tbuckley/cabot-search huggingface dataset:
Clinical phenotyping uncovers heterogeneous associations between corticosteroid treatment and survival in critically ill COVID-19 patients
Authors: Niklas Bruse, Anna Motos, Rombout van Amstel, Eckart de Bie, Emma J. Kooistra, Aron Jansen, Dirk van Lier, Jason Kennedy, Daniel Schwarzkopf, Daniel Thomas-Rüddel, Jesus F. Bermejo-Martin, Ferran Barbe, Nicolette F. de Keizer, Michael Bauer, Johannes G. van der Hoeven, Antoni Torres, Christopher Seymour, Lonneke van Vught, Peter Pickkers, Matthijs Kox
Journal: Intensive Care Medicine (2024)

Disease heterogeneity in coronavirus disease 2019 (COVID-19) may render the current one-size-fits-all treatment approach suboptimal. We aimed to identify and immunologically characterize clinical phenotypes among critically ill COVID-19 patients, and to assess heterogeneity of corticosteroid treatment effect. We applied consensus k-means clustering on 21 clinical parameters obtained within 24 h after admission to the intensive care unit (ICU) from 13,279 COVID-19 patients admitted to 82 Dutch ICUs from February 2020 to February 2022. Derived phenotypes were reproduced in 6225 COVID-19 ICU patients from Spain (February 2020 to December 2021). Longitudinal immunological characterization was performed in three COVID-19 ICU cohorts from the Netherlands and Germany, and associations between corticosteroid treatment and survival were assessed across phenotypes. We derived three phenotypes: COVIDICU1 (43% of patients) consisted of younger patients with the lowest Acute Physiology And Chronic Health Evaluation (APACHE) scores, highest body mass index (BMI), lowest PaO2/FiO2 ratio, and a 90-day in-hospital mortality rate of 18%. COVIDICU2 patients (37%) had the lowest BMI, were older and had higher APACHE scores and mortality rate (24%) than COVIDICU1. Patients with COVIDICU3 (20%) were the eldest with the most comorbidities, the highest APACHE scores, acute kidney injury and metabolic dysregulations, and the highest mortality rate (47%). These patients also displayed the most pronounced inflammatory response. Corticosteroid therapy started at day 5 [2–9] after ICU admission and administered for 5 [3–7] days was associated with an increased risk for 90-day mortality in patients with the COVIDICU1 and COVIDICU2 phenotypes (hazard ratio [HR] 1.59 [1.09–2.31], p = 0.015 and HR 1.79 [1.42–2.26], p < 0.001, respectively), but not in patients with the COVIDICU3 phenotype (HR 1.08 [0.76–1.54], p = 0.654). Our multinational study identified three distinct clinical COVID-19 phenotypes, each exhibiting marked differences in demographic, clinical, and immunological features, and in the response to late and short-term corticosteroid treatment.
Del(1p32) is an early and high-risk event in multiple myeloma patients with extraosseous disease
Authors: Martin Stork, Eva Ondrouskova, Michaela Bohunova, Ivanna Boichuk, Dominik Fric, Zdenek Adam, Marta Krejci, Viera Sandecka, Zdenka Knechtova, Lenka Radova, Zuzana Jelinkova, Tatana Adlerova, Milan Krticka, Vladimir Nekuda, Marek Borsky, Sabina Sevcikova, Marie Jarosova, Ludek Pour
Journal: Blood Cancer Journal (2024)

risk event in the clonal evolution and may play an important role in the initial stages of extraosseous disease development.
Nanocarrier design for pathogen-inspired innate immune agonist delivery
Authors: Griffin I. Kane, Meghan L. Brassil, Miranda B. Diaz-Infante, Prabhani U. Atukorale
Journal: Trends in Immunology (2024)

In complex diseases such as cancer, modulating cytokine signatures of disease using innate immune agonists holds therapeutic promise. Novel multi-agonist treatments offer tunable control of the immune system because they are uniquely pathogen inspired, eliciting robust antitumor responses by promoting synergistic cytokine responses. However, the chief strategic hurdle is ensuring multi-agonist delivery to the same target cells, highlighting the importance of using nanomaterial-based carriers. Here, we place nanocarriers in center stage and review the delivery hurdles related to the varying extra- and intracellular localizations of innate immune receptors. We discuss a range of nanomaterials used for multi-agonist delivery, highlighting their respective benefits and drawbacks. Our overarching stance is that rational nanocarrier design is crucial for developing pathogen-inspired multi-agonist immunotherapies.
CD64<sup>+</sup>fibroblast-targeted vilanterol and a STING agonist augment CLDN18.2 BiTEs efficacy against pancreatic cancer by reducing desmoplasia and enriching stem-like CD8<sup>+</sup>T cells
Authors: Tianxing Zhou, Xupeng Hou, Jingrui Yan, Lin Li, Yongjie Xie, Weiwei Bai, Wenna Jiang, Yiping Zou, Xueyang Li, Ziyun Liu, Zhaoyu Zhang, Bohang Xu, Guohua Mao, Yifei Wang, Song Gao, Xiuchao Wang, Tiansuo Zhao, Hongwei Wang, Hongxia Sun, Xiufeng Zhang, Jun Yu, Chongbiao Huang, Jing Liu, Jihui Hao
Journal: Gut (2024)

