tbuckley/cabot-search huggingface dataset:
Brentuximab Vedotin for Relapsed or Refractory Sézary Syndrome
Authors: Daniel J. Lewis, Paul L. Haun, Sara S. Samimi, Carmela C. Vittorio, Jennifer Villasenor-Park, Stefan K. Barta, Daniel J. Landsburg, Jakub Svoboda, Sunita D. Nasta, Stephen J. Schuster, Alain H. Rook, Ellen J. Kim
Journal: JAMA Dermatology (2020)

Treatment options for Sézary syndrome (SS) are limited and associated with low response rates. Brentuximab vedotin is a CD30-directed antibody-drug conjugate approved for refractory CD30-positive cutaneous T-cell lymphoma. However, limited data exist on its efficacy in SS, including in the pivotal phase 3 ALCANZA (A Phase 3 Trial of Brentuximab Vedotin (SGN-35) Versus Physician's Choice [Methotrexate or Bexarotene] in Participants With CD30-Positive Cutaneous T-Cell Lymphoma) trial.To assess the preliminary efficacy and tolerability of brentuximab vedotin for SS.From January 1, 2017, to July 31, 2020, a total of 13 patients with SS received brentuximab vedotin and were analyzed as part of a retrospective case series. Median follow-up was 10.4 months (range, 1.4-34.6 months). All patients were 18 years or older with a diagnosis of SS and with B2 blood involvement at the time brentuximab vedotin therapy was initiated. This single-center study was conducted at a major academic referral center.Intravenous brentuximab vedotin administration approximately every 3 weeks.The primary end point was the global response rate. Outcomes were assessed in the skin and lymph nodes per the 2011 European Organization for Research and Treatment of Cancer-International Society of Cutaneous Lymphoma response criteria and in the blood per the 2018 Prospective Cutaneous Lymphoma International Prognostic Index revised blood response criteria.The study included 13 patients (8 [62%] male; mean [SD] age, 68.2 [8.6] years). Of these 13 patients, 5 (38%) achieved a global response after a median of 6 cycles, including 1 complete response. Response rates by disease compartment were 38% in the skin, 63% in the blood, and 50% in the lymph nodes. Three of 11 patients (27%) with pruritus reported improvement. Skin CD30 positivity (>10%) was detected in 9 patients but was not associated with responses. Among responders, the median time to response was 6 weeks (range, 6-9 weeks), and the median duration of response was 5.5 months (range, 2.5-28.9 months). The median time to next treatment was 3.2 months (range, 1.5-36.7 months). Peripheral neuropathy occurred in 4 patients but resolved in 2 patients. Grade 2 adverse events were neuropathy (n = 2), constipation (n = 1), and hand-foot syndrome (n = 1).In this case series, brentuximab vedotin use was associated with some efficacy in SS across multiple disease compartments and in the setting of refractory disease or low CD30 skin expression. Brentuximab vedotin may offer a manageable treatment schedule and low incidence of significant toxic effects.
Abstract 339: A Novel Continuous Heart Rate Variability Based Analytic to Predict Clinical Hemodynamic Instability Requiring Intervention
Authors: Ashwin Belle, Kevin R Ward, Bryce Benson, Mark Salamango, Fadi Islim
Journal: Circulation (2018)

