tbuckley/cabot-search huggingface dataset:
Phase II study of perioperative Avelumab plus chemotherapy for patients with resectable gastric cancer or gastroesophageal junction cancer – the MONEO Study
Authors: Maria Alsina, Guillermo Villacampa, Carlos de Andrea, Ana Vivancos, Mariano Ponz-Sarvise, Virginia Arrazubi, Paula Jimenez-Fonseca, Marc Diez, Enrique Sanz-Garcia, Eva Martínez, Raquel Guardeño, Mariona Calvo, Cristina Bugés, Federico Longo, Víctor Navarro, Eduardo García-Galea, Alena Gros, Maria C. Ochoa, Alvaro Lopez-Janeiro, Sandra Sanchez-Gregorio, Claudia Herrero, Ibone Labiano, Maria Vila-Casadesús, Dario López, Raluca Alexandru, Susana Muñoz, Josep Tabernero, Ignacio Melero
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Immune checkpoints inhibitors (ICIs) combined with chemotherapy have provided successful results in patients with gastric and gastroesophageal junction (G/GEJ) cancers in the metastatic setting. Similar strategies have been explored in earlier stages. Here, we present final results of the phase II MONEO trial, which evaluated the addition of avelumab to neoadjuvant chemotherapy. Patients and methods: Patients with untreated, resectable G/GEJ adenocarcinoma received neoadjuvant treatment with four cycles of avelumab plus the FLOT4 regimen, followed by surgery. Upon postoperative recovery, patients underwent four additional adjuvant cycles of the same combination, followed by avelumab monotherapy for up to one year. The primary endpoint was pathological complete response (pCR) rate. Sequential flow cytometry and cytokine determination were performed in peripheral blood, along with multiplex tissue immunofluorescence and RNA sequencing (RNA-seq) in tumor specimens. Results: Forty patients were enrolled, achieving a pCR rate of 21.1% (95% CI: 10.0–37.0). Major pathological response rate was 28.9%, more pronounced in those patients with tumors expressing programmed cell death protein 1 (PD-L1) before treatment as measured by combined positive score (CPS cut-off 10; 33.3% vs. 21.1%). Results propose several potential biomarkers considering tumor immune infiltrate, circulating immune cells, and cytokines. Eighty percent of patients experienced treatment-related grade ≥3 adverse events. Conclusions: The combination of avelumab plus the FLOT4 regimen showed relatively modest efficacy in resectable G/GEJ adenocarcinoma. Better results were observed in PD-L1 CPS ≥10% tumors. Exploratory biomarker analyses provide insights that may help to identify candidates most likely to benefit from chemoimmunotherapy as a neoadjuvant treatment.
Capecitabine maintenance therapy in patients with residual nasopharyngeal carcinoma: a single-arm, phase 2 trial
Authors: Xun Cao, Zhuo-Ying Luo, Hao-Yang Huang, Jia-Yu Zhou, Xi Chen, Ying-Ying Huang, Liang-Ru Ke, Lu-Jun Han, Yue Xia, Wei-Xiong Xia, Lin-Quan Tang, Shan-Shan Guo, Xiang Guo, Xing Lyu
Journal: Clinical Cancer Research (2025)

Abstract Purpose: Patients with residual nasopharyngeal carcinoma after receiving standard-of-care treatment have poor prognoses. In this trial, we aimed to assess the efficacy and safety of capecitabine maintenance therapy in patients with residual nasopharyngeal carcinoma. Patients and Methods: This open-label, single-arm, phase 2 trial was conducted at Sun Yat-sen University Cancer Center. We recruited patients aged 18–70 years with an ECOG performance-status score of 0–1, histopathological, cytological confirmed nasopharyngeal carcinoma (without distant metastasis), who had residual disease after receiving definitive treatment. Patients received 1 year of capecitabine maintenance therapy. The primary endpoint was 2-year progression-free survival. Results: Between January 1, 2019, and December 30, 2022, 111 patients were recruited and commenced capecitabine maintenance therapy for 1 year. After a median follow-up duration of 34.8 months (IQR 30.5–45.2), progression-free survival was 92% at 1-year; 86% at 2 years; and 81% at 3 years. Adverse events were reported in 97.3% of patients. Hand-foot syndrome was the most common adverse event (59.5%). In addition, 28.7% of patients experienced grade 3 treatment-related adverse events, the most common of which was hand-foot syndrome (7.2%); no grade 4–5 adverse events were recorded. 72.1% of patients received the full dosage of capecitabine. 76.6% of patients completed the 1-year capecitabine maintenance therapy. Conclusions: The anti-tumor efficacy of capecitabine maintenance therapy is promising, and the safety profile is manageable in patients with residual nasopharyngeal carcinoma after receiving standard-of-care treatment.
