tbuckley/cabot-search huggingface dataset:
Diagnostic Accuracy of Endobronchial Optical Coherence Tomography for the Microscopic Diagnosis of Usual Interstitial Pneumonia
Authors: Sreyankar Nandy, Rebecca A. Raphaely, Ashok Muniappan, Angela Shih, Benjamin W. Roop, Amita Sharma, Colleen M. Keyes, Thomas V. Colby, Hugh G. Auchincloss, Henning A. Gaissert, Michael Lanuti, Christopher R. Morse, Harald C. Ott, John C. Wain, Cameron D. Wright, Maria L. Garcia-Moliner, Maxwell L. Smith, Paul A. VanderLaan, Sarita R. Berigei, Mari Mino-Kenudson, Nora K. Horick, Lloyd L. Liang, Diane L. Davies, Margit V. Szabari, Peter Caravan, Benjamin D. Medoff, Andrew M. Tager, Melissa J. Suter, Lida P. Hariri
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Early, accurate diagnosis of interstitial lung disease (ILD) informs prognosis and therapy, especially in idiopathic pulmonary fibrosis (IPF). Current diagnostic methods are imperfect. High-resolution computed tomography has limited resolution, and surgical lung biopsy (SLB) carries risks of morbidity and mortality. Endobronchial optical coherence tomography (EB-OCT) is a low-risk, bronchoscope-compatible modality that images large lung volumes in vivo with microscopic resolution, including subpleural lung, and has the potential to improve the diagnostic accuracy of bronchoscopy for ILD diagnosis. Objectives: We performed a prospective diagnostic accuracy study of EB-OCT in patients with ILD with a low-confidence diagnosis undergoing SLB. The primary endpoints were EB-OCT sensitivity/specificity for diagnosis of the histopathologic pattern of usual interstitial pneumonia (UIP) and clinical IPF. The secondary endpoint was agreement between EB-OCT and SLB for diagnosis of the ILD fibrosis pattern. Methods: EB-OCT was performed immediately before SLB. The resulting EB-OCT images and histopathology were interpreted by blinded, independent pathologists. Clinical diagnosis was obtained from the treating pulmonologists after SLB, blinded to EB-OCT. Measurements and Main Results: We enrolled 31 patients, and 4 were excluded because of inconclusive histopathology or lack of EB-OCT data. Twenty-seven patients were included in the analysis (16 men, average age: 65.0 yr): 12 were diagnosed with UIP and 15 with non-UIP ILD. Average FVC and DlCO were 75.3% (SD, 18.5) and 53.5% (SD, 16.4), respectively. Sensitivity and specificity of EB-OCT was 100% (95% confidence interval, 75.8–100.0%) and 100% (79.6–100%), respectively, for both histopathologic UIP and clinical diagnosis of IPF. There was high agreement between EB-OCT and histopathology for diagnosis of ILD fibrosis pattern (weighted κ: 0.87 [0.72–1.0]). Conclusions: EB-OCT is a safe, accurate method for microscopic ILD diagnosis, as a complement to high-resolution computed tomography and an alternative to SLB.
Axioms and postulates: Finding the right match through logical inference
Authors: Niccolò Negro
Journal: Behavioral and Brain Sciences (2022)

Abstract Merker et al. argue that integrated information theory (IIT) is not a theory of consciousness because the IIT formalism does not match phenomenology. I argue that the authors ultimately fail to articulate the problem of the inference of the postulates from the axioms. I suggest a different version of this problem, and argue that this can help rethink IIT's potential for consciousness science.
Colorectal Cancer Develops Inherent Radiosensitivity That Can Be Predicted Using Patient-Derived Organoids
Authors: Kuo-Shun Hsu, Mohammad Adileh, Maria Laura Martin, Vladimir Makarov, Jiapeng Chen, Chao Wu, Sahra Bodo, Stefan Klingler, Charles-Etienne Gabriel Sauvé, Bryan C. Szeglin, J. Joshua Smith, Zvi Fuks, Nadeem Riaz, Timothy A. Chan, Makoto Nishimura, Philip B. Paty, Richard Kolesnick
Journal: Cancer Research (2022)

