tbuckley/cabot-search huggingface dataset:
Circulating Chromogranin A as Surveillance Biomarker in Patients with Carcinoids – The CASPAR Study
Authors: Qing H. Meng, Thorvardur R. Halfdanarson, Joshua A. Bornhorst, Henning Jann, Shagufta Shaheen, Run Zhang Shi, Andrej Schwabe, Katrin Stade, Daniel M. Halperin
Journal: Clinical Cancer Research (2024)

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are relatively indolent but can be more aggressive. The current recommendations for the use of serum CgA for GEP-NET patients are equivocal. This study was designed to validate an automated CgA immunofluorescence assay for monitoring disease progression in GEP-NET patients.
Efficacy, Safety, and Influence on Tumor Microenvironment of Neoadjuvant Pembrolizumab plus Ramucirumab for PD-L1 Positive NSCLC: A Phase 2 Trial (EAST ENERGY)
Authors: Keiju Aokage, Shohei Koyama, Shogo Kumagai, Kotaro Nomura, Yoshihisa Shimada, Kiyotaka Yoh, Masashi Wakabayashi, Miki Fukutani, Hideki Furuya, Tomohiro Miyoshi, Kenta Tane, Joji Samejima, Tetsuro Taki, Takuo Hayashi, Jun Matsubayashi, Genichiro Ishii, Hiroyoshi Nishikawa, Norihiko Ikeda, Masahiro Tsuboi
Journal: Clinical Cancer Research (2024)

Angiogenesis inhibitors are known to modify tumor immunity. Combination of angiogenesis inhibitors with immune checkpoint inhibitors (ICIs) has shown efficacy against many types of cancers, including non-small cell lung cancer (NSCLC). We investigated the feasibility of neoadjuvant therapy with pembrolizumab and ramucirumab, a vascular endothelial growth factor (VEGF) receptor-2 antagonist for patients with PD-L1-positive NSCLC and its influence on the tumor microenvironment (TME).
Effect of correcting iron deficiency on the risk of serious infection in heart failure: Insights from the <scp>IRONMAN</scp> trial
Authors: Paul W. Foley, Paul R. Kalra, John G.F. Cleland, Mark C. Petrie, Philip A. Kalra, Ian Squire, Philip Campbell, Callum Chapman, Patrick Donnelly, Fraser Graham, Andrew Hannah, Ninian N. Lang, Iain Matthews, Stephen J. Leslie, Pierpaolo Pellicori, Sue Piper, Robin Ray, Hernry O. Savage, Chales Spencer, John Walsh, Yuk‐Ki Wong, Ian Ford
Journal: European Journal of Heart Failure (2024)

Concerns exist that intravenous (IV) iron might increase the risk of infections. The IRONMAN trial provided an opportunity to investigate whether giving IV ferric derisomaltose (FDI) to patients with heart failure and iron deficiency alters the rate of hospitalization or death due to infections.
Antibody blockade of the PSGL-1 immune checkpoint enhances T-cell responses to B-cell lymphoma
Authors: João L. Pereira, Liliana Arede, Francisca Ferreira, Andreia Matos, Dulcineia Pereira, Rita F. Santos, Alexandre M. Carmo, Maria J. Oliveira, José C. Machado, Delfim Duarte, Nuno R. dos Santos
Journal: Leukemia (2024)
Amino acid is a major carbon source for hepatic lipogenesis
Authors: Yilie Liao, Qishan Chen, Lei Liu, Haipeng Huang, Jingyun Sun, Xiaojie Bai, Chenchen Jin, Honghao Li, Fangfang Sun, Xia Xiao, Yahong Zhang, Jia Li, Weiping Han, Suneng Fu
Journal: Cell Metabolism (2024)