The objective of this study is to improve the efficacy of CLDN18.2/CD3 bispecific T-cell engagers (BiTEs) as a promising immunotherapy against pancreatic ductal adenocarcinoma (PDAC).
Paid Family Leave and Prevention of Acute Respiratory Infections in Young Infants
Authors: Katherine A. Ahrens, Teresa Janevic, Erin C. Strumpf, Arijit Nandi, Justin R. Ortiz, Jennifer A. Hutcheon
Journal: JAMA Pediatrics (2024)

Acute respiratory tract infections are the leading cause of emergency department visits and hospitalizations in US children, with highest risks in the first 2 months after birth. Out-of-home childcare settings increase the spread of respiratory tract infections. The study team hypothesized that access to state-paid family leave could reduce acute care encounters (hospital admissions or emergency department visits) for respiratory tract infections in young infants by reducing out-of-home childcare transmissions.
Intermittent Energy Restriction for Adolescents With Obesity
Authors: Natalie B. Lister, Louise A. Baur, Eve T. House, Shirley Alexander, Justin Brown, Clare E. Collins, Christopher T. Cowell, Kaitlin Day, Sarah P. Garnett, Megan L. Gow, Alicia M. Grunseit, Maddison Henderson, Mary-Kate Inkster, Cathy Kwok, Sarah Lang, Susan J. Paxton, Helen Truby, Krista A. Varady, Hiba Jebeile
Journal: JAMA Pediatrics (2024)

Adolescent obesity requires effective and accessible treatment. Intensive dietary interventions have the potential to be used as adjunctive therapy for behavioral weight management.
Clinical Outcomes in Pediatric Patients With Type 1 Diabetes With Early Versus Late Diagnosis: Analysis From the DPV Registry
Authors: Johanna Hammersen, Sascha R. Tittel, Clemens Kamrath, Katharina Warncke, Angela Galler, Ulrike Menzel, Melanie Hess, Thomas Meißner, Beate Karges, Reinhard W. Holl
Journal: Diabetes Care (2024)

This study was conducted to evaluate the effects of early clinical diagnosis of type 1 diabetes by comparison of clinical parameters at diagnosis and during follow-up in patients with pediatric type 1 diabetes with early, intermediate, and late diagnosis.
Development and validation of a virtual teaching method for minimally invasive surgery skills: a prospective cohort study
Authors: Bibek Das, Frances Ledesma, Ravi Naik, Sarah Law, Payam Soleimani-Nouri, Omar A Khan, George Mylonas, Madhava Pai, Hutan Ashrafian, Duncan Spalding, Matyas Fehervari
Journal: International Journal of Surgery (2024)

The COVID-19 pandemic led to a significant reduction in operative exposure for surgical trainees, necessitating alternative training methods to mitigate the impact on surgical education. This study sought to evaluate whether minimally invasive surgery (MIS) skills could be taught remotely using widely available technology with objective assessments of proficiency.
<i>APOL1</i> Variant and Kidney Disease—Reply
Authors: Timothy Hopper, Opeyemi A. Olabisi
Journal: JAMA (2024)

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Final results of a randomized controlled trial: comparison of the efficacy and safety between totally laparoscopic and laparoscopic-assisted total gastrectomy for advanced siewert III esophagogastric junction cancer and upper and middle third gastric cancer
Authors: Juan Wang, Shushang Liu, Haixiang Chen, Jialin Luo, Guanghui Xu, Xiangying Feng, Xuewen Yang, Jianjun Yang, Ji Gang
Journal: International Journal of Surgery (2024)

