tbuckley/cabot-search huggingface dataset:
Long-term endoscopic follow-up after closure of a post-bariatric surgery fistula with a cardiac septal defect occluder
Authors: Diogo Turiani Hourneaux de Moura, Mateus Bond Boghossian, Bruno Salomão Hirsch, Thomas R. McCarty, Alberto Jose Baptista, Eduardo Guimarães Hourneaux de Moura
Journal: Endoscopy (2021)

Bariatric surgery is currently the most effective treatment strategy for obesity; however, post-surgical fistulas may occur in up to 8.3 % of patients following traditional Roux-en-Y gastric bypass (RYGB) [1]. Currently endoscopic treatment of these complications remains challenging, with unsuccessful fistula closure occurring in 20 % of patients [1] [2]. More recently, the use of a cardiac septal defect occluder (CSDO) device has been proposed as a novel treatment for the closure of gastrointestinal fistulas. A CSDO is a double-disc self-expanding closure device made of nitinol and interwoven polyester. The successful use of CSDOs in the management of gastrointestinal surgical and bariatric leaks has been reported; however, there are limited data regarding long-term outcomes [3] [4]. In this video, we describe the successful closure of a gastrocutaneous fistula using a CSDO and demonstrate persistent closure at long-term follow-up ([Video 1]).
Abstract 14244: Comprehensive Gene Evaluation in Early-Onset Atrial Fibrillation Using Whole Exome Sequencing
Authors: Brandon Chalazan, Jason Roberts, Rafik Tadros, Emma Leach, Anna Lehman, Zachary Laksman
Journal: Circulation (2019)

Background: Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with significant morbidity and mortality. Genetic approaches with genome wide association studies and ...
Medical records-based chronic kidney disease phenotype for clinical care and “big data” observational and genetic studies
Authors: Ning Shang, Atlas Khan, Fernanda Polubriaginof, Francesca Zanoni, Karla Mehl, David Fasel, Paul E. Drawz, Robert J. Carrol, Joshua C. Denny, Matthew A. Hathcock, Adelaide M. Arruda-Olson, Peggy L. Peissig, Richard A. Dart, Murray H. Brilliant, Eric B. Larson, David S. Carrell, Sarah Pendergrass, Shefali Setia Verma, Marylyn D. Ritchie, Barbara Benoit, Vivian S. Gainer, Elizabeth W. Karlson, Adam S. Gordon, Gail P. Jarvik, Ian B. Stanaway, David R. Crosslin, Sumit Mohan, Iuliana Ionita-Laza, Nicholas P. Tatonetti, Ali G. Gharavi, George Hripcsak, Chunhua Weng, Krzysztof Kiryluk
Journal: npj Digital Medicine (2021)

Abstract Chronic Kidney Disease (CKD) represents a slowly progressive disorder that is typically silent until late stages, but early intervention can significantly delay its progression. We designed a portable and scalable electronic CKD phenotype to facilitate early disease recognition and empower large-scale observational and genetic studies of kidney traits. The algorithm uses a combination of rule-based and machine-learning methods to automatically place patients on the staging grid of albuminuria by glomerular filtration rate (“A-by-G” grid). We manually validated the algorithm by 451 chart reviews across three medical systems, demonstrating overall positive predictive value of 95% for CKD cases and 97% for healthy controls. Independent case-control validation using 2350 patient records demonstrated diagnostic specificity of 97% and sensitivity of 87%. Application of the phenotype to 1.3 million patients demonstrated that over 80% of CKD cases are undetected using ICD codes alone. We also demonstrated several large-scale applications of the phenotype, including identifying stage-specific kidney disease comorbidities, in silico estimation of kidney trait heritability in thousands of pedigrees reconstructed from medical records, and biobank-based multicenter genome-wide and phenome-wide association studies.
Disparities in European healthcare system approaches to maintaining continuity of medication for non-communicable diseases during the COVID-19 outbreak
Authors: Przemyslaw Kardas, Job Frank Martien van Boven, Hilary Pinnock, Enrica Menditto, Björn Wettermark, Ioanna Tsiligianni, Tamás Ágh
Journal: The Lancet Regional Health - Europe (2021)
Transcriptional Silencing of <i>ALDH2</i> Confers a Dependency on Fanconi Anemia Proteins in Acute Myeloid Leukemia
Authors: Zhaolin Yang, Xiaoli S. Wu, Yiliang Wei, Sofya A. Polyanskaya, Shruti V. Iyer, Moonjung Jung, Francis P. Lach, Emmalee R. Adelman, Olaf Klingbeil, Joseph P. Milazzo, Melissa Kramer, Osama E. Demerdash, Kenneth Chang, Sara Goodwin, Emily Hodges, W. Richard McCombie, Maria E. Figueroa, Agata Smogorzewska, Christopher R. Vakoc
Journal: Cancer Discovery (2021)