Response by Bulluck and Hausenloy to Letter Regarding Article, “Effect of Cangrelor on Infarct Size in ST-Segment–Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (the PITRI Trial)”
Authors: Heerajnarain Bulluck, Derek J. Hausenloy
Journal: Circulation (2025)
Diagnostic Yield and Outcomes of Incidental Thoracic Aortic Dilatation in the National Health Service Targeted Lung Health Check Program: Novel Insights from a Regional Tertiary Center in the United Kingdom
Authors: Dalia Ahmed, Nehan Khalid, Vivek Shrivastava, Claudette Philips, Kanwal Tariq, Imran Sunderji, Oliver Byass, Raghav T. Bhatia
Journal: Circulation (2025)
Partial Heart Transplantation: Early Experience With Pediatric Heart Valve Replacements That Grow
Authors: Neel K. Prabhu, Berk Aykut, Michael Mensah-Mamfo, Douglas M. Overbey, Joseph W. Turek
Journal: Circulation (2025)

Heart valve replacement in children is fraught with long-term morbidity and mortality rates, largely because conventional implants lack the capacity to grow with the child. Partial heart transplantation presents a potential solution by transplanting only specific segments of a donor heart, thereby providing a living and growing heart valve implant. This approach harnesses the full spectrum of cardiac tissues, which, when freshly procured and supported by immunosuppression, can integrate as functional and potentially growth-capable tissue. This state-of-the-art review discusses the history and development of partial heart transplantation, its indications, recent clinical experiences, regulation, and future directions.
Nerandomilast in Patients with Progressive Pulmonary Fibrosis
Authors: Toby M. Maher, Shervin Assassi, Arata Azuma, Vincent Cottin, Anna-Maria Hoffmann-Vold, Michael Kreuter, Justin M. Oldham, Luca Richeldi, Claudia Valenzuela, Marlies S. Wijsenbeek, Emmanuelle Clerisme-Beaty, Carl Coeck, Hui Gu, Ivana Ritter, Arno Schlosser, Susanne Stowasser, Florian Voss, Gerrit Weimann, Donald F. Zoz, Fernando J. Martinez
Journal: New England Journal of Medicine (2025)

Nerandomilast (BI 1015550) is an orally administered preferential inhibitor of phosphodiesterase 4B with antifibrotic and immunomodulatory properties. Nerandomilast has been shown to slow the progression of idiopathic pulmonary fibrosis, but an assessment of its effects in other types of progressive pulmonary fibrosis is needed. In a phase 3, double-blind trial, we randomly assigned patients with progressive pulmonary fibrosis in a 1:1:1 ratio to receive nerandomilast at a dose of 18 mg twice daily, nerandomilast at a dose of 9 mg twice daily, or placebo, with stratification according to background therapy (nintedanib vs. none) and fibrotic pattern on high-resolution computed tomography (usual interstitial pneumonia-like pattern vs. other patterns). The primary end point was the absolute change from baseline in the forced vital capacity (FVC), measured in milliliters, at week 52. A total of 1176 patients received at least one dose of nerandomilast or placebo, of whom 43.5% were taking background nintedanib therapy at baseline. The adjusted mean change in the FVC at week 52 was -98.6 ml (95% confidence interval [CI], -123.7 to -73.4) in the nerandomilast 18-mg group, -84.6 ml (95% CI, -109.6 to -59.7) in the nerandomilast 9-mg group, and -165.8 ml (95% CI, -190.5 to -141.0) in the placebo group. The adjusted difference between the nerandomilast 18-mg group and the placebo group was 67.2 ml (95% CI, 31.9 to 102.5; P<0.001), and the adjusted difference between the nerandomilast 9-mg group and the placebo group was 81.1 ml (95% CI, 46.0 to 116.3; P<0.001). The most frequent adverse event was diarrhea, reported in 36.6% of the patients in the nerandomilast 18-mg group, 29.5% of those in the nerandomilast 9-mg group, and 24.7% of those in the placebo group. Serious adverse events occurred in similar percentages of patients in the trial groups. In patients with progressive pulmonary fibrosis, treatment with nerandomilast led to a smaller decline in the FVC than placebo over a period of 52 weeks. (Funded by Boehringer Ingelheim; FIBRONEER-ILD ClinicalTrials.gov number, NCT05321082.).