Abstract Identifying colorectal cancer patient populations responsive to chemotherapy or chemoradiation therapy before surgery remains a challenge. Recently validated mouse protocols for organoid irradiation employ the single hit multi-target (SHMT) algorithm, which yields a single value, the D0, as a measure of inherent tissue radiosensitivity. Here, we translate these protocols to human tissue to evaluate radioresponsiveness of patient-derived organoids (PDO) generated from normal human intestines and rectal tumors of patients undergoing neoadjuvant therapy. While PDOs from adenomas with a logarithmically expanded Lgr5+ intestinal stem cell population retain the radioresistant phenotype of normal colorectal PDOs, malignant transformation yields PDOs from a large patient subpopulation displaying marked radiosensitivity due to reduced homologous recombination–mediated DNA repair. A proof-of-principle pilot clinical trial demonstrated that rectal cancer patient responses to neoadjuvant chemoradiation, including complete response, correlate closely with their PDO D0 values. Overall, upon transformation to colorectal adenocarcinoma, broad radiation sensitivity occurs in a large subset of patients that can be identified using SHMT analysis of PDO radiation responses. Significance: Analysis of inherent tissue radiosensitivity of patient-derived organoids may provide a readout predictive of neoadjuvant therapy response to radiation in rectal cancer, potentially allowing pretreatment stratification of patients likely to benefit from this approach.
A Comparison of 18F-PSMA-1007 and 64Cu-PSMA in 2 Patients With Metastatic Prostate Cancer
Authors: David R. Cardoza-Ochoa, Belén Rivera-Bravo
Journal: Clinical Nuclear Medicine (2021)

Abstract 18 F–prostate-specific membrane antigen (PSMA) 1007 is one of the most promising radiotracers for PET imaging in prostate cancer, minimal urinary clearance, and higher spatial resolution, which are the most outstanding features. PSMA can also be labeled with 64 Cu, offering a longer half-life and different resolution imaging. We present images of metastatic prostate cancer in two patients, where 64 Cu-PSMA PET/CT was performed one day after 18 F-PSMA-1007 PET/CT. In the two patients, both radiotracers provided high image quality and a similar range of detection for metastatic lesions.
Abstract P055: Reweighting Diet Quality Score Components Strengthens All-cause Mortality Risk Associations
Authors: Haley W Parker, Brietta Oaks, Ashley Buchanan, Maya Vadiveloo
Journal: Circulation (2022)

Introduction: The Dietary Patterns Methods Project concluded that various high-quality diets comparably reduce mortality, but it is unclear whether some individual components are more integral to risk reduction than reflected in current indexes. Thus, we examined mortality risk associated with standard vs. modified diet quality weighting schemes. Hypothesis: High scores on a data-driven (vs. standard) diet quality weighting scheme will be associated with stronger mortality risk reduction. Methods: National Health and Nutrition Examination and Survey III (1988-94) data from 10,789 non-pregnant adults ≥20 yrs. with valid mortality and dietary data were analyzed. Diet quality was scored from a single 24-hr recall with the Healthy Eating Index (HEI)-2015. The standard HEI 9 adequacy and 4 moderation components were reweighted creating: 1) the Key Facets HEI with fruits, vegetables, whole grains, and plant proteins equally weighted, emphasizing components present in virtually all diet quality indexes; and 2) the Machine Learning (ML)-weighted HEI where data-driven LASSO models determined relative component contribution to all-cause mortality associations. For all 3 HEIs, energy-residualized scores were ranked and assigned to quintiles (Q); covariate-adjusted sex-stratified Cox models with attained age as the timescale assessed all-cause and CVD mortality risk associations across HEI Qs. Results: In all 3 HEIs, high (Q5 vs. Q1) scores were associated with reduced all-cause mortality risk, ranging from 16% to 38%. The ML-weighted HEI had the strongest risk reduction (38% in women, 23% in men), 7 to 8% lower than standard HEI scores. Key Facets (vs. standard) scores yielded equivalent risk in men (16%) and 2% greater risk reduction in women. There was no association between any of the HEI scores and CVD mortality. Conclusions: All-cause mortality risk associations were 7-8% stronger in the ML-weighted vs. standard HEI. Findings suggest data-driven diet quality weighting schemes warrant further examination.
Characteristics of publicly available skin cancer image datasets: a systematic review
Authors: David Wen, Saad M Khan, Antonio Ji Xu, Hussein Ibrahim, Luke Smith, Jose Caballero, Luis Zepeda, Carlos de Blas Perez, Alastair K Denniston, Xiaoxuan Liu, Rubeta N Matin
Journal: The Lancet Digital Health (2021)

