tbuckley/cabot-search huggingface dataset:
Artificial intelligence (AI) systems for detection of Barrett’s neoplasia: time to bridge domain gaps and explore human–AI interaction
Authors: Albert Jeroen De Groof
Journal: Endoscopy (2024)

Endoscopic recognition of early Barrett's neoplasia may be difficult; lesions often only show subtle abnormalities and most endoscopists rarely encounter early Barrett's neoplasia, making them unfamiliar with the appearance of these lesions [1] [2]. Assistance for detection of Barrett's neoplasia has therefore always been one of the most appealing artificial intelligence (AI) applications.
A meta-analysis of randomized controlled clinical trials for implications of acute treatment effects on glomerular filtration rate for long-term kidney protection
Authors: Hiddo J.L. Heerspink, Devin Eddington, Juhi Chaudhari, Raymond Estacio, Enyu Imai, Marian Goicoechea, Thierry Hannedouche, Richard Haynes, Tazeen H. Jafar, David W. Johnson, Rob C.M. van Kruijsdijk, Julia B. Lewis, Philip K.T. Li, Brendon L. Neuen, Ronald D. Perrone, Piero Ruggenenti, Christoph Wanner, Mark Woodward, Di Xie, Tom Greene, Lesley A. Inker
Journal: Kidney International (2024)
Immobilized Multi‐Enzyme/Nanozyme Biomimetic Cascade Catalysis for Biosensing Applications
Authors: Xiaoli Cai, Yuteng Huang, Chengzhou Zhu
Journal: Advanced Healthcare Materials (2024)

Multiple enzyme-induced cascade catalysis has an indispensable role in the process of complex life activities, and is widely used to construct robust biosensors for analyzing various targets. The immobilized multi-enzyme cascade catalysis system is a novel biomimetic catalysis strategy that immobilizes various enzymes with different functions in stable carriers to simulate the synergistic catalysis of multiple enzymes in biological systems, which enables high stability of enzymes and efficiency enzymatic cascade catalysis. Nanozymes, a type of nanomaterial with intrinsic enzyme-like characteristics and excellent stabilities, are also widely applied instead of enzymes to construct immobilized cascade systems, achieving better catalytic performance and reaction stability. Due to good stability, reusability, and remarkably high efficiency, the immobilized multi-enzyme/nanozyme biomimetic cascade catalysis systems show distinct advantages in promoting signal transduction and amplification, thereby attracting vast research interest in biosensing applications. This review focuses on the research progress of the immobilized multi-enzyme/nanozyme biomimetic cascade catalysis systems in recent years. The construction approaches, factors affecting the efficiency, and applications for sensitive biosensing are discussed in detail. Further, their challenges and outlooks for future study are also provided.
Adjuvant nivolumab plus chemotherapy versus placebo plus chemotherapy for stage III gastric or gastro-oesophageal junction cancer after gastrectomy with D2 or more extensive lymph-node dissection (ATTRACTION-5): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial
Authors: Yoon-Koo Kang, Masanori Terashima, Young-Woo Kim, Narikazu Boku, Hyun Cheol Chung, Jen-Shi Chen, Jiafu Ji, Ta-Sen Yeh, Li-Tzong Chen, Min-Hee Ryu, Jong Gwang Kim, Takeshi Omori, Sun Young Rha, Tae Yong Kim, Keun Won Ryu, Shinichi Sakuramoto, Yasunori Nishida, Norimasa Fukushima, Takanobu Yamada, Li-Yuan Bai, Yoshinori Hirashima, Shunsuke Hagihara, Takashi Nakada, Mitsuru Sasako
Journal: The Lancet. Gastroenterology & hepatology (2024)
An integrated diabetes and mental health intervention for people with type 1 diabetes and severe disordered eating: a prospective proof-of-concept cohort study
Authors: Khalida Ismail, Diane Turner, Jennie Brown, Miranda Rosenthal, Salma Ayis, Nick Oliver, Yuk-Fun Liu, Amy Harrison, Chris Garrett, David Hopkins, Janet Treasure, Jonathan Valabhji, Stephen Thomas, Marietta Stadler