Hundreds of genes become aberrantly silenced in acute myeloid leukemia (AML), with most of these epigenetic changes being of unknown functional consequence. Here, we demonstrate how gene silencing can lead to an acquired dependency on the DNA repair machinery in AML. We make this observation by profiling the essentiality of the ubiquitination machinery in cancer cell lines using domain-focused CRISPR screening, which revealed Fanconi anemia (FA) proteins UBE2T and FANCL as unique dependencies in AML. We demonstrate that these dependencies are due to a synthetic lethal interaction between FA proteins and aldehyde dehydrogenase 2 (ALDH2), which function in parallel pathways to counteract the genotoxicity of endogenous aldehydes. We show DNA hypermethylation and silencing of ALDH2 occur in a recurrent manner in human AML, which is sufficient to confer FA pathway dependency. Our study suggests that targeting of the ubiquitination reaction catalyzed by FA proteins can eliminate ALDH2-deficient AML. SIGNIFICANCE: Aberrant gene silencing is an epigenetic hallmark of human cancer, but the functional consequences of this process are largely unknown. In this study, we show how an epigenetic alteration leads to an actionable dependency on a DNA repair pathway through the disabling of genetic redundancy.This article is highlighted in the In This Issue feature, p. 2113.
POS0981 COMPUTED TOMOGRAPHY-BASED ASSESSMENT OF RADIOGRAPHIC PROGRESSION IN SPINE AND SACROILIAC JOINTS AFTER PREGNANCY IN WOMEN WITH ANKYLOSING SPONDYLITIS
Authors: K. A. Lee, S. Y. Lee, H. S. Kim, H. R. Kim, S. H. Lee
Journal: Annals of the Rheumatic Diseases (2021)

Background: Mechanical stress are one of the pathogenesis of ankylosing spondlitis (AS). During pregnancy, the mechanical overload on the spine and pelvis increases due to gravid uterus. Recently, computed tomography syndesmophyte score (CTSS) has been developed to analysis of the spinal damage in patients with AS. Indeed, CT has higher sensitivity and reliability compared to conventional radiography in the detection of sacroiliitis. Objectives: We aimed to investigate whether pregnancy and delivery affect radiographic progression of spine and SIJ in women with AS based on CT evaluation. Methods: This retrospective study included women aged 19-49 years with AS who performed at least twice CT scans of whole-spine or sacroilliac joints (SIJ) at intervals of 2 to 4 years. To compare the radiographic progression after delivery, we classified into 2 groups: delivery group or controls. Delivery group was restricted to subjects who had the first CT scans ~2 years before delivery and the second CT scans ~2 years after delivery. CTSS (0-522) and SIJ scores (0-40) were used to evaluate the spinal syndesmophyte and erosion, joint space narrowing, and sclerosis of SIJ. Results: A total of 21 women in delivery group and 38 women in controls were included. The median (Q1-Q3) CTSS at baseline in delivery group and controls were 19 (16-23) and 20 (13.25-27.75), and median progression was 1 (0-3) and 0 (0-1) during the median 2.9 year follow-up. The median (Q1-Q3) SIJ scores at baseline in delivery group and controls were 13 (8-22) and 11 (6-22), and median progression was 1.5 (0-3) and 1 (0-2). The CTSS and SIJ scores significantly increased in both groups, but no difference in absolute score changes per time point between was observed. The changes in SIJ scores was comparable according to the delivery methods. Conclusion: This study suggests that pregnancy and delivery had no effect on radiographic progression of spine and SIJ in female with AS. References: [1]de Bruin F, de Koning A, van den Berg R, Baraliakos X, Braun J, Ramiro S. Development of the CT Syndesmophyte Score (CTSS) in patients with ankylosing spondylitis: data from the SIAS cohort. 2018;77(3):371-7. Disclosure of Interests: None declared.
Author Correction: Sonic hedgehog accelerates DNA replication to cause replication stress promoting cancer initiation in medulloblastoma
Authors: Lukas Tamayo-Orrego, David Gallo, Frédéric Racicot, Amandine Bemmo, Sushmetha Mohan, Brandon Ho, Samer Salameh, Trang Hoang, Andrew P. Jackson, Grant W. Brown, Frédéric Charron
Journal: Nature Cancer (2021)
Performance of Mechanical and Biological Mitral Prostheses in Young Rheumatics Aged Below 45 Years
Authors: Ujjwal Chowdhury
Journal: Clinical Cardiology and Cardiovascular Interventions (2021)

