tbuckley/cabot-search huggingface dataset:
Pretreatment CT-based machine learning radiomics model predicts response in unresectable hepatocellular carcinoma treated with lenvatinib plus PD-1 inhibitors and interventional therapy
Authors: Yonglin Hua, Zhixian Sun, Yuxin Xiao, Huilong Li, Xiaowu Ma, Xuan Luo, Wenliang Tan, Zhiqin Xie, Ziyu Zhang, Chenwei Tang, Hongkai Zhuang, Weikai Xu, Haihong Zhu, Yajin Chen, Changzhen Shang
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Lenvatinib plus PD-1 inhibitors and interventional (LPI) therapy have demonstrated promising treatment effects in unresectable hepatocellular carcinoma (HCC). However, biomarkers for predicting the response to LPI therapy remain to be further explored. We aimed to develop a radiomics model to noninvasively predict the efficacy of LPI therapy. Methods Clinical data of patients with HCC receiving LPI therapy were collected in our institution. The clinical model was built with clinical information. Nine machine learning classifiers were tested and the multilayer perceptron classifier with optimal performance was used as the radiomics model. The clinical-radiomics model was constructed by integrating clinical and radiomics scores through logistic regression analysis. Results 151 patients were enrolled in this study (2:1 randomization, 101 and 50 in the training and validation cohorts), of which three achieved complete response, 69 showed partial response, 46 showed stable disease, and 33 showed progressive disease. The objective response rate, disease control rate, and conversion resection rates were 47.7, 78.1 and 23.2%. 14 features were selected from the initially extracted 1223 for radiomics model construction. The area under the curves of the radiomics model (0.900 for training and 0.893 for validation) were comparable to that of the clinical-radiomics model (0.912 for training and 0.892 for validation), and both were superior to the clinical model (0.669 for training and 0.585 for validation). Meanwhile, the radiomics model can categorize participants into high-risk and low-risk groups for progression-free survival (PFS) and overall survival (OS) in the training (HR 1.913, 95% CI 1.121 to 3.265, p=0.016 for PFS; HR 4.252, 95% CI 2.051 to 8.816, p=0.001 for OS) and validation sets (HR 2.347, 95% CI 1.095 to 5.031, p=0.012 for PFS; HR 2.592, 95% CI 1.050 to 6.394, p=0.019 for OS). Conclusion The promising machine learning radiomics model was developed and validated to predict the efficacy of LPI therapy for patients with HCC and perform risk stratification, with comparable performance to clinical-radiomics model.
High altitudes and partial pressure of arterial oxygen in patients with chronic obstructive pulmonary disease - A systematic review and meta-analysis
Authors: A. Sevik, T. Gaisl, A. Forrer, L. Graf, S. Ulrich, K.E. Bloch, M. Lichtblau, M. Furian
Journal: Pulmonology (2024)