Increased de novo lipogenesis is a hallmark of metabolic dysfunction-associated steatotic liver disease (MASLD) in obesity, but the macronutrient carbon source for over half of hepatic fatty acid synthesis remains undetermined. Here, we discover that dietary protein, rather than carbohydrates or fat, is the primary nutritional risk factor for MASLD in humans. Consistently, ex vivo tracing studies identify amino acids as a major carbon supplier for the tricarboxylic acid (TCA) cycle and lipogenesis in isolated mouse hepatocytes. In vivo, dietary amino acids are twice as efficient as glucose in fueling hepatic fatty acid synthesis. The onset of obesity further drives amino acids into fatty acid synthesis through reductive carboxylation, while genetic and chemical interventions that divert amino acid carbon away from lipogenesis alleviate hepatic steatosis. Finally, low-protein diets (LPDs) not only prevent body weight gain in obese mice but also reduce hepatic lipid accumulation and liver damage. Together, this study uncovers the significant role of amino acids in hepatic lipogenesis and suggests a previously unappreciated nutritional intervention target for MASLD.
Intra-channel bi-epitopic crosslinking unleashes ultrapotent antibodies targeting NaV1.7 for pain alleviation
Authors: Yaning Zhang, Yanchao Ding, Ziyan Zeng, Rui Zhu, Peiyuan Zheng, Shilong Fan, Qingjuan Cao, Hang Chen, Weishuai Ren, Mengling Wu, Luyao Wang, Juanjuan Du
Journal: Cell Reports Medicine (2024)

Crucial for cell activities, ion channels are key drug discovery targets. Although small-molecule and peptide modulators dominate ion channel drug discovery, antibodies are emerging as an alternative modality. However, challenges persist in generating potent antibodies, especially for channels with limited extracellular epitopes. We herein present a bi-epitopic crosslinking strategy to overcome these challenges, focusing on Na
Applicability of heart failure clinical practice guidelines in low‐ and middle‐income countries
Authors: Shelley Zieroth, Clara Inés Saldarriaga Giraldo, Fausto Pinto, Stefan D. Anker, William T. Abraham, John J. Atherton, Javed Butler, Vijay Chopra, Andrew J.S. Coats, Veronica Dean, Gerasimos Filippatos, Jose Luis Zamorano, Yuhui Zhang, Richard B. Weiskopf, Yann Colardelle
Journal: European Journal of Heart Failure (2024)

Abstract Aims Clinical practice guidelines are commonly written by professional societies in high‐income countries (HIC) with limited anticipation of implementation obstacles in other environments. We used heart failure (HF) guidelines as a paradigm to examine this concern, by conducting a survey to understand clinicians' ability to implement HF guidelines and their perceptions of the current HF guideline applicability in low‐ and middle‐income countries (LMIC). Methods and results An online survey of physicians in the database of the Translational Medicine Academy who treat HF patients was offered by email from 5 October to 27 November 2023, inquiring of participants' demographic information, experience, and views of HF guidelines as related to their practice. Of 2622 participating clinicians, 1592 partially completed, and an additional 1030 fully completed the survey. Participants were from 138 countries; 668 practiced in HIC, and 1954 in LMIC. Those from LMIC regarded HF guidelines to be less applicable in their country than did those from HIC ( p = 0.0002). Of all those responding, 75.3% indicated that it was somewhat or mostly true that the HF guidelines were mostly applicable to HIC. Those from LMIC, but not HIC indicated that the greatest implementation obstacle was that the guidelines were for HIC (51.3% vs. 43.1%; p = 0.0387). A significantly higher proportion of respondents from LMIC indicated that resources for caring for their patients were somewhat or mostly limiting in most cases, than did those in HIC (41.6% vs. 32.5%, p = 0.0068). Conclusion This survey examined the widely‐held thought that HF guidelines are broadly applicable to all regions of the world, concluding that such a perception is incorrect. Clinicians from LMIC view the absence of consideration of local resource limitations as the greatest obstacle for guideline implementation. The results regarding HF guidelines likely also have implications for other guidelines and resultant patient outcomes.
Environmental sustainability in cardiovascular practice: current challenges and future directions
Authors: Sanjay Rajagopalan, Scott McAlister, Jason Jay, Richard D. Pham, Robert D. Brook, Khurram Nasir, Mark. J. Nieuwenhuijsen, Philip Landrigan, Allegra Wiesler, Christina Vernon Sanborn, Justin R. Carron, Kara Hammond Brooks, Aruni Bhatnagar, Sadeer Al-Kindi
Journal: Nature Reviews Cardiology (2024)
Prospective Longitudinal Analysis of Physiologic MRI-based Tumor Habitat Predicts Short-term Patient Outcomes in IDH-wildtype Glioblastoma
Authors: Hye Hyeon Moon, Ji Eun Park, Nak Young Kim, Seo Young Park, Young-Hoon Kim, Sang Woo Song, Chang Ki Hong, Jeong Hoon Kim, Ho Sung Kim
Journal: Neuro-Oncology (2024)

