tbuckley/cabot-search huggingface dataset:
Arterial Thromboembolism in Japanese Patients With Cancer
Authors: Yasufumi Gon, Toshitaka Morishima, Tomohiro Kawano, Shuhei Okazaki, Kenichi Todo, Tsutomu Sasaki, Hideki Mochizuki, Isao Miyashiro
Journal: JACC CardioOncology (2024)

Thromboembolism is a significant complication for patients with cancer, leading to treatment interruptions and poor outcomes. The aim of this study was to investigate the incidence of arterial thromboembolism (ATE) within cancer populations, identify the predictors of ATE, and determine its survival impact. A retrospective multicenter study was performed using data from the Osaka Cancer Registry linked with administrative data from 2010 to 2015. Patients were monitored for 5 years after cancer diagnosis, and ATE incidence was calculated with death as a competing risk. Fine and Gray competing risk regression models and Cox proportional hazards models were used to evaluate the predictors of ATE and the survival impact. Restricted mean survival time (RMST) was used to assess whether antithrombotic therapy after ATE contributed to improved survival. The cohort comprised 97,448 patients with cancer (42.3% women, median age 70 years). ATE incidence displayed an annual increase, peaking 1 year after cancer diagnosis (1-, 2-, 3-, 4-, and 5-year cumulative incidences were 1.29%, 1.77%, 2.05%, 2.22%, and 2.32%, respectively). Male sex, advanced age, advanced cancer stage, and hematologic malignancies correlated with a high risk for ATE. Patients with ATE had a 2-fold increased risk for mortality compared with those without ATE. The 90-day and 1-year RMST differences for those on antithrombotic therapy were 13.3 days (95% CI: 10.4-16.2 days; P < 0.001) and 57.8 days (95% CI: 43.1-72.5 days; P < 0.001), favoring the antithrombotic therapy group. The RMST differences varied by cancer stage. The risk for ATE varies according to sex, age, and cancer progression and type. Antithrombotic therapy after ATE is associated with improved survival among patients with cancer.
Clickable Granular Hydrogel Scaffolds for Delivery of Neural Progenitor Cells to Sites of Spinal Cord Injury
Authors: Thomas J. Tigner, Gabrielle Dampf, Ashley Tucker, Yu‐Chi Huang, Vipin Jagrit, Abigail J. Clevenger, Arpita Mohapatra, Shreya A. Raghavan, Jennifer N. Dulin, Daniel L. Alge
Journal: Advanced Healthcare Materials (2024)

Spinal cord injury (SCI) is a serious condition with limited treatment options. Neural progenitor cell (NPC) transplantation is a promising treatment option, and the identification of novel biomaterial scaffolds that support NPC engraftment and therapeutic activity is a top research priority. The objective of this study is to evaluate in situ assembled poly (ethylene glycol) (PEG)-based granular hydrogels for NPC delivery in a murine model of SCI. Microgel precursors are synthesized by using thiol-norbornene click chemistry to react four-armed PEG-amide-norbornene with enzymatically degradable and cell adhesive peptides. Unreacted norbornene groups are utilized for in situ assembly into scaffolds using a PEG-di-tetrazine linker. The granular hydrogel scaffolds exhibit good biocompatibility and do not adversely affect the inflammatory response after SCI. Moreover, when used to deliver NPCs, the granular hydrogel scaffolds supported NPC engraftment, do not adversely affect the immune response to the NPC grafts, and successfully support graft differentiation toward neuronal or astrocytic lineages as well as axonal extension into the host tissue. Collectively, these data establish PEG-based granular hydrogel scaffolds as a suitable biomaterial platform for NPC delivery and justify further testing, particularly in the context of more severe SCI.
Functionalized lipid nanoparticles modulate the blood-brain barrier and eliminate α-synuclein to repair dopamine neurons
Authors: Xiaomei Wu, Renxiang Yuan, Yichong Xu, Kai Wang, Hong Yuan, Tingting Meng, Fuqiang Hu
Journal: Asian Journal of Pharmaceutical Sciences (2024)

