tbuckley/cabot-search huggingface dataset:
Equitably Allocating Resources during Crises: Racial Differences in Mortality Prediction Models
Authors: Deepshikha Charan Ashana, George L. Anesi, Vincent X. Liu, Gabriel J. Escobar, Christopher Chesley, Nwamaka D. Eneanya, Gary E. Weissman, William Dwight Miller, Michael O. Harhay, Scott D. Halpern
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Crisis standards of care (CSCs) guide critical care resource allocation during crises. Most recommend ranking patients on the basis of their expected in-hospital mortality using the Sequential Organ Failure Assessment (SOFA) score, but it is unknown how SOFA or other acuity scores perform among patients of different races. Objectives: To test the prognostic accuracy of the SOFA score and version 2 of the Laboratory-based Acute Physiology Score (LAPS2) among Black and white patients. Methods: We included Black and white patients admitted for sepsis or acute respiratory failure at 27 hospitals. We calculated the discrimination and calibration for in-hospital mortality of SOFA, LAPS2, and modified versions of each, including categorical SOFA groups recommended in a popular CSC and a SOFA score without creatinine to reduce the influence of race. Measurements and Main Results: Of 113,158 patients, 27,644 (24.4%) identified as Black. The LAPS2 demonstrated higher discrimination (area under the receiver operating characteristic curve [AUC], 0.76; 95% confidence interval [CI], 0.76–0.77) than the SOFA score (AUC, 0.68; 95% CI, 0.68–0.69). The LAPS2 was also better calibrated than the SOFA score, but both underestimated in-hospital mortality for white patients and overestimated in-hospital mortality for Black patients. Thus, in a simulation using observed mortality, 81.6% of Black patients were included in lower-priority CSC categories, and 9.4% of all Black patients were erroneously excluded from receiving the highest prioritization. The SOFA score without creatinine reduced racial miscalibration. Conclusions: Using SOFA in CSCs may lead to racial disparities in resource allocation. More equitable mortality prediction scores are needed.
Atherosclerotic Carotid Plaque Composition and Incident Stroke and Coronary Events
Authors: Daniel Bos, Banafsheh Arshi, Quirijn J.A. van den Bouwhuijsen, M. Kamran Ikram, Mariana Selwaness, Meike W. Vernooij, Maryam Kavousi, Aad van der Lugt
Journal: Journal of the American College of Cardiology (2021)

Increasing evidence suggests that atherosclerotic plaque composition rather than plaque size is linked to ischemic cardiovascular events, yet largescale population-based data in asymptomatic individuals remain scarce. This study sought to investigate carotid plaque composition in relation to incident stroke and coronary heart disease (CHD) in a population-based setting. Between 2007 and 2012, 1,349 persons (mean age 72 years, 49.5% women) from the population-based Rotterdam Study who were free from a history of stroke or CHD, in whom carotid ultrasonography showed subclinical atherosclerosis, and who underwent high-resolution magnetic resonance imaging of the carotid arteries to assess plaque characteristics. These included the presence of specific plaque components (intraplaque hemorrhage [IPH], lipid-rich necrotic core, and calcification), and measures of plaque size (maximum plaque thickness and presence of stenosis of more than 30%). Individuals were continuously followed for the occurrence of stroke or CHD until January 1, 2015. The authors used Cox regression models to assess the association of the plaque characteristics with the incidence of stroke and CHD, with adjustments for age, sex, and cardiovascular risk factors. During a median of 5.1 years’ follow-up for stroke and 4.8 years for CHD, 51 individuals had a stroke and 83 developed CHD. Independent of maximum plaque thickness and cardiovascular risk factors, the presence of IPH was associated with incident stroke and CHD (fully adjusted hazard ratio: 2.42 [95% confidence interval: 1.30 to 4.50], and 1.95 [95% confidence interval: 1.20 to 3.14]). Presence of a lipid-rich necrotic core and calcification were not associated with stroke or CHD. The presence of IPH in the carotid atherosclerotic plaque is an independent risk factor for stroke and CHD. These findings indicate the promise of IPH as a marker of plaque vulnerability in healthy persons with subclinical atherosclerosis.
Acute-on-chronic liver failure in East Asia: an underestimated issue with limited data
Authors: Zhujun Cao, Qing Xie
Journal: Gut (2021)

