tbuckley/cabot-search huggingface dataset:
A deep learning-based clinical-radiomics model predicting the treatment response of immune checkpoint inhibitors (ICIs)-based conversion therapy in potentially convertible hepatocelluar carcinoma patients: a tumour marker prognostic study
Authors: Zijian Lin, Weidong Wang, Yongcong Yan, Zifeng Ma, Zhiyu Xiao, Kai Mao
Journal: International Journal of Surgery (2025)

Background: The majority of patients with hepatocellular carcinoma (HCC) miss the opportunity of radical resection, making ICIs-based conversion therapy a primary option. However, challenges persist in predicting response and identifying the optimal patient subset. The objective is to develop a CT-based clinical-radiomics model to predict durable clinical benefit (DCB) of ICIs-based treatment in potentially convertible HCC patients. Methods: The radiomics features were extracted by pyradiomics in training set, and machine learning models was generated based on the selected radiomics features. Deep learning models were created using two different protocols. Integrated models were constructed by incorporating radiomics scores, deep learning scores, and clinical variables selected through multivariate analysis. Furthermore, we analyzed the relationship between integrated model scores and clinical outcomes related to conversion therapy in the entire cohort. Finally, radiogenomic analysis was conducted on bulk RNA and DNA sequencing data. Results: The top-performing integrated model demonstrated excellent predictive accuracy with an area under the curve (AUC) of 0.96 (95%CI: 0.94 ~ 0.99) in the training set and 0.88 (95%CI: 0.77 ~ 0.99) in the test set, effectively stratifying survival risk across the entire cohort and revealing significant disparity in overall survival (OS), as evidenced by Kaplan-Meier survival curves (p&lt;0.0001). Moreover, integrated model scores exhibited associations with sequential resection among patients who achieved DCB and pathological complete response (pCR) among those who underwent sequential resection procedures. Notably, higher radiomics model was correlated with MHC I expression, angiogenesis-related processes, CD8 T cell-related gene sets, as well as a higher frequency of TP53 mutations along with increased levels of mutation burden and neoantigen. Conclusion: The deep learning-based clinical-radiomics model exhibited satisfactory predictive capability in forecasting the DCB derived from ICIs-based conversion therapy in potentially convertible HCC, and was associated with a diverse range of immune-related mechanisms.
Surgery and technical skill decay: a literature review
Authors: Marta de Andres Crespo, Panagis Michael Lykoudis, Fiona Pwint-Oo Myint, Pasquale Berlingieri
Journal: International Journal of Surgery (2025)

Background: An increasing number of surgical trainees are taking time out of clinical training for research, parental leave or other interests. A comprehensive review was carried out to evaluate the current evidence on whether and how such time results in surgical skill decay. Methods: A PubMed, Embase, Web of Science, and Cochrane Library search was performed using the phrase: (“skills decay” OR “skills fade”) AND “surgery.” All relevant literature was analysed and summarised. Results: A total of 41 relevant articles were identified. The skills that are most adversely affected by time out of training are technical operative skills and, within those, speed and accuracy in operations. Factors that affect skill decay include the complexity of the task itself, the degree of overlearning (i.e. the skill of the surgeon prior to time out of training) and the retention interval (i.e. the length of time for which the trainee is out of training and whether or not spaced practice is carried out). The articles suggest that simulation may be of assistance in mitigating skill decay, however, this has yet to be fully investigated. Conclusions: As an increasing number of surgical trainees are taking time away from clinical training for academic research, higher degrees, parental leave, or other interests, further research is required to investigate how to mitigate the resulting surgical skill decay, potentially through the use of simulation.
The existing evidence for the use of extracellular vesicles in the treatment of osteoporosis: a review
Authors: Zixiang Geng, Tiancheng Sun, Long Yuan, Yongfang Zhao
Journal: International Journal of Surgery (2025)