Publicly available skin image datasets are increasingly used to develop machine learning algorithms for skin cancer diagnosis. However, the total number of datasets and their respective content is currently unclear. This systematic review aimed to identify and evaluate all publicly available skin image datasets used for skin cancer diagnosis by exploring their characteristics, data access requirements, and associated image metadata. A combined MEDLINE, Google, and Google Dataset search identified 21 open access datasets containing 106 950 skin lesion images, 17 open access atlases, eight regulated access datasets, and three regulated access atlases. Images and accompanying data from open access datasets were evaluated by two independent reviewers. Among the 14 datasets that reported country of origin, most (11 [79%]) originated from Europe, North America, and Oceania exclusively. Most datasets (19 [91%]) contained dermoscopic images or macroscopic photographs only. Clinical information was available regarding age for 81 662 images (76·4%), sex for 82 848 (77·5%), and body site for 79 561 (74·4%). Subject ethnicity data were available for 1415 images (1·3%), and Fitzpatrick skin type data for 2236 (2·1%). There was limited and variable reporting of characteristics and metadata among datasets, with substantial under-representation of darker skin types. This is the first systematic review to characterise publicly available skin image datasets, highlighting limited applicability to real-life clinical settings and restricted population representation, precluding generalisability. Quality standards for characteristics and metadata reporting for skin image datasets are needed.
Portal Biliopathy and Cavernous Transformation of the Portal Vein Revealed by 68Ga-FAPI PET/CT
Authors: Rongxi Wang, Xuehan Gao, Xianlin Han, Zhaohui Zhu, Xiaodong He
Journal: Clinical Nuclear Medicine (2021)

Abstract A 47-year-old man presented with right upper abdominal pain for 1 month. Contrast-enhanced CT revealed hilar bile duct stenosis with dilatation of the intrahepatic bile ducts, and his serum CA19-9 and CA242 levels were significantly elevated. 18 F-FDG and 68 Ga-FAPI PET/CT were performed for differential diagnosis. 18 F-FDG PET/CT showed only mild FDG uptake in the hepatic hilum. Astonishingly, in 68 Ga-FAPI PET/CT, intense radioactivity was presented on the same region, which indicated massive fibroblasts aggregation in hepatic hilum. The patient was finally diagnosed as portal biliopathy caused by cavernous transformation of the portal vein.
Oxidized Low-Density Lipoprotein Links Hypercholesterolemia and Bladder Cancer Aggressiveness by Promoting Cancer Stemness
Authors: Lin Yang, Jingya Sun, Meiqian Li, Yiming Long, Dianzheng Zhang, Hongqian Guo, Ruimin Huang, Jun Yan
Journal: Cancer Research (2021)

