tbuckley/cabot-search huggingface dataset:
Independent blinded validation of a novel blood-based early pancreatic cancer detection test.
Authors: Patrick Christian Strasser, Maarten F. Bijlsma, Tessa Y.S. Le Large, Geert Kazemier, Norbert Thumfart, Maximilian Schneider
Journal: Journal of Clinical Oncology (2024)

4166 Background: Pancreatic ductal adenocarcinoma (PDAC) frequently presents at late stages, resulting in increased mortality. Early detection is crucial for enhancing survival rates; however, available screening methods are limited. This gap underscores the critical need for advancements in early PDAC detection. To address this, Wholomics developed a proprietary early detection assay, leveraging molecular signatures found in the blood, and has further validated its efficacy through a comprehensive blinded validation study. Methods: Wholomics conducted retrospective analysis of serum samples from the Amsterdam UMC Liquid Biopsy Center and the Bank of Biological Material of the Masaryk Memorial Cancer Institute. A training cohort included 290 control subjects, 12 patients with a confirmed diagnosis of chronic pancreatitis, and 71 patients with a histopathologically confirmed diagnosis of PDAC (20 stage I, 30 stage II, 13 stage III, 8 stage IV). A blinded validation cohort comprised samples from 20 control subjects, 24 patients with non-cancerous conditions (5 with benign tumors, 10 with IPMNs, 9 with chronic pancreatitis), and 60 patients with histologically confirmed PDAC. Peripheral blood samples of cancer patients were drawn before surgery or treatment. Wholomics used its proprietary NMR-based technology to quantitatively analyze serum samples. Disease-specific molecular signatures were identified and used to develop a computational biomarker specific to PDAC. A comparative analysis via 10-fold cross-validation and a blinded validation were conducted. The accuracy, specificity and sensitivity are reported. Results: In this study, a dual-cohort design, comprising both a training and a blinded validation cohort, was utilized to assess the capability of the Wholomics technology in detecting cancer-specific molecular signatures. In the training cohort, a 94.6% accuracy was achieved in distinguishing PDAC patients from non-cancer controls. A specificity of 95.7% and sensitivity of 90.7% were reached. A similar performance was observed in the blinded validation cohort, where the blood-based test accurately differentiated PDAC patients from controls with an accuracy of 92.5%. In more detail, a specificity of 95% (noting a single false positive) and a sensitivity of 91.7% were achieved. Conclusions: The collective findings of this research indicate that utilizing disease-specific molecular markers in peripheral blood offers a highly accurate method for differentiating between PDAC patients, healthy subjects, and those with pre-cancerous diseases. Should future studies across broader cohorts corroborate these results, this testing approach has potential for consideration as a screening mechanism for PDAC, aiming to facilitate early detection and consequently enhance patient prognoses.
KRAS mutations allelic frequency dynamics using plasma extracellular vesicles: Association with survival outcomes in localized pancreatic adenocarcinoma.
Authors: Asmita Chopra, Hongzhang He, Jadranka Milosevic, Nikhil Tirukkovalur, Rudy El Asmar, Ibrahim Nassour, Geoffrey Nunns, Mingxi Chen, Jiaqi Chen, Siyu Jiang, Aatur D. Singhi, Anwaar Saeed, Janie Yue Zhang, Kenneth K. Lee, Amer H. Zureikat, Si-Yang Jiang, Alessandro Paniccia
Journal: Journal of Clinical Oncology (2024)