Background: This study aimed to compare the efficacy and safety of TLTG with the overlap technique to LATG in patients with advanced Siewert III Esophagogastric Junction Cancer and upper and middle third gastric cancer. Methods: This single-center RCT enrolled 292 patients with the mentioned cancers, randomly assigned to TLTG overlap (n=146) or LATG (n=146) groups. Data on demographics, pathology, intraoperative variables, postoperative complications, recovery parameters, and 3-year survival were collected. Main outcome: postoperative complications within 30 days. Secondary outcomes: 3-year disease-free and overall survival. Results: TLTG versus LATG: TLTG had shorter incision, faster flatus/defecation, reduced analgesia, less opioid use, and shorter hospital stay. Similar operation time, anastomosis time, blood loss, and lymph node harvest. TLTG had lower overall post-op complication rate ( P =0.047), no significant difference in serious complications ( P =0.310). Variances in anastomotic stenosis occurrence at 3 months. No rehospitalization or mortality at 30 days. No significant differences in 3-month disease-free survival ( P =0.058) or overall survival ( P =0.236). Conclusion: Overlap method for anastomosis in TLTG is safe and feasible for advanced middle-upper-third gastric cancer, with positive short-term outcomes. This technique has potential as the preferred esophagojejunostomy approach in TLTG. Trial registration: This trial has been registered at Chinese Clinical Trial Registry: XXXXXXXX (registration date: September 4, 2019).
Injurious Fall Risk Differences Among Older Adults With First-Line Depression Treatments
Authors: Grace Hsin-Min Wang, Edward Chia-Cheng Lai, Amie J. Goodin, Rachel C. Reise, Ronald I. Shorr, Wei-Hsuan Lo-Ciganic
Journal: JAMA Network Open (2024)

Importance One-third of older adults in the US have depression, often treated with psychotherapy and antidepressants. Previous studies suggesting an increased risk of falls and related injuries (FRI) associated with antidepressant use may be affected by confounding by indication or immortal time bias. Objective To evaluate the association between FRI risk and first-line treatments in older adults with depression. Design, Setting, and Participants This cohort study used a target trial emulation framework with a cloning-censoring-weighting approach with Medicare claims data from 2016 to 2019. Participants included fee-for-service beneficiaries aged 65 years or older with newly diagnosed depression. Data were analyzed from October 1, 2023, to March 31, 2024. Exposures First-line depression treatments including psychotherapy, sertraline, escitalopram, citalopram, mirtazapine, duloxetine, trazodone, fluoxetine, bupropion, paroxetine, and venlafaxine. Main Outcome and Measure One-year FRI rate, restricted mean survival time (RMST), and adjusted hazard ratio (aHR) with 95% CI. Results Among 101 953 eligible beneficiaries (mean [SD] age, 76 [8] years), 63 344 (62.1%) were female, 7404 (7.3%) were Black individuals, and 81 856 (80.3%) were White individuals. Compared with the untreated group, psychotherapy use was not associated with FRI risk (aHR, 0.94 [95% CI, 0.82-1.17]), while other first-line antidepressants were associated with a decreased FRI risk (aHR ranged from 0.74 [95% CI, 0.59-0.89] for bupropion to 0.83 [95% CI, 0.67-0.98] for escitalopram). The FRI incidence ranged from 63 (95% CI, 53-75) per 1000 person-year for those treated with bupropion to 87 (95% CI, 83-90) per 1000 person-year for those who were untreated. The RMST ranged from 349 (95% CI, 346-350) days for those who were untreated to 353 (95% CI, 350-356) days for those treated with bupropion. Conclusions and Relevance In this cohort study of older Medicare beneficiaries with depression, first-line antidepressants were associated with a decreased FRI risk compared with untreated individuals. These findings provide valuable insights into their safety profiles, aiding clinicians in their consideration for treating depression in older adults.
Standardizing designed and emergent quantitative features in microphysiological systems
Authors: Dennis M. Nahon, Renée Moerkens, Hande Aydogmus, Bas Lendemeijer, Adriana Martínez-Silgado, Jeroen M. Stein, Milica Dostanić, Jean-Philippe Frimat, Cristina Gontan, Mees N. S. de Graaf, Michel Hu, Dhanesh G. Kasi, Lena S. Koch, Kieu T. T. Le, Sangho Lim, Heleen H. T. Middelkamp, Joram Mooiweer, Paul Motreuil-Ragot, Eva Niggl, Cayetano Pleguezuelos-Manzano, Jens Puschhof, Nele Revyn, José M. Rivera-Arbelaez, Jelle Slager, Laura M. Windt, Mariia Zakharova, Berend J. van Meer, Valeria V. Orlova, Femke M. S. de Vrij, Sebo Withoff, Massimo Mastrangeli, Andries D. van der Meer, Christine L. Mummery
Journal: Nature Biomedical Engineering (2024)
Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress
Authors: Lindsey D. Goodman, Isha Ralhan, Xin Li, Shenzhao Lu, Matthew J. Moulton, Ye-Jin Park, Pinghan Zhao, Oguz Kanca, Ziyaneh S. Ghaderpour Taleghani, Julie Jacquemyn, Joshua M. Shulman, Kanae Ando, Kai Sun, Maria S. Ioannou, Hugo J. Bellen
Journal: Nature Neuroscience (2024)
Fine-mapping across diverse ancestries drives the discovery of putative causal variants underlying human complex traits and diseases
Authors: Kai Yuan, Ryan J. Longchamps, Antonio F. Pardiñas, Mingrui Yu, Tzu-Ting Chen, Shu-Chin Lin, Yu Chen, Max Lam, Ruize Liu, Yan Xia, Zhenglin Guo, Wenzhao Shi, Chengguo Shen, Mark J. Daly, Benjamin M. Neale, Yen-Chen A. Feng, Yen-Feng Lin, Chia-Yen Chen, Michael C. O’Donovan, Tian Ge, Hailiang Huang
Journal: Nature Genetics (2024)
A vision–language foundation model for the generation of realistic chest X-ray images
Authors: Christian Bluethgen, Pierre Chambon, Jean-Benoit Delbrouck, Rogier van der Sluijs, Małgorzata Połacin, Juan Manuel Zambrano Chaves, Tanishq Mathew Abraham, Shivanshu Purohit, Curtis P. Langlotz, Akshay S. Chaudhari
Journal: Nature Biomedical Engineering (2024)
Microtubules Sequester Acetylated YAP in the Cytoplasm and Inhibit Heart Regeneration
Authors: Shijie Liu, Vaibhav Deshmukh, Fansen Meng, Yidan Wang, Yuka Morikawa, Jeffrey D. Steimle, Rich Gang Li, Jun Wang, James F. Martin
Journal: Circulation (2024)