Prior study in healthy subjects has shown a reduction of partial pressure of arterial oxygen (PaO2) by -1.60 kPa/kilometre of altitude gain. However, the association of altitude-related change in PaO2 and altitude-related adverse health effects (ARAHE) in patients with chronic obstructive pulmonary disease (COPD) remain unknown. To provide an effect size estimate for the decline in PaO2 with each kilometre of altitude gain and to identify ARAHE in relation to altitude in patients with COPD. www.crd.york.ac.uk/prospero: CRD42020217938. A systematic search of PubMed and Embase was performed from inception to May 30, 2023. Peer-reviewed and prospective studies in patients with COPD staying at altitudes >1500 m providing arterial blood gases within the first 3 days at the target altitude. Aggregate data (AD) on study characteristics were extracted, and individual patient data (IPD) were requested. Estimates were pooled using random-effects meta-analysis. Relative risk estimates and 95 % confidence intervals for the association between PaO2 and altitude in patients with COPD. Thirteen studies were included in the AD analysis, of which 6 studies (222 patients, 45.2 % female) provided IPD, thus were included in the quantitative analysis. The estimated effect size of PaO2 was -0.84 kPa [95 %CI, -0.92 to -0.76] per 1000 m of altitude gain (I2=65.0 %, P < 0.001). In multivariable regression analysis, COPD severity, baseline PaO2, age and time spent at altitude were predictors for PaO2 at altitude. Overall, 37.8 % of COPD patients experienced an ARAHE, whereas older age, female sex, COPD severity, baseline PaO2, and target altitude were predictors for the occurrence of ARAHE (area under ROC curve: 0.9275, P < 0.001). This meta-analysis, providing altitude-related decrease in PaO2 and risk of ARAHE in patients with COPD ascending to altitudes >1500 m, revealed a lower altitude-related decrease in PaO2 in COPD patients compared with healthy. However, these findings might improve patient care and facilitate decisions about initiating preventive measures against hypoxaemia and ARAHE in patients with COPD planning an altitude sojourn or intercontinental flight, i.e. supplemental oxygen or acetazolamide.
Overcoming effector T cell exhaustion in ovarian cancer ascites with a novel adenovirus encoding for a MUC1 bispecific antibody engager and IL-2 cytokine
Authors: Saru Basnet, Mirte Van der Heijden, Dafne C.A. Quixabeira, Elise Jirovec, Susanna A.M. Grönberg-Vähä-Koskela, James H.A. Clubb, Anna Kanerva, Santeri Pakola, Lyna Haybout, Victor Arias, Otto Hemminki, Tatiana Kudling, Sadia Zafar, Victor Cervera-Carrascon, Joao M. Santos, Akseli Hemminki
Journal: Molecular Therapy (2024)
FetMRQC: A robust quality control system for multi-centric fetal brain MRI
Authors: Thomas Sanchez, Oscar Esteban, Yvan Gomez, Alexandre Pron, Mériam Koob, Vincent Dunet, Nadine Girard, Andras Jakab, Elisenda Eixarch, Guillaume Auzias, Meritxell Bach Cuadra
Journal: Medical Image Analysis (2024)

Fetal brain MRI is becoming an increasingly relevant complement to neurosonography for perinatal diagnosis, allowing fundamental insights into fetal brain development throughout gestation. However, uncontrolled fetal motion and heterogeneity in acquisition protocols lead to data of variable quality, potentially biasing the outcome of subsequent studies. We present FetMRQC, an open-source machine-learning framework for automated image quality assessment and quality control that is robust to domain shifts induced by the heterogeneity of clinical data. FetMRQC extracts an ensemble of quality metrics from unprocessed anatomical MRI and combines them to predict experts' ratings using random forests. We validate our framework on a pioneeringly large and diverse dataset of more than 1600 manually rated fetal brain T2-weighted images from four clinical centers and 13 different scanners. Our study shows that FetMRQC's predictions generalize well to unseen data while being interpretable. FetMRQC is a step towards more robust fetal brain neuroimaging, which has the potential to shed new insights on the developing human brain.
The oral microbiota and periodontal health in orthodontic patients
Authors: Brandon W. Peterson, Geerten‐Has Tjakkes, Anne‐Marie Renkema, David J. Manton, Yijin Ren
Journal: Periodontology 2000 (2024)

