tbuckley/cabot-search huggingface dataset:
Outcomes after Sequential Tyrosine Kinase Inhibitors Treatment in Chronic Phase Chronic Myeloid Leukemia
Authors: Jee Hyun Kong, Elliott F. Winton, Leonard Heffner, Manila Gaddh, Brittany Hill, Martha Arellano, Fuad El-Rassi, Audrey Kim, Anand Jillella, Vamsi K Kota
Journal: Blood (2017)
Placental HTRA1 cleaves α1-antitrypsin to generate a NET-inhibitory peptide
Authors: Robert A. Campbell, Heather D. Campbell, J. Samuel Bircher, Claudia Valeria de Araujo, Frederik Denorme, Jacob L. Crandell, John L. Rustad, Josh Monts, Mark J. Cody, Yasuhiro Kosaka, Christian C. Yost
Journal: Blood (2021)
SURGICAL SIMULATION OF PEDIATRIC BRAIN TUMORS USING VOLUME RENDERED 3D RECONSTRUCTION WITH FUSION IMAGES OF MULTIPLE HIGH-RESOLUTION 3D MR IMAGING TECHNIQUES
Authors: Aihara T, Fujita A, Fujii H, Miyata S, Kawamura Y, Annou T, Oguma H, Gomi A
Journal: Neuro-Oncology (2010)
Associations of Suicidality Trends With Cannabis Use as a Function of Sex and Depression Status
Authors: Beth Han, Wilson M. Compton, Emily B. Einstein, Nora D. Volkow
Journal: JAMA Network Open (2021)

<h3>Importance</h3> During the past decade, cannabis use among US adults has increased markedly, with a parallel increase in suicidality (ideation, plan, attempt, and death). However, associations between cannabis use and suicidality among young adults are poorly understood. <h3>Objective</h3> To determine whether cannabis use and cannabis use disorder (CUD) are associated with a higher prevalence of suicidality among young adults with or without depression and to assess whether these associations vary by sex. <h3>Design, Setting, and Participants</h3> This survey study examined data from 281 650 adults aged 18 to 34 years who participated in the National Surveys on Drug Use and Health. Data were collected from January 1, 2008, to December 31, 2019. <h3>Exposures</h3> Prevalence of past-year daily or near-daily cannabis use (≥300 days in the past year), CUD, and major depressive episode (MDE). Past-year CUD and MDE were based on<i>DSM-IV</i>diagnostic criteria. <h3>Main Outcomes and Measures</h3> Past-year suicidal ideation, plan, and attempt. <h3>Results</h3> Among the 281 650 adults aged 18 to 34 (men, 49.9% [95% CI, 49.6%-50.2%]; women, 50.1% [95% CI, 49.8%-50.4%]) included in the analysis, past-year suicidal ideation and plan along with daily cannabis use increased among all examined sociodemographic subgroups (except daily cannabis use among current high-school students), and past-year suicide attempt increased among most subgroups. National trends in adjusted prevalence of past-year suicidal ideation, plan, and attempt varied by daily and nondaily cannabis use and CUD among adults with or without MDE. After controlling for MDE, CUD, cannabis use status, and potential confounding factors, the adjusted prevalence of suicidal ideation, plan, and attempt increased 1.4 to 1.6 times from the 2008-2009 to 2018-2019 periods (adjusted risk ratio [ARR] for suicidal ideation, 1.4 [95% CI, 1.3-1.5]; ARR for suicide plan, 1.6 [95% CI, 1.5-1.9]; ARR for suicide attempt, 1.4 [95% CI, 1.2-1.7]), with 2008 to 2009 as the reference period. Past-year CUD, daily cannabis use, and nondaily cannabis use were associated with a higher prevalence of past-year suicidal ideation, plan, and attempt in both sexes (eg, among individuals without MDE, prevalence of suicidal ideation for those with vs without CUD was 13.9% vs 3.5% among women and 9.9% vs 3.0% among men;<i>P</i>&lt; .001), but significantly more so in women than men (eg, suicide plan among those with CUD and MDE was 52% higher for women [23.7%] than men [15.6%];<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> From 2008 to 2019, suicidal ideation, plan, and attempt increased 40% to 60% over increases ascribed to cannabis use and MDE. Future research is needed to examine this increase in suicidality and to determine whether it is due to cannabis use or overlapping risk factors.
