tbuckley/cabot-search huggingface dataset:
Ten years of robot-assisted versus laparoscopic total mesorectal excision for rectal cancer (short-term RESOLUTION)
Authors: Rauand Duhoky, Ritch T J Geitenbeek, Guglielmo Niccolò Piozzi, Thijs A Burghgraef, Christina A Fleming, Shamsul Masum, Adrian Hopgood, Timothy Rockall, Quentin Denost, Christophe Taoum, Roel Hompes, Jim Briggs, Esther C J Consten, Jim S Khan
Journal: JNCI Journal of the National Cancer Institute (2025)

Total mesorectal excision is the gold standard for rectal cancer surgery, with laparoscopic and robot-assisted approaches commonly employed. While robot-assisted surgery may offer technical advantages, there is limited evidence comparing short-term outcomes of laparoscopic and robot-assisted techniques, particularly in Western European populations. This study aimed to assess the short-term outcomes of laparoscopic vs robot-assisted total mesorectal excision for rectal cancer. This multicentre, international, retrospective cohort study included 1749 patients who underwent laparoscopic or robot-assisted total mesorectal excision from January 2014 to January 2024. Inverse probability of treatment weighting was applied to minimise confounding. Primary outcomes were length of stay, operative time, and conversion rates. Secondary outcomes included complications and pathological outcomes within 90 days, and readmissions and reinterventions within 30 days. The final cohort included 680.9 laparoscopic and 1057.5 robot-assisted cases after weighting. Robot-assisted surgery showed lower conversion rates (6.1% vs 3.5%, p = .025), higher rates of primary anastomosis (80.1% vs 92.1%, p < .001), and fewer stoma formations (78.4% vs 63.7%, p < .001). Pathological outcomes indicated a higher rate of complete mesorectal excision in the robot-assisted group (77.2% vs 86.0%, p < .001), though this data was not available for all centres. Operative time was longer in the robot-assisted cohort (181.0 vs 220.0 minutes, p < .001), but no significant differences were observed in postoperative complications, length of stay, anastomotic leakage or 30-day reintervention rates. Robot-assisted surgery low anterior resection demonstrated improved short-term outcomes with lower conversion rates, higher rates of complete mesorectal excision, and higher restorative procedure rates, which may influence longer-term oncological and patient quality of life outcomes. https://www.isrctn.com/ISRCTN75281193.
Secondary malignancies after treatment of testicular germ cell tumors: a systematic review &amp; meta-analysis
Authors: Ahmad Mousa, Ali Amiri, Sanchit Kaushal, Emma Wilson, Viranda Jayalath, David-Dan Nguyen, Isabelle Tan, Robert J Hamilton
Journal: JNCI Journal of the National Cancer Institute (2025)

Testicular germ cell tumours (TGCTs) are the most common malignancy in men 15-35 years of age. Management options for men with TGCTs include surgery, radiation and/or chemotherapy. Given TGCTs' excellent survival, most patients live long enough to experience delayed treatment toxicities, warranting careful consideration of therapeutic decisions. An important outcome of interest is the development of secondary malignant neoplasms (SMNs). A systematic literature search was conducted through a combination of database searches (Medline, EMBASE, and Cochrane library) and manual review. Studies evaluating the incidence of SMNs in patients following treatment for TGCTs were identified. Our primary outcome was the diagnosis of any non-germ cell SMN following treatment, compared to the general population. Meta-analyses were performed using random-effects models, with outcomes reported as standardized incidence ratios (SIR). Strength of evidence was evaluated using the GRADE framework. Twenty-one studies including 88,863 patients with 5,180 SMNs were included. Median follow-up was 12.5 years. The incidence of non-germ cell SMNs following definitive treatment of TGCTs varied by treatment modality. Surgery alone was not associated with an increased risk (SIR: 0.99, 95% CI: 0.84-1.17); radiation (SIR: 1.66, 95% CI: 1.43-1.93), chemotherapy (SIR: 1.65, 95% CI: 1.39-1.96), and combined chemotherapy and radiation (SIR: 2.73, 95% CI: 2.23-3.33) were associated with a moderate to large increase in risk. There was low to moderate certainty in quality of evidence by GRADE framework. Chemotherapy, radiation, and their combination are associated with an increased risk of non-germ cell SMNs after the treatment of TGCTs.