Abstract Hypercholesterolemia is a prevalent metabolic disorder that has been implicated in the development of steroid-targeted cancers. However, the link between hypercholesterolemia and urinary bladder cancer (UBC), a non–steroid-targeted cancer, remains unresolved. Here we show that diet-induced and Ldlr deficiency–induced hypercholesterolemia enhances both UBC stemness and progression. Inhibition of intestinal cholesterol absorption by ezetimibe reversed diet-induced hypercholesterolemia and cancer stemness. As a key component in hypercholesterolemic sera, oxidized low-density lipoprotein (ox-LDL), but not native low-density lipoprotein-cholesterol or metabolite 27-hydroxycholesterol, increased cancer stemness through its receptor CD36. Depletion of CD36, ectopic expression of an ox-LDL binding–disabled mutant form of CD36(K164A), and the neutralization of ox-LDL and CD36 via neutralizing antibodies all reversed ox-LDL–induced cancer stemness. Mechanistically, ox-LDL enhanced the interaction of CD36 and JAK2, inducing phosphorylation of JAK2 and subsequently activating STAT3 signaling, which was not mediated by JAK1 or Src in UBC cells. Finally, ox-LDL levels in serum predicted poor prognosis, and the ox-LDLhigh signature predicted worse survival in patients with UBC. These findings indicate that ox-LDL links hypercholesterolemia with UBC progression by enhancing cancer stemness. Lowering serum ox-LDL or targeting the CD36/JAK2/STAT3 axis might serve as a potential therapeutic strategy for UBCs with hypercholesterolemia. Moreover, elevated ox-LDL may serve as a biomarker for UBC. Significance: This study demonstrates how hypercholesterolemia-induced oxidized LDL promotes urinary bladder cancer stemness via a CD36/STAT3 signaling axis, highlighting these factors as biomarkers and potential therapeutic targets of aggressive disease.
Abstract P174: Toxic Heavy Metals Are Associated With Increased Risk Of Cardiometabolic Disorders
Authors: Emmanuel I Agaba, Tamunoseledia L Brown, Sally N Adebamowo
Journal: Circulation (2022)

Background: Cardiometabolic disorders (CMDs) are the leading cause of morbidity and mortality globally. For decades, heart disease, stroke, diabetes mellitus (DM) and chronic kidney disease (CKD) have remained leading causes of death for both men and women in the US. Identification of preventable risk factors is needed to help ameliorate the burden of CMDs. While exposure to toxic heavy metals may contribute to the risk of CMDs, the results of studies examining their association have been inconsistent. Objective: To evaluate the association between blood levels of toxic heavy metals - cadmium, lead and mercury - and coronary heart disease (CHD), stroke, CKD, DM, metabolic syndrome (MetS), dyslipidemia, hypertension, and central obesity in a representative sample of US adults. Methods: We analyzed data from 36,862 adults aged 20 to 80 years in the US National Health and Nutrition Examination Survey (NHANES) 1999 to 2018 cycles. We dichotomized the levels of each metal using the median levels of the individuals without the outcomes, as the cut point. Results: A total of 816 adults had CHD, 1,251 had stroke, 653 had CKD, 6,341 had DM, 6,692 had IR, 18,251 had MetS, 3,597 had dyslipidemia, 20,024 had hypertension and 20,388 had central obesity. In models adjusted for sociodemographic factors and underlying medical diagnoses, we found that cadmium levels were positively associated with CHD [odds ratio: 1.28 (95% confidence interval: 1.06 - 1.55)], stroke [1.21 (1.03 - 1.41)], CKD [1.62 (1.51 - 1.74)] and dyslipidemia [1.17 (1.08 - 1.28)]; and inversely associated with DM [0.65 (0.60 - 0.70)], MetS [0.77 (0.72 - 0.82)] and central obesity [0.72 (0.68 - 0.76)]. In similarly adjusted models, lead levels were positively associated with CKD [1.90 (1.77 - 2.04)] and dyslipidemia [1.18 (1.08 - 1.12)]; and inversely associated with DM [0.51 (0.48 - 0.55)] and central obesity [0.72 (0.68 - 0.76)]. Mercury was positively associated with stroke [1.27 (1.12 - 1.45)], CKD [2.38 (2.23 - 2.54)], MetS [1.14 (1.08 - 1.21)], dyslipidemia [1.09 (1.01 - 1.17)], hypertension [1.19 (1.13 - 1.25)] and central obesity [1.10 (1.04 - 1.15)]. Conclusion: The results of this large cross-sectional analyses support the findings that cadmium, lead and mercury are significantly associated with several CMDs.
Abstract MP74: The Effect Of BMI On Metabolic Traits Is Mediated By A Novel Diabetes Marker
Authors: Ruiyuan Zhang, Xiao Sun, Zhijie Huang, Yang Pan, Adrianna Westbrook, Shengxu Li, Lydia A Bazzano, Wei Chen, Jiang He, Tanika N Kelly, Changwei Li
Journal: Circulation (2022)