Background and Aim: We compared 22-year composites of valve-related reoperation, morbidity, and mortality following mitral mechanical and bioprostheses in young rheumatics aged &lt;45years. Methods: Retrospective comparative analysis of valve-related reoperations and survival data were performed from 466 consecutive propensity matched patients undergoing either bioprosthetic MVR (Group I, n=233) or mechanical MVR (Group II, n=233) between 1998 and 2019. Results: The median age was 33 (IQR: 27-40) and 34 (IQR: 28-39) years for Group I and II respectively. The mean follow-up was 3278.9 patient-years in the biological arm and 3384.4 patient-years in mechanical arm. Bioprosthetic arm exhibited lesser cumulative mortality (4.5% vs 9.9%, SMD= -0.04, p=0.65). Hazard regression for mortality included (HR, 95% CI) preoperative congestive heart failure (CHF) 11.44 (8.44, 624.9), p&lt;0.0001; renal failure 19.51 (8.04, 47.35), p&lt;0.0001; previous operation 6.84 (2.48, 18.84), p&lt;0.0001; atrial fibrillation (AF) 7.64 (1.02, 57.13), p=0.006; LA clot 61.94 (8.28, 463.08), p&lt;0.0001; giant LA &gt;65 mm 7.87 (2.62, 23.56), p&lt;0.0001; poor left ventricular (LV) function 0.94 (0.92, 0.97), p&lt;0.0001; and prolonged aortic clamp time 1.07 (1.04, 1.11), p&lt;0.0001). Propensity matching did not exhibit any difference in reoperations between bioprostheses and mechanical prostheses (18.8% vs 13.3%, SMD= -0.152, p=0.1). At a median follow-up of 136 (IQR: 76-197) months, actuarial survival was 90.32%±0.02% (p=0.09) and there was no difference between the groups (p=0.09). Conclusions: Bioprostheses are an acceptable alternative to mechanical prostheses in young rheumatics aged &lt;45 years unwilling for mechanical valve, redo surgeries, life-long anticoagulation, and those desirous of pregnancy.
Representativeness in Premarketing vs Postmarketing US Food and Drug Administration Trials
Authors: Joseph M. Unger
Journal: JAMA Network Open (2021)

Tanvee Varma, BA; Joshua D. Wallach, PhD, MS; Jennifer E. Miller, PhD; Dominic Schnabel, MPH; Joshua J. Skydel, BS; Audrey D. Zhang, MD; Michaela A. Dinan, PhD; Joseph S. Ross, MD, MHS; Cary P. Gross, MD
Machine learning prediction of blood alcohol concentration: a digital signature of smart-breathalyzer behavior
Authors: Kirstin Aschbacher, Christian S. Hendershot, Geoffrey Tison, Judith A. Hahn, Robert Avram, Jeffrey E. Olgin, Gregory M. Marcus
Journal: npj Digital Medicine (2021)