Improved post‐transplant outcomes since 2000 for Ph‐positive acute lymphoblastic leukemia in first remission: A study from the EBMT Acute Leukemia Working Party
Authors: Ali Bazarbachi, Myriam Labopin, Iman Abou Dalle, Ibrahim Yakoub‐Agha, Gérard Socié, Thomas Schroeder, Didier Blaise, Xavier Poiré, Marie Balsat, Urpu Salmenniemi, Nicolaus Kröger, Alexander Kulagin, Eva Maria Wagner‐Drouet, Depei Wu, Eolia Brissot, Arnon Nagler, Sebastian Giebel, Fabio Ciceri, Mohamad Mohty
Journal: HemaSphere (2025)

Allogeneic hematopoietic cell transplantation (allo-HCT) remains a curative treatment for patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) in their first complete remission (CR1). Recent results using the combination of blinatumomab and second- or third-generation tyrosine kinase inhibitors have challenged the necessity of allo-HCT in CR1. Here we assessed real-world changes over time in transplant characteristics and outcomes in adult patients with Ph+ ALL in CR1, using a large dataset from the European Society for Blood and Marrow Transplantation registry. A total of 3292 patients (45% female; median age 45 years) who underwent allo-HCT from 2001 to 2020 were included. Over four periods (2001-2005, 2006-2010, 2011-2015, and 2016-2020), the 3-year cumulative incidence of relapse decreased from 41% to 19%, and non-relapse mortality decreased from 25% to 17% (p < 0.001 for both). Correspondingly, 3-year leukemia-free survival (LFS) improved from 34% to 64%, and overall survival (OS) from 47% to 75% (p < 0.001 for both). Graft versus host disease-free and relapse-free survival also improved from 26% to 49% (p < 0.001). Factors negatively affecting LFS included older age, male gender, male donor and measurable residual disease (MRD) positivity pre-transplant, while total body conditioning (TBI) positively affected LFS. OS was positively influenced by younger age, female gender, matched sibling donor, TBI, and T cell depletion. Importantly, improvement in post-transplant outcomes over time was observed regardless of pre-transplant MRD status. In conclusion, we observed an impressive improvement over time in post-transplant outcomes of Ph+ ALL. These large-scale data can serve as a benchmark for future studies.
Minimal residual disease assessment following CD19‐targeted therapy in B‐cell precursor acute lymphoblastic leukemia using standardized 12‐color flow cytometry: A EuroFlow study
Authors: Martijn W. C. Verbeek, Michaela Reiterová, Anna Laqua, Beatriz Soriano Rodríguez, Lukasz Sedek, Chiara Buracchi, Malicorne Buysse, Elen Oliveira, Robby Engelmann, Joana Desterro, Anja X. De Jong, Sebastian Boettcher, Romana Jugooa, Susana Barrena, Saskia Kohlscheen, Stefan Nierkens, Joana G. Rodriques, Mattias Hofmans, Giuseppe Gaipa, Elaine Sobral de Costa, Ester Mejstrikova, Tomasz Szczepanski, Monika Brüggemann, Jacques J. M. van Dongen, Alberto Orfao, Vincent H. J. van der Velden
Journal: HemaSphere (2025)

Detection of minimal/measurable residual disease (MRD) is a critical prognostic marker in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The EuroFlow Consortium previously developed an 8-color flow cytometric MRD protocol, effective for >98% of BCP-ALL patients treated with chemotherapy. This study aimed to enhance MRD detection, particularly for patients treated with CD19-targeted therapies, by expanding the EuroFlow protocol to a 12-color panel. This new panel incorporates additional B-cell markers and exclusion T/NK-cell markers (CD3 and CD7). Through an evaluation of 237 diagnostic BCP-ALL samples, CD22, CD24, and HLA-DR were selected as additional B-cell gating markers. Two 12-color tubes were technically optimized and clinically validated across 101 patient follow-up samples, demonstrating excellent concordance with molecular MRD levels (R 2 = 0.88). The 12-color BCP-ALL MRD tubes were compatible with the previously developed 8-color automated gating and identification (AGI) tool and demonstrated good reproducibility. Our findings indicate that the 12-color panel performs comparably to the 8-color BCP-ALL MRD panel, including both CD19-positive and CD19-negative cases. However, it offers an improved definition of the B-cell lineage, particularly for expert-guided manual data analysis, and provides additional information on the expression of the targetable marker CD22.