4167 Background: Pancreatic ductal adenocarcinoma (PDAC) lacks an effective and consistent biomarker to emulate treatment response and predict survival. Extracellular vesicles (EV) carrying tumor-specific mutations are disease-specific biomarkers that hold promise to address this unmet need. Methods: Informed by tumor profiling, plasma from 44 PDAC patients with confirmed KRAS mutations, treated with neoadjuvant therapy (NAT) and definitive surgery between 2019 and 2021, was analyzed. Samples were collected at diagnosis, day of surgery, and 1-month post-surgery. A lipid nanoprobe technique was used for EV isolation and droplet digital PCR was used for detection of tumor-specific KRAS mutations. Patients were categorized based on the temporal change in KRAS mutation allelic frequencies (MAF) into ND (no detection at any time point), ID (increasing MAF detection), or DD (decreasing MAF detection). Optimal CA19-9 response was defined as &gt;50% reduction from baseline and normalization (&lt;37 U/mL) before surgery. Survival associations were evaluated using Kaplan-Meier analysis and log-rank tests. The median follow-up was 36.1 months. Results: Among the cohort (mean age 66.5±8.2 years, 36% females), 29 (65.9%) patients had ND, 7 (15.9%) had ID and 8 (18.2%) had DD of KRAS MAF. No significant differences were noted in demographic or clinical variables (p &gt; 0.05). Stages III, II, and I PDAC had detectable mutant KRAS in 50%, 30%, and 21% cases, respectively. The ND group exhibited significantly longer restricted mean disease-free survival (rmDFS) [31.2 months (95% CI: 24.1–38.3)] compared to DD [27.8 months (95% CI: 12.4–43.1)] and ID [9.8 months (95% CI: 0.1–19.7)] (p=0.010). The ND group also showed a superior rmOS [40.3 months (95% CI: 34.2–46.4)] outperforming DD [35.7 months (95% CI: 22.1–49.2)] and ID [17.7 months (95% CI: 6.4–28.9] (p = 0.012). Eleven patients (25%) exhibited optimal CA19-9 response. Patients in ND cohort with optimal CA19-9 response (n=6; 20%) had the longest DFS and OS (median DFS and OS not reached), outperforming all other subgroups (p&lt;0.001). Conversely, patients in ID group had the lowest rmDFS (5.1 months 95%CI 2.4-7.8), irrespective of CA19-9 response (p&lt;0.001). Conclusions: Detection and temporal increase of EV-KRAS MAF are significant indicators of reduced DFS and OS in PDAC patients. These findings highlight the potential of dynamic EV-KRAS profiling as a prognostic biomarker and underscore the need for expansive validation studies.
Does non-alcoholic fatty liver disease increase the risk for pancreatic cancer? A multi-center retrospective cohort study.
Authors: Rituraj Raj Singh, Eileen M. O'Reilly
Journal: Journal of Clinical Oncology (2024)

4165 Background: Recent studies suggest that patients with non-alcoholic fatty liver disease (NAFLD) are at increased risk of hepatic and extra-hepatic gastrointestinal cancers. However, there is limited data exploring the risk of pancreatic cancer (PC) in patients with NAFLD. We aim to investigate the risk of PC in patients with biopsy proven NAFLD. Methods: We performed a multicenter retrospective cohort study utilizing an electronic health record database (TriNetX) to study the risk of PC in patients with NAFLD. The study group comprised adults ≥40 years with NAFLD who had undergone liver biopsy between January 2016 to December 2019. Comparison group was obese individuals (body mass index ≥30 kg/m 2 ) without NAFLD. We excluded patients with other etiologies of chronic liver disease. The median follow up was 5 years. Patients who had follow up visits 1-4 years were selected. The primary outcome was a new diagnosis of PC. Results: We identified 18,513 patients with NAFLD and had undergone liver biopsy, predominantly white (75.3%) females (59.7%). Diabetes mellitus (29.4% vs. 18.8%), chronic pancreatitis (1.3% vs. 0.2%), pancreatic cyst (0.8% vs. 0.2%), tobacco use (9.4% vs. 7.7%), and a family history of GI cancers (2.7% vs. 1.5%) were observed more commonly in the NAFLD group compared with the obese control. After propensity score matching for confounding variables, the 5-year risk of developing PC was higher in NAFLD cohort (risk ratio, RR 2.18, 95% CI 1.56-3.03) compared with the control group. Overall, 5-year mortality was higher in the NAFLD cohort (8.2% vs 6.6%, RR 1.25, 95% CI 1.16-1.37). Conclusions: NAFLD probably increases the risk of pancreatic cancer in middle-aged and elderly individuals and the risk exists despite controlling for obesity and other known risk factors for PC. NAFLD should be considered in the risk stratification strategy for pancreatic cancer. Moreover, patients with NAFLD and advanced fibrosis who undergo screening for hepatoma may be considered for abdominal CT or MRI for pancreatic cancer screening if other risk factors exist. [Table: see text]
Perioperative fuzuloparib plus mFOLFIRINOX for resectable pancreatic adenocarcinoma: A phase 1 study.
Authors: Qian Zhan, Chenlei Wen, Siyi Zou, Fanlu Li, Dongjie Chen, Zhen Sheng, Zhixin Yu, Denghui Gao, Baiyong Shen
Journal: Journal of Clinical Oncology (2024)