Abstract Background This study validates MRI-based tumor habitats in predicting time-to-progression (TTP), overall survival (OS), and progression site in isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients. Methods Seventy-nine patients were prospectively enrolled between January 2020 and June 2022. MRI, including diffusion-weighted and dynamic susceptibility contrast imaging, were obtained immediately post-operation and at three serial timepoints. Voxels from cerebral blood volume and apparent diffusion coefficient maps were grouped into three habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue) using k-means clustering. Pre-defined cutoffs for increases in hypervascular and hypovascular cellular habitat were applied to calculate the habitat risk score. Associations between spatiotemporal habitats, habitat risk score, TTP, and OS were investigated using Cox proportional hazards modeling. Habitat risk score was compared to tumor volume using time-dependent receiver operating characteristics analysis. Progression sites were matched with spatial habitats. Results Increases in hypervascular and hypovascular cellular habitats and habitat risk scores were associated with shorter TTP and OS (all p &amp;lt; .05). Hypovascular cellular habitat and habitat risk scores 1 and 2 independently predicted TTP (hazard ratio [HR], 4.14; p=.03, HR, 4.51; p=.001 and HR, 10.02; p&amp;lt;.001, respectively). Hypovascular cellular habitat and habitat risk score 2 independently predicted OS (HR, 4.01, p=.003; and HR, 3.27, p&amp;lt;.001, respectively). Habitat risk score outperformed tumor volume in predicting TTP (12-month AUC, 0.762 vs. 0.646, p=.048). Hypovascular cellular habitat predicted progression sites (mean Dice index: 0.31). Conclusions Multiparametric physiologic MRI-based spatiotemporal tumor habitats and habitat risk scores are useful biomarkers for early tumor progression and outcomes in IDH-wildtype glioblastoma patients
Thrombosis in myeloproliferative neoplasms: a viewpoint on its impact on myelofibrosis, mortality, and solid tumors
Authors: Tiziano Barbui, Arianna Ghirardi, Alessandra Carobbio, Valerio De Stefano, Alessandro Rambaldi, Ayalew Tefferi, Alessandro M. Vannucchi
Journal: Blood Cancer Journal (2024)

This viewpoint summarizes findings from analyses of large personal patient databases of myeloproliferative neoplasms (MPNs) to assess the impact of thrombosis on mortality, disease progression, and second cancers (SC). Despite advances, the current incidence of arterial and venous thrombosis remains a challenge. These events appear to signal a more aggressive disease course, as evidenced by their association with myelofibrosis progression and mortality using multistate models and time-dependent multivariable analysis. Inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR), are associated with the aggressiveness of polycythemia vera (PV) and essential thrombocythemia (ET), linking thrombosis to SC risk. This suggests a common inflammatory pathway likely influencing cardiovascular disease and cancer incidence. Notably, this is observed more frequently in younger patients, likely due to prolonged exposure to MPN and environmental inflammatory triggers. These data underscore the need for new studies to validate these associations, delineate the sequence of events, and identify therapeutic targets to mitigate thrombotic events and potentially improve overall patient outcomes in MPN.
pan-Draft: automated reconstruction of species-representative metabolic models from multiple genomes
Authors: Nicola De Bernardini, Guido Zampieri, Stefano Campanaro, Johannes Zimmermann, Silvio Waschina, Laura Treu
Journal: Genome biology (2024)