Association of Glucagon-Like Peptide-1 Receptor Agonist with Progression to Liver Cirrhosis and Alcohol-Related Admissions in Patients with Alcohol Use Disorder and Diabetes: A Retrospective Cohort Study
Authors: Feras Al-Moussally, Saud Khan, Vinay Katukuri, Mustafa Kinaan, Ishak A Mansi
Journal: Drugs (2025)
Editorial expression of concern: Yin Yang-1 suppresses invasion and metastasis of pancreatic ductal adenocarcinoma by downregulating MMP10 in a MUC4/ErbB2/p38/MEF2C-dependent mechanism
Authors: Jing-Jing Zhang, Yi Zhu, Kun-Ling Xie, Yun-Peng Peng, Jin-Qiu Tao, Jie Tang, Zheng Li, Ze-Kuan Xu, Cun-Cai Dai, Zhu-Yin Qian, Kui-Rong Jiang, Jun-Li Wu, Wen-Tao Gao, Qing Du, Yi Miao
Journal: Molecular Cancer (2025)
Finerenone, chronic obstructive pulmonary disease, and heart failure with mildly reduced or preserved ejection fraction: A prespecified analysis of the <scp>FINEARTS</scp>‐<scp>HF</scp> trial
Authors: Jawad H. Butt, Pardeep S. Jhund, Alasdair D. Henderson, Brian L. Claggett, Akshay S. Desai, Carolyn S.P. Lam, Katharina Mueller, Markus F. Scheerer, Prabhakar Viswanathan, Michele Senni, Sanjiv J. Shah, Adriaan A. Voors, Faiez Zannad, Bertram Pitt, Muthiah Vaduganathan, Scott D. Solomon, John J.V. McMurray
Journal: European Journal of Heart Failure (2025)

Chronic obstructive pulmonary disease (COPD) is associated with worse outcomes in heart failure (HF) with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF). A post hoc analysis of TOPCAT suggested that the effectiveness of the steroidal mineralocorticoid receptor antagonist (MRA), spironolactone, may be modified by pulmonary disease, with a greater benefit in patients with COPD/asthma. We examined the effects of the non-steroidal MRA, finerenone, compared to placebo, according to COPD status in a prespecified analysis of FINEARTS-HF. A history of COPD was investigator-reported. The primary outcome was the composite of cardiovascular death and total worsening HF events. Of the 6001 patients randomized in FINEARTS-HF, 773 patients (12.9%) had COPD. Compared to patients without COPD, those with COPD had more adverse clinical features, including worse New York Heart Association class and Kansas City Cardiomyopathy Questionnaire (KCCQ) scores, more prior HF hospitalization, atrial fibrillation/flutter, obesity, peripheral artery disease, and hypertension, as well as elevated high-sensitivity troponin T levels. Patients with COPD had a higher risk of the primary endpoint (adjusted rate ratio [RR] 1.44, 95% confidence interval [CI] 1.21-1.71). The benefit of finerenone on the primary outcome was consistent irrespective of COPD status (no COPD: RR 0.84 [95% CI 0.73-0.97]; COPD: 0.84 [95% CI 0.61-1.16]; pinteraction = 0.93). Consistent effects were also observed for all secondary outcomes. Finerenone improved KCCQ total symptom score from baseline to 12 months to a similar extent in patients with and without COPD (pinteraction = 0.46). In patients with HFmrEF/HFpEF, the beneficial effects of finerenone on clinical events and symptoms were consistent, regardless of COPD status. ClinicalTrials.gov ID NCT04435626.