Journal: The Lancet Diabetes & Endocrinology (2024)
MUP1 mediates urolithin A alleviation of chronic alcohol-related liver disease via gut-microbiota-liver axis
Authors: Hongbo Zhang, Chaoyue Li, Lin Han, Yao Xiao, Ji Bian, Chao Liu, Lan Gong, Zhigang Liu, Min Wang
Journal: Gut Microbes (2024)

Alcohol-related liver disease (ALD) is recognized as a global health crisis, contributing to approximately 20% of liver cancer-associated fatalities. Dysbiosis of the gut microbiome is associated with the development of ALD, with the gut microbial metabolite urolithin A (UA) exhibiting a potential for alleviating liver symptoms. However, the protective efficacy of UA against ALD and its underlying mechanism mediated by microbiota remain elusive. In this study, we provide evidence demonstrating that UA effectively ameliorates alcohol-induced metabolic disorders and hepatic endoplasmic reticulum (ER) stress through a specific gut-microbiota-liver axis mediated by major urinary protein 1 (MUP1). Moreover, UA exhibited the potential to restore alcohol-induced dysbiosis of the intestinal microbiota by enriching the abundance of
Tocilizumab for advanced non-small cell lung cancer with concomitant inflammatory cachexia: A single-centre study.
Authors: Yang Du, Xiao-Yian Liu, RuiLi Pan, Xiao-Tong Zhang, Xiao-Yan Si, Minjiang Chen, Mengzhao Wang, Li Zhang
Journal: Journal of Clinical Oncology (2024)

2647 Background: Cancer cachexia significantly contributes to morbidity and mortality in patients with non-small cell lung cancer (NSCLC). Inflammatory pathways mediated by interleukin-6 play a crucial role in the development of cancer cachexia. This study aimed to investigate the use of tocilizumab, an anti-interleukin-6 receptor inhibitor, in the management of NSCLC with coexisting inflammatory cachexia. Methods: Data were collected from patients with NSCLC and concurrent inflammatory cachexia who received either tocilizumab plus anti-tumour therapy or anti-tumour therapy alone. The primary endpoints were overall survival (OS) and improved modified Glasgow Prognostic Score (mGPS) at week 12, while secondary endpoints included changes from baseline over 12 weeks in body weight, albumin, C-reactive protein and mGPS. Qualitative improvements in patient self-rated appetite and fatigue were reported as exploratory analysis. Results: The study included 49 patients diagnosed with NSCLC and coexisting inflammatory cachexia, of which 26 received tocilizumab in combination with anti-tumour therapy, and 23 received anti-tumour therapy alone. The tocilizumab group demonstrated a significantly longer median OS compared to the control group (15.1 vs. 3.2 months; hazard ratio 0.18, 95% confidence interval 0.08-0.38; p &lt; 0.001). The rate of patients surviving with mGPS improvement at week 12 was significantly higher in the tocilizumab group than in the control group (OR 168.7, 95% CI 16.3-1746.5; p &lt; 0.001). Over the 12-week period, significant improvements were observed in body weight, albumin, C-reactive protein, and mGPS in the tocilizumab group compared to the control group. Additionally, the tocilizumab group displayed significantly higher rates of improvement in appetite and fatigue. The incidence of grade 3 or higher adverse events was 34.6% in the tocilizumab group compared to 78.3% in the control group. Tocilizumab-related adverse events were observed in three patients (11.5%), including two cases of neutropenia and one case of skin and subcutaneous tissue infection. Conclusions: Tocilizumab demonstrated significant benefits in survival and various clinical parameters, including body weight, albumin, C-reactive protein, mGPS, and symptom burden in patients with NSCLC and concurrent inflammatory cachexia. Given the existing unmet medical need for effective interventions for cancer cachexia, tocilizumab may be considered as a potential treatment option.