Osteoporosis is a systemic metabolic bone disease characterized by decreased bone mass, microstructural deterioration, and increased fracture risk. The crucial role of extracellular vesicles(EVs) in the occurrence and development of osteoporosis has garnered attention, with vesicle-based treatments showing significant promise. Compared to conventional osteoporosis medications, EVs possess characteristics of naturalness, selectivity, and adaptability, and more importantly, they have negligible side effects. Hence, this review discusses the applications of natural and engineered extracellular vesicles in osteoporosis are comprehensively outlined. Unfortunately, the absence of consensus on the extraction, purification, characterization, and storage of EVs has resulted in a lack of clinical evidence supporting their application in patients with osteoporosis. Although significant progress is still needed before the clinical use of EVs can be achieved, their substantial potential remains undeniable. Moreover, considering the complexity of bone metabolism in osteoporosis and the heterogeneity of EVs, further investigation into the functional subpopulations of different exosomes will facilitate their application.
Clarifying the misinterpretation of case-fatality rate as mortality in thyroid cancer studies
Authors: Kyu-Won Jung, Eun Hye Park, Mee Joo Kang
Journal: International Journal of Surgery (2025)

aKorea Central Cancer Registry, National Cancer Center, Goyang, Korea bDivision of Cancer Registration and Surveillance, National Cancer Control Institute, National Cancer Center, Goyang, Korea Corresponding author. Address: Head, Division of Cancer Registration and Surveillance, National Cancer Control Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, 10408, Korea, Tel: +82-31-920-2015, E-mail: [email protected] (K.-W. Jung). Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms.
Reflections on the HORSE Trial: Hyperthermic Intraperitoneal Chemotherapy, <i>BRCA</i> Status, and Clinical Implications
Authors: Hamdullah Sözen, Yagmur Minareci, Atahan Toyran, Mustafa Albayrak, Samet Topuz, Yavuz Salihoglu
Journal: Journal of Clinical Oncology (2025)
Erratum: Paclitaxel, Ifosfamide, and Cisplatin as Initial Salvage Chemotherapy for Germ Cell Tumors: Long-Term Follow-Up and Outcomes for Favorable- and Unfavorable-Risk Disease
Authors: Jack P. Gleeson, Andrea Knezevic, Maria Bromberg, Sujata Patil, Joel Sheinfeld, Brett S. Carver, Manjit Bains, David R. Jones, Dean F. Bajorin, George J. Bosl, Deaglan J. McHugh, Samuel A. Funt, Robert J. Motzer, Darren R. Feldman
Journal: Journal of Clinical Oncology (2025)
Blood pressure and the brain: the conundrum of hypertension and dementia
Authors: Rebecca F Gottesman, Marco Egle, Renee C Groechel, Amreen Mughal
Journal: Cardiovascular Research (2025)

Abstract As the population ages, the anticipated rates of dementia worldwide are likely to increase dramatically, especially in low- and middle-income countries; thus, any opportunity to modify dementia risk is especially critical. Hypertension is one risk factor that is highly prevalent, consistently important for late-life brain health, and which could represent a target for prevention of dementia. Furthermore, hypertension is the most significant modifiable risk factor for stroke. This review will summarize existing literature linking hypertension with dementia and brain health more broadly, will discuss potential mechanisms linking hypertension with brain health, and will consider specific factors that may impact not only the relationship between hypertension and the brain but also the importance of treatment, including different associations over the life course.
Circulating lncRNAs as biomarkers for severe dengue using a machine learning approach
Authors: Rodolfo Katz, Nguyen Minh Nam, Tulio de Lima Campos, Victoria Indenbaum, Sophie Terenteva, Dinh Thi Thu Hang, Le Thi Hoi, Amos Danielli, Yaniv Lustig, Eli Schwartz, Hoang Van Tong, Ella H Sklan
Journal: Journal of Infection (2025)

Dengue virus (DENV) infection is a significant global health concern, causing severe morbidity and mortality. While many cases present as a mild febrile illness, some progress to life-threatening severe dengue (SD). Early intervention is essential to improve outcomes, but current predictive methods lack specificity, burdening healthcare systems in endemic regions. Circulating long non-coding RNAs (lncRNAs) have emerged as stable and promising biomarkers. This study explored the use of lncRNAs as predictive markers for SD. Differential expression and qPCR arrays were employed to identify lncRNAs associated with SD. Candidate lncRNAs were validated, and their plasma levels were measured in a cohort of Vietnamese dengue patients (n =377) and healthy controls (n=128) at admission. Machine learning algorithms were applied to predict the probability of SD progression. The predictive model demonstrated high sensitivity and specificity, with an area under the curve (AUC) of 0.98 (95% CI: 0.96-1.0). At admission, it accurately identified 17 of 18 patients who later died as high-risk, compared to traditional warning signs, which flagged only 9 of these cases. Our findings suggest that this panel of lncRNAs has the potential to predict SD, which could help reduce healthcare burden and improve patient management in endemic countries.
Activating autophagy to eliminate toxic protein aggregates with small molecules in neurodegenerative diseases
Authors: Yuqi Fu, Jin Zhang, Rui Qin, Yueting Ren, Tingting Zhou, Bo Han, Bo Liu
Journal: Pharmacological Reviews (2025)