Respiratory disease, and treatment / thematic poster session role of bronchoalveolar lavage in COVID-19 infection
Authors: E. Fountain, R. Munagala, S. Islam, V. S. Taskar
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Introduction: Mortality due to Coronavirus Disease 2019 (COVID-19) is nearly 50% in the intensive care unit (ICU).1,5 There is limited evidence on the role of bronchoalveolar lavage (BAL) to guide appropriate therapy in critically ill COVID-19 infection.2,3,4 We present our experience on the role of BAL identifying bacterial co-infection and to confirm diagnosis of COVID-19 in the ICU. Methods: This is an IRB approved, retrospective study of critically ill COVID-19 patients from March 2020 through July 2020. Critical illness was defined by: hypoxemia requiring >40% oxygen, septic shock or severe organ failure. COVID-19 was detected using reverse transcriptase polymerase chain reaction (rTPCR) performed on nasopharyngeal (NP) swab, BAL, or Mini-BAL. The Halyard Sampling Catheter was used at the time of intubation by respiratory therapists (RT) for mini-BAL. Bronchoscopic BAL was performed by physicians using a disposable bronchoscope. Results: 102 Patients were included. Mean age was 65±15 years with 56% males. 57% were African American, 33% Caucasian, and 9% Hispanic. Hypertension was present in 81% while 68% had BMI >30, and 48% had diabetes. 71% required mechanical ventilation for a median duration of 6 days. Median ICU length of stay was 10 days (range 1-51). Of 72 patients requiring intubation, mini-BAL was performed in 41 (57%) while bronchoscopic BAL was obtained in 8 (11%). 24 out of 49 (49%) had positive cultures. Staphylococcus aureus was identified in 15 of 24;53% of which were methicillin resistant. Other bacterial cultures are presented in Figure 1. Bacterial pneumonia was present <48hours post intubation in 6 of 24 patients. Mortality for those requiring intubation was 38% but increased to 46% with bacterial co-infection. Due to limited reagent availability, COVID-19 testing was not performed on all BAL specimens. Two patients in this cohort had imaging and clinical presentation consistent with COVID-19 but had negative NP swabs. BAL confirmed COVID-19 in both cases. Conclusion: The majority of critically ill COVID-19 patients were obese, African American males with hypertension. Most required mechanical ventilation and culture proven bacterial pneumonia was present in 8% within 48 hours of intubation. BAL provided critical information on bacterial coinfection which contributed to increased mortality in COVID-19. Furthermore, BAL may have a limited role in confirming COVID-19 when NP swab is negative. We recommend that all patients with critical COVID-19 undergo BAL at the time of intubation as identification and treatment of concomitant bacterial pneumonia may impact survival. .