BACKGROUND: The Hippo pathway effector YAP (Yes-associated protein) plays an essential role in cardiomyocyte proliferation and heart regeneration. In response to physiological changes, YAP moves in and out of the nucleus. The pathophysiological mechanisms regulating YAP subcellular localization after myocardial infarction remain poorly defined. METHODS: We identified YAP acetylation at site K265 by in vitro acetylation followed by mass spectrometry analysis. We used adeno-associated virus to express YAP-containing mutations that either abolished acetylation (YAP-K265R) or mimicked acetylation (YAP-K265Q) and studied how acetylation regulates YAP subcellular localization in mouse hearts. We generated a cell line with YAP-K265R mutation and investigated the protein-protein interactors by YAP immunoprecipitation followed by mass spectrometry, then validated the YAP interaction in neonatal rat ventricular myocytes. We examined colocalization of YAP and TUBA4A (tubulin α 4A) by superresolution imaging. Furthermore, we developed YAP-K265R and αMHC-MerCreMer (MCM); Yap-loxP/K265R mutant mice to examine the pathophysiological role of YAP acetylation in cardiomyocytes during cardiac regeneration. RESULTS: We found that YAP is acetylated at K265 by CBP (CREB-binding protein)/P300 (E1A-binding protein P300) and is deacetylated by nicotinamide phosphoribosyltransferase/nicotinamide adenine dinucleotide/sirtuins axis in cardiomyocytes. After myocardial infarction, YAP acetylation is increased, which promotes YAP cytoplasmic localization. Compared with controls, mice that were genetically engineered to express a K265R mutation that prevents YAP K265 acetylation showed improved cardiac regenerative ability and increased YAP nuclear localization. Mechanistically, YAP acetylation facilitates its interaction with TUBA4A, a component of the microtubule network that sequesters acetylated YAP in the cytoplasm. After myocardial infarction, the microtubule network increased in cardiomyocytes, resulting in the accumulation of YAP in the cytoplasm. CONCLUSIONS: After myocardial infarction, decreased sirtuin activity enriches YAP acetylation at K265. The growing TUBA4A network sequesters acetylated YAP within the cytoplasm, which is detrimental to cardiac regeneration.
Enzymes in Addressing Hypoxia for Biomaterials Engineering
Authors: Pejman Ghaffari‐Bohlouli, Hafez Jafari, Lei Nie, Ashok Kakkar, Amin Shavandi
Journal: Advanced Healthcare Materials (2024)