Prediction and prognostic role of left ventricular systolic dysfunction in family screening for dilated cardiomyopathy and non‐dilated left ventricular cardiomyopathy
Authors: Eva Del Mestre, Alessia Paldino, Carola Pio Loco Detto Gava, Ilaria Gandin, Marta Gigli, Davide Stolfo, Martina Setti, Giovanni Maria Severini, Beatrice Spedicati, Stefania Lenarduzzi, Giorgia Girotto, Alessandro Folgheraiter, Jacopo Giulio Rizzi, Renata Korcova, Luisa Mestroni, Marco Merlo, Matteo Dal Ferro, Gianfranco Sinagra
Journal: European Journal of Heart Failure (2025)

The prognostic significance of detecting left ventricular (LV) systolic dysfunction during family screening programmes (FSPs) in relatives of probands affected by dilated (DCM) and non-dilated left ventricular (NDLVC) cardiomyopathies remain unclear. This study sought to evaluate the prognostic role of LV systolic dysfunction detection in relatives of DCM/NDLVC probands and to define the most accurate FSP. Baseline and follow-up data of first-degree relatives of probands affected by DCM/NDLVC were collected. The primary outcome was all-cause death and heart transplantation. Secondary heart failure (HF) and arrhythmic outcomes were also included. A total of 492 first degree relatives were enrolled. During a median follow-up of 110 months (interquartile range 57-188 months), only subjects that previously developed LV systolic dysfunction had primary outcomes (19 vs. 0, p < 0.001) and secondary outcomes (HF: 12 vs. 0, p = 0.005; arrhythmic: 30 vs. 0, p < 0.001). Subjects with LV systolic dysfunction detected by FSP showed lower rate of primary outcomes (FSP: n = 19 [14%]; no-FSP: n = 40 [37%]; p < 0.001) and secondary arrhythmic outcomes (FSP: n = 18 [13%]; no-FSP: n = 41 [38%]; p < 0.001). In this setting, family history of arrhythmia and being carrier of a pathogenic/likely pathogenic variant are the main risk factors for LV systolic dysfunction, while LV global longitudinal strain (LV-GLS) and Holter electrocardiogram (ECG) showed a relevant role in terms of prediction of LV systolic dysfunction and outcomes. Relatives of DCM/NDLVC probands who developed LV systolic dysfunction during a long follow-up had a significant increased risk of major adverse cardiovascular outcomes. However, LV systolic dysfunction detected by FSP showed a better prognosis. In this context, genetics, Holter ECG and LV-GLS demonstrated their functional role for disease and event prediction.
BIRC2 blockade facilitates immunotherapy of hepatocellular carcinoma
Authors: Lingyi Fu, Shuo Li, Jie Mei, Ziteng Li, Xia Yang, Chengyou Zheng, Nai Li, Yansong Lin, Chao Cao, Lixuan Liu, Liyun Huang, Xiujiao Shen, Yuhua Huang, Jingping Yun
Journal: Molecular Cancer (2025)

The effectiveness of immunotherapy in hepatocellular carcinoma (HCC) is limited, however, the molecular mechanism remains unclear. In this study, we identified baculoviral IAP repeat-containing protein 2 (BIRC2) as a key regulator involved in immune evasion of HCC. Genome-wide CRISPR/Cas9 screening was conducted to identify tumor-intrinsic genes pivotal for immune escape. In vitro and in vivo models demonstrated the role of BIRC2 in protecting HCC cells from immune killing. Then the function and relevant signaling pathways of BIRC2 were explored. The therapeutic efficacy of BIRC2 inhibitor was examined in different in situ and xenograft HCC models. Elevated expression of BIRC2 correlated with adverse prognosis and resistance to immunotherapy in HCC patients. Mechanistically, BIRC2 interacted with and promoted the ubiquitination-dependent degradation of NFκB-inducing kinase (NIK), leading to the inactivation of the non-canonical NFκB signaling pathway. This resulted in the decrease of major histocompatibility complex class I (MHC-I) expression, thereby protecting HCC cells from T cell-mediated cytotoxicity. Silencing BIRC2 using shRNA or inhibiting it with small molecules increased the sensitivity of HCC cells to immune killing. Meanwhile, BIRC2 blockade improved the function of T cells both in vitro and in vivo. Targeting BIRC2 significantly inhibited tumor growth, and enhanced the efficacy of anti-programmed death protein 1 (PD-1) therapy. Our findings suggested that BIRC2 blockade facilitated immunotherapy of HCC by simultaneously sensitizing tumor cells to immune attack and boosting the anti-tumor immune response of T cells.