The challenge in the clinical treatment of Parkinson's disease lies in the lack of disease-modifying therapies that can halt or slow down the progression. Peptide drugs, such as exenatide (Exe), with potential disease-modifying efficacy, have difficulty in crossing the blood-brain barrier (BBB) due to their large molecular weight. Herein, we fabricate multi-functionalized lipid nanoparticles (LNP) Lpc-BoSA/CSO with BBB targeting, permeability-increasing and responsive release functions. Borneol is chemically bonded with stearic acid and, as one of the components of Lpc-BoSA/CSO, is used to increase BBB permeability. Immunofluorescence results of brain tissue of 15-month-old C57BL/6 mice show that Lpc-BoSA/CSO disperses across the BBB into brain parenchyma, and the amount is 4.21 times greater than that of conventional LNP. Motor symptoms of mice in Lpc-BoSA/CSO-Exe group are significantly improved, and the content of dopamine is 1.85 times (substantia nigra compacta) and 1.49 times (striatum) that of PD mice. α-Synuclein expression and Lewy bodies deposition are reduced to 51.85% and 44.72% of PD mice, respectively. Immunohistochemical mechanism studies show AKT expression in Lpc-BoSA/CSO-Exe is 4.23 times that of PD mice and GSK-3β expression is reduced to 18.41%. Lpc-BoSA/CSO-Exe could reduce the production of α-synuclein and Lewy bodies through AKT/GSK-3β pathway, and effectively prevent the progressive deterioration of Parkinson's disease. In summary, Lpc-BoSA/CSO-Exe increases the entry of exenatide into brain and promotes its clinical application for Parkinson's disease therapy.
Use of superpixels for improvement of inter-rater and intra-rater reliability during annotation of medical images
Authors: Daniel Gut, Marco Trombini, Iwona Kucybała, Kamil Krupa, Miłosz Rozynek, Silvana Dellepiane, Zbisław Tabor, Wadim Wojciechowski
Journal: Medical Image Analysis (2024)

In the context of automatic medical image segmentation based on statistical learning, raters' variability of ground truth segmentations in training datasets is a widely recognized issue. Indeed, the reference information is provided by experts but bias due to their knowledge may affect the quality of the ground truth data, thus hindering creation of robust and reliable datasets employed in segmentation, classification or detection tasks. In such a framework, automatic medical image segmentation would significantly benefit from utilizing some form of presegmentation during training data preparation process, which could lower the impact of experts' knowledge and reduce time-consuming labeling efforts. The present manuscript proposes a superpixels-driven procedure for annotating medical images. Three different superpixeling methods with two different number of superpixels were evaluated on three different medical segmentation tasks and compared with manual annotations. Within the superpixels-based annotation procedure medical experts interactively select superpixels of interest, apply manual corrections, when necessary, and then the accuracy of the annotations, the time needed to prepare them, and the number of manual corrections are assessed. In this study, it is proven that the proposed procedure reduces inter- and intra-rater variability leading to more reliable annotations datasets which, in turn, may be beneficial for the development of more robust classification or segmentation models. In addition, the proposed approach reduces time needed to prepare the annotations.
Measurement properties of tools used to assess self-harm in autistic and general population adults
Authors: Victoria Newell, Ellen Townsend, Caroline Richards, Sarah Cassidy
Journal: Clinical Psychology Review (2024)

Autistic people are at increased risk of experiencing self-harm compared to the general population. However, it is unclear which tools are being used to assess self-harm in autistic people, or whether existing tools need to be adapted for this group. This two-stage systematic review aimed to identify tools used to assess self-harm in autistic and general population adults, evaluate these tools on their measurement properties, and make recommendations for their appropriate use in research and clinical practice. Four databases were systematically searched (PsycINFO, Embase, MEDLINE and Web of Science). Eight frequently used self-harm assessment tools were identified and assessed for risk of bias, criteria for good measurement properties, and quality of evidence using the COSMIN checklist. Of these, only two tools had sufficient evidence of internal consistency (ISAS, QNSSI), and one had been frequently used with autistic adults (NSSI-AT). These three tools may have potential for use with autistic adults but require further investigation for content validity and measurement properties in the autistic population. More research and potential adaptations to current self-harm assessment tools are recommended in order to better conceptualise and understand self-harm and its measurement in autism.
Activated sputum eosinophils associated with exacerbations in children on mepolizumab
Authors: Gabriella E Wilson, James Knight, Qing Liu, Ashish Shelar, Emma Stewart, Xiaomei Wang, Xiting Yan, Joshua Sanders, Cynthia Visness, Michelle Gill, Rebecca Gruchalla, Andrew H Liu, Meyer Kattan, Gurjit K Khurana Hershey, Alkis Togias, Patrice M Becker, Matthew C Altman, William W Busse, Daniel J Jackson, Ruth R Montgomery, Geoffrey L Chupp
Journal: Journal of Allergy and Clinical Immunology (2024)