Background: Sudden in-hospital hemodynamic instability (HI) due to cardiovascular and/or cardiorespiratory distress is a common occurrence. Causes can include hemorrhage, sepsis, pneumonia, heart failure, and others. Due to the body’s compensatory mechanisms, heart and respiratory rate, and blood pressure can be late indicators of HI. When detected late or left unrecognized HI can lead to complications and even death. Heart rate variability (HRV) has been demonstrated to reflect the status of the autonomic nervous system with changes in HRV linked to HI. However, to date, HRV has not demonstrated sufficient accuracies in adults to warrant widespread adoption. We have developed a novel nonlinear single lead ECG HRV analytic based on signal processing and machine learning features specific to HI physiology. Objective: Validate the capability, accuracy, and lead times of the HRV analytic to predict HI in hospitalized patients who were subjects of Rapid Response Team (RRT) activations. Methods: We retrospectively analyzed 4483 hours of ECG data from 22 RRT patient cases (16 male, 6 female) using the previously developed HRV analytic. A multi-clinician review adjudicated the occurrence of HI and need for intervention. The prediction lead time prior to the RRT call was calculated for these cases. Results: Of the 22 RRT cases, 13 calls were due to HI requiring a range of life-saving interventions, and 9 RRT cases for reasons not associated with HI and requiring no life-saving interventions. The analytic correctly distinguished between HI vs. non-HI RRT calls with 100% accuracy thus displaying 100% positive and negative predictive values. In the HI cases, the analytic detected HI with a median lead time of 7.7 hours prior to the RRT call with a range of 14 minutes to 38.4 hours. Conclusion: In this RRT cohort, a novel HRV analytic developed through machine learning based on HI physiology demonstrated its potential to forecast HI well before vital signs and other factors led to RRT activation resulting in life-saving interventions. These substantial lead times, as well as the ability to distinguish HI from non-HI RRT calls, may lead to the ability to reduce HI and improve outcomes while reducing unnecessary RRT activations.
Cocaine use disorder: A look at metabotropic glutamate receptors and glutamate transporters
Authors: Ewa Niedzielska-Andres, Lucyna Pomierny-Chamioło, Michał Andres, Maria Walczak, Lori A. Knackstedt, Małgorzata Filip, Edmund Przegaliński
Journal: Pharmacology & Therapeutics (2021)
2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy: Executive Summary
Authors: Steve R. Ommen, Seema Mital, Michael A. Burke, Sharlene M. Day, Anita Deswal, Perry Elliott, Lauren L. Evanovich, Judy Hung, José A. Joglar, Paul Kantor, Carey Kimmelstiel, Michelle Kittleson, Mark S. Link, Martin S. Maron, Matthew W. Martinez, Christina Y. Miyake, Hartzell V. Schaff, Christopher Semsarian, Paul Sorajja
Journal: Circulation (2020)

Aim This executive summary of the hypertrophic cardiomyopathy clinical practice guideline provides recommendations and algorithms for clinicians to diagnose and manage hypertrophic cardiomyopathy in adult and pediatric patients as well as supporting documentation to encourage their use. Methods A comprehensive literature search was conducted from January 1, 2010, to April 30, 2020, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Collaboration, Agency for Healthcare Research and Quality reports, and other relevant databases. Structure Many recommendations from the earlier hypertrophic cardiomyopathy guidelines have been updated with new evidence or a better understanding of earlier evidence. This summary operationalizes the recommendations from the full guideline and presents a combination of diagnostic work-up, genetic and family screening, risk stratification approaches, lifestyle modifications, surgical and catheter interventions, and medications that constitute components of guideline directed medical therapy. For both guideline-directed medical therapy and other recommended drug treatment regimens, the reader is advised to follow dosing, contraindications and drug-drug interactions based on product insert materials.
특발성 비신단락을 동반한 간경변증 환자의 간성 척수병증 2예
Authors: 구자은, 임영석, 명선정, 서경석, 김강모, 이한주, 정영화, 이영상, 서동진
Journal: Clinical and Molecular Hepatology (2008)

Hepatic myelopathy is a rare complication of chronic liver disease that is associated with extensive portosystemic shunts. The main clinical feature of hepatic myelopathy is progressive spastic paraparesis in the absence of sensory or sphincter impainn1ent. Early and accurate diagnosis of hepatic myelopathy is important because patients with early stages of the disease can fully recover following liver transplantation. Motor-evoked potential studies may be suitable for the early diagnosis of hepatic myelopathy, even in patients with preclinical stages of the disease. Here we describe two patients who presented with spastic paraparesis associated with a spontaneous splenorenal shunt and without any previous episode of hepatic encephalopathy. One patient experienced improved neurologic symptoms after liver transplantation, whereas the other patient only received medical treatment, which did not prevent the progression of spastic paraparesis. (Korean J Hepatol 2008;14:89-96)
Stimulation of B Cell Immunity in Flavivirus-Naive Individuals by the Tetravalent Live Attenuated Dengue Vaccine TV003
Authors: Huy A. Tu, Usha K. Nivarthi, Nancy R. Graham, Philip Eisenhauer, Matthew J. Delacruz, Kristen K. Pierce, Stephen S. Whitehead, Jonathan E. Boyson, Jason W. Botten, Beth D. Kirkpatrick, Anna P. Durbin, Aravinda M. deSilva, Sean A. Diehl
Journal: Cell Reports Medicine (2020)