Development of a novel risk stratification model for immune-related adverse events for patients with advanced melanoma and non-small cell lung cancer treated with immune checkpoint inhibitors.
Authors: Yizhuo Kelly Gao, Andrew Tran, Mehul Gupta, Daniel Yick Chin Heng, Tina Cheng, Igor Stukalin, Daniel E. Meyers, Winson Y. Cheung, Jose Gerard Monzon, Vishal Navani
Journal: Journal of Clinical Oncology (2024)

2649 Background: Immune checkpoint inhibitors (ICI) transformed treatment paradigm across cancers. There remain few reliable, clinically accessible predictors of ICI-induced immune related adverse events (irAEs). We derive a novel risk stratification model for irAEs using baseline patient, tumor and treatment variables in a large cohort of patients with advanced melanoma (AM) or non-small cell lung cancer (NSCLC) treated with ICI. Methods: We conducted a multi-centre retrospective observational cohort study of consecutive patients with AM or NSCLC receiving ≥ 1 cycle of single-agent or combination ICI, in any line, 2015 - 2023, in Alberta, Canada. Clinically significant irAEs, defined as those requiring treatment delay or systemic steroids/steroid sparing agents, were identified as outcome of interest. The association between irAEs, overall survival (OS), and time to next treatment (TTNT) was assessed with Cox Proportional Hazards regression. Stepwise logistic regression was used to select and weight baseline variables associated with development of irAEs to derive a predictive risk score. Model validation was carried out on 500 iterations of bootstrapped samples. Harrel’s C-index was calculated and internally validated to ascertain the model’s discriminatory performance. Results: 1,292 total patients were included, 519 (218/489 [44.6%] AM and 301/803 [37.5%] NSCLC) developing a clinically significant irAE. Using a subset of 801 patients with available baseline characteristics, the following variables were identified and weighted for creation of risk model (risk score attributed): tumor type (NSCLC) (+1), age &gt;60 (+1), ECOG ≥1 (-1), BMI ≥ 25 (+1), ICI after first line (-1), combination ICI (+4), &gt;10 cycles of ICI (+2), albumin level &lt; LLN (+2), adrenal metastasis (+1), multiple sites of metastasis (-1). Patients were stratified into 3 irAE risk groups based on combined score: low (n = 230, risk score ≤ 0), intermediate (n = 412, risk score 1-2), high (n = 159, risk score ≥3). The risk model performed well with an optimism-corrected c-index of 0.707 in internal validation, and strong association with odds of irAE occurrence (Table). The development of irAE was associated with an improvement in OS (HR 0.48, 95% CI 0.41-0.44, p&lt;0.001), with a median OS of 34.3 (95% CI 28.8-39.6) months compared to 12.0 (95% CI 10.6-14.3) months for those who did not develop an irAE. Similar robust stratification was also seen with TTNT. Conclusions: We presented and internally validated, a simple risk stratification tool that utilizes readily available baseline patient, tumor, and treatment characteristics to robustly stratify risk of irAE development. [Table: see text]
The impact of COVID-19 mRNA vaccines on immune-related adverse events in patients with cancer receiving immune checkpoint inhibitors.