Abstract The accurate reconstruction of genome-scale metabolic models (GEMs) for unculturable species poses challenges due to the incomplete and fragmented genetic information typical of metagenome-assembled genomes (MAGs). While existing tools leverage sequence homology from single genomes, this study introduces pan-Draft , a pan-reactome-based approach exploiting recurrent genetic evidence to determine the solid core structure of species-level GEMs. By comparing MAGs clustered at the species-level, pan-Draft addresses the issues due to the incompleteness and contamination of individual genomes, providing high-quality draft models and an accessory reactions catalog supporting the gapfilling step. This approach will improve our comprehension of metabolic functions of uncultured species.
Transmission line model as a digital twin for abdominal aortic aneurysm patients
Authors: Donghyeon Kim, Divyesh Narayanan, Shih-Hsien Sung, Hao-Min Cheng, Chen-Huan Chen, Chang-Sei Kim, Ramakrishna Mukkamala, Jin-Oh Hahn
Journal: npj Digital Medicine (2024)

We investigated the potential of the transmission line model as a digital twin of aneurysmal aorta by comparatively analyzing how a uniform lossless tube-load model were fitted to the carotid and femoral artery tonometry waveforms pertaining to (i) 79 abdominal aortic aneurysm (AAA) patients vs their matched controls (CON) and (ii) 35 AAA patients before vs after endovascular aneurysm repair (EVAR). The uniform lossless tube-load model fitted the tonometry waveforms pertaining to AAA as well as CON and EVAR. In addition, the parameters in the tube-load model exhibited physiologically explainable changes: when normalized, both pulse transit time and reflection coefficient increased with AAA and decreased after EVAR, which can be explained by the increase in arterial compliance and the decrease in arterial inertance due to the aortic expansion associated with AAA. In sum, the tube-load model may have the potential as a digital twin to enable personalized AAA monitoring.
Long‐term efficacy and safety of stapokibart for moderate‐to‐severe atopic dermatitis: 52‐week results from a phase 3 trial
Authors: Yan Zhao, Litao Zhang, Liming Wu, Bin Yang, Jinyan Wang, Yumei Li, Jingyi Li, Qingchun Diao, Qing Sun, Xiaohong Zhu, Xiaoyong Man, Lihua Wang, Linfeng Li, Yanyan Feng, Huiming Zeng, Tao Cai, Hong Ren, Jianyun Lu, Qianjin Lu, Xiaohua Tao, Rong Xiao, Chao Ji, Fuqiu Li, Jianzhong Zhang
Journal: Allergy (2024)

Abstract Background Management of moderate‐to‐severe atopic dermatitis (AD) needs long‐term therapy. Stapokibart is a humanized monoclonal antibody targeting interleukin‐4 receptor α subunit (IL‐4Rα), a shared receptor for IL‐4 and IL‐13 which are key pathogenic drivers of AD. In a pivotal phase 3 trial (NCT05265923), significant higher proportions of adult AD patients receiving stapokibart than placebo achieved ≥75% improvement from baseline in Eczema Area and Severity Index (EASI‐75; 66.9% vs. 25.8%) and Investigator's Global Assessment (IGA) score of 0/1 with ≥2‐point reduction (44.2% vs. 16.1%) at Week 16. Herein, we report long‐term (52 weeks) efficacy and safety of stapokibart from this trial. Methods After 16‐week double‐blind treatment completed, patients in both stapokibart and placebo groups entered a 36‐week maintenance treatment period and received stapokibart 300 mg every 2 weeks. Concomitant use of topical medications for AD was permitted throughout the maintenance period. Results Of 476 patients entering maintenance period, 430 completed the treatment. At Week 52, EASI‐75 was achieved in 92.5% of patients continuing stapokibart and 88.7% of those switching from placebo to stapokibart, respectively; an IGA score of 0 or 1 with a ≥2‐point reduction was achieved in 67.3% and 64.2% of patients, respectively; a ≥4‐point reduction in weekly average of daily Peak Pruritus Numerical Rating Scale (PP‐NRS) was achieved in 67.3% and 60.5% of patients, respectively. Over the 52‐week treatment period, 88.1% of patients reported treatment‐emergent adverse events, most were mild or moderate. Conclusion Long‐term treatment with stapokibart demonstrated a sustained efficacy and favorable safety profile in adults with moderate‐to‐severe AD.
Political polarization and health
Authors: Jay J Van Bavel, Shana Kushner Gadarian, Eric Knowles, Kai Ruggeri
Journal: Nature Medicine (2024)