Introduction: 2-aminoadipic acid (2-AAA) secreted during adipogenesis is a novel marker for diabetes. Hypothesis: 2-AAA mediates the associations between body mass index (BMI) and metabolic measures, and the effect of 2-AAA can be modified by environmental factors. Methods: We performed cross-sectional analyses among all 1,252 participants in the Bogalusa Heart Study 2016 survey. Serum 2-AAA and 110 xenobiotics were profiled through untargeted UPLC-MS/MS. Mediation effects of 2-AAA on the associations between BMI and metabolic traits were estimated by comparing the BMI-traits associations before and after controlling for 2-AAA. P value for a mediation effect was estimated by 1,000,000 times Monte-Carlo simulation. We further performed interaction analyses to identify xenobiotics that modify the effect of 2-AAA on metabolic traits. Age, sex, race, education, smoking, drinking, and use of lipid, glucose, or blood pressure lowering medications were adjusted in all analyses. Results: After Bonferroni correction, 2-AAA significantly mediated the association of BMI with high density lipoprotein cholesterol (HDLC) (beta= -0.03 mg/dL, p=1.70х10 -4 ), log transformed triglyceride (lgTG) (beta=0.002, p=1х10 -6 ), fasting glucose (beta=0.05 mg/dL, p=2.87х10 -3 ), and hemoglobin A1c (HbA1c) (beta=0.002%, p=8.50х10 -4 ). The proportions of associations explained by 2-AAA ranged from 5.12% for HDLC to 13.23% for lgTG. When stratified by race and medication usage, the mediation effects were stronger among Whites and those not taking medications (P for interaction &lt;0.05). Furthermore, 14 xenobiotics modified the associations of 2-AAA with HDLC/lgTG or glucose/HbA1c (Table), e.g., the association between 2-AAA and HbA1c was much stronger among participants with higher levels of 4-acetaminophen sulfate (P for interaction=3.03х10 -5 ), a metabolite of commonly used over-the-counter analgesics. Conclusion: 2-AAA mediated the effect of BMI on metabolic traits, and this effect was modified by environmental factors.
Social robots as depictions of social agents
Authors: Herbert H. Clark, Kerstin Fischer
Journal: Behavioral and Brain Sciences (2022)

Abstract Social robots serve people as tutors, caretakers, receptionists, companions, and other social agents. People know that the robots are mechanical artifacts, yet they interact with them as if they were actual agents. How is this possible? The proposal here is that people construe social robots not as social agents per se , but as depictions of social agents. They interpret them much as they interpret ventriloquist dummies, hand puppets, virtual assistants, and other interactive depictions of people and animals. Depictions as a class consist of three physical scenes with part-by-part mappings between them: (a) a base scene (the raw physical artifact), (b) the depiction proper (the artifact construed as a depiction), and (c) the scene depicted (the scene people are to imagine). With social robots, evidence shows people form the same three scenes plus mappings: They perceive the raw machinery of a robot, construe it as a depiction of a character, and, using the depiction as a guide, engage in the pretense that they are interacting with the character depicted. With social robots, people also recognize three classes of agents – the characters depicted, the intended recipients of the depictions (those who view or interact with the robots), and the authorities responsible for the robots (the designers, makers, and owners). Construing social robots as depictions, we argue, accounts for many phenomena not covered by alternative models.
Abstract 029: Proteins Linking Chronic Kidney Disease To Incident Heart Failure In Adults With Chronic Kidney Disease: The Atherosclerosis Risk In Communities Study
Authors: Leo F Buckley, Pranav Dorbala, Morgan Grams, Josef Coresh, Kuni Matsushita, Brian Claggett, Ryan Demmer, Christie M Ballantyne, Ron C Hoogeveen, Bing Yu, Amil M Shah
Journal: Circulation (2022)