As-Needed Albuterol–Budesonide in Mild Asthma
Authors: Craig LaForce, Frank Albers, Anna Danilewicz, Allison Jeynes-Ellis, Monica Kraft, Reynold A. Panettieri, Robert Rees, Samuel Bardsley, Lynn Dunsire, Tim Harrison, Olami Sobande, Raulin Surujbally, Frank Trudo, Christy Cappelletti, Alberto Papi, Richard Beasley, Bradley E. Chipps, Elliot Israel, Hitesh Pandya, Martin Clancy, Leonard B. Bacharier
Journal: New England Journal of Medicine (2025)

As-needed use of albuterol-budesonide has been shown to result in a significantly lower risk of severe asthma exacerbation than as-needed use of albuterol alone among patients with moderate-to-severe asthma. Data on albuterol-budesonide in mild asthma are needed. We conducted a fully virtual, decentralized, phase 3b, multicenter, double-blind, event-driven trial involving persons 12 years of age or older with disease that was uncontrolled despite treatment for mild asthma with a short-acting β2-agonist (SABA) with or without a low-dose inhaled glucocorticoid or leukotriene-receptor antagonist. Participants were randomly assigned in a 1:1 ratio to a fixed-dose combination of 180 μg of albuterol and 160 μg of budesonide (with each dose consisting of two inhaler actuations of 90 μg and 80 μg, respectively) or 180 μg of albuterol (with each dose consisting of two inhaler actuations of 90 μg) on an as-needed basis for up to 52 weeks. The primary end point was the first severe asthma exacerbation, assessed in a time-to-event analysis, in the on-treatment efficacy population, and the key secondary end point was the first severe exacerbation in the intention-to-treat population. Secondary end points included the annualized rate of severe asthma exacerbations and exposure to systemic glucocorticoids. A total of 2516 participants underwent randomization; 1797 (71.4%) completed the trial. Of 2421 participants in the full analysis population (1209 assigned to the albuterol-budesonide group and 1212 to the albuterol group), 97.2% were 18 years of age or older; 74.4% used a SABA alone at baseline. The trial was stopped for efficacy at a prespecified interim analysis. A severe exacerbation occurred in 5.1% of the participants in the albuterol-budesonide group and in 9.1% of those in the albuterol group in the on-treatment efficacy population (hazard ratio, 0.53; 95% confidence interval [CI], 0.39 to 0.73) and in 5.3% and 9.4%, respectively, in the intention-to-treat population (hazard ratio, 0.54; 95% CI, 0.40 to 0.73) (P<0.001 for both comparisons). The annualized rate of severe asthma exacerbations was lower with albuterol-budesonide than with albuterol (0.15 vs. 0.32; rate ratio, 0.47; 95% CI, 0.34 to 0.64), as was the mean annualized total dose of systemic glucocorticoids (23.2 vs. 61.9 mg per year). Adverse events were similar in the two treatment groups. As-needed use of albuterol-budesonide resulted in a lower risk of a severe asthma exacerbation than as-needed use of albuterol alone among participants with disease that was uncontrolled despite treatment for mild asthma. (Funded by Bond Avillion 2 Development and AstraZeneca; BATURA ClinicalTrials.gov number, NCT05505734.).
