tbuckley/cabot-search huggingface dataset:
<i>Notes from the Field:</i> COVID-19 Vaccination Coverage Among Persons Experiencing Homelessness — Six U.S. Jurisdictions, December 2020–August 2021
Authors: Martha P. Montgomery, Ashley A. Meehan, Antea Cooper, Karrie-Ann Toews, Isaac Ghinai, Mary Kate Schroeter, Rachael Gibbs, Najibah Rehman, Katerina S. Stylianou, David Yeh, Nikki Thomas-Campbell, Nathalie C. Washington, Hannah K. Brosnan, Alicia H. Chang, Ayodele Gomih, Cathy Ngo, Katherine Diaz Vickery, Blair Harrison, Tyler N.A. Winkelman, Adam Gerstenfeld, Laura Zeilinger, Emily Mosites
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

COVID-19 outbreaks have been reported in homeless shelters across the United States (1).Many persons experiencing homelessness are older adults or persons with underlying medical conditions, placing them at increased risk for severe COVID-19-associated illness.The proportion of persons experiencing homelessness who are fully vaccinated against COVID-19 in the United States is currently unknown.Many persons experiencing homelessness express a willingness to receive the COVID-19 vaccine (2,3).Through conversations with public health and housing assistance partners, CDC identified six* urban public health jurisdictions with data on vaccination coverage among persons experiencing homelessness.These six jurisdictions reported data on COVID-19 vaccinations † administered to persons experiencing intermittent homelessness during December 13, 2020-August 31, 2021.Full vaccination status § and evidence of coverage with at least 1 COVID-19 vaccine dose ¶ among persons experiencing homelessness were obtained by performing data linkage between immunization information systems and homeless services data systems or through data collection during vaccination events at homeless service sites.Total populations of persons experiencing homelessness were estimated using either the total number of persons accessing homeless * The six jurisdictions included Chicago, Illinois; Detroit, Michigan; Fairfax, Virginia; Los Angeles County, California; Hennepin County, Minnesota; and the District of Columbia.Most jurisdictions included persons living sheltered and those living unsheltered.† On December 12, 2020, the Advisory Committee on Immunization Practices issued an interim recommendation for the use of a vaccine for the prevention of COVID-19 in persons aged ≥16 years.§ Fully vaccinated persons included those who received 2 doses on different days (regardless of time interval) of the 2-dose mRNA series or received 1 dose of a single-dose vaccine, at least 14 days earlier.¶ Coverage with at least 1 dose included all persons who received at least 1 dose of the 2-dose mRNA series COVID-19 vaccine or those who received 1 dose of the single-dose vaccine.
Abstract 12543: Limited Blood Biomarker Changes After Reverse Remodelling: A Markers and Response to CRT (Marc) Substudy
Authors: Alexander H Maass, Marielle Kloosterman, Adriaan A Voors, Kevin Vernooy, Mathias Meine, Cornelis Allaart, Marc A Vos, Maarten J Cramer, Isabelle C Van Gelder, Michiel Rienstra
Journal: Circulation (2021)

Objectives: Investigate if the amount of reverse remodelling after CRT coincides with blood biomarker changes. Background: Blood biomarkers are predictors of heart failure, but sparse data exist on the correlation between blood biomarkers changes and reverse remodelling. Methods: Fourteen blood biomarkers, reflecting collagen turnover (PIIINP, CICP, MMP-9, TIMP-1, ICTP), inflammation (hsCRP, IL-6), myocardial stretch and injury (NT-proBNP, hsTroponin-T), inflammatory-, fibrotic- and apoptotic pathways (Galectin-3, ST2, GDF-15) and renal function (creatinine, BUN), were assessed before and six months after CRT in 213 patients from the Markers and Response to CRT study. Additionally, baseline peripheral venous (PV) and coronary sinus (CS) samples were compared. Patients were divided in 4 groups based on indexed left ventricular end systolic volume change (LVESVi): no remodelling, lower, middle, and upper tertile. Results: Mean age was 66±10 years, 62% were men, 42% had ischemic aetiology. 169 patients experienced LVESVi reduction: lower tertile 12% (5-16%), middle tertile 32% (25-37%), upper tertile 53% (44-58%). Collagen markers increased in all groups. Inflammation markers remained in normal range. hsTroponin-T decreased in all groups. Renal markers showed no clinical significant change. GDF-15, ST2 and Galectin-3 remained elevated, showing no distinct pattern. Only NT-proBNP changes corresponded to LVESVi reduction (β -1.72, P&lt;0.001). Between all CS-PV samples was a positive correlation (R-range: 0.72-0.97, all P&lt;0.001). Conclusions: NT-proBNP changes are associated with amount of reverse remodelling 6 months after CRT. Thirteen other blood biomarkers, reflecting, among others, collagen turnover, fibrotic- and apoptotic pathways, are not. CS and PV samples correspond well, CS sampling does not seem to provide additional information in assessing reverse remodelling.