Abstract Excess alcohol use is an important determinant of death and disability. Machine learning (ML)-driven interventions leveraging smart-breathalyzer data may help reduce these harms. We developed a digital phenotype of long-term smart-breathalyzer behavior to predict individuals’ breath alcohol concentration (BrAC) levels trained on data from a smart breathalyzer. We analyzed roughly one million datapoints from 33,452 users of a commercial smart-breathalyzer device, collected between 2013 and 2017. For validation, we analyzed the associations between state-level observed smart-breathalyzer BrAC levels and impaired-driving motor vehicle death rates. Behavioral, geolocation-based, and time-series-derived features were fed to an ML algorithm using training (70% of the cohort), development (10% of the cohort), and test (20% of the cohort) sets to predict the likelihood of a BrAC exceeding the legal driving limit (0.08 g/dL). States with higher average BrAC levels had significantly higher alcohol-related driving death rates, adjusted for the number of users per state B (SE) = 91.38 (15.16), p &lt; 0.01. In the independent test set, the ML algorithm predicted the likelihood of a given user-initiated BrAC sample exceeding BrAC ≥ 0.08 g/dL, with an area under the curve (AUC) of 85%. Highly predictive features included users’ prior BrAC trends, subjective estimation of their BrAC (or AUC = 82% without the self-estimate), engagement and self-monitoring, time since the last measure, and hour of the day. In conclusion, an ML algorithm successfully quantified a digital phenotype of behavior, predicting naturalistic BrAC levels exceeding 0.08 g/dL (a threshold associated with alcohol-related harm) with good discrimination capability. This result establishes a foundation for future research on precision behavioral medicine digital health interventions using smart breathalyzers and passive monitoring approaches.
Women with poor response to IVF have lowered circulating gonadotrophin surge-attenuating factor (GnSAF) bioactivity during spontaneous and stimulated cycles
Authors: F Martinez, P N Barri, B Coroleu, R Tur, T Sorsa-Leslie, W J Harris, N P Groome, P G Knight, P A Fowler
Journal: Human Reproduction Update (2002)

BACKGROUND Up to 13% of IVF cancellations are due to  responses during down-regulated cycles. Because premature luteinization occurs more frequently in older or poor responder patients, defective production of gonadotrophin surge-attenuating factor (GnSAF) may be involved. METHODS Nine women with normal previous IVF response (NORM) and 9 with previous  IVF response (POOR) were monitored in a spontaneous cycle (blood samples: days 2, 7, 11, 15 and 20) and then stimulated with recombinant human FSH (rFSH) under GnRH agonist (blood samples: treatment days GnRH agonist + 2, GnRH agonist + 7, day of HCG administration and days HCG + 1 and HCG + 8). LH, FSH, estradiol, progesterone and inhibin-A and -B were assayed in individual samples while GnSAF bioactivity was determined in samples pooled according to day, cycle and IVF response. RESULTS During spontaneous cycles LH, steroids and inhibins were similar between NORM and POOR women, FSH was elevated in POOR women (4.9 +/- 0.3 versus 6.7 +/- 0.6 mIU/l, P < 0.01) and GnSAF bioactivity was detectable on days 2, 7 and 11 in NORM women only. During IVF cycles inhibin-A and -B rose more markedly in NORM than POOR women. Similarly GnSAF production peaked on day GnRH agonist + 7 in NORM women, but on the day of HCG administration in POOR women. CONCLUSIONS Defects in ovarian responsiveness to FSH include reduced GnSAF production. This suggests that GnSAF should be investigated as a marker of ovarian reserve once an immunoassay becomes available.
Mechanically induced integrin ligation mediates intracellular calcium signaling with single pulsating cavitation bubbles
Authors: Fenfang Li, Tae Hyun Park, George Sankin, Christopher Gilchrist, Defei Liao, Chon U Chan, Zheng Mao, Brenton D. Hoffman, Pei Zhong
Journal: Theranostics (2021)