Abstract The oral microbiota develops within the first 2 years of childhood and becomes distinct from the parents by 4 years‐of‐age. The oral microbiota plays an important role in the overall health/symbiosis of the individual. Deviations from the state of symbiosis leads to dysbiosis and an increased risk of pathogenicity. Deviations can occur not only from daily life activities but also from orthodontic interventions. Orthodontic appliances are formed from a variety of biomaterials. Once inserted, they serve as a breeding ground for microbial attachment, not only from new surface areas and crevices but also from material physicochemical interactions different than in the symbiotic state. Individuals undergoing orthodontic treatment show, compared with untreated people, qualitative and quantitative differences in activity within the oral microbiota, induced by increased retention of supra‐ and subgingival microbial plaque throughout the treatment period. These changes are at the root of the main undesirable effects, such as gingivitis, white spot lesions (WSL), and more severe caries lesions. Notably, the oral microbiota profile in the first weeks of orthodontic intervention might be a valuable indicator to predict and identify higher‐risk individuals with respect to periodontal health and caries risk within an otherwise healthy population. Antimicrobial coatings have been used to dissuade microbes from adhering to the biomaterial; however, they disrupt the host microbiota, and several bacterial strains have become resistant. Smart biomaterials that can reduce the antimicrobial load preventing microbial adhesion to orthodontic appliances have shown promising results, but their complexity has kept many solutions from reaching the clinic. 3D printing technology provides opportunities for complex chemical syntheses to be performed uniformly, reducing the cost of producing smart biomaterials giving hope that they may reach the clinic in the near future. The purpose of this review is to emphasize the importance of the oral microbiota during orthodontic therapy and to use innovative technologies to better maintain its healthy balance during surgical procedures.
An international multi-institutional validation of T1 sub-staging of intraductal papillary mucinous neoplasm-derived pancreatic cancer
Authors: Joseph R Habib, Ingmar F Rompen, Brady A Campbell, Paul C M Andel, Benedict Kinny-Köster, Ryte Damaseviciute, D Brock Hewitt, Greg D Sacks, Ammar A Javed, Marc G Besselink, Hjalmar C van Santvoort, Lois A Daamen, Martin Loos, Jin He, I Quintus Molenaar, Markus W Büchler, Christopher L Wolfgang
Journal: JNCI Journal of the National Cancer Institute (2024)

Intraductal papillary mucinous neoplasm (IPMN)-derived pancreatic ductal adenocarcinoma (PDAC) is resected at smaller sizes compared with its biologically distinct counterpart, pancreatic intraepithelial neoplasia (PanIN)-derived PDAC. Thus, experts proposed T1 sub-staging for IPMN-derived PDAC. However, this has never been validated. Consecutive upfront surgery patients with IPMN-derived PDAC from 5 international high-volume centers were classified by the proposed T1 sub-staging classification (T1a ≤0.5, T1b >0.5 and ≤1.0, and T1c >1.0 and ≤2.0 cm) using the invasive component size. Kaplan-Meier and log-rank tests were used to compare overall survival (OS). A multivariable Cox regression was used to determine hazard ratios (HRs) with confidence intervals (95% CIs). Among 747 patients, 69 (9.2%), 50 (6.7%), 99 (13.0%), and 531 patients (71.1%), comprised the T1a, T1b, T1c, and T2-4 subgroups, respectively. Increasing T-stage was associated with elevated CA19-9, poorer grade, nodal positivity, R1 margin, and tubular subtype. Median OS for T1a, T1b, T1c, and T2-4 were 159.0 (95% CI = 126.0 to NR), 128.8 (98.3 to NR), 77.6 (48.3 to 108.2), and 31.4 (27.5 to 37.7) months, respectively (P < .001). OS decreased with increasing T-stage for all pairwise comparisons (all P < .05). After risk adjustment, older than age 65, elevated CA19-9, T1b [HR = 2.55 (1.22 to 5.32)], T1c [HR = 3.04 (1.60 to 5.76)], and T2-4 [HR = 3.41 (1.89 to 6.17)] compared with T1a, nodal positivity, R1 margin, and no adjuvant chemotherapy were associated with worse OS. Disease recurrence was more common in T2-4 tumors (56.4%) compared with T1a (18.2%), T1b (23.9%), and T1c (36.1%, P < .001). T1 sub-staging of IPMN-derived PDAC is valid and has significant prognostic value. Advancing T1 sub-stage is associated with worse histopathology, survival, and recurrence. T1 sub-staging is recommended for future guidelines.
Protonated-chitosan sponge with procoagulation activity for hemostasis in coagulopathy
Authors: Zhenhua Huang, Dong Zhang, Laiqiang Tong, Fan Gao, Shaozan Zhang, Xinqing Wang, Yina Xie, Fangping Chen, Changsheng Liu
Journal: Bioactive Materials (2024)