CTNI-51. ADJUVANT TROTABRESIB, A REVERSIBLE POTENT BROMODOMAIN AND EXTRATERMINAL INHIBITOR, PLUS TEMOZOLOMIDE IN PATIENTS WITH NEWLY DIAGNOSED GLIOBLASTOMA: INTERIM RESULTS FROM A PHASE 1B DOSE-FINDING STUDY
Authors: Maria Vieito, Matteo Simonelli, Filip de Vos, Victor Moreno, Marjolein Geurts, Elena Lorenzi, Marina Macchini, Martin van den Bent, Gianluca Del Conte, Maja de Jonge, Barbara Amoroso, Tania Sanchez-Perez, Marlene Zuraek, Bishoy Hanna, Ida Aronchik, Ellen Filvaroff, Cristina Mendez, Xin Wei, Zariana Nikolova, Juan Manuel Sepulveda
Journal: Neuro-Oncology (2021)

Abstract Trotabresib (CC-90010) demonstrated antitumor activity as monotherapy in patients with advanced malignancies (Moreno et al. ESMO 2020. Abstract 5270) and enhanced the antiproliferative effects of temozolomide in preclinical studies. CC-90010-GBM-002 (NCT04324840) is a phase 1B dose-finding study investigating standard-of-care temozolomide + radiotherapy followed by adjuvant trotabresib + temozolomide or concomitant trotabresib + temozolomide + radiotherapy followed by adjuvant trotabresib + temozolomide, post-resection, in patients with newly diagnosed glioblastoma. We present interim results for adjuvant trotabresib + temozolomide. Patients received trotabresib 15, 30, or 45 mg daily (4 days on/24 days off) + temozolomide administered per label for 6 cycles, followed by trotabresib 45 mg monotherapy daily (4 days on/24 days off). Primary objectives are to establish the safety, maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) of trotabresib. Preliminary efficacy, pharmacokinetics, and pharmacodynamics are also being investigated. Of 13 patients enrolled, 5, 6, and 2 received trotabresib 15, 30, and 45 mg, respectively, plus temozolomide. Grade 3/4 treatment-related adverse events were reported in 2, 4, and 1 patients receiving trotabresib 15, 30, and 45 mg, respectively. MTD and RP2D are not yet reached; dose limiting toxicity (grade 4 thrombocytopenia) was reported in 1 patient in the 30-mg group. Of 10 evaluable patients, 1 had complete response and 7 had stable disease per RANO criteria. Trotabresib exposure increased proportionally with dose. Day 4 time to peak trotabresib concentration was 0.5–2.0 hours; mean terminal half life was 60–70 hours. Day 4 blood CCR1 RNA 2–4 hours post-dose was downregulated below baseline in the 15-mg group and ≥ 50% in the 30-mg group. Adjuvant trotabresib + temozolomide appears well tolerated, with promising preliminary efficacy. Treatment was ongoing at data cutoff in 9 patients in the adjuvant cohort; enrollment is continuing in the adjuvant and concomitant therapy dose-escalation cohorts.
NIMG-32. THE FEDERATED TUMOR SEGMENTATION (FETS) INITIATIVE: THE FIRST REAL-WORLD LARGE-SCALE DATA-PRIVATE COLLABORATION FOCUSING ON NEURO-ONCOLOGY
Authors: Ujjwal Baid, Sarthak Pati, Siddhesh Thakur, Brandon Edwards, Micah Sheller, Jason Martin, Spyridon Bakas
Journal: Neuro-Oncology (2021)

Abstract PURPOSE Robustness and generalizability of artificial intelligent (AI) methods is reliant on the training data size and diversity, which are currently hindered in multi-institutional healthcare collaborations by data ownership and legal concerns. To address these, we introduce the Federated Tumor Segmentation (FeTS) Initiative, as an international consortium using federated learning (FL) for data-private multi-institutional collaborations, where AI models leverage data at participating institutions, without sharing data between them. The initial FeTS use-case focused on detecting brain tumor boundaries in MRI. METHODS The FeTS tool incorporates: 1) MRI pre-processing, including image registration and brain extraction; 2) automatic delineation of tumor sub-regions, by label fusion of pretrained top-performing BraTS methods; 3) tools for manual delineation refinements; 4) model training. 55 international institutions identified local retrospective cohorts of glioblastoma patients. Ground truth was generated using the first 3 FeTS functionality modes as mentioned earlier. Finally, the FL training mode comprises of i) an AI model trained on local data, ii) local model updates shared with an aggregator, which iii) combines updates from all collaborators to generate a consensus model, and iv) circulates the consensus model back to all collaborators for iterative performance improvements. RESULTS The first FeTS consensus model, from 23 institutions with data of 2,200 patients, showed an average improvement of 11.1% in the performance of the model on each collaborator’s validation data, when compared to a model trained on the publicly available BraTS data (n=231). CONCLUSION Our findings support that data increase alone would lead to AI performance improvements without any algorithmic development, hence indicating that the model performance would improve further when trained with all 55 collaborating institutions. FL enables AI model training with knowledge from data of geographically-distinct collaborators, without ever having to share any data, hence overcoming hurdles relating to legal, ownership, and technical concerns of data sharing.