Authors: Mengni Guo, Zohaib Ahmed, Phuong Nguyen, Kashaf Zaidi, Raphael Itzkowitz, Esther G Chong, Dani Ran Castillo, Huynh Le Cao
Journal: Journal of Clinical Oncology (2024)

2648 Background: Cancer patients are a vulnerable population to COVID-19. COVID-19 mRNA vaccines have shown to decrease hospitalization and death risk from COVID-19 in cancer patients. Concurrent COVID-19 vaccination and immune checkpoint inhibitors (ICIs) use may impact immune-related adverse events (irAEs) synergistically. Limited data exist on how COVID-19 mRNA vaccines affect irAEs in ICI-treated cancer patients, especially those with breakthrough infections. Methods: We retrospectively analyzed adult patients with malignant solid tumors receiving ICIs at a single cancer institute (January 2020 to July 2021). Fully vaccinated status is defined as two consecutive doses of mRNA vaccines (BNT162b2 and mRNA-1273). Patients who were partially vaccinated, fully vaccinated post COVID-19 infection, vaccinated with non-mRNA COVID-19 vaccines, or last visit within 30 days post vaccination were excluded. All COVID-19 infections were confirmed by PCR. In the vaccinated group, only post-vaccination irAEs were considered as events. Results: 443 patients were included in our study, with 251 (56.7%) vaccinated and 192 (43.3%) unvaccinated. The baseline characteristics were similar between the two groups, except for age (vaccinated median 68 years, unvaccinated median 62 years, p=0.004). With a median follow-up of 12 months, incidences of all-grade irAEs (19.1% vs. 20.3%, p=0.72) and severe irAEs (5.6% vs. 4.2%, p=0.66) were comparable between vaccinated and unvaccinated groups. 34 breakthrough COVID-19 infections occurred. In the vaccinated group, a non-significant trend of higher all-grade irAEs incidence was noted in the COVID-19 infected subgroup compared to uninfected subgroup (29.4% vs. 17.5%, p = 0.11). Univariate analysis linked COVID-19 vaccination (OR 1.54, 95% CI 1.01-2.35, p=0.04) and ipilimumab + nivolumab use (OR 5.57, 95% CI 1.79-17.35, p=0.003) to a higher risk of all-grade irAEs in the entire cohort. After multivariate adjustment, ipilimumab + nivolumab use remained the only variable associated with all-grade irAEs (OR 4.95, 95% CI 1.57-15.64, p=0.006). Conclusions: Our study suggests that COVID-19 mRNA vaccines do not increase irAE risk in cancer patients on ICIs. Fully vaccinated patients with breakthrough COVID-19 infections may safely continue ICI treatment without an increased irAE risk. [Table: see text]
Out-of-pocket cost modeling of adjuvant radiation therapy duration in standard-of-care treatment of glioblastoma across Medicaid and Medicare plans.
Authors: Victoria Wu, Martha Khlopin, Shearwood McClelland
Journal: Journal of Clinical Oncology (2024)

2045 Background: The optimal radiation treatment (RT) length (6 weeks of 60 Gy in 30 fractions versus 3 weeks of 40 Gy in 15 fractions) for older adults with glioblastoma is debatable, with Level 1 evidence (PMID 15051755) revealing no difference in survival between RT regimens. However, there remains a paucity of evidence describing the role of insurance on out-of-pocket (OOP) costs for patients undergoing varying lengths of RT. This project aims to quantify expenses by insurance plans, enhancing transparency in treatment cost understanding. Methods: We utilized the National Comprehensive Cancer Network guidelines to determine the standard treatment protocol, including 30-fraction or 15-fraction RT with concurrent and post-radiation temozolomide for 12 cycles. The model assumes a Medicare- and/or Medicaid-eligible patient ≥ 65 years of age with glioblastoma. The total aggregate out-of-pocket (OOP) costs were determined from the sum of treatment costs, deductibles, and copays/coinsurance based on Medicaid, Original Medicare, Medigap Plan G, and Medicare Part D Rx plan over a two-year time horizon (not adjusted for inflation). All procedures were assumed to take place within the premises of an Ohio hospital. Results: Treatment charges include neurosurgery, neuro-oncology, and radiation oncology initial consultation, follow-up visits, diagnostic head CT, MRI, craniotomy with maximum safe resection, surveillance brain MRI, temozolomide, antiemetics, prophylactic TMP-SMX, weekly CBC, and tumor treating fields. RT-specific treatment charges include treatment planning, simulation and verification, RT delivery, and on-treatment visits. Original Medicare beneficiaries face an OOP cost of 20% for Medicare Part B claims with no cost cap for approved procedures after the deductible. Medications are covered under Medicare Part D with copays. This results in a total OOP treatment charge of $4,454.01 for 30 fractions and $3,913.86 for 15 fractions. Medigap Plan G beneficiaries face a total OOP charge of $2,387.22 for 30 fractions and $2,369.61 for 15 fractions. For Medicaid beneficiaries (assuming all treatments are approved by Medicaid), all expenses are covered without limit, resulting in no OOP expense for either treatment plan. Conclusions: Three-week versus six-week RT for GBM reduces OOP costs facing patients by 10%. By understanding the financial implications, healthcare providers, policymakers, and patients can make informed decisions about treatment options, and healthcare systems can develop strategies to mitigate the economic burden associated with GBM care.