Hemostatic materials are essential for managing acute bleeding in medical settings. Chitosan (CS) shows promise in hemostasis but its underlying mechanism remains incompletely understood. We unexpectedly discovered that certain protonated-chitosan (PCS) rapidly assembled plasma proteins to form protein membrane (PM) upon contact with platelet-poor plasma (PPP). We hypothesized that the novel observation was intricately related to the procoagulant effect of chitosan. Herein, the study aimed to elucidate the conditions necessary and mechanism for PM formation, identify the proteins within the PM and PCS's procoagulant action at the molecule levels. We confirmed that the amount of -NH
Astroglial membrane camouflaged Ptbp1 siRNA delivery hinders glutamate homeostasis via SDH/Nrf2 pathway
Authors: Yan Liu, Jian Ren, Wenlong Zhang, Liuyan Ding, Runfang Ma, Mengran Zhang, Shaohui Zheng, Ruijing Liang, Yunlong Zhang
Journal: Biomaterials (2024)
Subunit-specific analysis of cohesin-mutant myeloid malignancies reveals distinct ontogeny and outcomes
Authors: Johann-Christoph Jann, Christopher B. Hergott, Marisa Winkler, Yiwen Liu, Benjamin Braun, Anne Charles, Kevin M. Copson, Shougat Barua, Manja Meggendorfer, Niroshan Nadarajah, Shai Shimony, Eric S. Winer, Martha Wadleigh, Richard M. Stone, Daniel J. DeAngelo, Jacqueline S. Garcia, Torsten Haferlach, R. Coleman Lindsley, Marlise R. Luskin, Maximilian Stahl, Zuzana Tothova
Journal: Leukemia (2024)

Abstract Mutations in the cohesin complex components ( STAG2, RAD21, SMC1A, SMC3 , and PDS5B) are recurrent genetic drivers in myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). Whether the different cohesin subunit mutations share clinical characteristics and prognostic significance is not known. We analyzed 790 cohesin-mutant patients from the Dana-Farber Cancer Institute (DFCI) and the Munich Leukemia Laboratory (MLL), 390 of which had available outcome data, and identified subunit-specific clinical, prognostic, and genetic characteristics suggestive of distinct ontogenies. We found that STAG2 mutations are acquired at MDS stage and are associated with secondary AML, adverse prognosis, and co-occurrence of secondary AML-type mutations. In contrast, mutations in RAD21, SMC1A and SMC3 share features with de novo AML with better prognosis, and co-occurrence with de novo AML-type lesions. The findings show the heterogeneous nature of cohesin complex mutations, and inform clinical and prognostic classification, as well as distinct biology of the cohesin complex.
ESC pre-test probability estimates for obstructive coronary artery disease: can they be used in Brazil?
Authors: Fernanda Erthal, Ronaldo Lima, Filipe Penna, Benjamin J W Chow, Ronaldo Gismondi
Journal:  (2024)