Abstract 14193: Bmp-7 Ameliorates Lipid Accumulation Induced, Hmgb1 Initiated Pyroptosis Leading To Sarcopenia, Muscle Deterioration And Adverse Muscle Remodeling In Diabetes
Authors: Chandrakala A Aluganti Narasimhulu, Dinender K Singla
Journal: Circulation (2021)

Introduction: Diabetic muscle myopathy involves hyperglycemia and inflammation that causes skeletal muscle dysfunction. However, the potential cellular mechanisms that occur during hyperglycemia and inflammation, which induces sarcopenia, muscle deterioration and muscle dysfunction remains unknown. Hypothesis: We hypothesize that, Bone morphogenetic protein-7 (BMP-7) ameliorates hyperlipidemia induced inflammation and pyroptosis in the development and progression of diabetic myopathy. Methods: C57BL6 mice were treated with saline, streptozotocin (STZ), or STZ+BMP-7 to generate diabetic muscle myopathy. Diabetes was established by increased fasting glucose levels and GTT. Gastrocnemius muscle and blood samples were collected. Blood was used to determine the lipid levels. Skeletal muscle was used to investigate lipid accumulation, pyroptosis, muscle deterioration, atrophy, and adverse structural remodeling using histology, immunohistochemistry, western blot, and RT-PCR. Results: We observed a significant ( p &lt;0.05) increase in blood glucose and serum lipid levels in diabetic animals. A significant ( p &lt;0.05) increase in hyperglycemia lead an increase in lipid accumulation, inflammasome formation and further an up-regulation of the downstream pyroptotic markers as well as signaling markers [TGFβ, Smad2 and Smad3] in diabetic muscle cells. Structural analysis showed the significant ( p &lt;0.05) loss of muscle weight, decreased myofibrillar area, increased muscle deterioration and fibrosis leading to muscle dysfunction. Whereas, BMP-7 attenuated hyperglycemia, hyperlipidemia, lipid accumulation, inflammation, pyroptosis, signaling markers and diabetic adverse structural modifications resulting in significantly ( p &lt;0.05) improved muscle function. Conclusion: We report for the first time that increased hyperlipidemia aggravates inflammation involved cellular pyroptosis that induces significant muscle cell loss and adverse remodeling in diabetic muscle myopathy. Targeting pyroptosis and lipid accumulation in muscle cells, with BMP-7 improves diabetic muscle pathophysiology and muscle function. These findings shows BMP-7 as a potential therapeutic option to treat diabetic myopathy.