The TAC-GReD trial: The combination of talazoparib and carboplatin in DNA damage repair deficient recurrent high-grade glioma.
Authors: Marc Lecoultre, Peter Yat Ming Woo, Gilberto Leung, Shuk Wan Joyce Chow, Jason Ho, Ji Hyung Hong, Chi Leung Chiang, Dennis Kwok Chuen Leung, Tai-Chung Lam, Aya EL Helali
Journal: Journal of Clinical Oncology (2024)

2047 Background: Recurrent high-grade glioma (rHGG) has a dismal prognosis with limited treatment options. Given that a high proportion of these gliomas harbor deficiencies in the DNA damage repair (DDRd) pathway, this genomic occurrence may confer synergistic lethality and sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. Therefore, we hypothesize that DDRd rHGG may be sensitive to the combination of a PARP inhibitor, talazoparib, and carboplatin. Methods: This is a prospective phase II, single-arm open-label biomarker stratified single-institution trial conducted in Hong Kong (NCT04740190). Tumor tissue was sent for comprehensive next-generation sequencing (C-NGS) to screen for genomic aberrations associated with the DDRd pathway. Patients with rHGG (WHO grade III-IV) and at least one pathogenic mutation in the DDR pathway were deemed eligible. Patients were initially treated with whole-brain radiotherapy (2 Gy/1 Fr) on C1D1. Starting at dose level 0, talazoparib (0.75mg on Days 1-4) and carboplatin (AUC 1.5 on Day 1), were administered weekly for a total of 18 cycles, followed by maintenance talazoparib. The primary endpoint was the 6-month progression-free survival (PFS-6). Results: 61 patients were screened and 33 patients with DDRd rHGG were enrolled, 23 males, 10 females, and a median age of 55 years (range: 29-70 years). 73% (n=24) had a baseline ECOG PS of 0-1. Among the recruited patients, 12% (n=4) were classified as WHO grade III, while the remaining 88% (n=29) were WHO grade IV. Dose level escalation was achieved in 27% (n=9) of the cohort. The 6-PFS was 29% (95% CI 16.2-51.9%) and the median PFS was 3.5 months (95% CI: 2.4-6.3 months). The OS at 3 and 12 months were 90.4% (95% CI 80.7-100%) and 30% (95% CI 17-53%), respectively. The most common grade 3-4 toxicities were neutropenia (21.2%, n=7), thrombocytopenia (18.2%, n=6) and anemia (9.1%, n=3). One patient developed a grade 4 thromboembolic event. Dose level reduction was implemented in 54% (n=18) of patients and treatment was terminated in 6.1% (n=2) due to toxicity. Conclusions: Talazoparib and carboplatin in a DDRd-enriched rHGG is feasible and tolerable. Additional analysis including correlation of biomarkers with long-term outcomes is underway. Clinical trial information: NCT04740190 .
