, Shu-Ling Chiu
Journal: Gut Microbes (2024)

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting over 1% of the global population. Individuals with ASD often exhibit complex behavioral conditions, including significant social difficulties and repetitive behaviors. Moreover, ASD often co-occurs with several other conditions, including intellectual disabilities and anxiety disorders. The etiology of ASD remains largely unknown owing to its complex genetic variations and associated environmental risks. Ultimately, this poses a fundamental challenge for the development of effective ASD treatment strategies. Previously, we demonstrated that daily supplementation with the probiotic
Antigenic operon fragmentation and diversification mechanism in <i>Bacteroidota</i> impacts gut metagenomics and pathobionts in Crohn's disease microlesions
Authors: Nicholas C. Bank, Vaidhvi Singh, Blake McCourt, Aaron Burberry, Kyle D. Roberts, Brandon Grubb, Alex Rodriguez-Palacios
Journal: Gut Microbes (2024)

Comensal
Novel thrombolytic treatments of acute ischaemic stroke, choosing the right safety belt to drive this car
Authors: Heleen M M van Beusekom, Meiqi Wang, Diederik W J Dippel
Journal: Cardiovascular Research (2024)

The role of thrombosis in acute myocardial infarction and stroke has a long history.Virchow already recognized and studied vascular thrombosis and its sequelae in the 1850s. 1 Interventions to treat the arterial thrombotic blockade by means of thrombolysis became a first line treatment of acute myocardial infarction in the 1990s.Success was evident as it reduced infarct size and could already be started in the ambulance but complications were also apparent: bleeding risk and, interestingly, an increased risk of both acute ischemic stroke and brain haemorrhages.However, with the success of acute percutaneous coronary interventions (PCI), it soon became apparent that PCI was the preferred (more effective) treatment. 2the fastest in vitro thrombolytic activity and was resistant to inactivation by PAI-1.Two in vivo rodent