Abstract 13550: Genotype-Phenotype Mismatch of Val122Ile Transthyretin Mutation in Dilated Cardiomyopathy
Authors: Thomas E Bigham, Matthew T Brown, Eric Johns, Kunal N Bhatt
Journal: Circulation (2021)

Introduction: An estimated 3.4% of African Americans carry the Valine 122 Isoleucine (Val122Ile) mutation associated with hereditary transthyretin (TTR) amyloidosis cardiomyopathy (hATTR-CM). Val122Ile is inherited in an autosomal dominant pattern, but penetrance of the clinical disease is variable and incompletely understood. Asymptomatic carriers therefore require screening for phenotypic manifestations of hATTR-CM before initiation of TTR-targeted therapies. Case Description: A 57-year-old African American male with non-ischemic dilated cardiomyopathy (DCM) presented in cardiogenic shock for advanced therapy evaluation. DCM was diagnosed 20 years prior, and family history was pertinent for cardiomyopathy in both parents. Echocardiography on admission revealed severely reduced left ventricular systolic function (EF 10%) with moderate cavitary dilation but no evidence of concentric or septal hypertrophy (LVeDd 6.1 cm, IVSd 0.9 cm, LVPWd 1.0 cm &amp; LVMI 103 g/m 2 ). His family history prompted genetic testing to evaluate hereditary etiologies of DCM. However, his genetic test only revealed a heterozygous Val122Ile mutation. He underwent left ventricular assist device (LVAD) implantation, after which LV apical core biopsy was negative for Congo red staining. Discussion: This case illustrates a clear genotype (Val122Ile) - phenotype (DCM) mismatch. Although positive for the Val122Ile mutation, the lack of Congo red staining on his LV core biopsy rules out cardiac infiltration of mutated TTR amyloid fibrils and instead suggests an entirely independent, idiopathic DCM. The increasing ease and availability of genetic testing, combined with the known high prevalence of the Val122Ile mutation in the African American population will inevitably lead to more cases of genotype-phenotype mismatch. The variable penetrance of this pathogenic mutation (Val122Ile) may lead to inappropriate treatment with TTR-targeted therapies in patients without clear disease, potentially increasing patient and healthcare costs unnecessarily. Further research is needed to understand the variable penetrance of Val122Ile and factors that may predict development of clinical disease in the future.
Abstract 11005: Electrophysiological Remodelling of Right Atria in Atrial Fibrillation Sheep Model and Role of Succinate in Electrophysiological Properties
Authors: Bastien Guillot, Girish Ramlugun, Guido Caluori, Néstor Pallares Lupon, Richard Walton, Virginie Loyer, Pierre Jais, Philippe Pasdois, Olivier Bernus
Journal: Circulation (2021)

Introduction: Atrial fibrillation (AF) is the most common arrhythmia and is associated with deleterious remodelling processes. In AF patients, the plasmatic succinate content increases, indicating a potential role for metabolic remodelling in AF progression. Objective: To assess the impact of succinate on the electrophysiological properties of right atria (RA) in a persistent AF sheep model. Methods: Optical mapping experiments were performed in ex vivo RA from a burst pacing AF sheep model (SHAM=5; AF=5). The right coronary artery was perfused with Tyrode solution initially containing glucose (5.6mM), subsequently replaced by succinate (5mM). Action potential durations at 80% of repolarization (APD80) and mean conduction velocities (CV) were assessed from 2 to 5Hz pacing frequency and during sinus rhythm (SR). An S1S2 protocol was used to determine effective refractory period (ERP) and a burst pacing procotol (20Hz) to assess ex vivo AF vulnerability. Finally, an organ donation program allowed us to investigate these properties in a human RA from an AF patient. Results: SR frequency was higher in AF than SHAM sheep (2.0 vs. 1.6 Hz; p=0.19). Succinate perfusion decreased SR frequency by 18% in SHAM sheep (1.7 vs. 1.4 Hz; p=0.12) and by 43% in AF sheep (2.0 vs. 1.2 Hz; p=0.009). The ERP was lower in AF than SHAM sheep (184 vs. 210 ms; p=0.5) and succinate induced a significant increase of 136% in SHAM sheep (210 vs. 286 ms; p=0.06) and of 188% in AF sheep (184 vs. 346 ms; p=0.0008). Epicardial APD80 was lower when pacing at 2.5Hz in AF than SHAM sheep (165 vs. 197 ms ; p=0.3). Succinate increased APD80 in both SHAM and AF RA (191 to 224 ms; 165 to 231 ms) but its effect was more important in AF than SHAM sheep (148 vs. 117 %; p=0.1). Mean CV was slower in AF sheep than SHAM sheep (110 vs. 130 cm/s; p=0.47). Succinate slowed mean CV on AF sheep (110 vs. 76; p=0.4) but did not affect SHAM RA. In the human RA, APD80 (257 vs; 309 ms) and total activation time were increased by succinate. Conclusions: Our results indicate that succinate alters atrial electrophysiological properties, most likely through the associated ROS overproduction. Importantly, AF sheep showed an increased sensitivity to succinate perfusion. Preliminary data in a human RA are in line with these observations.