PErsistence and safety of subcutaneous infliximab 1 year after switch from intravenous route in IBD patients in REMission
Authors: Nicolas Mathieu, Marianne Hupé, Frédéric Heluwaert, Pauline Rivière, Xavier Hébuterne, Antoine Chupin, Vered Abitbol, Guillaume Bouguen, Lucine Vuitton, Jean-Marc Gornet, Céline Montuclard, Stéphane Nancey, Guillaume Cadiot, Pauline Wils, Cyrielle Gilletta, Astrid de Maissin, Romain Altwegg, Elise Chanteloup, Laurianne Plastaras, Philippe Ah Soune, Arnaud Bourreille, Carmen Stefanescu, Philippe Seksik, Marion Simon, Mathieu Uzzan, Pierre Andrau, Cléa Rouillon, Yves Arondel, Anthony Buisson, Laurent Peyrin-Biroulet, Bassirou Mboup, Eric Vicaut, David Laharie
Journal: Clinical Gastroenterology and Hepatology (2025)
The Effectiveness of an Educational Intervention to Introduce Adolescents From Marginalized Backgrounds to Dermatology: A Pilot Initiative
Authors: Heli Patel, Hrushikesh Patel, Ross O'Hagan, Robert Smith, Adam Friedman, Rishab Revankar, Pamela Allen, Seemal R Desai
Journal: Journal of the American Academy of Dermatology (2025)
Addendum: Sensitive in vivo imaging of T cells using a membrane-bound Gaussia princeps luciferase
Authors: Elmer B Santos, Raymond Yeh, James Lee, Yan Nikhamin, Blesida Punzalan, Blesserene Punzalan, Krista La Perle, Steven M Larson, Michel Sadelain, Renier J Brentjens
Journal: Nature Medicine (2025)
The Risk of Decompensation in Steatotic Liver Disease Related Hepatocellular Carcinoma: A Comparison with Viral-controlled Cases
Authors: Yuki Matsushita, Tatsuya Minami, Yoshikuni Kawaguchi, Akihiko Ichida, Ryo Oikawa, Keisuke Mabuchi, Makoto Moriyama, Tomoharu Yamada, Kazuya Okushin, Takuma Nakatsuka, Masaya Sato, Yotaro Kudo, Mitsuhiro Fujishiro, Kiyoshi Hasegawa, Ryosuke Tateishi
Journal: Liver Cancer (2025)

Background and Aims: Treatment options for steatotic liver disease (SLD) are limited compared to those for viral hepatitis, which may affect the prognosis of patients with hepatocellular carcinoma (HCC). Methods: This retrospective cohort study included 255 and 125 patients with SLD-related HCC and viral-controlled HCC (80 hepatitis C and 45 hepatitis B) who underwent curative radiofrequency ablation (RFA) for primary HCC (maximum tumor diameter ≤ 3 cm and ≤3 lesions). Viral control was defined as a sustained virological response to hepatitis C and undetectable hepatitis B viruses on a nucleos(t)ide analog before HCC diagnosis. Overall survival, recurrence rates, and hepatic decompensation rates were evaluated using the Kaplan-Meier method and Cox proportional hazard models between the two groups. Validation was performed in a surgical cohort of 120 patients (70 with SLD and 50 controls). Results: The 1-, 3-, and 5-year survival rates were 97%, 81%, and 62% for patients with SLD-related HCC, and 100%, 94%, and 89% for viral-controlled patients in the RFA cohort, respectively (p &lt; 0.001, log-rank test). Multivariate analysis showed no significant difference in recurrence between the two groups (adjusted hazard ratio [aHR] 1.06, p = 0.75); however, a higher risk of hepatic decompensation was observed in patients with SLD-related HCC (aHR 6.17; p &lt;0.001) and a worse overall survival (aHR 2.04; p = 0.003). Similar results were observed in the surgical cohort. Conclusion: Patients with SLD-related HCC have a higher risk of decompensation than viral-controlled patients with HCC, which leads to a worse overall survival.