Graphical abstractAbstractBackgroundMUPPITS-2 was a randomized, placebo-controlled clinical trial that demonstrated mepolizumab (anti-IL-5) reduced exacerbations and blood and airway eosinophils in urban children with severe eosinophilic asthma. Despite this reduction in eosinophilia, exacerbation risk persisted in certain patients treated with mepolizumab. This raises the possibility that subpopulations of airway eosinophils exist that contribute to breakthrough exacerbations.ObjectiveWe aimed to determine the effect of mepolizumab on airway eosinophils in childhood asthma.MethodsSputum samples were obtained from 53 MUPPITS-2 participants. Airway eosinophils were characterized using mass cytometry and grouped into subpopulations using unsupervised clustering analyses of 38 surface and intracellular markers. Differences in frequency and immunophenotype of sputum eosinophil subpopulations were assessed based on treatment arm and frequency of exacerbations.ResultsMedian sputum eosinophils were significantly lower among participants treated with mepolizumab compared with placebo (58% lower, 0.35% difference [95% CI 0.01, 0.74], P = .04). Clustering analysis identified 3 subpopulations of sputum eosinophils with varied expression of CD62L. CD62Lint and CD62Lhi eosinophils exhibited significantly elevated activation marker and eosinophil peroxidase expression, respectively. In mepolizumab-treated participants, CD62Lint and CD62Lhi eosinophils were more abundant in participants who experienced exacerbations than in those who did not (100% higher for CD62Lint, 0.04% difference [95% CI 0.0, 0.13], P = .04; 93% higher for CD62Lhi, 0.21% difference [95% CI 0.0, 0.77], P = .04).ConclusionsChildren with eosinophilic asthma treated with mepolizumab had significantly lower sputum eosinophils. However, CD62Lint and CD62Lhi eosinophils were significantly elevated in children on mepolizumab who had exacerbations, suggesting that eosinophil subpopulations exist that contribute to exacerbations despite anti-IL-5 treatment.
Longitudinal profiling of the microbiome at four body sites reveals core stability and individualized dynamics during health and disease
Authors: Xin Zhou, Xiaotao Shen, Jethro S Johnson, Daniel J Spakowicz, Melissa Agnello, Wenyu Zhou, Monica Avina, Alexander Honkala, Faye Chleilat, Shirley Jingyi Chen, Kexin Cha, Shana Leopold, Chenchen Zhu, Lei Chen, Lin Lyu, Daniel Hornburg, Si Wu, Xinyue Zhang, Chao Jiang, Liuyiqi Jiang, Lihua Jiang, Ruiqi Jian, Andrew W Brooks, Meng Wang, Kévin Contrepois, Peng Gao, Sophia Miryam Schüssler-Fiorenza Rose, Thi Dong Binh Tran, Hoan Nguyen, Alessandra Celli, Bo-Young Hong, Eddy J Bautista, Yair Dorsett, Paula B Kavathas, Yanjiao Zhou, Erica Sodergren, George M Weinstock, Michael P Snyder
Journal: Cell Host & Microbe (2024)

To understand the dynamic interplay between the human microbiome and host during health and disease, we analyzed the microbial composition, temporal dynamics, and associations with host multi-omics, immune, and clinical markers of microbiomes from four body sites in 86 participants over 6 years. We found that microbiome stability and individuality are body-site specific and heavily influenced by the host. The stool and oral microbiome are more stable than the skin and nasal microbiomes, possibly due to their interaction with the host and environment. We identify individual-specific and commonly shared bacterial taxa, with individualized taxa showing greater stability. Interestingly, microbiome dynamics correlate across body sites, suggesting systemic dynamics influenced by host-microbial-environment interactions. Notably, insulin-resistant individuals show altered microbial stability and associations among microbiome, molecular markers, and clinical features, suggesting their disrupted interaction in metabolic disease. Our study offers comprehensive views of multi-site microbial dynamics and their relationship with host health and disease.
Bile acids modified by the intestinal microbiota promote colorectal cancer growth by suppressing CD8+ T cell effector functions
Authors: Jingjing Cong, Pianpian Liu, Zili Han, Wei Ying, Chaoliang Li, Yifei Yang, Shuling Wang, Jianbo Yang, Fei Cao, Juntao Shen, Yu Zeng, Yu Bai, Congzhao Zhou, Lilin Ye, Rongbin Zhou, Chunjun Guo, Chunlei Cang, Dennis L. Kasper, Xinyang Song, Lei Dai, Linfeng Sun, Wen Pan, Shu Zhu
Journal: Immunity (2024)
Human cytomegalovirus degrades DMXL1 to inhibit autophagy, lysosomal acidification, and viral assembly
Authors: Hanqi Li, Alice Fletcher-Etherington, Leah M. Hunter, Swati Keshri, Ceri A. Fielding, Katie Nightingale, Benjamin Ravenhill, Luis Nobre, Martin Potts, Robin Antrobus, Colin M. Crump, David C. Rubinsztein, Richard J. Stanton, Michael P. Weekes
Journal: Cell Host & Microbe (2024)