4163 Background: Surgical resection followed by adjuvant mFOLFIRINOX is currently the standard of care for resectable pancreatic adenocarcinoma. Neoadjuvant therapy has the potential to induce tumor downsizing and improve R0 resection rate. In this study, we aimed to explore the feasibility of the PARP inhibitor fuzuloparib in combination with mFOLFIRINOX as the neoadjuvant and adjuvant therapy in patients (pts) with resectable pancreatic adenocarcinoma. Methods: This was a dose escalation and expansion phase 1 study in pts with histologically or cytologically confirmed, high-risk resectable or borderline resectable pancreatic adenocarcinoma. Eligible pts received perioperative treatment with fuzuloparib plus mFOLFIRINOX (up to 12 cycles of 14 days each, with 4 to 6 cycles administered preoperatively; fuzuloparib at escalating doses starting at 30 mg BID), followed by maintenance fuzuloparib at 150 mg BID. Dose-limiting toxicities (DLTs) were observed during the first 2 treatment cycles. The primary objectives were safety and tolerability. Results: As of Oct 31, 2023, 15 pts were enrolled, including 3 pts in the fuzuloparib 30 mg cohort and 12 pts in the 60 mg cohort. Twelve (80.0%) pts completed neoadjuvant therapy as planned. Eight (53.3%) pts underwent surgical resection, and all pts achieved R0 resections (100.0%; 95% CI, 63.1–100.0). Four of the 8 (50.0%) pts proceeded to adjuvant therapy (30 mg cohort: 0/2 [0%]; 60 mg cohort: 4/6 [66.7%]). There were no DLTs identified. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 12 (80.0%) pts, with the most common being decreased neutrophil count, decreased white blood cell count, hypokalemia, and anemia. No unexpected TRAEs were reported. No patients discontinued study treatment due to TRAEs. Conclusions: Perioperative fuzuloparib plus mFOLFIRINOX was generally tolerated and had acceptable safety profile in pts withresectable pancreatic adenocarcinoma. Neoadjuvant fuzuloparib plus mFOLFIRINOX prior to surgery achieved a R0 resection rate of 100%. Clinical trial information: NCT04425876 .
Comorbid functional dyspepsia reflects IL-33–mediated airway neuronal dysfunction in asthma
Authors: Keima Ito, Yoshihiro Kanemitsu, Takashi Ueda, Takeshi Kamiya, Eiji Kubota, Yuta Mori, Kensuke Fukumitsu, Tomoko Tajiri, Satoshi Fukuda, Takehiro Uemura, Hirotsugu Ohkubo, Yutaka Ito, Yasuhiro Shibata, Natsuko Kumamoto, Shinya Ugawa, Akio Niimi
Journal: Journal of Allergy and Clinical Immunology (2024)
Simplified <i>Helicobacter pylori</i> therapy for patients with penicillin allergy: a randomised controlled trial of vonoprazan-tetracycline dual therapy
Authors: Wen Gao, Jianxiang Liu, Xiaolei Wang, Jingwen Li, Xuezhi Zhang, Hui Ye, Jiang Li, Xinhong Dong, Binbin Liu, Chi Wang, Ying Xu, Guigen Teng, Yuling Tian, Jinpei Dong, Chaoyi Ge, Hong Cheng
Journal: Gut (2024)