In Utero Exposure to Maternal Hyperglycemia and Offspring Type 2 Diabetes Genetic Risk Score Are Independently Associated With Risk of Impaired Glucose Tolerance in Youth
Authors: Abigayil C. Dieguez, Alan Kuang, Jami L. Josefson, Denise M. Scholtens, William L. Lowe, M. Geoffrey Hayes, Marie-France Hivert
Journal: Diabetes Care (2025)

OBJECTIVE We tested associations of type 2 diabetes genetic risk score (T2D-GRS) and exposure to maternal hyperglycemia with childhood impaired glucose tolerance (IGT) and T2D and glycemic outcomes in youth from the Hyperglycemia and Adverse Pregnancy Outcome Follow-Up Study. RESEARCH DESIGN AND METHODS We calculated T2D-GRS using 1,150 known genetic variants associated with T2D in adults. In utero exposures included gestational diabetes (GDM) and sum-of-glucose z scores during oral glucose tolerance test at ∼28 weeks’ gestation. IGT + T2D and continuous glycemic outcomes were measured when children were 10–14 years old. RESULTS In 3,444 children (mean age, 11.4 years), higher maternal sum-of-glucose z scores and child T2D-GRS were both associated with higher glucose levels. In children exposed to GDM and with T2D-GRS &amp;gt;75th percentile, 15.9% had IGT + T2D, compared with 5.6% in nonexposed children. CONCLUSIONS High genetic risk for diabetes and in utero exposure to maternal hyperglycemia are additively associated with IGT + T2D and glycemic outcomes in youth.
DeTox: an <i>In-Silico</i> Alternative to Animal Testing for Predicting Developmental Toxicity Potential
Authors: Ricardo Scheufen Tieghi, Marielle Rath, José Teófilo Moreira-Filho, James Wellnitz, Holli-Joi Martin, Kathleen Gates, Helena T. Hogberg, Nicole Kleinstreuer, Alexander Tropsha, Eugene N. Muratov
Journal: Environmental Health Perspectives (2025)

Medication use among pregnant women is common, yet the safety of these medications for the developing fetus/baby is widely understudied. Quantitative Structure-Activity Relationship (QSAR) models can be used to predict the overall and trimester-specific developmental toxicity potential of chemicals, supporting the development of safer medications for pregnant women and regulatory assessment aligned with the 3Rs (refining, reducing, and replacing) of animal testing. This study aimed to collect and curate a database of compounds classified according to their developmental toxicity potential, use this database to develop and validate QSAR models for predicting prenatal developmental toxicity, and implement models via a user-friendly online platform to support regulatory assessments of drug candidates. We compiled and curated data from the FDA and Teratogen Information System (TERIS) databases and validated annotations with rigorous literature searches. The database was leveraged to create QSAR models using machine learning algorithms (RF, SVM, LightGBM) with Bayesian hyperparameter optimization. These models were implemented into a web tool. We built a binary classification QSAR model for overall pregnancy risk, and separate QSAR models for trimester-specific risk, exhibiting correct classification rates of and 76% (overall), 80% (1st trimester), 95% (2nd trimester), and 95% (3rd trimester). Models showed a sensitivity between 53% and 90%, specificity between 46% and 100%, and coverage of 76% assessed using a five-fold external validation protocol. We established a publicly accessible web portal (https://detox.mml.unc.edu/) for developmental toxicity prediction of both overall and trimester-specific toxicity predictions. DeTox can be employed to support regulatory assessment of pharmaceutical and cosmetic products aligned with the 3Rs of animal testing and to guide the development of safer drugs for pregnant populations. The curated dataset of developmental toxicants is publicly available, and all models are implemented in a public, user-friendly web tool, DeTox (Developmental Toxicity), at https://detox.mml.unc.edu/. https://doi.org/10.1289/EHP15307.