Human cytomegalovirus (HCMV) is an important human pathogen that regulates host immunity and hijacks host compartments, including lysosomes, to assemble virions. We combined a quantitative proteomic analysis of HCMV infection with a database of proteins involved in vacuolar acidification, revealing Dmx-like protein-1 (DMXL1) as the only protein that acidifies vacuoles yet is degraded by HCMV. Systematic comparison of viral deletion mutants reveals the uncharacterized 7 kDa US33A protein as necessary and sufficient for DMXL1 degradation, which occurs via recruitment of the E3 ubiquitin ligase Kip1 ubiquitination-promoting complex (KPC). US33A-mediated DMXL1 degradation inhibits lysosome acidification and autophagic cargo degradation. Formation of the virion assembly compartment, which requires lysosomes, occurs significantly later with US33A-expressing virus infection, with reduced viral replication. These data thus identify a viral strategy for cellular remodeling, with the potential to employ US33A in therapies for viral infection or rheumatic conditions, in which inhibition of lysosome acidification can attenuate disease.
Pathophysiology of chikungunya virus infection associated with fatal outcomes
Authors: William M de Souza, Marcilio J Fumagalli, Shirlene T S de Lima, Pierina L Parise, Deyse C M Carvalho, Cristian Hernandez, Ronaldo de Jesus, Jeany Delafiori, Darlan S Candido, Victor C Carregari, Stefanie P Muraro, Gabriela F Souza, Leda M Simões Mello, Ingra M Claro, Yamilka Díaz, Rodrigo B Kato, Lucas N Trentin, Clauber H S Costa, Ana Carolina B M Maximo, Karene F Cavalcante, Tayna S Fiuza, Vânia A F Viana, Maria Elisabeth L Melo, Clarissa P M Ferraz, Débora B Silva, Larissa M F Duarte, Priscilla P Barbosa, Mariene R Amorim, Carla C Judice, Daniel A Toledo-Teixeira, Mariana S Ramundo, Patricia V Aguilar, Emerson L L Araújo, Fabio T M Costa, Thiago Cerqueira-Silva, Ricardo Khouri, Viviane S Boaventura, Luiz Tadeu M Figueiredo, Rong Fang, Brechla Moreno, Sandra López-Vergès, Liana Perdigão Mello, Munir S Skaf, Rodrigo R Catharino, Fabiana Granja, Daniel Martins-de-Souza, Jessica A Plante, Kenneth S Plante, Ester C Sabino, Michael S Diamond, Eliseo Eugenin, José Luiz Proença-Módena, Nuno R Faria, Scott C Weaver
Journal: Cell Host & Microbe (2024)

Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.
Sugar transporters spatially organize microbiota colonization along the longitudinal root axis of Arabidopsis
Authors: Eliza P.-I. Loo, Paloma Durán, Tin Yau Pang, Philipp Westhoff, Chen Deng, Carlos Durán, Martin Lercher, Ruben Garrido-Oter, Wolf B. Frommer
Journal: Cell Host & Microbe (2024)