Background and aims This study aimed to evaluate the efficacy and safety of vonoprazan and tetracycline (VT) dual therapy as first-line treatment for Helicobacter pylori infection in patients with penicillin allergy. Methods In this randomised controlled trial, treatment-naïve adults with H. pylori infection and penicillin allergy were randomised 1:1 to receive either open-label VT dual therapy (vonoprazan 20 mg two times per day+tetracycline 500 mg three times a day) or bismuth quadruple therapy (BQT; lansoprazole 30 mg two times per day+colloidal bismuth 150 mg three times a day+tetracycline 500 mg three times a day+metronidazole 400 mg three times a day) for 14 days. The primary outcome was non-inferiority in eradication rates in the VT dual group compared with the BQT group. Secondary outcomes included assessing adverse effects. Results 300 patients were randomised. The eradication rates in the VT group and the BQT group were: 92.0% (138/150, 95% CI 86.1% to 95.6%) and 89.3% (134/150, 95% CI 83.0% to 93.6%) in intention-to-treat analysis (difference 2.7%; 95% CI −4.6% to 10.0%; non-inferiority p=0.000); 94.5% (138/146, 95% CI 89.1% to 97.4%) and 93.1% (134/144, 95% CI 87.3% to 96.4%) in modiﬁed intention-to-treat analysis (difference 1.5%; 95% CI −4.9% to 8.0%; non-inferiority p=0.001); 95.1% (135/142, 95% CI 89.7% to 97.8%) and 97.7% (128/131, 95% CI 92.9% to 99.4%) in per-protocol analysis (difference 2.6%; 95% CI −2.9% to 8.3%; non-inferiority p=0.000). The treatment-emergent adverse events (TEAEs) were significantly lower in the VT group (14.0% vs 48.0%, p=0.000), with fewer treatment discontinuations due to TEAEs (2.0% vs 8.7%, p=0.010). Conclusions VT dual therapy demonstrated efficacy and safety as a first-line treatment for H. pylori infection in the penicillin-allergic population, with comparable efficacy and a lower incidence of TEAEs compared with traditional BQT. Trial registration number ChiCTR2300074693.
Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine as first line chemotherapy in patients with recurrent or metastatic nasopharyngeal carcinoma: randomised phase 3 clinical trial
Journal: BMJ (2024)

Nab-paclitaxel, cisplatin, and capecitabine versus cisplatin and gemcitabine
Renal mass biopsy — a practical and clinicopathologically relevant approach to diagnosis
Authors: Hussein Mansour, My-Anh Tran-Dang, Miles Walkden, Ekaterini Boleti, Ravi Barod, Prasad Patki, Faiz Mumtaz, Maxine G. B. Tran, Axel Bex, Soha El Sheikh
Journal: Nature Reviews Urology (2024)
Human angiotensin-converting enzyme 2–specific antisense oligonucleotides reduce infection with SARS-CoV-2 variants
Authors: Tong Lu, Chengcheng Zhang, Zhengqi Li, Yi Wei, Anne Sadewasser, Yan Yan, Lin Sun, Jian Li, Yihui Wen, Shimin Lai, Changhui Chen, Hua Zhong, Marta Reyes Jiménez, Richard Klar, Monika Schell, Stefanie Raith, Sven Michel, Bixia Ke, Huanying Zheng, Frank Jaschinski, Nan Zhang, Haipeng Xiao, Claus Bachert, Weiping Wen
Journal: Journal of Allergy and Clinical Immunology (2024)
Covid-19: Study sheds light on how some people avoid the disease
Authors: Matthew Limb
Journal: BMJ (2024)

Study sheds light on how some people avoid the disease Matthew LimbScientists say that they have discovered novel immune responses that help explain how some people avoid getting covid-19.High levels of a key gene in volunteers who managed to quickly fight off infection suggest that this has a protective effect against SARS-CoV-2.
Oral Device More Effectively Relieved Snoring Than Other Common Approach
Authors: Anna Bock
Journal: JAMA (2024)

Patrick Ioerger, BS; Azadeh Afshari, DDS; Firas Hentati, MD, MSCI; William Strober, MD; Dorina Kallogjeri, MD, MPH; Yo-El Ju, MD, MSCI; Jay F. Piccirillo, MD
Antihypertensives Might Explain Some Older Adults’ New Eczema Diagnoses
Authors: Anna Bock
Journal: JAMA (2024)

Morgan Ye, MPH; Leslie N. Chan, MD; Ian Douglas, PhD; David J. Margolis, MD, PhD; Sinéad M. Langan, MSc, PhD; Katrina Abuabara, MD, MA, MSCE
Riluzole for Cervical Myelopathy
Authors: Zoher Ghogawala
Journal: JAMA Network Open (2024)