In addition to social determinants of health, such as economic resources, education, access to care and various environmental factors, there is growing evidence that political polarization poses a substantial risk to individual and collective well-being. Here we review the impact of political polarization on public health. We describe the different forms of polarization and how they are connected to health outcomes, highlighting the COVID-19 pandemic as a case study of the health risks of polarization. We then offer strategies for mitigating potential harms associated with polarization, with an emphasis on building social trust. Finally, we propose future research directions on this topic, underscore the need for more work in a global context and encourage greater collaboration between social scientists and medical scientists. We conclude that polarization is a serious—if largely overlooked—determinant of health, whose impacts must be more thoroughly understood and mitigated. Political polarization is an understudied determinant of health. This Review describes the types of political polarization and how they impact the health of populations and individuals, including potential mitigation strategies and research priorities.
Viscoelastic synthetic antigen-presenting cells for augmenting the potency of cancer therapies
Authors: Zeyang Liu, Yan-Ruide Li, Youcheng Yang, Yu Zhu, Weihao Yuan, Tyler Hoffman, Yifan Wu, Enbo Zhu, Jana Zarubova, Jun Shen, Haochen Nan, Kun-Wei Yeh, Mohammad Mahdi Hasani-Sadrabadi, Yichen Zhu, Ying Fang, Xinyang Ge, Zhizhong Li, Jennifer Soto, Tzung Hsiai, Lili Yang, Song Li
Journal: Nature Biomedical Engineering (2024)
Increasing trends in hepatitis E hospitalisations in Spain, 1997 to 2019
Authors: María Guerrero-Vadillo, Marina Peñuelas, Rocío Carmona, Inmaculada León-Gómez, Carmen Varela
Journal: Eurosurveillance (2024)

Background Hepatitis E, a viral hepatitis caused mainly by the ingestion of raw or undercooked food, is not a notifiable disease in Spain. Aim To analyse the temporal trends, epidemiological characteristics and factors associated with severe disease from hepatitis E hospitalisations in Spain from 1997 to 2019. Methods Hospitalisation records were obtained from the Spanish National Hospital Discharge Database. Temporal trends and seasonality were analysed by Poisson regression in years 1997–2015 and 2016–19, given changes in hospital discharge databases. Multivariate logistic regression was used to identify factors associated with severe disease. Results Hepatitis E hospitalisation incidence increased from 0.22 cases per 1,000,000 inhabitants in 1997 to a maximum of 2.95 in 2018. Seasonality was observed during 2016–19 period, with more cases in the second and third quarters of the year. The incidence was higher in men vs women, and in the population aged over 40 years. Factors independently associated with death were age ≥ 50 years (adjusted odds ratio (aOR): 2.43), chronic liver disease (aOR: 4.29), HIV infection (aOR: 3.00) and hepatitis B/C (aOR: 2.11). Conclusions Hepatitis E hospitalisations have increased in Spain in recent years, being more severe in cases with older age, chronic hepatic diseases and HIV infection. A greater incidence in men over 40 years and a possible seasonality were observed. Further studies are needed to assess the seasonality, geographical distribution and impact of the disease to guide public health actions for prevention and control.
Contact behaviour before, during and after the COVID-19 pandemic in the Netherlands: evidence from contact surveys, 2016 to 2017 and 2020 to 2023
Authors: Jantien A Backer, Eric R A Vos, Gerco den Hartog, Cheyenne C E van Hagen, Hester E de Melker, Fiona R M van der Klis, Jacco Wallinga
Journal: Eurosurveillance (2024)