Neurodegenerative diseases (NDs), such as Alzheimer disease, Parkinson disease, Huntington disease, amyotrophic lateral sclerosis, and frontotemporal dementia, are well known to pose formidable challenges for their treatment due to their intricate pathogenesis and substantial variability among patients, including differences in environmental exposures and genetic predispositions. One of the defining characteristics of NDs is widely reported to be the buildup of misfolded proteins. For example, Alzheimer disease is marked by amyloid beta and hyperphosphorylated Tau aggregates, whereas Parkinson disease exhibits α-synuclein aggregates. Amyotrophic lateral sclerosis and frontotemporal dementia exhibit TAR DNA-binding protein 43, superoxide dismutase 1, and fused-in sarcoma protein aggregates, and Huntington disease involves mutant huntingtin and polyglutamine aggregates. These misfolded proteins are the key biomarkers of NDs and also serve as potential therapeutic targets, as they can be addressed through autophagy, a process that removes excess cellular inclusions to maintain homeostasis. Various forms of autophagy, including macroautophagy, chaperone-mediated autophagy, and microautophagy, hold a promise in eliminating toxic proteins implicated in NDs. In this review, we focus on elucidating the regulatory connections between autophagy and toxic proteins in NDs, summarizing the cause of the aggregates, exploring their impact on autophagy mechanisms, and discussing how autophagy can regulate toxic protein aggregation. Moreover, we underscore the activation of autophagy as a potential therapeutic strategy across different NDs and small molecules capable of activating autophagy pathways, such as rapamycin targeting the mTOR pathway to clear α-synuclein and Sertraline targeting the AMPK/mTOR/RPS6KB1 pathway to clear Tau, to further illustrate their potential in NDs' therapeutic intervention. Together, these findings would provide new insights into current research trends and propose small-molecule drugs targeting autophagy as promising potential strategies for the future ND therapies. SIGNIFICANCE STATEMENT: This review provides an in-depth overview of the potential of activating autophagy to eliminate toxic protein aggregates in the treatment of neurodegenerative diseases. It also elucidates the fascinating interrelationships between toxic proteins and the process of autophagy of "chasing and escaping" phenomenon. Moreover, the review further discusses the progress utilizing small molecules to activate autophagy to improve the efficacy of therapies for neurodegenerative diseases by removing toxic protein aggregates.
Outcomes and prognostic factors in patients with Burkitt lymphoma/leukemia in adolescents and adults: an experience from hematology cancer consortium
Authors: Akhil Rajendra, Manju Sengar, Anu Korula, Prasanth Ganesan, Hasmukh Jain, Divya K, Prasanna Samuel, Jayachandran Perumal Kalaiyarasi, Gaurav Prakash, M. Joseph John, Rasmi Palassery, Chandran K. Nair, Tanuja Shet, Sushil Selvarajan, Lingaraj Nayak, Parathan Karunakaran, N. A. Fouzia, Om Prakash, Bhausaheb Bagal, Nikita Mehra, Saranya Kumaran, Sridhar Epari, Jayshree Thorat, Venkatraman Radhakrishnan, Aby Abraham
Journal: Blood Cancer Journal (2025)