Time-restricted feeding protects against septic liver injury by reshaping gut microbiota and metabolite 3-hydroxybutyrate
Authors: Jing-Juan Hu, Fan Deng, Qi-Shun Sun, Qing-Ming Xiong, Yue Min, Si-Yuan Feng, Ze-Bin Lin, Peng-Han Chen, Zhen Hu, Ling Wu, Xiao-Feng Chen, Sun Xie, Wei-Feng Liu, Cai Li, Ke-Xuan Liu
Journal: Gut Microbes (2025)

Liver injury is an independent risk factor for multiple organ dysfunction and high mortality in patients with sepsis. However, the pathological mechanisms and therapeutic strategies for sepsis-associated liver injury have not been fully elucidated. Time-restricted feeding (TRF) is a promising dietary regime, but its role in septic liver injury remains unknown. Using 16S rRNA gene sequencing, Q200 targeted metabolomics, transcriptomics, germ-free mice, Hmgcs2/Lpin1 gene knockout mice, and Aml12 cells experiments, we revealed that TRF can mitigate septic liver injury by modulating the gut microbiota, particularly by increasing Lactobacillus murinus (L. murinus) abundance, which was significantly reduced in septic mice. Further study revealed that live L. murinus could markedly elevate serum levels of metabolite 3-hydroxybutyrate (3-HB) and alleviate sepsis-related injury, while the knockout of the key enzyme for 3-HB synthesis (3-hydroxy-3-methylglutaryl-CoA synthase 2, Hmgcs2) in the liver negated this protective effect. Additionally, serum 3-HB levels were significantly positively correlated with L. murinus abundance and negatively correlated with liver injury indicators in septic patients, demonstrating a strong predictive value for septic liver injury (AUC = 0.8429). Mechanistically, 3-HB significantly inhibited hepatocyte ferroptosis by activating the PI3K/AKT/mTOR/LPIN1 pathway, reducing ACSL4, MDA, LPO, and Fe2+ levels. This study demonstrates that TRF reduces septic liver injury by modulating gut microbiota to increase L. murinus, which elevates 3-HB to activate PI3K/AKT/mTOR/LPIN1 and inhibit hepatocyte ferroptosis. Overall, this study elucidates the protective mechanism of TRF against septic liver injury and identifies 3-HB as a potential therapeutic target and predictive biomarker, thereby providing new insights into the clinical management and diagnosis of septic liver injury.