Abstract Oxygen is essential for normal cellular functions. Hypoxia impacts various cellular processes, such as metabolism, growth, proliferation, angiogenesis, metastasis, tumorigenesis, microbial infection, and immune response, mediated by hypoxia‐inducible factors (HIFs). Hypoxia contributes to the progression and development of cancer, cardiovascular diseases, metabolic disorders, kidney diseases, and infections. The potential alleviation of hypoxia has been explored through the enzymatic in situ decomposition of hydrogen peroxide, leading to the generation of oxygen. However, challenges such as limited stability restrict the effectiveness of enzymes such as catalase in biomedical and in vivo applications. To overcome these limitations, targeted delivery of the enzymes has been proposed. This review offers a critical comparison of i) current approaches to enhance the in vivo stability of catalase; and ii) the structure, mechanism of action, and kinetics of catalase and catalase‐like nanozymes.
An inflammatory liquid fingerprint predicting tumor recurrence after liver transplantation for hepatocellular carcinoma
Authors: Modan Yang, Zuyuan Lin, Li Zhuang, Linhui Pan, Rui Wang, Hao Chen, Zhihang Hu, Wei Shen, Jianyong Zhuo, Xinyu Yang, Huigang Li, Chiyu He, Zhe Yang, Qinfen Xie, Siyi Dong, Junli Chen, Renyi Su, Xuyong Wei, Junjie Yin, Shusen Zheng, Di Lu, Xiao Xu
Journal: MedComm (2024)

Abstract Tumor recurrence is a life‐threatening complication after liver transplantation (LT) for hepatocellular carcinoma (HCC). Precise recurrence risk stratification before transplantation is essential for the management of recipients. Here, we aimed to establish an inflammation‐related prediction model for posttransplant HCC recurrence based on pretransplant peripheral cytokine profiling. Two hundred and ninety‐three patients who underwent LT in two independent medical centers were enrolled, and their pretransplant plasma samples were sent for cytokine profiling. We identified four independent risk factors, including alpha‐fetoprotein, systemic immune‐inflammation index, interleukin 6, and osteocalcin in the training cohort ( n = 190) by COX regression analysis. A prediction model named inflammatory fingerprint (IFP) was established based on the above factors. The IFP effectively predicted posttransplant recurrence (area under the receiver operating characteristic curve [AUROC]: 0.792, C‐index: 0.736). The high IFP group recipients had significantly worse 3‐year recurrence‐free survival rates (37.9 vs. 86.9%, p &lt; 0.001). Simultaneous T‐cell profiling revealed that recipients with high IFP were characterized by impaired T cell function. The IFP also performed well in the validation cohort ( n = 103, AUROC: 0.807, C‐index: 0.681). In conclusion, the IFP efficiently predicted posttransplant HCC recurrence and helped to refine pretransplant risk stratification. Impaired T cell function might be the intrinsic mechanism for the high recurrence risk of recipients in the high IFP group.
Reshaping the tumor immune microenvironment to improve CAR-T cell-based cancer immunotherapy
Authors: Xueting Xia, Zongxin Yang, Qisi Lu, Zhenyun Liu, Lei Wang, Jinwen Du, Yuhua Li, Dong-Hua Yang, Shaojie Wu
Journal: Molecular Cancer (2024)

In many hematologic malignancies, the adoptive transfer of chimeric antigen receptor (CAR) T cells has demonstrated notable success; nevertheless, further improvements are necessary to optimize treatment efficacy. Current CAR-T therapies are particularly discouraging for solid tumor treatment. The immunosuppressive microenvironment of tumors affects CAR-T cells, limiting the treatment's effectiveness and safety. Therefore, enhancing CAR-T cell infiltration capacity and resolving the immunosuppressive responses within the tumor microenvironment could boost the anti-tumor effect. Specific strategies include structurally altering CAR-T cells combined with targeted therapy, radiotherapy, or chemotherapy. Overall, monitoring the tumor microenvironment and the status of CAR-T cells is beneficial in further investigating the viability of such strategies and advancing CAR-T cell therapy.
Ancestry-aligned polygenic scores combined with conventional risk factors improve prediction of cardiometabolic outcomes in African populations
Authors: Michelle Kamp, Oliver Pain, Cathryn M. Lewis, Michèle Ramsay
Journal: Genome Medicine (2024)

Cardiovascular diseases (CVD) are a major health concern in Africa. Improved identification and treatment of high-risk individuals can reduce adverse health outcomes. Current CVD risk calculators are largely unvalidated in African populations and overlook genetic factors. Polygenic scores (PGS) can enhance risk prediction by measuring genetic susceptibility to CVD, but their effectiveness in genetically diverse populations is limited by a European-ancestry bias. To address this, we developed models integrating genetic data and conventional risk factors to assess the risk of developing cardiometabolic outcomes in African populations.