Abstract Aims Cardiovascular disease, primarily coronary artery disease (CAD), is the leading cause of mortality worldwide. Accurate diagnosis of CAD often requires pre-test probability (PTP) estimation, traditionally performed using scoring systems like the Diamond-Forrester (DF) and European Society of Cardiology (ESC) models. However, the applicability of such models in specific populations may vary. This study compares the performance of DF and PTP scores in the Brazilian context, using coronary computed tomography angiography (CCTA) as a reference standard. Methods and results PTP for obstructive CAD was calculated using DF and ESC scores in 409 symptomatic patients without known CAD who underwent CCTA between 2019 and 2022. Predicted PTP was compared with actual CAD prevalence. DF overestimated CAD prevalence across age and symptom categories, while ESC showed better alignment with actual prevalence. Conclusion Our study confirms that the ESC PTP model is more appropriate than the DF model for determining PTP in the Brazilian population.
WHO global research priorities for sexually transmitted infections
Authors: Sami L Gottlieb, Erica Spielman, Laith Abu-Raddad, Adeniyi Kolade Aderoba, Laura H Bachmann, Karel Blondeel, Xiang-Sheng Chen, Tania Crucitti, Gabriela Garcia Camacho, Sheela Godbole, Rodolfo Gómez Ponce de Leon, Somesh Gupta, Joumana Hermez, Naoko Ishikawa, Jeffrey D Klausner, Firdavs Kurbonov, Ismael Maatouk, Ahmed Mandil, Maeve B Mello, Angelica Espinosa Miranda, Fausta Shakiwa Mosha, Joseph Chukwudi Okeibunor, Jason J Ong, Remco P H Peters, Freddy Pérez, Nicole Seguy, Kate L Seib, Mukta Sharma, Tim Sladden, Barbara Van Der Pol, Peter J White, Teodora Wi, Nathalie Broutet
Journal: The Lancet Global Health (2024)
IAPAC–Lancet HIV Commission on the future of urban HIV responses
Authors: José M Zuniga, Corey Prachniak, Nicoletta Policek, Nombulelo Magula, Anisha Gandhi, Jane Anderson, Dázon Dixon Diallo, Viviane Dias Lima, Sindhu Ravishankar, Shrikala Acharya, Angeli Achrekar, Monsurat Adeleke, Élodie Aïna, Solange Baptiste, Geoffrey Barrow, Josip Begovac, Elizabeth Bukusi, Amanda Castel, Erika Castellanos, Jorge Cestou, Gertrude Chirambo, Jeffrey Crowley, Nikos Dedes, Lucica Ditiu, Meg Doherty, Chris Duncombe, Adriana Durán, Donna Futterman, Shannon Hader, Chyrol Kounkeu, Fran Lawless, Jeffrey V Lazarus, Sabine Lex, Carlos Lobos, Kenneth Mayer, Maria Mejia, H Rodrigo Moheno, Antonella d'Arminio Monforte, Mónica Morán-Arribas, Daniel Nagel, Robert Ndugwa, Carol Ngunu, Midnight Poonkasetwattana, Maria Prins, Amara Quesada, Olga Rudnieva, Simon Ruth, Jorge Saavedra, Lance Toma, Lucy Wanjiku Njenga, Brian Williams
Journal: The Lancet HIV (2024)
Alcohol consumption in relation to cognitive dysfunction and dementia: A systematic review and dose-response meta-analysis of comparative longitudinal studies
Authors: Meysam Zarezadeh, Mahsa Mahmoudinezhad, Amir Hossein Faghfouri, Niyaz Mohammadzadeh Honarvar, Quentin R Regestein, Stefania I Papatheodorou, Rania A Mekary, Walter C Willett
Journal: Ageing Research Reviews (2024)
Mind the gap: why we need to consider teenage and young adult cancers across the research pipeline
Authors: Laura Danielson, Phil Prime, Rosanna Larter
Journal: Trends in cancer (2024)

Historically, teenage and young adult (TYA) cancers have been understudied, with research largely focussing on paediatric or older adult (OA) indications. With increasing TYA cancer incidence rates internationally, now is the time to focus on teenagers and young adults across the research pipeline to improve not only outcomes but also the quality of life for this underserved group.
Biomedical applications of stimuli‐responsive nanomaterials
Authors: Xiaojie Chen, Di Wu, Zhong Chen
Journal: MedComm (2024)