KF1601, a dual inhibitor of BCR::ABL1 and FLT3, overcomes drug resistance in FLT3+ blast phase chronic myeloid leukemia
Authors: Hyun-Jin Kwon, Ji Eun Shin, Amir Khan, So Yeon Park, Jiyoung Kim, Jee-Young Lee, Doohyun Lee, Seungyeon Lee, Chun Young Im, Heegyum Moon, Ye Ri Han, Minori Tamai, Koshi Akahane, Takeshi Inukai, Wonhwa Lee, Hyelim Kim, Hong Nam Kim, Sung-Min Ahn, Hyun Woo Park, Dong-Wook Kim
Journal: Molecular Cancer (2025)
Cell‐Free Biomimetic Tracheal Graft via Hybrid 3D Printing for Enhanced Tracheal Reconstruction
Authors: Young Su Yu, Sun Hwa Park, Seon Young Choi, Hyun Ji Lee, Kuk Hui Son, Jin Woo Lee, Sung Won Kim
Journal: Advanced Healthcare Materials (2025)

Abstract When the trachea is excessively damaged because of diseases, accidents, or surgery, it is difficult to achieve both mucosal reconstruction and structural stability using current technologies. Here, a biomimetic tracheal graft (BTG) is developed through a hybrid process of 3D printing and electrospinning using polycaprolactone (PCL)polymer. First, a flexible PCL tracheal frame with a high rotation angle is prepared using 3D printing. Second, PCL nanofibers for mucosal reconstruction are placed inside the lumen, and PCL microfibers are placed on the outside of the frame to promote blood vessel formation. Air–liquid interface cultures of human bronchial epithelial cells on the nanofibers demonstrated the generation of epithelium, goblet cells, and ciliated cells after 14 days. Chondrocyte cultures and co‐cultures of chondrocytes and human umbilical vein endothelial cells confirmed higher cell attachment and survival on the BTG than on the conventional tracheal graft (CTG). In a rabbit tracheal defect model, transplantation of the BTG and CTG revealed smooth cell infiltration and proliferation in the BTG, leading to the formation of epithelial, vascular, and connective tissues after 8 weeks without tracheal obstruction. These results demonstrate that the transplantation of cell‐free biomimetic grafts alone is effective for reconstructing damaged tracheal tissue.
Alzheimer disease seen through the lens of sex and gender
Authors: Laura Castro-Aldrete, Melanie Einsiedler, Julie Novakova Martinkova, Herman Depypere, Ting Fang Alvin Ang, Michelle M Mielke, Shireen Sindi, Harris A Eyre, Rhoda Au, Anne Marie Schumacher Dimech, Anna Dé, Cassandra Szoeke, Maria Carmela Tartaglia, Antonella Santuccione Chadha
Journal: Nature Reviews Neurology (2025)
Genome-wide analyses identify 25 infertility loci and relationships with reproductive traits across the allele frequency spectrum
Authors: Samvida S Venkatesh, Laura B L Wittemans, Duncan S Palmer, Nikolas A Baya, Teresa Ferreira, Barney Hill, Frederik Heymann Lassen, Melody J Parker, Saskia Reibe, Ahmed Elhakeem, Karina Banasik, Mie T Bruun, Christian Erikstrup, Bitten Aagard Jensen, Anders Juul, Christina Mikkelsen, Henriette S Nielsen, Sisse R Ostrowski, Ole B Pedersen, Palle Duun Rohde, Erik Sørensen, Henrik Ullum, David Westergaard, Asgeir Haraldsson, Hilma Holm, Ingileif Jonsdottir, Isleifur Olafsson, Thora Steingrimsdottir, Valgerdur Steinthorsdottir, Gudmar Thorleifsson, Jessica Figueredo, Minna K Karjalainen, Anu Pasanen, Benjamin M Jacobs, Georgios Kalantzis, Nikki Hubers, Margaret Lippincott, Abigail Fraser, Deborah A Lawlor, Nicholas J Timpson, Mette Nyegaard, Kari Stefansson, Reedik Magi, Hannele Laivuori, David A van Heel, Dorret I Boomsma, Ravikumar Balasubramanian, Stephanie B Seminara, Yee-Ming Chan, Triin Laisk, Cecilia M Lindgren
Journal: Nature Genetics (2025)

Abstract Genome-wide association studies (GWASs) may help inform the etiology of infertility. Here, we perform GWAS meta-analyses across seven cohorts in up to 42,629 cases and 740,619 controls and identify 25 genetic risk loci for male and female infertility. We additionally identify up to 269 genetic loci associated with follicle-stimulating hormone, luteinizing hormone, estradiol and testosterone through sex-specific GWAS meta-analyses ( n = 6,095–246,862). Exome sequencing analyses reveal that women carrying testosterone-lowering rare variants in some genes are at risk of infertility. However, we find no local or genome-wide genetic correlation between female infertility and reproductive hormones. While infertility is genetically correlated with endometriosis and polycystic ovary syndrome, we find limited genetic overlap between infertility and obesity. Finally, we show that the evolutionary persistence of infertility-risk alleles may be explained by directional selection. Taken together, we provide a comprehensive view of the genetic determinants of infertility across multiple diagnostic criteria.