Mezzano et al reported that in a meta-analysis of 30 selected cohort studies in which acute-on-chronic liver failure (ACLF) was defined using the European Association for the Study of the Liver-Chronic Liver Failure Consortium (EASL-CLIF-C) criteria, the global prevalence of ACLF was estimated to be 35%, being lowest in East Asia (15%).1 This reported prevalence in East Asia was unexpectedly low, contradicting our clinical observations in this region. Several concerns arise when interpreting the results of this study. First, there were overlaps in the two cohorts from China …
P48.09 Anlotinib Plus Etoposide and Carboplatin as First-Line Treatment for Extensive-Stage Small Cell Lung Cancer: A Single Arm Phase II Trial
Authors: B. Han, W. Zhang, B. Zhang, Y. Chen, Y. Zhang, Y. Lou, Y. Dong, F. Qian, W. Zhou, Z. Yang
Journal: Journal of Thoracic Oncology (2021)
GPR43 deficiency protects against podocyte insulin resistance in diabetic nephropathy through the restoration of AMPKα activity
Authors: Jian Lu, Pei Pei Chen, Jia Xiu Zhang, Xue Qi Li, Gui Hua Wang, Ben Yin Yuan, Si Jia Huang, Xiao Qi Liu, Ting Ting Jiang, Meng Ying Wang, Wen Tao Liu, Xiong Zhong Ruan, Bi Cheng Liu, Kun Ling Ma
Journal: Theranostics (2021)

Rationale: Albuminuria is an early clinical feature in the progression of diabetic nephropathy (DN). Podocyte insulin resistance is a main cause of podocyte injury, playing crucial roles by contributing to albuminuria in early DN. G protein-coupled receptor 43 (GPR43) is a metabolite sensor modulating the cell signalling pathways to maintain metabolic homeostasis. However, the roles of GPR43 in podocyte insulin resistance and its potential mechanisms in the development of DN are unclear. Methods: The experiments were conducted by using kidney tissues from biopsied DN patients, streptozotocin (STZ) induced diabetic mice with or without global GPR43 gene knockout, diabetic rats treated with broad-spectrum oral antibiotics or fecal microbiota transplantation, and cell culture model of podocytes. Renal pathological injuries were evaluated by periodic acid-schiff staining and transmission electron microscopy. The expression of GPR43 with other podocyte insulin resistance related molecules was checked by immunofluorescent staining, real-time PCR, and Western blotting. Serum acetate level was examined by gas chromatographic analysis. The distribution of gut microbiota was measured by 16S ribosomal DNA sequencing with faeces. Results: Our results demonstrated that GPR43 expression was increased in kidney samples of DN patients, diabetic animal models, and high glucose-stimulated podocytes. Interestingly, deletion of GPR43 alleviated albuminuria and renal injury in diabetic mice. Pharmacological inhibition and knockdown of GPR43 expression in podocytes increased insulin-induced Akt phosphorylation through the restoration of adenosine 5'-monophosphate-activated protein kinase α (AMPKα) activity. This effect was associated with the suppression of AMPKα activity through post-transcriptional phosphorylation via the protein kinase C-phospholipase C (PKC-PLC) pathway. Antibiotic treatment-mediated gut microbiota depletion, and faecal microbiota transplantation from the healthy donor controls substantially improved podocyte insulin sensitivity and attenuated glomerular injury in diabetic rats accompanied by the downregulation of the GPR43 expression and a decrease in the level of serum acetate. Conclusion: These findings suggested that dysbiosis of gut microbiota-modulated GPR43 activation contributed to albuminuria in DN, which could be mediated by podocyte insulin resistance through the inhibition of AMPKα activity.
P04.04 Thrombus Formation at Stump of Pulmonary Vein after Pulmonary Lobectomy: A Prospective Multi-institutional Study
Authors: T. Yamamoto, K. Tanaka, Y. Sakairi, H. Wada, H. Suzuki, T. Nakajima, T. Iwata, T. Iizasa, T. Tagawa, S. Yoshida, R. Takemura, Y. Sato, I. Yoshino
Journal: Journal of Thoracic Oncology (2021)
CT colonography remains an important test for colorectal cancer
Authors: Nicholas Ewin Burr, Andrew Plumb, Ruchit Sood, Bjorn Rembacken, Damian J M Tolan
Journal: Gut (2021)