Diaphragmatic eventration associated with megacolon: a narrative review
Authors: Guillaume Tcheutchoua Soh, Abdourahmane Ndong, Jacques Noel Tendeng, Papa Mamadou Faye, Ousmane Thiam, Ngouanfo Tchoffo Josiane, Philippe Manyacka Ma Nyemb, Ibrahima Konate, Mamadou Cisse
Journal: International Journal of Surgery (2025)

Background: Diaphragmatic eventration is a rare condition classified as acquired or congenital. Diaphragmatic eventration associated with megacolon is a clinical finding that does not fit the existing principles of treatment. This study aimed to review this association in order to update the knowledge available on diaphragmatic eventration. Method: We included articles about diaphragmatic eventration associated with megacolon. The search databases included PubMed, Google Scholar, and African Journal Online, which were added to other articles obtained by manual search. Results: We included 21 case reports in the study. From these, we identified four common points: the left side was involved in 95.2% (except one case where the liver was displaced), all patients were adults, the clinical presentations were respiratory symptoms in (90.4%, n = 19), and abdominal emergency syndrome in (38%, n = 8). The condition is easily detected on standard X-rays, and no cause has been identified for the acquired eventration. The surgical approaches were laparotomy (61.9%), thoracotomy (19%), and laparotomy and thoracotomy (4.8%). This treatment consists of management of eventration and megacolon. Treatment was surgical in 86.7% ( n = 18) of patients. It consisted of diaphragm plication in 23.8% ( n = 5), colonic resection in 19% ( n = 4), diaphragmatic plication, and colonic resection in 42.9% ( n = 9). Conclusion: Megacolon can reveal diaphragmatic eventration in adults, especially on the left side. The diagnosis is easily detected on radiography. This can present as a major surgical abdominal emergency and therefore must be managed using an open abdominal approach. Other cases can be managed through the abdominal or thoracic route; however, treatment of colonic distension must be considered.
Laparoscopic radical hysterectomy-karez technique for stage IB3 and IIA2 cervical cancer: a multicenter retrospective cohort study
Authors: Xiaoming Yang, Sibang Chen, Yuhong Li, Jin Peng, Jiaxi Wang, Xinyu Ni, Roufei Lu, Jiangtao Fan, Shiqian Zhang, Yudong Wang
Journal: International Journal of Surgery (2025)

Background: Laparoscopic radical hysterectomy with Karez technique (LRH-Karez) is a practical method which is based on special space anatomy. This study investigates the efficacy and safety of LRH-Karez against traditional surgical methods including abdominal radical hysterectomy (ARH) and conventional minimally invasive surgery (MIS). Methods: A multicenter retrospective cohort study was conducted, involving 413 eligible patients diagnosed with 2018 FIGO stage IB3 and IIA2 cervical cancer treated from January 2012 to January 2022. Among these, 66 patients underwent LRH-Karez, 56 patients underwent conventional laparoscopic or robotic surgery (Conventional MIS) and 291 patients received ARH. Patient data were obtained from three tertiary hospitals in China. Surgical outcomes, pathological results, and follow-up data were analyzed using SPSS and R statistical software. Kaplan–Meier survival analysis was performed alongside univariate and multivariate Cox regression analyses. Results: LRH-Karez has less intraoperative blood loss but longer operative time. The five-year progression-free survival (PFS) rates were 85% for LRH-Karez, significantly higher than the 53.6% from conventional MIS ( P = 0.002) and comparable to ARH (78.3%, P = 0.898). In terms of overall survival, the five-year overall survival (OS) rate for the LRH-Karez group was 92.2%, compared to 51.9% for the conventional MIS group and 78.3% for the ARH group. Patients who underwent conventional MIS had significantly lower OS compared to those in the LRH-Karez group ( P &lt; 0.001). The log-rank test indicated no significant difference in OS between the LRH-Karez group and the ARH group ( P = 0.218). However, the Gehan-Breslow-Wilcoxon test revealed a significant difference between the two groups during the early follow-up period ( P = 0.047). Conclusions: The LRH-Karez technique has demonstrated superior intraoperative safety and survival prognosis compared to conventional MIS in patients with locally advanced cervical cancer (FIGO stages IB3 and IIA2), with its long-term survival outcomes comparable to ARH. This practical technique, based on refined understanding of surgical space anatomy, may represent a valuable minimally invasive surgical option that warrants further exploration.