Background The first wave of the COVID-19 pandemic in 2020 was largely mitigated by limiting contacts in the general population. In early 2022, most contact-reducing measures were lifted. Aim To assess whether the population has reverted to pre-pandemic contact behaviour and how this would affect transmission potential of a newly emerging pathogen. Methods We compared two studies on contact behaviour in the Netherlands: the PIENTER Corona study, conducted during and after the pandemic (held every 2–6 months from April 2020) and the PIENTER3 study (2016–17, as pre-pandemic baseline). In both, participants (ages 1–85 years) reported number and age group of all face-to-face persons contacted on the previous day in a survey. Transmission potential was examined using the next-generation matrix approach. Results We found an average of 15.4 (95% CI: 14.3–16.4) community contacts per person per day after the pandemic in May 2023, 13% lower than baseline (17.8; 95% CI: 17.0–18.5). Among all ages, children (5–9 years) had the highest number of contacts, both pre- and post-pandemic. Mainly adults aged 20–59 years had not reverted to pre-pandemic behaviours, possibly because they more often work from home. Although the number of contacts is lower compared to the pre-pandemic period, the effect on transmission potential of a newly emerging respiratory pathogen is limited if all age groups were equally susceptible. Conclusion Continuous monitoring of contacts can signal changes in contact patterns and can define a ‘new normal’ baseline. Both aspects are needed to prepare for a future pandemic.
Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma
Authors: Daniel H. Shu, Won Jin Ho, Luciane T. Kagohara, Alexander Girgis, Sarah M. Shin, Ludmila Danilova, Jae W. Lee, Dimitrios N. Sidiropoulos, Sarah Mitchell, Kabeer Munjal, Kathryn Howe, Kayla J. Bendinelli, Emma Kartalia, Hanfei Qi, Guanglan Mo, Janelle Montagne, James M. Leatherman, Tamara Y. Lopez-Vidal, Qingfeng Zhu, Amanda L. Huff, Xuan Yuan, Alexei Hernandez, Erin M. Coyne, Neeha Zaidi, Daniel J. Zabransky, Logan L. Engle, Aleksandra Ogurtsova, Marina Baretti, Daniel Laheru, Jennifer N. Durham, Hao Wang, Joel C. Sunshine, Robert J. Johnston, Julie Stein Deutsch, Janis M. Taube, Robert A. Anders, Elizabeth M. Jaffee, Elana J. Fertig, Mark Yarchoan
Journal: Nature Immunology (2024)
Developing a European framework for the prevention of communicable diseases: three points for attention
Authors: Daniel H de Vries, Mandy Geise, Anna Christina Maukner, Piotr Kramarz, Charlotte Deogan, John Kinsman
Journal: Eurosurveillance (2024)

The capacity to deliver programmes that prevent and control infectious diseases is a key public health function. The European Centre for Disease Prevention and Control (ECDC) aims to support and strengthen this capacity in European Union/ European Economic Area (EU/EEA) countries as part of its 2021–27 strategy which includes explicit attention to social and behavioural aspects of disease prevention. To achieve its strategic goals, it is important that ECDC improves its knowledge of prevention strategies, actors and activities in EU/EEA countries. In this Perspective, we summarise three challenges to implementing the prevention framework proposed by ECDC: (i) defining, recognising and identifying with ‘prevention’, (ii) integrating new understandings into established ways of thinking, and (iii) the need for more attention to prevention in governance. These challenges are derived from the findings of a project which conducted a preliminary mapping of prevention actors, networks and activities in four EU countries to support the development of a community of practice within the new ECDC prevention framework. This Perspective serves to draw attention to this prevention framework and the three identified challenges for those working on its implementation.
A trainee-informed model for undergraduate neuroscience research programs serving marginalized students
Authors: Christian Cazares, Maribel Patiño, Minerva Contreras, Julia C. Gorman, Jillybeth Burgado, Sana A. Ali, Quirine van Engen, Eena L. Kosik, Pamela Riviere, Emily T. Baltz, Chimuanya K. Agba, Michael Preston, Akshay Nagarajan, Jianna Cressy, Natalie Paredes, Chiaki Santiago, Kevin L. White
Journal: Nature Neuroscience (2024)