Plant roots are functionally heterogeneous in cellular architecture, transcriptome profile, metabolic state, and microbial immunity. We hypothesized that axial differentiation may also impact spatial colonization by root microbiota along the root axis. We developed two growth systems, ArtSoil and CD-Rhizotron, to grow and then dissect Arabidopsis thaliana roots into three segments. We demonstrate that distinct endospheric and rhizosphere bacterial communities colonize the segments, supporting the hypothesis of microbiota differentiation along the axis. Root metabolite profiling of each segment reveals differential metabolite enrichment and specificity. Bioinformatic analyses and GUS histochemistry indicate microbe-induced accumulation of SWEET2, 4, and 12 sugar uniporters. Profiling of root segments from sweet mutants shows altered spatial metabolic profiles and reorganization of endospheric root microbiota. This work reveals the interdependency between root metabolites and microbial colonization and the contribution of SWEETs to spatial diversity and stability of microbial ecosystem.
Reduced incretin effect precedes diabetes development following duodenopancreatectomy in individuals without diabetes
Authors: Gianfranco Di Giuseppe, Laura Soldovieri, Gea Ciccarelli, Pietro Manuel Ferraro, Giuseppe Quero, Francesca Cinti, Umberto Capece, Simona Moffa, Enrico Celestino Nista, Antonio Gasbarrini, Andrea Mari, Sergio Alfieri, Vincenzo Tondolo, Alfredo Pontecorvi, Jens Juul Holst, Andrea Giaccari, Teresa Mezza
Journal: Journal of Clinical Investigation (2024)
Cervical pessary versus vaginal progesterone in women with a singleton pregnancy, a short cervix, and no history of spontaneous preterm birth at less than 34 weeks’ gestation: open label, multicentre, randomised, controlled trial
Authors: Charlotte E van Dijk, Annabelle L van Gils, Maud D van Zijl, Bouchra Koullali, Marijke C van der Weide, Eline S van den Akker, Brenda J Hermsen, Wilhelmina M van Baal, Henricus Visser, Joris van Drongelen, Karlijn C Vollebregt, Moira Muller, Flip W van der Made, Sanne J Gordijn, Yolanda M de Mooij, Martijn A Oudijk, Marjon A de Boer, Ben WJ Mol, Brenda M Kazemier, Eva Pajkrt
Journal: BMJ (2024)

To compare the effectiveness of cervical pessary and vaginal progesterone in the prevention of adverse perinatal outcomes and preterm birth in pregnant women of singletons with no prior spontaneous preterm birth at less than 34 weeks' gestation and who have a short cervix of 35 mm or less.
Institutional and Regional Variation in Opioid Prescribing for Hospitalized Infants in the US
Authors: Olivia A. Keane, Shadassa Ourshalimian, Ashwini Lakshmanan, Henry C. Lee, Susan R. Hintz, Nam Nguyen, Madeleine C. Ing, Cynthia L. Gong, Cameron Kaplan, Lorraine I. Kelley-Quon
Journal: JAMA Network Open (2024)

Importance High-risk infants, defined as newborns with substantial neonatal-perinatal morbidities, often undergo multiple procedures and require prolonged intubation, resulting in extended opioid exposure that is associated with poor outcomes. Understanding variation in opioid prescribing can inform quality improvement and best-practice initiatives. Objective To examine regional and institutional variation in opioid prescribing, including short- and long-acting agents, in high-risk hospitalized infants. Design, Setting, and Participants This retrospective cohort study assessed high-risk infants younger than 1 year from January 1, 2016, to December 31, 2022, at 47 children’s hospitals participating in the Pediatric Health Information System (PHIS). The cohort was stratified by US Census region (Northeast, South, Midwest, and West). Variation in cumulative days of opioid exposure and methadone treatment was examined among institutions using a hierarchical generalized linear model. High-risk infants were identified by International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes for congenital heart disease surgery, medical and surgical necrotizing enterocolitis, extremely low birth weight, very low birth weight, hypoxemic ischemic encephalopathy, extracorporeal membrane oxygenation, and other abdominal surgery. Infants with neonatal opioid withdrawal syndrome, in utero substance exposure, or malignant tumors were excluded. Exposure Any opioid exposure and methadone treatment. Main Outcomes and Measures Regional and institutional variations in opioid exposure. Results Overall, 132 658 high-risk infants were identified (median [IQR] gestational age, 34 [28-38] weeks; 54.5% male). Prematurity occurred in 30.3%, and 55.3% underwent surgery. During hospitalization, 76.5% of high-risk infants were exposed to opioids and 7.9% received methadone. Median (IQR) length of any opioid exposure was 5 (2-12) cumulative days, and median (IQR) length of methadone treatment was 19 (7-46) cumulative days. There was significant hospital-level variation in opioid and methadone exposure and cumulative days of exposure within each US region. The computed intraclass correlation coefficient estimated that 16% of the variability in overall opioid prescribing and 20% of the variability in methadone treatment was attributed to the individual hospital. Conclusions and Relevance In this retrospective cohort study of high-risk hospitalized infants, institution-level variation in overall opioid exposure and methadone treatment persisted across the US. These findings highlight the need for standardization of opioid prescribing in this vulnerable population.
Survival in Patients With De Novo Metastatic Prostate Cancer
Authors: Martin W. Schoen, R. Bruce Montgomery, Lukas Owens, Saira Khan, Kristen M. Sanfilippo, Ruth B. Etzioni
Journal: JAMA Network Open (2024)

This cross-sectional study investigates trends in overall survival among patients with newly diagnosed metastatic prostate cancer in 2 national registries in the United States.