We read with interest the recent article by Cash et al comparing colon capsule (CCE) and CT colonography (CTC) with optical colonoscopy (OC) for detecting colonic polyps and colorectal cancer (CRC) in a screening population.1 The study reports low CTC detection rates for ≥6 mm and ≥10 mm polyps of only 8.6% and 6.3%, respectively. These were much lower than the detection rates seen for CCE and OC. These results contradict larger trials, where the performance of CTC and OC tests are similar. The Dutch COCOS randomised controlled trial (RCT) in a screening population ultimately reported identical advanced neoplasia detection rates for CTC and OC.2 3 The UK SIGGAR RCT reported identical detection rates of 11% for large polyps or CRC.4 Earlier studies from the USA also support the use of CTC.5 6 The 8.6% …
Routine KIT p.D816V screening identifies clonal mast cell disease in patients with Hymenoptera allergy regularly missed using baseline tryptase levels alone
Authors: Julij Šelb, Matija Rijavec, Renato Eržen, Mihaela Zidarn, Peter Kopač, Matevž Škerget, Nissera Bajrović, Ajda Demšar Luzar, Young Hwan Park, Yihui Liu, Vladka Čurin Šerbec, Samo Zver, Mitja Košnik, Jonathan J. Lyons, Peter Korošec
Journal: Journal of Allergy and Clinical Immunology (2021)
P09.17 Changes in the Management of Patients Having Radical Radiotherapy in the UK During the COVID-19 Pandemic (COVID-RT Lung)
Authors: K. Banfill, G. Price, C. Peedell, K. Harland, C. Powell, N. Panakis, K. Thippu Jayaprakash, D. Mokhtar, M. Hatton, C. Faivre-Finn
Journal: Journal of Thoracic Oncology (2021)
ILC3s control splenic cDC homeostasis via lymphotoxin signaling
Authors: Matthias Vanderkerken, Antonio P. Baptista, Marco De Giovanni, Satoshi Fukuyama, Robin Browaeys, Charlotte L. Scott, Paula S. Norris, Gerard Eberl, James P. Di Santo, Eric Vivier, Yvan Saeys, Hamida Hammad, Jason G. Cyster, Carl F. Ware, Alexei V. Tumanov, Carl De Trez, Bart N. Lambrecht
Journal: The Journal of Experimental Medicine (2021)

The spleen contains a myriad of conventional dendritic cell (cDC) subsets that protect against systemic pathogen dissemination by bridging antigen detection to the induction of adaptive immunity. How cDC subsets differentiate in the splenic environment is poorly understood. Here, we report that LTα1β2-expressing Rorgt+ ILC3s, together with B cells, control the splenic cDC niche size and the terminal differentiation of Sirpα+CD4+Esam+ cDC2s, independently of the microbiota and of bone marrow pre-cDC output. Whereas the size of the splenic cDC niche depended on lymphotoxin signaling only during a restricted time frame, the homeostasis of Sirpα+CD4+Esam+ cDC2s required continuous lymphotoxin input. This latter property made Sirpα+CD4+Esam+ cDC2s uniquely susceptible to pharmacological interventions with LTβR agonists and antagonists and to ILC reconstitution strategies. Together, our findings demonstrate that LTα1β2-expressing Rorgt+ ILC3s drive splenic cDC differentiation and highlight the critical role of ILC3s as perpetual regulators of lymphoid tissue homeostasis.
Isolation and characterization of human embryonic stem cell-derived heart field-specific cardiomyocytes unravels new insights into their transcriptional and electrophysiological profiles
Authors: Arash Pezhouman, James L Engel, Ngoc B Nguyen, Rhys J P Skelton, William Blake Gilmore, Rong Qiao, Debashis Sahoo, Peng Zhao, David A Elliott, Reza Ardehali
Journal: Cardiovascular Research (2021)