Cost-Effectiveness of a Biomarker-Based Screening Strategy for Hepatocellular Carcinoma in Patients with Cirrhosis
Authors: Amit G Singal, Jagpreet Chhatwal, Neehar Parikh, Elliot Tapper
Journal: Liver Cancer (2024)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Given suboptimal performance of ultrasound-based surveillance for early hepatocellular carcinoma (HCC) detection in patients with cirrhosis, there is interest in alternative surveillance strategies, including blood-based biomarkers. We aimed to evaluate the cost-effectiveness of biomarker-based surveillance in patients with cirrhosis. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We constructed a decision-analytic model to compare ultrasound/alpha-fetoprotein (AFP) and biomarker-based surveillance strategies in 1,000,000 simulated patients with compensated cirrhosis. Model inputs for adherence, benefits, and harms of each strategy were based on literature review, and costs were derived from the Medicare fee schedule. Primary outcomes were quality-adjusted life-years (QALY) and incremental cost-effectiveness ratio (ICER) of the surveillance strategies, with cost-effectiveness assessed at a threshold of USD 150,000 per QALY. We performed sensitivity analyses for HCC incidence, test performance characteristics, surveillance adherence, and biomarker costs. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In the base case, both ultrasound/AFP and biomarker-based surveillance were cost-effective versus no surveillance, with ICERs of USD 105,620, and USD 101,295, per QALY, respectively. Biomarker-based surveillance was also cost-effective versus ultrasound/AFP, with an ICER of USD 14,800 per QALY. Biomarker sensitivity exceeding 80%, cost below USD 210, or adherence exceeding 58% were necessary for biomarker-based screening to be cost-effective versus ultrasound/AFP. In two-way sensitivity analyses, biomarker costs were directly related with test sensitivity and adherence, whereas sensitivity and adherence were inversely related. In a probabilistic sensitivity analysis, biomarker-based screening was the most cost-effective strategy in most (65%) simulations. &lt;b&gt;&lt;i&gt;Conclusion:&lt;/i&gt;&lt;/b&gt; Biomarker-based screening appears cost-effective for HCC screening, but results are sensitive to test sensitivity, adherence, and costs.
CDKN2A deletion and radiation sensitivity in IDH-mutant astrocytomas.
Authors: Logan Muzyka, Yosuke Kitagawa, Ali Mohamed Nasser, Ethan A Wetzel, Julie J. Miller, Hiroaki Wakimoto, Daniel P. Cahill
Journal: Journal of Clinical Oncology (2024)

2041 Background: IDH-mutant astrocytomas represent the most prevalent primary tumors in younger adults (&lt;45yo). A substantial minority of these tumors exhibit the deletion of CDKN2A (Cyclin-Dependent Kinase Inhibitor Gene 2A). Homozygous deletion of this gene– which encodes the tumor suppressor protein p16 – is associated with a malignant phenotype and poorer prognosis in IDH-mutant astrocytoma. CDKN2A deletions are primarily observed in tumors that have received radiation therapy (RT), suggesting a potential mechanistic relationship between RT and deletion. This observation gives rise to two alternative hypotheses: either RT is causing DNA damage in irradiated cells, leading to the induction of subclonal CDKN2A deletion, or a subset of cells already possesses the CDKN2A deletion and is resistant to RT, resulting in the treatment selecting for the subsequent emergence of these cells. Here, we sought to ascertain the influence of CDKN2A deletion on IDH-mutant astrocytoma cellular response to RT. Methods: The antitumor effect of RT was evaluated in vitro using patient-derived IDH-mutant astrocytoma cells, MGG152. A homozygous CDKN2A deletion was engineered in this parental line, creating a paired line to permit an isogenic comparison between CDKN2A intact versus CDKN2A deleted tumor cells. A photon irradiator was used to deliver a range of clinically-relevant RT doses spanning from 0 to 20 gray (Gy). Differences in cell viability after a predetermined incubation period were examined and relevant statistical comparisons performed. Results: Dose-response curves in response to radiation therapy, comparing CDKN2A intact and deleted cell lines, were generated (Table). Both CDKN2A intact and deleted cell lines exhibited significant reductions in viability following radiation exposure at and above 2Gy (p &lt; 0.001). CDKN2A-deleted cells displayed a small but significantly greater sensitivity than CDKN2A-intact at 1, 2, and 5Gy (Table). Conclusions: Our findings offer evidence indicating that p16 loss does not bestow radioresistance in IDH-mutant astrocytomas. These findings align with a hypothesis that radiotherapy (RT) might promote DNA damage, and consequently, subclonal CDKN2A deletion, in irradiated IDH-mutant tumors. [Table: see text]