Michael G. Fehlings, MD, PhD; Karlo M. Pedro, MD; Mohammed Ali Alvi, MD; Jetan H. Badhiwala, MD, PhD; Henry Ahn, MD; H. Francis Farhadi, MD; Christopher I. Shaffrey, MD; Ahmad Nassr, MD; Praveen Mummaneni, MD; Paul M. Arnold, MD; W. Bradley Jacobs, MD; K. Daniel Riew, MD; Michael Kelly, MD; Darrel S. Brodke, MD; Alexander R. Vaccaro, MD; Alan S. Hilibrand, MD; Jason Wilson, MD; James S. Harrop, MD; S. Tim Yoon, MD; Kee D. Kim, MD; Daryl R. Fourney, MD; Carlo Santaguida, MD; Eric M. Massicotte, MD; Peng Huang, PhD
A 5:2 Intermittent Fasting Meal Replacement Diet and Glycemic Control for Adults With Diabetes
Authors: Lixin Guo, Yue Xi, Wenbo Jin, Huijuan Yuan, Guijun Qin, Shuchun Chen, Lihui Zhang, Yu Liu, Xingbo Cheng, Wen Liu, Dongni Yu
Journal: JAMA Network Open (2024)

An intermittent fasting plan consisting of 2 nonconsecutive fasting days and 5 days of habitual intake per week and meal replacement diet (5:2 MR) could provide additional benefits to patients with type 2 diabetes.
Angiographic Findings and Post–Percutaneous Coronary Intervention Fractional Flow Reserve
Authors: Jinlong Zhang, Doyeon Hwang, Seokhun Yang, Xinyang Hu, Joo Myung Lee, Chang-Wook Nam, Eun-Seok Shin, Joon-Hyung Doh, Masahiro Hoshino, Rikuta Hamaya, Yoshihisa Kanaji, Tadashi Murai, Jun-Jie Zhang, Fei Ye, Xiaobo Li, Zhen Ge, Shao-Liang Chen, Tsunekazu Kakuta, Jian’an Wang, Bon-Kwon Koo
Journal: JAMA Network Open (2024)

The associations between angiographic findings and post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) and their clinical relevance according to residual functional disease burden have not been thoroughly investigated.
Evaluating Intensity, Complexity, and Potential for Causal Inference in Social Needs Interventions
Authors: Meera Viswanathan, Sara M. Kennedy, Nila Sathe, Michelle L. Eder, Valerie Ng, Shannon Kugley, Megan A. Lewis, Laura M. Gottlieb
Journal: JAMA Network Open (2024)

Interventions that address needs such as low income, housing instability, and safety are increasingly appearing in the health care sector as part of multifaceted efforts to improve health and health equity, but evidence relevant to scaling these social needs interventions is limited.
Cannabis, Tobacco Use, and COVID-19 Outcomes
Authors: Nicholas B. Griffith, Timothy B. Baker, Brendan T. Heiden, Nina Smock, Giang Pham, Jingling Chen, Justin Yu, James Reddy, Albert M. Lai, Eric Hogue, Laura J. Bierut, Li-Shiun Chen
Journal: JAMA Network Open (2024)

It is unclear whether cannabis use is associated with adverse health outcomes in patients with COVID-19 when accounting for known risk factors, including tobacco use.
Potentially Inappropriate Medication Use in Primary Care in Switzerland
Authors: Simeon Schietzel, Stefan Zechmann, Yael Rachamin, Stefan Neuner-Jehle, Oliver Senn, Thomas Grischott
Journal: JAMA Network Open (2024)

Potentially inappropriate medication (PIM) exposes patients to an increased risk of adverse outcomes. Many lists of explicit criteria provide guidance on identifying PIM and recommend alternative prescribing, but the complexity of available lists limits their applicability and the amount of data available on PIM prescribing.
Policy on Liver Transplants May Have Worsened US Health Disparities
Authors: Anna Bock
Journal: JAMA (2024)