Zenker’s peroral endoscopic myotomy, or flexible or rigid septotomy for Zenker’s diverticulum: a multicenter retrospective comparison
Authors: Sarah S. Al Ghamdi, Jad Farha, Robert A. Moran, Mathieu Pioche, Frédéric Moll, Dennis J. Yang, Oscar V. Hernández Mondragón, Michael Ujiki, Harry Wong, Alina Tantau, Alireza Sedarat, M. Phillip Fejleh, Kenneth Chang, David P. Lee, Jose M. Nieto, Sherif Andrawes, Gregory G. Ginsberg, Monica Saumoy, Amol Bapaye, Parag Dashatwar, Mohamad Aghaie Meybodi, Ariana C. Lopez, Omid Sanaei, Muhammad N. Yousaf, Manol Jovani, Yervant Ichkhanian, Olaya I. Brewer Gutierrez, Vivek Kumbhari, Ashli K. O’Rourke, Eric J. Lentsch, B. Joseph Elmunzer, Mouen A. Khashab
Journal: Endoscopy (2021)

<b>Background</b> Treatment of Zenker's diverticulum has evolved from open surgery to endoscopic techniques, including flexible and rigid endoscopic septotomy, and more recently, peroral endoscopic myotomy (Z-POEM). This study compared the effectiveness of flexible and rigid endoscopic septotomy with that of Z-POEM. <b>Methods</b> Consecutive patients who underwent endoscopic septotomy (flexible/rigid) or Z-POEM for Zenker's diverticulum between 1/2016 and 9/2019 were included. Primary outcomes were clinical success (decrease in Dakkak and Bennett dysphagia score to ≤ 1), clinical failure, and clinical recurrence. Secondary outcomes included technical success and rate/severity of adverse events. <b>Results</b> 245 patients (110 females, mean age 72.63 years, standard deviation [SD] 12.37 years) from 12 centers were included. Z-POEM was the most common management modality (n = 119), followed by flexible (n = 86) and rigid (n = 40) endoscopic septotomy. Clinical success was 92.7 % for Z-POEM, 89.2 % for rigid septotomy, and 86.7 % for flexible septotomy (<i>P</i> = 0.26). Symptoms recurred in 24 patients (15 Z-POEM during a mean follow-up of 282.04 [SD 300.48] days, 6 flexible, 3 rigid [<i>P</i> = 0.47]). Adverse events occurred in 30.0 % rigid septotomy patients, 16.8 % Z-POEM patients, and 2.3 % flexible septotomy patients (<i>P</i> < 0.05). <b>Conclusions</b> There was no difference in outcomes between the three treatment approaches for symptomatic Zenker's diverticulum. Rigid endoscopic septotomy was associated with the highest rate of complications, while flexible endoscopic septotomy appeared to be the safest. Recurrence following Z-POEM was similar to flexible and rigid endoscopic septotomy. Prospective studies with long-term follow-up are required.
Germline Tissues and DNA Sequencing Analysis Methods for Optimal Somatic Variant Detection in Myelodysplastic Syndrome (MDS)
Authors: Eric Padron, Jamie Teer, Markus Christian Ball, Jeffrey S Painter, Rami S. Komrokji, Ling Zhang, Lynn C. Moscinski, Mikkael A. Sekeres, Steven D. Gore, Rafael Bejar, Matthew J. Walter, Pearlie Epling-Burnette
Journal: Blood (2017)
The Evolutionary History of Wild, Domesticated, and Feral<i>Brassica oleracea</i>(Brassicaceae)
Authors: Makenzie E Mabry, Sarah D Turner-Hissong, Evan Y Gallagher, Alex C McAlvay, Hong An, Patrick P Edger, Jonathan D Moore, David A C Pink, Graham R Teakle, Chris J Stevens, Guy Barker, Joanne Labate, Dorian Q Fuller, Robin G Allaby, Timothy Beissinger, Jared E Decker, Michael A Gore, J Chris Pires
Journal: Molecular Biology and Evolution (2021)

Understanding the evolutionary history of crops, including identifying wild relatives, helps to provide insight for conservation and crop breeding efforts. Cultivated Brassica oleracea has intrigued researchers for centuries due to its wide diversity in forms, which include cabbage, broccoli, cauliflower, kale, kohlrabi, and Brussels sprouts. Yet, the evolutionary history of this species remains understudied. With such different vegetables produced from a single species, B. oleracea is a model organism for understanding the power of artificial selection. Persistent challenges in the study of B. oleracea include conflicting hypotheses regarding domestication and the identity of the closest living wild relative. Using newly generated RNA-seq data for a diversity panel of 224 accessions, which represents 14 different B. oleracea crop types and nine potential wild progenitor species, we integrate phylogenetic and population genetic techniques with ecological niche modeling, archaeological, and literary evidence to examine relationships among cultivars and wild relatives to clarify the origin of this horticulturally important species. Our analyses point to the Aegean endemic B. cretica as the closest living relative of cultivated B. oleracea, supporting an origin of cultivation in the Eastern Mediterranean region. Additionally, we identify several feral lineages, suggesting that cultivated plants of this species can revert to a wild-like state with relative ease. By expanding our understanding of the evolutionary history in B. oleracea, these results contribute to a growing body of knowledge on crop domestication that will facilitate continued breeding efforts including adaptation to changing environmental conditions.