Treatment of Burkitt Lymphoma/Leukemia (BL/L) in adults has evolved from the use of pediatric inspired regimens (CODOX-M/IVAC, hyper-CVAD, GMALL) to the use of lower intensity EPOCH regimens. The addition of rituximab has led to improvements in overall survival. Survival with these regimens in the real world was shown to be inferior as compared to those found in the prospective trials. In low- and middle-income country (LMIC) settings, unique problems like delays in seeking care, treatment-related toxicities, and treatment abandonment may hamper outcomes. We performed this retrospective multicenter analysis amongst eight centers in India, to study the disease characteristics, treatment patterns, outcomes, and prognostic factors for BL/L. Between 2012–2019, 265 patients were treated at these centers. Common regimens were methotrexate-based (N – 108(40.7%)) and EPOCH-based (N – 103(38.8%)). After a median follow-up of 42 months, 3-year event-free and overall survival were 58% (95% CI: 55–61%) and 66% (95%CI: 63–69%) respectively. In a propensity matched analysis comparing methotrexate-based protocol and EPOCH-based protocol, the EFS and OS were similar with both the protocols. EPOCH based protocol yielded inferior outcomes in patients with bone marrow, and central nervous system involvement. Factors like rituximab incorporation, baseline ECOG PS 0–2, lower serum LDH, early stage(I/II), achievement of complete response (CR) and low/intermediate BL-IPI risk scores were associated with better survival. However, on multivariable analysis, major factor impacting outcome was achievement of CR.
Validation of the GPAT – the Global Polypectomy Assessment Tool: European Society of Gastrointestinal Endoscopy (ESGE) Position Statement
Authors: Sander Smeets, Maria Eva Argenziano, Alexander C. De Crem, Lobke Desomer, John Anderson, Pradeep Bhandari, Ivo Boškoski, Marek Bugajski, Michael J. Bourke, Lynn Debels, Steven J. Heitman, Hiroshi Kashida, Ralph R.T. Lee, Ivan Lyutakov, Liseth Rivero-Sánchez, Christophe Schoonjans, Siwan Thomas-Gibson, Henrik Thorlacius, Lorenzo Fuccio, Tony C. Tham, Raf Bisschops, David J. Tate
Journal: Endoscopy (2025)

BACKGROUND : Colorectal polypectomy is operator dependent, with variable rates of complete resection. The currently available assessment tools do not provide specific competency-based evaluation of provider technique. We aimed to validate the Global Polypectomy Assessment Tool (GPAT), a novel competency assessment tool for colorectal polypectomy. METHODS : GPAT was derived from the ESGE Curriculum for Training in endoscopic mucosal resection in the colon. Members of the curriculum taskforce plus three invited trainees and three medical students (collectively: the assessors) anonymously assessed nine endoscopic-view only polypectomy videos. The primary end point was the correlation of the assessors' GPAT scores with a consensus-derived reference GPAT score per video. Secondary end points were the assessors' subjective impression versus their GPAT score and interobserver agreement among assessors' GPAT scores. RESULTS : 171 GPAT assessments by 19 assessors (consultant gastroenterologists [n = 10], trainee gastroenterologists [n = 4], consultant surgeons [n = 2], and medical students [n = 3]) were analyzed. Reference GPAT scores did not differ significantly from those of the assessors (73.1 % [95 %CI 64.6 %-81.6 %] vs. 69.3 % [95 %CI 64.9 %-81.2 %]; P = 0.47). There was moderate IOA in GPAT scores among gastroenterologists (intraclass correlation coefficient [ICC], 0.52 [moderate]) but not among nongastroenterologists (ICC 0.32 [poor]). GPAT correlated with assessors' subjective impression of polypectomy quality (correlation coefficient 0.98 [95 %CI 0.90-1.00]; P < 0.001). Overall assessors' qualitative usability scoring of GPAT was positive. CONCLUSIONS : GPAT allows standardized scoring of polypectomies, with moderate IOA among gastroenterologists and correlation with subjective impressions of polypectomy quality. GPAT could standardize assessment of trainee polypectomy competency offering structured feedback on performance.
Gene Therapy-Associated Uveitis (GTAU): Understanding and mitigating the adverse immune response in retinal gene therapy
Authors: Ryan Purdy, Molly John, Alissa Bray, Alison J Clare, David A Copland, Ying Kai Chan, Robert H Henderson, Fanny Nerinckx, Bart P Leroy, Paul Yang, Mark E Pennesi, Robert E MacLaren, M Dominik Fischer, Andrew D Dick, Kanmin Xue
Journal: Progress in Retinal and Eye Research (2025)