Therapeutic ultrasound or shockwave has shown its great potential to stimulate neural and muscle tissue, where cavitation microbubble induced Ca2+ signaling is believed to play an important role. However, the pertinent mechanisms are unknown, especially at the single-cell level. Particularly, it is still a major challenge to get a comprehensive understanding of the effect of potential mechanosensitive molecular players on the cellular responses, including mechanosensitive ion channels, purinergic signaling and integrin ligation by extracellular matrix. Methods: Here, laser-induced cavitation microbubble was used to stimulate individual HEK293T cells either genetically knocked out or expressing Piezo1 ion channels with different normalized bubble-cell distance. Ca2+ signaling and potential membrane poration were evaluated with a real-time fluorescence imaging system. Integrin-binding microbeads were attached to the apical surface of the cells at mild cavitation conditions, where the effect of Piezo1, P2X receptors and integrin ligation on single cell intracellular Ca2+ signaling was assessed. Results: Ca2+ responses were rare at normalized cell-bubble distances that avoided membrane poration, even with overexpression of Piezo1, but could be increased in frequency to 42% of cells by attaching integrin-binding beads. We identified key molecular players in the bead-enhanced Ca2+ response: increased integrin ligation by substrate ECM triggered ATP release and activation of P2X-but not Piezo1-ion channels. The resultant Ca2+ influx caused dynamic changes in cell spread area. Conclusion: This approach to safely eliciting a Ca2+ response with cavitation microbubbles and the uncovered mechanism by which increased integrin-ligation mediates ATP release and Ca2+ signaling will inform new strategies to stimulate tissues with ultrasound and shockwaves.
Abstract 20333: Increased Long-Term Adverse Outcomes of Diabetic Patients Undergoing Endovascular Therapy for Peripheral Arterial Disease Are Attributable to Distal Lesion Distribution
Authors: Yoonjee Park, Seung-Woon Rha, Byoung Geol Choi, Se Yeon Choi, Jae Kyeong Byun, Ahmed Mashaly, Won Young Jang, Woo Hyeun Kim, Ja Yeon Choi, Eun Jin Park, Jin Oh Na, Cheol Ung Choi, Hong Euy Lim, Eung Ju Kim, Chang Gyu Park, Hong Seog Seo, Dong Joo Oh, Ae-Young Her, Yong Hoon Kim
Journal: Circulation (2017)

Background: Diabetics with peripheral arterial disease (PAD), mainly below-the knee (BTK) lesions, are known to have higher risk for mortality and cardiovascular events, but long-term clinical outc...
Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆
Authors: A.-M.C. Dingemans, M. Früh, A. Ardizzoni, B. Besse, C. Faivre-Finn, L.E. Hendriks, S. Lantuejoul, S. Peters, N. Reguart, C.M. Rudin, D. De Ruysscher, P.E. Van Schil, J. Vansteenkiste, M. Reck
Journal: Annals of Oncology (2021)
Enhanced anti-PD-1 therapy in hepatocellular carcinoma by tumor vascular disruption and normalization dependent on combretastatin A4 nanoparticles and DC101
Authors: Xin Bao, Na Shen, Yan Lou, Haiyang Yu, Yue Wang, Linlin Liu, Zhaohui Tang, Xuesi Chen
Journal: Theranostics (2021)

Anti-programmed cell death protein 1 (PD-1) therapy has shown promising efficacy in hepatocellular carcinoma (HCC), but its response rates in advanced HCC are lower than 20%. A critical reason for this is the imbalance between CD8
Abstract #237: Tumor oxygen dynamics assessed non-invasively
Authors: Jesus Pacheco-Torres, Dawen Zhao, Peter Peschke, Sebastian Cerdan, Ralph Mason
Journal: Cancer Research (2009)