We prospectively isolate and characterize first and second heart field- and nodal-like cardiomyocytes using a double reporter line from human embryonic stem cells. Our double reporter line utilizes two important transcription factors in cardiac development, TBX5 and NKX2-5. TBX5 expression marks first heart field progenitors and cardiomyocytes while NKX2-5 is expressed in nearly all myocytes of the developing heart (excluding nodal cells). We address the shortcomings of prior work in the generation of heart field-specific cardiomyocytes from induced pluripotent stem cells and provide a comprehensive early developmental transcriptomic as well as electrophysiological analyses of these three populations.Transcriptional, immunocytochemical, and functional studies support the cellular identities of isolated populations based on the expression pattern of NKX2-5 and TBX5. Importantly, bulk and single-cell RNA sequencing analyses provide evidence of unique molecular signatures of isolated first and second heart field cardiomyocytes, as well as nodal-like cells. Extensive electrophysiological analyses reveal dominant atrial action potential phenotypes in first and second heart fields in alignment with our findings in single-cell RNA sequencing. Lastly, we identify two novel surface markers, POPDC2 and CORIN, that enable purification of cardiomyocytes and first heart field cardiomyocytes, respectively.We describe a high-yield approach for isolation and characterization of human embryonic stem cell-derived heart field-specific and nodal-like cardiomyocytes. Obtaining enriched populations of these different cardiomyocyte subtypes increases the resolution of gene expression profiling during early cardiogenesis, arrhythmia modelling, and drug screening. This paves the way for the development of effective stem cell therapy to treat diseases that affect specific regions of the heart- or chamber-specific congenital heart defects.
Uhambo — Twists and Turns on the Journey to an Efficacious HIV-1 Vaccine
Authors: Mark B. Feinberg
Journal: New England Journal of Medicine (2021)

As we approach the 40th anniversary of the first reported cases of AIDS, the need for a vaccine to prevent HIV infection remains imperative. The absence of natural immunity to HIV, coupled with its genetic diversity and ability to establish infection that is resistant to host immunologic clearance, have impeded elucidation of immunologic mechanisms to protect against incident infection. Lacking immunologic markers of protection to guide vaccine development,1 researchers have predicated large-scale efficacy trials on empirical approaches that seek to identify specific immune responses that are correlated with protection and build on the responses that are associated with even modest . . .
Association Between the Proportion of Black Patients Cared for at Hospitals and Financial Penalties Under Value-Based Payment Programs
Authors: Rahul Aggarwal, J. Gmerice Hammond, Karen E. Joynt Maddox, Robert W. Yeh, Rishi K. Wadhera
Journal: JAMA (2021)

This study evaluates whether US hospitals with mostly Black patients are more likely than other hospitals to have penalties associated with Centers for Medicare &amp; Medicaid Services (CMS) value-based payment programs.
P35.23 Integrated Analysis of Genomic and Immunological Features in Lung Adenocarcinoma with Micropapillary Component
Authors: S. Zhang, Y. Xu, P. Zhao, H. Bao, X. Wang, R. Liu, R. Xu, J. Xiang, H. Jiang, J. Yan, X. Wu, Y. Shao, J. Liang, Q. Wu, Z. Zhang, S. Lu, S. Ma
Journal: Journal of Thoracic Oncology (2021)
Diabetes fuels periodontal lesions via GLUT1-driven macrophage inflammaging
Authors: Qian Wang, Lulingxiao Nie, Pengfei Zhao, Xinyi Zhou, Yi Ding, Qianming Chen, Qi Wang
Journal: International Journal of Oral Science (2021)