The tetravalent live attenuated dengue vaccine candidate TV003 induces neutralizing antibodies against all four dengue virus serotypes (DENV1–DENV4) and protects against experimental challenge with DENV2 in humans. Here, we track vaccine viremia and B and T cell responses to this vaccination/challenge model to understand how vaccine viremia links adaptive immunity and development of protective antibody responses. TV003 viremia triggers an acute plasmablast response that, in combination with DENV-specific CD4+ T cells, correlates with serum neutralizing antibodies. TV003 vaccinees develop DENV2-reactive memory B cells, including serotype-specific and multivalent specificities in line with the composition of serum antibodies. There is no post-challenge plasmablast response in vaccinees, although stronger and earlier post-TV003 plasmablast responses associate with sterile humoral protection from DENV2 challenge. TV003 vaccine triggers plasmablasts and memory B cells, which, with support from CD4+ T cells, functionally link early vaccine viremia and the serum antibody responses.
Gastroesophageal Reflux Disease
Authors: John Maret-Ouda, Sheraz R. Markar, Jesper Lagergren
Journal: JAMA (2020)

<h3>Importance</h3> Gastroesophageal reflux disease (GERD) is defined by recurrent and troublesome heartburn and regurgitation or GERD-specific complications and affects approximately 20% of the adult population in high-income countries. <h3>Observations</h3> GERD can influence patients' health-related quality of life and is associated with an increased risk of esophagitis, esophageal strictures, Barrett esophagus, and esophageal adenocarcinoma. Obesity, tobacco smoking, and genetic predisposition increase the risk of developing GERD. Typical GERD symptoms are often sufficient to determine the diagnosis, but less common symptoms and signs, such as dysphagia and chronic cough, may occur. Patients with typical GERD symptoms can be medicated empirically with a proton pump inhibitor (PPI). Among patients who do not respond to such treatment or if the diagnosis is unclear, endoscopy, esophageal manometry, and esophageal pH monitoring are recommended. Patients with GERD symptoms combined with warning symptoms of malignancy (eg, dysphagia, weight loss, bleeding) and those with other main risk factors for esophageal adenocarcinoma, such as older age, male sex, and obesity, should undergo endoscopy. Lifestyle changes, medication, and surgery are the main treatment options for GERD. Weight loss and smoking cessation are often useful. Medication with a PPI is the most common treatment, and after initial full-dose therapy, which usually is omeprazole 20 mg once daily, the aim is to use the lowest effective dose. Observational studies have suggested several adverse effects after long-term PPI, but these findings need to be confirmed before influencing clinical decision making. Surgery with laparoscopic fundoplication is an invasive treatment alternative in select patients after thorough and objective assessments, particularly if they are young and healthy. Endoscopic and less invasive surgical techniques are emerging, which may reduce the use of long-term PPI and fundoplication, but the long-term safety and efficacy remain to be scientifically established. <h3>Conclusions and Relevance</h3> The clinical management of GERD influences the lives of many individuals and is responsible for substantial consumption of health care and societal resources. Treatments include lifestyle modification, PPI medication, and laparoscopic fundoplication. New endoscopic and less invasive surgical procedures are evolving. PPI use remains the dominant treatment, but long-term therapy requires follow-up and reevaluation for potential adverse effects.
High C-Reactive Protein and D-Dimer on Admission Predict the Development of AKI in Patients Hospitalized with COVID-19
Authors: Sandheep Venkataraman, Zhiying You, Jessica B. Kendrick
Journal: Journal of the American Society of Nephrology (2020)

Journal of the American Society of Nephrology 31(10S):p 250, October 2020. | DOI: 10.1681/ASN.20203110S1250b
Circuit Clotting on Continuous Venovenous Hemofiltration in COVID-19 Patients at New England’s Largest Health Safety-Net Hospital
Authors: Claire Avillach, Megan E. Feeney, Mohamed T. Hassan Kamel, Hassan Mahmoud, Aileen W. Zhen, Natasha Awais, Sandeep Ghai
Journal: Journal of the American Society of Nephrology (2020)

Avillach, Claire; Feeney, Megan E.; Hassan Kamel, Mohamed T.; Mahmoud, Hassan; Zhen, Aileen W.; Awais, Natasha; Ghai, Sandeep Author Information
Bortezomib, lenalidomide, and dexamethasone with or without elotuzumab in patients with untreated, high-risk multiple myeloma (SWOG-1211): primary analysis of a randomised, phase 2 trial
Authors: Saad Z Usmani, Antje Hoering, Sikander Ailawadhi, Rachael Sexton, Brea Lipe, Sandi Fredette Hita, Jason Valent, Michael Rosenzweig, Jeffrey A Zonder, Madhav Dhodapkar, Natalie Callander, Todd Zimmerman, Peter M Voorhees, Brian Durie, S Vincent Rajkumar, Paul G Richardson, Robert Z Orlowski
Journal: The Lancet Haematology (2020)
Identification of diverse tumor endothelial cell populations in malignant glioma
Authors: Jeff C Carlson, Manuel Cantu Gutierrez, Brittney Lozzi, Emmet Huang-Hobbs, Williamson D Turner, Burak Tepe, Yiqun Zhang, Alexander M Herman, Ganesh Rao, Chad J Creighton, Joshua D Wythe, Benjamin Deneen
Journal: Neuro-Oncology (2020)