Introduction: Decreased estimated glomerular filtration rate (eGFR), a kidney dysfunction marker, associates independently with an increased incident heart failure (HF) risk. Identifying mechanisms linking kidney dysfunction to incident HF may reveal potential therapeutic targets. We performed a proteome-wide analysis to identify eGFR-related pathways associated with incident HF. Methods: We studied ARIC participants at Visit 3 (n=10412) and Visit 5 (n=4841) who were free of HF and had aptamer-based proteomic data (SomaLogic, Boulder, CO). Multivariable linear regression models identified proteins associated with eGFR at Visits 3 and 5 at Bonferroni-adjusted P &lt; 1x10 -5 . Incident HF associations were assessed for eGFR-related proteins with multivariable Cox proportional hazards regression models at Bonferroni-adjusted P &lt; 1x10 -5 . All regression models were adjusted for demographics, hypertension, diabetes, coronary artery disease, atrial fibrillation, smoking status, eGFR and albuminuria. Pathway analysis (g:Profiler/KEGG) was performed using proteins associated with incident HF at a false discovery rate (FDR) of &lt; 0.05. Results: The mean age at Visit 3 was 62±6 years, 52% were women, 22% were Black, and 1127 incident HF events occurred post-Visit 3 (median follow-up: 14.8 years). The mean age at Visit 5 was 76±5 years, 58% were women, 18% were Black, and 488 incident HF events occurred post-Visit 5 (median follow-up: 7.2 years). One thousand and seventy-three proteins associated with eGFR at Visits 3 and 5 (P &lt; 1x10 -5 ). Of these eGFR-related proteins, 18 associated with incident HF at Visits 3 and 5 (P &lt; 5x10 -5 ) ( Figure ). Complement and coagulation cascades and cytokine-cytokine receptor interaction pathways were enriched within the 226 proteins associated with incident HF at FDR &lt; 0.05. Conclusions: Kidney dysfunction-related changes in innate immunity and thrombosis associate with an increased risk of incident HF.
Hourly Kinetics of Critical Organ Dysfunction in Extremely Preterm Infants
Authors: Orlyn C. Lavilla, Khyzer B. Aziz, Allison C. Lure, Daniel Gipson, Diomel de la Cruz, James L. Wynn
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Use of severity of illness scores to classify patients for clinical care and research is common outside of the neonatal ICU. Extremely premature (<29 weeks’ gestation) infants with extremely low birth weight (<1,000 g) experience significant mortality and develop severe pathology during the protracted birth hospitalization. Objectives: To measure at high resolution the changes in organ dysfunction that occur from birth to death or discharge home by gestational age and time, and among extremely preterm infants with and without clinically meaningful outcomes using the neonatal sequential organ failure assessment score. Methods: A single-center, retrospective, observational cohort study of inborn, extremely preterm infants with extremely low birth weight admitted between January 2012 and January 2020. Neonatal sequential organ failure assessment scores were calculated every hour for every patient from admission until death or discharge. Measurements and Main Results: Longitudinal, granular scores from 436 infants demonstrated early and sustained discrimination of those who died versus those who survived to discharge. The discrimination for mortality by the maximum score was excellent (area under curve, 0.91; 95% confidence intervals, 0.88–0.94). Among survivors with and without adverse outcomes, most score variation occurred at the patient level. The weekly average score over the first 28 days was associated with the sum of adverse outcomes at discharge. Conclusions: The neonatal sequential organ failure assessment score discriminates between survival and nonsurvival on the first day of life. The major contributor to score variation occurred at the patient level. There was a direct association between scores and major adverse outcomes, including death.