Abstract Hyperglycemia induces chronic low-grade inflammation (inflammaging), which is a newly identified contributor to diabetes-related tissue lesions, including the inflammatory bone loss in periodontitis. It is also a secondary senescent pattern mediated by an increased burden of senescent cells and senescence-associated secretory phenotype (SASP). Macrophage is a key SASP-spreading cell and may contribute to the maintenance of SASP response in the periodontal microenvironment. Using a transgenic diabetic model (BLKS/J- Lepr db / lepr db mice) we identified striking senescence of the periodontium in young (18-wk)-diabetic mice accompanied by amassed p16 + -macrophages and enhanced early SASP response. Exposed to high glucose in vitro, bone marrow-derived macrophage (BMDM) revealed a strong GLUT1 mRNA response driving the elevated-glucose uptake. GLUT1 is a representative and facilitative glucose transporter in macrophages with potential roles in hyperglycemia-induced inflammation. In this study, both GLUT1 and the downstream GTPase Rheb expression upregulated in the gingiva of diabetic mice with impaired condition. Furthermore, SASP release and p16/p21 signaling were proven to be triggered by mTOR phosphorylation in BMDM and antagonized by restricting glucose uptake in GLUT1 − /− BMDM. Taken together, our findings suggest that elevated-GLUT1 sensor responded to high glucose is important for macrophage senescence and SASP response, generated as a result of hyperglycemia, and it is a potential molecular mechanism for the exacerbation of periodontitis in diabetes.
Crowdsourcing digital health measures to predict Parkinson’s disease severity: the Parkinson’s Disease Digital Biomarker DREAM Challenge
Authors: Solveig K. Sieberts, Jennifer Schaff, Marlena Duda, Bálint Ármin Pataki, Ming Sun, Phil Snyder, Jean-Francois Daneault, Federico Parisi, Gianluca Costante, Udi Rubin, Peter Banda, Yooree Chae, Elias Chaibub Neto, E. Ray Dorsey, Zafer Aydın, Aipeng Chen, Laura L. Elo, Carlos Espino, Enrico Glaab, Ethan Goan, Fatemeh Noushin Golabchi, Yasin Görmez, Maria K. Jaakkola, Jitendra Jonnagaddala, Riku Klén, Dongmei Li, Christian McDaniel, Dimitri Perrin, Thanneer M. Perumal, Nastaran Mohammadian Rad, Erin Rainaldi, Stefano Sapienza, Patrick Schwab, Nikolai Shokhirev, Mikko S. Venäläinen, Gloria Vergara-Diaz, Yuqian Zhang, Avner Abrami, Aditya Adhikary, Carla Agurto, Sherry Bhalla, Halil Bilgin, Vittorio Caggiano, Jun Cheng, Eden Deng, Qiwei Gan, Rajan Girsa, Zhi Han, Stephen Heisig, Kun Huang, Samad Jahandideh, Wolfgang Kopp, Christoph F. Kurz, Gregor Lichtner, Raquel Norel, G. P. S. Raghava, Tavpritesh Sethi, Nicholas Shawen, Vaibhav Tripathi, Matthew Tsai, Tongxin Wang, Yi Wu, Jie Zhang, Xinyu Zhang, Yuanjia Wang, Yuanfang Guan, Daniela Brunner, Paolo Bonato, Lara M. Mangravite, Larsson Omberg
Journal: npj Digital Medicine (2021)

Abstract Consumer wearables and sensors are a rich source of data about patients’ daily disease and symptom burden, particularly in the case of movement disorders like Parkinson’s disease (PD). However, interpreting these complex data into so-called digital biomarkers requires complicated analytical approaches, and validating these biomarkers requires sufficient data and unbiased evaluation methods. Here we describe the use of crowdsourcing to specifically evaluate and benchmark features derived from accelerometer and gyroscope data in two different datasets to predict the presence of PD and severity of three PD symptoms: tremor, dyskinesia, and bradykinesia. Forty teams from around the world submitted features, and achieved drastically improved predictive performance for PD status (best AUROC = 0.87), as well as tremor- (best AUPR = 0.75), dyskinesia- (best AUPR = 0.48) and bradykinesia-severity (best AUPR = 0.95).
Abstract 17461: Efficacy of Long-Term Monitoring on Detecting Critical Cardiac Arrhythmias
Authors: Ruhi Mahajan, Alok Gambhir, Sameer Adumala
Journal: Circulation (2020)

Introduction: The ambulatory continuous ECG monitors can provide a comprehensive cardiac assessment in outpatient settings. Extended cardiac monitoring is often needed by physicians to assess the efficacy of treatment, evaluate symptoms, and to stratify patients at risk. In this study, we compare the impact of outpatient cardiac monitoring between 1-14 days and 15-30 days. Method: A retrospective analysis was done on ECG data collected from 2,679 patients using Zywie ECG monitors (Zywie, Inc., Georgia). These patients were monitored for 14-30 days. We evaluated three arrhythmias in this study: i) Atrial fibrillation (AF) of duration &gt;15s ii) Ventricular tachycardia (VT) consisting of more than 3 heartbeats iii) Pause of duration &gt;3s. We analyzed the first occurrence of arrhythmia episodes in every patient during their monitoring period. We identified at least one episode of AF in 486 patients, VT in 106 patients, and pause in 78 patients. Results: The incidence of the first episode of AF, VT, and pause was observed after 14 days of monitoring in 15.8%, 28.3%, and 23.1% patients, respectively (Figure 1). Furthermore, among the VT episodes, 85.3% episodes had a duration between 1-10s and 14.7% with a duration &gt;10s. Similarly, 76% of identified pauses had a duration between 3-4s, 12% between 4-5s, and 12% with a duration &gt;5s. Conclusion: The results demonstrate the incremental diagnostic yield of critical arrhythmic events when the monitoring is extended beyond 14 days. This study suggests that long-term outpatient monitoring can provide better diagnosis, especially for patients at a higher risk of developing critical arrhythmias.