Abstract Nanomaterials have aroused great interests in drug delivery due to their nanoscale structure, facile modifiability, and multifunctional physicochemical properties. Currently, stimuli‐responsive nanomaterials that can respond to endogenous or exogenous stimulus display strong potentials in biomedical applications. In comparison with conventional nanomaterials, stimuli‐responsive nanomaterials can improve therapeutic efficiency and reduce the toxicity of drugs toward normal tissues through specific targeting and on‐demand drug release at pathological sites. In this review, we summarize the responsive mechanism of a variety of stimulus, including pH, redox, and enzymes within pathological microenvironment, as well as exogenous stimulus such as thermal effect, magnetic field, light, and ultrasound. After that, biomedical applications (e.g., drug delivery, imaging, and theranostics) of stimuli‐responsive nanomaterials in a diverse array of common diseases, including cardiovascular diseases, cancer, neurological disorders, inflammation, and bacterial infection, are presented and discussed. Finally, the remaining challenges and outlooks of future research directions for the biomedical applications of stimuli‐responsive nanomaterials are also discussed. We hope that this review can provide valuable guidance for developing stimuli‐responsive nanomaterials and accelerate their biomedical applications in diseases diagnosis and treatment.
Cancer‐associated fibroblast‐derived colony‐stimulating factor 2 confers acquired osimertinib resistance in lung adenocarcinoma via promoting ribosome biosynthesis
Authors: Yutang Huang, Xiaoqing Wang, Chunjie Wen, Jingchan Wang, Honghao Zhou, Lanxiang Wu
Journal: MedComm (2024)

Abstract Acquired resistance is a major obstacle to the therapeutic efficacy of osimertinib in lung adenocarcinoma (LUAD), but the underlying mechanisms are still not fully understood. Cancer‐associated fibroblasts (CAFs) are the most abundant stromal cell type in LUAD tumor‐microenvironment (TME) and have emerged as a key player in chemoresistance. However, the function of CAFs in osimertinib resistance is still unclear. Here, we showed that CAFs derived from osimertinib‐resistant LUAD tissues (CAF OR ) produced much more colony‐stimulating factor 2 (CSF2) than those isolated from osimertinib‐sensitive tissues. CAF OR ‐derived CSF2 activated the Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) signaling pathway and upregulated lnc‐CSRNP3 in LUAD cells. Lnc‐CSRNP3 then promoted the expression of nearby gene CSRNP3 by recruiting chromodomain helicase DNA binding protein 9 (CHD9) and inhibited the phosphatase activity of the serine/threonine protein phosphatase 1 catalytic subunit α (PP1α), thereby induced osimertinib resistance by enhancing ribosome biogenesis. Collectively, our study reveals a critical role for CAFs in the development of osimertinib resistance and identifies the CSF2 pathway as an attractive target for monitoring osimertinib efficacy and overcoming osimertinib resistance in LUAD.
The gut microbiota–brain axis in neurological disorders
Authors: Mingming You, Nan Chen, Yuanyuan Yang, Lingjun Cheng, Hongzhang He, Yanhua Cai, Yating Liu, Haiyue Liu, Guolin Hong
Journal: MedComm (2024)

Abstract Previous studies have shown a bidirectional communication between human gut microbiota and the brain, known as the microbiota–gut–brain axis (MGBA). The MGBA influences the host's nervous system development, emotional regulation, and cognitive function through neurotransmitters, immune modulation, and metabolic pathways. Factors like diet, lifestyle, genetics, and environment shape the gut microbiota composition together. Most research have explored how gut microbiota regulates host physiology and its potential in preventing and treating neurological disorders. However, the individual heterogeneity of gut microbiota, strains playing a dominant role in neurological diseases, and the interactions of these microbial metabolites with the central/peripheral nervous systems still need exploration. This review summarizes the potential role of gut microbiota in driving neurodevelopmental disorders (autism spectrum disorder and attention deficit/hyperactivity disorder), neurodegenerative diseases (Alzheimer's and Parkinson's disease), and mood disorders (anxiety and depression) in recent years and discusses the current clinical and preclinical gut microbe‐based interventions, including dietary intervention, probiotics, prebiotics, and fecal microbiota transplantation. It also puts forward the current insufficient research on gut microbiota in neurological disorders and provides a framework for further research on neurological disorders.
Re: [177Lu]Lu-PSMA-617 plus Enzalutamide in Patients with Metastatic Castration-resistant Prostate Cancer (ENZA-p): An Open-label, Multicentre, Randomised, Phase 2 Trial
Authors: Elio Mazzone, Sachin Perera, Abhijeet L Neti, David C Chen, Haidar Al-Saffar, Alice Thomson, Marlon L Perera, Nathan Lawrentschuk, Declan G Murphy
Journal: European Urology (2024)