Response to Open Peer Commentaries on “Informed Consent: What Must Be Disclosed and What Must Be Understood?”
Authors: Danielle Bromwich, Joseph Millum
Journal: The American Journal of Bioethics (2021)

This article refers to:Informed Consent: What Must Be Disclosed and What Must Be Understood?Informed Consent, Understanding, and TrustWhen Does Nudging Represent Fraudulent Disclosure?Promoting Disclosure and Understanding in Informed Consent: Optimizing the Impact of the Common Rule “Key Information” RequirementUtilizing Community Research Committees to Improve the Informed Consent ProcessVarieties of Minimalism about Informed ConsentThe Grounds of the Disclosure Requirement for Informed ConsentWhy Have Uniform Informed Consent Documents When the Research Volunteers Are So Diverse?Informed Consent Conversations: Neither the Beginning nor the End
Therapeutic Targeting of GLI1 in Acute Myeloid Leukemia
Authors: Metis Hasipek, Sayer Al-Harbi, James G Phillips, Bartlomiej P. Przychodzen, Alek Nielsen, Yihong Guan, Dale Grabowski, Phillip J Maciejewski, Aziz Nazha, Hetty E. Carraway, Jaroslaw P. Maciejewski, Babal K Jha
Journal: Blood (2017)
Abstract 355: Heart Failure Impairs Bone Marrow Mesenchymal Stem Cell Renewing Capacity and Migration
Authors: Victoria Florea, Cristina Sanina, Darcy Difede, Krystalenia Valasaki, Aisha Khan, Joshua Hare
Journal: Circulation Research (2016)

Background: Clinical trials have shown a sustained beneficial effect of bone marrow mesenchymal stem cells (MSCs) as a therapy for acute and chronic heart failure (HF). Clinical grade cell manufacturing of autologous and allogeneic MSCs is becoming a standard procedure. This study investigates the differences of bone marrow MSC isolation and expansion in favorable in vitro conditions. We compared MSC production from both healthy young donors and chronic HF patients. Methods: We analyzed MSC manufacturing records from five clinical trials: TAC-HFT (Ischemic cardiomyopathy (CMP), patient and donors), POSEIDON (Ischemic CMP, donors), POSEIDON DCM (Dilated CMP, donors), TRIDENT (Ischemic CMP, donors), and CRATUS (Frailty, donors). Results: All cells expressed CD105, CD90 and lacked hematopoietic marker CD45. The age of healthy donors (25.5 ± 0.7 y.o., N=24) and HF patients (56.1 ± 2.5, y.o., N=23), was significantly different (P&lt;0.0001). Collectively, the number of mononuclear cells (MNCs) isolated from bone marrow (volume range 58-125ml) didn’t differ between the groups. However, plated MNCs from healthy adults generated more MSCs than MNCs from HF patients (p0: 5.9x10^6±0.5x10^6, N=23 vs 3.8x10^6±0.4x10^6, N=24, respectively, P=0.003 and p1: 15.4x10^6±2.5x10^6, N=23 vs 10.8x10^6±1.1x10^6, N=24, respectively, P=0.036). No correlation was found between stem cell growth and age (35 to 78y.o.). Left ventricular ejection fraction (LVEF) in patients with HF had a direct correlation with MSC growth rate (P=0.03), particularly, in patients with severely depressed LVEF (&lt;30%), which had a tendency to generate less MSCs overall. Moreover, MSCs from HF patients demonstrated less migration compared to MSCs from healthy donors at 6, 10 and 24 hours (h) relative to baseline (6 h: 9.5±3.0% vs 30.7±2.1%; 10 h: 19.9±13.7% vs 53.1±2.5% and 24 h: 41.5±15.8% vs 88.9±1.6%, N=4, respectively. P=0.03). Conclusions: Despite equivalent numbers of MNCs, healthy young donors generate significantly more MSCs than HF patients, due to increased growth rate and higher number of resident stromal bone marrow stem cells. MSC migration was impaired in HF patients compared to healthy donors. HF appears to be an independent factor for MSC renewal capacity and culture phenotype.