Retinal gene therapy using adeno-associated viral (AAV) vectors has been a groundbreaking step-change in the treatment of inherited retinal diseases (IRDs) and could also be used to treat more common retinal diseases such as age-related macular degeneration and diabetic retinopathy. The delivery and expression of therapeutic transgenes in the eye is limited by innate and adaptive immune responses against components of the vector product, which has been termed gene therapy-associated uveitis (GTAU). This is clinically important as intraocular inflammation could lead to irreversible loss of retinal cells, deterioration of visual function and reduced durability of treatment effect associated with a costly one-off treatment. For retinal gene therapy to achieve an improved efficacy and safety profile for treating additional IRDs and more common diseases, the risk of GTAU must be minimised. We have collated insights from pre-clinical research, clinical trials, and the real-world implementation of AAV-mediated retinal gene therapy to help understand the risk factors for GTAU. We draw attention to an emerging framework, which includes patient demographics, vector construct, vector dose, route of administration, and choice of immunosuppression regime. Importantly, we consider efforts to date and potential future strategies to mitigate the adverse immune response across each of these domains. We advocate for more targeted immunomodulatory approaches to the prevention and treatment of GTAU based on better understanding of the underlying immune response.
Genetic and reproductive strategies to prevent mitochondrial diseases
Authors: Noemi Castelluccio, Katharina Spath, Danyang Li, Irenaeus F M De Coo, Lyndsey Butterworth, Dagan Wells, Heidi Mertes, Joanna Poulton, Björn Heindryckx
Journal: Human Reproduction Update (2025)

Abstract Mitochondrial DNA (mtDNA) diseases pose unique challenges for genetic counselling and require tailored approaches to address recurrence risks and reproductive options. The intricate dynamics of mtDNA segregation and heteroplasmy shift significantly impact the chances of having affected children. In addition to natural pregnancy, oocyte donation, and adoption, IVF-based approaches can reduce the risk of disease transmission. Prenatal diagnosis (PND) and preimplantation genetic testing (PGT) remain the standard methods for women carrying pathogenic mtDNA mutations; nevertheless, they are not suitable for every patient. Germline nuclear transfer (NT) has emerged as a novel therapeutic strategy, while mitochondrial gene editing has increasingly become a promising research area in the field. However, challenges and safety concerns associated with all these techniques remain, highlighting the need for long-term follow-up studies, an improved understanding of disease mechanisms, and personalized approaches to diagnosis and treatment. Given the inherent risks of adverse maternal and child outcomes, careful consideration of the balance between potential benefits and drawbacks is also warranted. This review will provide critical insights, identify knowledge gaps, and underscore the importance of advancing mitochondrial disease research in reproductive health.
Emergent feedback between symbiosis form and population dynamics
Authors: Lutz Becks, Ursula Gaedke, Toni Klauschies
Journal: Trends in Ecology & Evolution (2025)

Symbiotic relationships represent prolonged physical interactions between different species and include various forms such as mutualism, commensalism, exploitation, and competition. Here, we show that the form of symbiosis may change with the densities of the symbiotic partners as they influence the costs and benefits each species experiences. In turn, the form of symbiosis is expected to influence species persistence, population dynamics, and ultimately ecosystem stability. Based on this, we introduce the theoretical concept of a density-symbiosis feedback, where population densities affect the form of symbiosis, and symbiosis form in return affects population dynamics. This dynamic interplay calls for a re-evaluation of traditional ecological concepts and a framework considering the flexibility in symbiosis forms.
Catch Bonds in Immunology
Authors: Hyun-Kyu Choi, Cheng Zhu
Journal: Annual Review of Immunology (2025)

Catch bonds are molecular bonds that last longer under force than slip bonds, which become shorter-lived under force. Although catch bonds were initially discovered in studies of leukocyte and bacterial adhesions two decades ago, they have since been found in many other contexts, including platelet binding to blood vessel walls during clotting, structural support within the cell and between cells, force transmission in the cell's machineries for motility and mechanotransduction, viral infection of host cells, and immunoreceptor mechanosensing. Catch bonds are strengthened by increasing force, which induces structural changes in one or both interacting molecules either locally or allosterically to enable additional contacts at their binding interface, thus lengthening bond lifetimes. They can be modeled by the kinetics of a system escaping from the energy well(s) of the bound state(s) over the energy barrier(s) to the free state by traversing along the dissociation path(s) across a hilly energy landscape modulated by force. Catch bond studies are important for understanding the mechanics of biological systems and developing treatment strategies for infectious diseases, immune disorders, cancer, and other ailments.