Abstract 13327: Development and Validation of a Clinical Risk Score to Predict the Critical Illness in Hospitalized Patients With COVID-19
Authors: Anthi Katsouli, Sadia Gazi, Paula Marfia, Helen Lee, Sameer Qazi, Monica Komorowski, Ann-Marie Bertino, Neeraj Joshi
Journal: Circulation (2021)

The Covid-19 pandemic has obligated healthcare systems to triage patients efficiently in order to utilize resources in the proper manner. Robust, validated clinical prediction tools are lacking that identify patients with coronavirus disease 2019 who are at the highest risk of mortality. A cohort of 661 positive COVID patients admitted to the Loyola hospital from 3/11/2020 to 10/12/2020 was used to validate previously published results with the composite outcome of ‘critically ill’, defined as invasive ventilation, ICU admission, or in-hospital death. Epidemiological, clinical, laboratory, and imaging variables ascertained at hospital admission were screened using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive risk score. Accuracy of the score was measured by the area under the receiver operating characteristic curve (AUC). Fifty-two (52) percent of our cohort had critical illness compared to 8% in the Liang paper (the first predictor model which was developed in China). Our population was older, had significantly higher abnormal chest x-ray, dyspnea, and number of comorbidities compared to their population. In addition, our population had higher values for NLR and LDH and lower direct bilirubin. Using the model coefficients presenting in Liang et al, the AUC was only 0.68 (95% CI: 0.64, 0.72), considerably lower than .88 presented in their publication. LASSO variable selection identified 8 variables (HR, SBP, fever, SpO2&lt;90, LDH, ferritin, D dimer, CRP on admission) for a multivariable model. In the multivariable model: SpO2 &lt;90, fever at admission, and increasing LDH were found to be statistically associated with our outcome. We finally added baseline predictors of age, sex, race, and number of comorbidities to the LASSO predictors which resulted in an AUC of 0.75 (95% CI: 0.71, 0.78). In our study, we found that three predictors (SpO2 &lt;90, fever, and increasing LDH on admission) were selected by the LASSO analysis to construct a predictive nomogram. The application of our model would help clinicians make a prompt decision to optimize patient stratification management. However, this quantitative tool needs to be validated by further large-scale prospective studies.
NCMP-01. NOVEL BIOMARKERS FOR RADIATION-INDUCED NEUROTOXICITY
Authors: Chen Makranz, Asel Lubotzky, Hai Zemmour, Ruth Shemer, Benjamin Glaser, Jonathan Cohen, Myriam Maoz, Eli Sapir, Noam Weizman, John Feldman, Alexander Lossos, Yuval Dor, Aviad Zick
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Brain radiotherapy is the main therapeutic modality for brain metastases (BM), but carries short and long term toxicities, termed radiation-induced neurotoxicity (RIN), and classified to acute, early-delayed and late-delayed RIN according to its time onset. Although diagnosis of RIN is crucial for patient management, there is an unmet need for sensitive biomarkers for RIN. Here we report on a novel non-invasive biomarker for detection and monitoring RIN. As radiotherapy is known to induce brain cells apoptosis as well as BBB disruption, we hypothesized that circulating cell free DNA fragments derived from dying brain cells will be elevated in the blood of patients with RIN. Using comparative methylome analysis we identified 13 genomic loci showing brain-specific DNA methylation patterns, including markers for neurons, oligodendrocytes, and astrocytes. We searched for these brain-derived cfDNA (bncfDNA) in plasma samples of patients following brain irradiation. METHODS We followed 24 patients treated by brain radiotherapy for BM by clinical and radiological examinations before, during and after treatment. In addition, we serially collected blood samples for DNA analysis, and correlated bncfDNA levels with clinical and radiological assessment. RESULTS Patient`s median age was 60 years. Most common primary tumor sites were breast (25%), lung (20.8%) and melanoma (12.5%). RIN was detected in 10 patients (62%). BncfDNA levels increased up to 292.4 fold in acute RIN, up to 138533.1 in early-delayed RIN, and up to 58.4 fold in late-delayed RIN. Resolution of RIN correlated with decrease in bncfDNA. Changes in bncfDNA levels were independent of tumor response and suggested to reflect both symptomatic and asymptomatic RIN. CONCLUSION Increase in bncfDNA levels characterizes RIN independent of tumor response. Thus, BncfDNA may serve as a novel biomarker for brain cells death incurred by radiotherapy. Further studies are required to explore the clinical utility of bncfDNA as a RIN biomarker.
Normal B Cell-Derived iPSCs Capable of Inducing RAS Mutants and Aid to Explore Myeloma-Initiating Cells
Authors: Ken-ichi Kudo, Naohiro Tsuyama, Misaki Takahashi Sugai, Yusuke Azami, Miwa Fukami, Yu Abe, Akinobu Ota, Karnan Sivasundaram, Moe Muramatsu, Megumi Sasatani, Yuko Hashimoto, Shigehira Saji, Kenji Kamiya, Ichiro Hanamura, Takayuki Ikezoe, Masafumi Onodera, Akira Sakai
Journal: Blood (2021)