Abstract Background Glioblastoma is the most common and aggressive type of primary brain tumor, as most patients succumb to the disease less than two years after diagnosis. Critically, studies demonstrate that glioma recruits surrounding blood vessels, while some work suggests that tumor stem cells themselves directly differentiate into endothelial cells, yet the molecular and cellular dynamics of the endothelium in glioma are poorly characterized. The goal of this study was to establish molecular and morphological benchmarks for tumor associated vessels (TAVs) and tumor derived endothelial cells (TDECs) during glioblastoma progression. Methods Using In-Utero Electroporation and CRISPR/Cas9 genome engineering to generate a native, immunocompetent mouse model of glioma, we characterized vascular-tumor dynamics in three dimensions during tumor progression. We employed bulk and single-cell RNA-Sequencing to elucidate the relationship between TAVs and TDECs. We confirmed our findings in a patient derived orthotopic xenograft (PDOX) model. Results Using a mouse model of glioma, we identified progressive alteration of vessel function and morphogenesis over time. We also showed in our mouse model that TDECs are a rare subpopulation that contributes to vessels within the tumor, albeit to a limited degree. Furthermore, transcriptional profiling demonstrates that both TAVs and TDECs are molecularly distinct, and both populations feature extensive molecular heterogeneity. Finally, the distinct molecular signatures of these heterogeneous populations are also present in human glioma. Conclusions Our findings show extensive endothelial heterogeneity within the tumor and tumor microenvironment and provide insights into the diverse cellular and molecular mechanisms that drive glioma vascularization and angiogenesis during tumorigenesis.
The Global Landscape of SARS-CoV-2 Genomes, Variants, and Haplotypes in 2019nCoVR
Authors: Shuhui Song, Lina Ma, Dong Zou, Dongmei Tian, Cuiping Li, Junwei Zhu, Meili Chen, Anke Wang, Yingke Ma, Mengwei Li, Xufei Teng, Ying Cui, Guangya Duan, Mochen Zhang, Tong Jin, Chengmin Shi, Zhenglin Du, Yadong Zhang, Chuandong Liu, Rujiao Li, Jingyao Zeng, Lili Hao, Shuai Jiang, Hua Chen, Dali Han, Jingfa Xiao, Zhang Zhang, Wenming Zhao, Yongbiao Xue, Yiming Bao
Journal: Genomics Proteomics & Bioinformatics (2020)

Abstract On January 22, 2020, China National Center for Bioinformation (CNCB) released the 2019 Novel Coronavirus Resource (2019nCoVR), an open-access information resource for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 2019nCoVR features a comprehensive integration of sequence and clinical information for all publicly available SARS-CoV-2 isolates, which are manually curated with value-added annotations and quality evaluated by an automated in-house pipeline. Of particular note, 2019nCoVR offers systematic analyses to generate a dynamic landscape of SARS-CoV-2 genomic variations at a global scale. It provides all identified variants and their detailed statistics for each virus isolate, and congregates the quality score, functional annotation, and population frequency for each variant. Spatiotemporal change for each variant can be visualized and historical viral haplotype network maps for the course of the outbreak are also generated based on all complete and high-quality genomes available. Moreover, 2019nCoVR provides a full collection of SARS-CoV-2 relevant literature on the coronavirus disease 2019 (COVID-19), including published papers from PubMed as well as preprints from services such as bioRxiv and medRxiv through Europe PMC. Furthermore, by linking with relevant databases in CNCB, 2019nCoVR offers data submission services for raw sequence reads and assembled genomes, and data sharing with NCBI. Collectively, SARS-CoV-2 is updated daily to collect the latest information on genome sequences, variants, haplotypes, and literature for a timely reflection, making 2019nCoVR a valuable resource for the global research community. 2019nCoVR is accessible at https://bigd.big.ac.cn/ncov/.
Chemical Control of Pulmonary Ventilation
Authors: Hans Winterstein
Journal: New England Journal of Medicine (1956)