Ola Ahmed, MD, PhD, MMEd; Maria Bernadette Majella Doyle, MD, MBA; Marwan S. Abouljoud, MD; Diane Alonso, MD; Ramesh Batra, MBBS, MA; Kenneth L. Brayman, MD, PhD; Diane Brockmeier, RN, MHA; Robert M. Cannon, MD; Kenneth Chavin, MD, PhD; Aaron M. Delman, MD; Derek A. DuBay, MD; Jan Finn, RN, MSN; Jonathan A. Fridell, MD; Barry S. Friedman, RN, MBA; Danielle M. Fritze, MD; Derek Ginos, MHA; David S. Goldberg, MD; Glenn A. Halff, MD; Seth J. Karp, MD; Vivek K. Kohli, MD; Sean C. Kumer, MD, PhD; Alan Langnas, DO; Jayme E. Locke, MD, MPH; Daniel Maluf, MD; Raphael P. H. Meier, MD, PhD; Alejandro Mejia, MD; Shaheed Merani, MD, PhD; David C. Mulligan, MD; Bobby Nibuhanupudy, MD; Madhukar S. Patel, MD; Shawn J. Pelletier, MD; Shimul A. Shah, MD; Parsia A. Vagefi, MD; Rodrigo Vianna, MD, PhD; Gazi B. Zibari, MD; Teresa J. Shafer, RN, MSN, CPTC; Susan L. Orloff, MD
Duration of New-Onset Depressive Symptoms During Medical Residency
Authors: Erin Kim, Brandy R. Sinco, Joan Zhao, Yu Fang, Carrie Cunningham, Elena Frank, Srijan Sen, Amy Bohnert, Tasha M. Hughes
Journal: JAMA Network Open (2024)

The implications of new-onset depressive symptoms during residency, particularly for first-year physicians (ie, interns), on the long-term mental health of physicians are unknown.
Federated Abnormal Heart Sound Detection with Weak to No Labels
Authors: Wanyong Qiu, Chen Quan, Yongzi Yu, Eda Kara, Kun Qian, Bin Hu, Björn W. Schuller, Yoshiharu Yamamoto
Journal: Cyborg and Bionic Systems (2024)

Cardiovascular diseases are a prominent cause of mortality, emphasizing the need for early prevention and diagnosis. Utilizing artificial intelligence (AI) models, heart sound analysis emerges as a noninvasive and universally applicable approach for assessing cardiovascular health conditions. However, real-world medical data are dispersed across medical institutions, forming “data islands” due to data sharing limitations for security reasons. To this end, federated learning (FL) has been extensively employed in the medical field, which can effectively model across multiple institutions. Additionally, conventional supervised classification methods require fully labeled data classes, e.g., binary classification requires labeling of positive and negative samples. Nevertheless, the process of labeling healthcare data is time-consuming and labor-intensive, leading to the possibility of mislabeling negative samples. In this study, we validate an FL framework with a naive positive-unlabeled ( PU ) learning strategy. Semisupervised FL model can directly learn from a limited set of positive samples and an extensive pool of unlabeled samples. Our emphasis is on vertical-FL to enhance collaboration across institutions with different medical record feature spaces. Additionally, our contribution extends to feature importance analysis, where we explore 6 methods and provide practical recommendations for detecting abnormal heart sounds. The study demonstrated an impressive accuracy of 84%, comparable to outcomes in supervised learning, thereby advancing the application of FL in abnormal heart sound detection.
Glucose Load Following Prolonged Fasting Increases Oxidative Stress-Linked Response in Individuals With Diabetic Complications
Authors: Ekaterina von Rauchhaupt, Claus Rodemer, Elisabeth Kliemank, Ruben Bulkescher, Marta Campos, Stefan Kopf, Thomas Fleming, Stephan Herzig, Peter P. Nawroth, Julia Szendroedi, Johanna Zemva, Alba Sulaj
Journal: Diabetes Care (2024)

Prolonged catabolic states in type 2 diabetes (T2D), exacerbated by excess substrate flux and hyperglycemia, can challenge metabolic flexibility and antioxidative capacity. We investigated cellular responses to glucose load after prolonged fasting in T2D.
Cellular spermine targets JAK signaling to restrain cytokine-mediated autoimmunity
Authors: Henan Xu, Xiao Zhang, Xin Wang, Bo Li, Hang Yu, Yuan Quan, Yan Jiang, Yuling You, Yan Wang, Mingyue Wen, Juan Liu, Min Wang, Bo Zhang, Yixian Li, Xuan Zhang, Qianjin Lu, Chu-Yi Yu, Xuetao Cao
Journal: Immunity (2024)