Tumor oxygenation influences response to various therapies and plays important roles in malignant progression, angiogenesis, and metastasis. While methods are available to quantitatively map pO2 dynamics in pre-clinical studies there is a pressing need for methods to non-invasively characterize tumor hypoxia and response to interventions in patients. Blood Oxygenation Level Dependent (BOLD) MRI based on T2* contrast induced by [deoxyhemoglobin], is sensitive to tumor vascular oxygenation and blood flow. Recent studies suggest a possibility of assessing tissue oxygenation based on the shortening of the tissue water T1 due to oxygen. This has prompted us to investigate the utility of BOLD and TOLD (Tissue Oxygenation Level Dependent contrast) to evaluate tumor hypoxia and response to interventions. Specifically, we are investigating differences in T1- and T2*-weighted signal intensity in response to carbogen breathing between two Dunning prostate R3327 rat tumor sublines. Syngeneic Dunning prostate R3327 rat tumor sublines: anaplastic and poorly vascularized AT1 (volume doubling time (VDT) = 5 days) and moderately well differentiated and vascularized HI (VDT = 7 days) were used. Tumors were implanted subcutaneously on the thigh of adult male Copenhagen rats. Tumors were grouped based on their size in big (>3.5 cm3) and small (  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 237.
Synchronous Bilateral Adrenal Gland Metastases of Bladder Carcinoma Revealed on 18F-FDG PET/CT
Authors: Özge Erol, Nurhan Ergül, Arzu Algün Gedik, Ediz Beyhan, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2021)

Abstract Bilateral adrenal metastases from bladder carcinoma have been reported rarely. We report an 86-year-old man with urothelial bladder carcinoma who had received chemotherapy and radiotherapy. Bilateral synchronous adrenal gland metastases were observed on 18 F-FDG PET/CT.
Surgery After Response to Chemotherapy for Locally Advanced Pancreatic Ductal Adenocarcinoma: A Guide for Management
Authors: Zhi Ven Fong, Cristina R. Ferrone
Journal: Journal of the National Comprehensive Cancer Network (2021)

Because of the biologic aggressiveness and late presentation of pancreatic ductal adenocarcinoma (PDAC), up to 80% of patients have locally advanced or metastatic disease at presentation. The success of multiagent chemotherapy regimens in the management of metastatic disease has been translated to patients with locally advanced PDAC. Both FOLFIRINOX (fluorouracil/folinic acid/irinotecan/oxaliplatin) and gemcitabine/nab-paclitaxel are used to downstage locally advanced PDAC to render it eligible for resection with curative intent. This paradigm shift has significantly expanded the pool of patients who are eligible for resection with curative intent. However, the generalizability of present studies and the patient selection process are unclear. This article provides an evidence-based review of patient selection considerations and management algorithms, and details our institution’s approach to patients with locally advanced PDAC after preoperative chemotherapy.
Personalising left-ventricular biophysical models of the heart using parametric physics-informed neural networks
Authors: Stefano Buoso, Thomas Joyce, Sebastian Kozerke
Journal: Medical Image Analysis (2021)

We present a parametric physics-informed neural network for the simulation of personalised left-ventricular biomechanics. The neural network is constrained to the biophysical problem in two ways: (i) the network output is restricted to a subspace built from radial basis functions capturing characteristic deformations of left ventricles and (ii) the cost function used for training is the energy potential functional specifically tailored for hyperelastic, anisotropic, nearly-incompressible active materials. The radial bases are generated from the results of a nonlinear Finite Element model coupled with an anatomical shape model derived from high-resolution cardiac images. We show that, by coupling the neural network with a simplified circulation model, we can efficiently generate computationally inexpensive estimations of cardiac mechanics. Our model is 30 times faster than the reference Finite Element model used, including training time, while yielding satisfactory average errors in the predictions of ejection fraction (-3%), peak systolic pressure (7%), stroke work (4%) and myocardial strains (14%). This physics-informed neural network is well suited to efficiently augment cardiac images with functional data and to generate large sets of synthetic cases for training deep network classifiers while it provides efficient personalization to the specific patient of interest with a high level of detail.