THE strange phenomena observed during a stay in high mountains attracted attention long before even the most elementary bases of respiratory physiology had been laid down by Lavoisier and Spallanzani. In the present age, in which airplanes take man easily to heights previously undreamed of, there is an infinitely greater interest in these problems. The conquerors of the highest of the earth's peaks have shown that man can become adapted to altitude conditions that would soon kill him if he were suddenly exposed to them. I cannot trace the historical aspects of this problem, which is surely among the most . . .
Differential Regulation of Cancer Progression by CDK4/6 Plays a Central Role in DNA Replication and Repair Pathways
Authors: Meiou Dai, Julien Boudreault, Ni Wang, Sophie Poulet, Girija Daliah, Gang Yan, Alaa Moamer, Sergio A. Burgos, Siham Sabri, Suhad Ali, Jean-Jacques Lebrun
Journal: Cancer Research (2020)

Abstract Although the cyclin-dependent kinases CDK4 and CDK6 play fundamental roles in cancer, the specific pathways and downstream targets by which they exert their tumorigenic effects remain elusive. In this study, we uncover distinct and novel functions for these kinases in regulating tumor formation and metastatic colonization in various solid tumors, including those of the breast, prostate, and pancreas. Combining in vivo CRISPR-based CDK4 and CDK6 gene editing with pharmacologic inhibition approaches in orthotopic transplantation and patient-derived xenograft preclinical models, we defined clear functions for CDK4 and CDK6 in facilitating tumor growth and progression in metastatic cancers. Transcriptomic profiling of CDK4/6 CRISPR knockouts in breast cancer revealed these two kinases to regulate cancer progression through distinct mechanisms. CDK4 regulated prometastatic inflammatory cytokine signaling, whereas CDK6 mainly controlled DNA replication and repair processes. Inhibition of CDK6 but not CDK4 resulted in defective DNA repair and increased DNA damage. Multiple CDK6 DNA replication/repair genes were not only associated with cancer subtype, grades, and poor clinical outcomes, but also facilitated primary tumor growth and metastasis in vivo. CRISPR-based genomic deletion of CDK6 efficiently blocked tumor formation and progression in preestablished cell- and patient-derived xenograft preclinical models of breast cancer, providing a potential novel targeted therapy for these deadly tumors. Significance: In-depth transcriptomic analysis identifies cyclin-dependent kinases CDK4 and CDK6 as regulators of metastasis through distinct signaling pathways and reveals the DNA replication/repair pathway as central in promoting these effects.
Letter regarding the article ‘<scp>Effects</scp> of hyperkalaemia and non‐adherence to renin–angiotensin–aldosterone system inhibitor therapy in patients with heart failure in <scp>Italy</scp>: a propensity‐matched study’
Authors: Hidenori Moriyama, Takashi Kohno, Shun Kohsaka
Journal: European Journal of Heart Failure (2020)
Unhealthy Alcohol Use—A Common Iatrogenic Complication of Bariatric Surgery
Authors: Anne C. Fernandez
Journal: JAMA Network Open (2020)

Matthew L. Maciejewski, PhD; Valerie A. Smith, DrPH; Theodore S. Z. Berkowitz, MS; David E. Arterburn, MD, MPH; James E. Mitchell, MD; Maren K. Olsen, PhD; Chuan-Fen Liu, PhD; Edward H. Livingston, MD, MS; Luke M. Funk, MD, MPH; Adenike Adeyemo, MPH; Katharine A. Bradley, MD
123I Scan With Whole-Body Retention Measurement at 48 Hours for Simplified Dosimetry Before 131I Treatment of Metastatic Thyroid Cancer
Authors: Jolanta M. Durski, Carrie B. Hruska, Trond V. Bogsrud, Mabel Ryder, Geoffrey B. Johnson
Journal: Clinical Nuclear Medicine (2020)

A previously published model (Atkins) allows for calculation of 131I maximum tolerated activity on the basis of 48-hour whole-body retention of 131I on a pretherapy diagnostic scan. Our practice uses iodine 123I for diagnostic imaging of metastatic thyroid cancer for staging before 131I therapy, with images typically acquired 24 hours after administration of the radiopharmaceutical. We explored the feasibility of an additional 123I whole-body scan and retention measurement at 48 hours, with application of the model to estimate maximum tolerated activity of radioiodine before 131I treatment of metastatic thyroid cancer.