Management of Blood Pressure in Patients With Chronic Kidney Disease Not Receiving Dialysis: Synopsis of the 2021 KDIGO Clinical Practice Guideline
Authors: Charles R.V. Tomson, Alfred K. Cheung, Johannes F.E. Mann, Tara I. Chang, William C. Cushman, Susan L. Furth, Fan Fan Hou, Gregory A. Knoll, Paul Muntner, Roberto Pecoits-Filho, Sheldon W. Tobe, Lyubov Lytvyn, Jonathan C. Craig, David J. Tunnicliffe, Martin Howell, Marcello Tonelli, Michael Cheung, Amy Earley, Joachim H. Ix, Mark J. Sarnak
Journal: Annals of Internal Medicine (2021)

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) 2021 clinical practice guideline for the management of blood pressure (BP) in patients with chronic kidney disease (CKD) not receiving dialysis is an update of the KDIGO 2012 guideline on the same topic and reflects new evidence on the risks and benefits of BP-lowering therapy among patients with CKD. It is intended to support shared decision making by health care professionals working with patients with CKD worldwide. This article is a synopsis of the full guideline. Methods: The KDIGO leadership commissioned 2 co-chairs to convene an international Work Group of researchers and clinicians. After a Controversies Conference in September 2017, the Work Group defined the scope of the evidence review, which was undertaken by an evidence review team between October 2017 and April 2020. Evidence reviews were done according to the Cochrane Handbook. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to guide the development of the recommendations and rate the strength and quality of the evidence. Practice points were included to provide guidance when evidence was insufficient to make a graded recommendation. The guideline was revised after public consultation between January and March 2020. Recommendations: The updated guideline comprises 11 recommendations and 20 practice points. This synopsis summarizes key recommendations pertinent to the diagnosis and management of high BP in adults with CKD, excluding those receiving kidney replacement therapy. In particular, the synopsis focuses on recommendations for standardized BP measurement and a target systolic BP of less than 120 mm Hg, because these recommendations differ from some other guidelines.
Abstract 14143: Renal Function on Admission is Associated With Future Left Ventricular Ejection Fraction Recovery in Patients With Acute Heart Failure: Insights From an Exploratory Analysis of General Clinical Parameters
Authors: Yuki Irie, Hiroyuki Takahama, Yasuhiro Hamatani, Masashi Amano, Atsushi Okada, Makoto Amaki, Takuya Hasegawa, Hideaki Kanzaki, Satoshi Yasuda, Chisato Izumi
Journal: Circulation (2019)

Backgrounds: Heart failure (HF) with recovered (improved) ejection fraction (HFiEF) has been recognized as a new category of HF. Although long-term prognosis differs between patients with HFiEF and...
Preclinical evaluation of eltrombopag in a PDX model of myelodysplastic syndromes
Authors: Nanni Schmitt, Johann-Christoph Jann, Eva Altrock, Johanna Flach, Justine Danner, Stefanie Uhlig, Alexander Streuer, Antje Knaflic, Vladimir Riabov, Qingyu Xu, Arwin Mehralivand, Iris Palme, Verena Nowak, Julia Obländer, Nadine Weimer, Verena Haselmann, Ahmed Jawhar, Ali Darwich, Cleo-Aron Weis, Alexander Marx, Laurenz Steiner, Mohamad Jawhar, Georgia Metzgeroth, Tobias Boch, Florian Nolte, Wolf-Karsten Hofmann, Daniel Nowak
Journal: Leukemia (2021)

Abstract Preclinical research of myelodysplastic syndromes (MDSs) is hampered by a lack of feasible disease models. Previously, we have established a robust patient-derived xenograft (PDX) model for MDS. Here we demonstrate for the first time that this model is applicable as a preclinical platform to address pending clinical questions by interrogating the efficacy and safety of the thrombopoietin receptor agonist eltrombopag. Our preclinical study included n = 49 xenografts generated from n = 9 MDS patient samples. Substance efficacy was evidenced by FACS-based human platelet quantification and clonal bone marrow evolution was reconstructed by serial whole-exome sequencing of the PDX samples. In contrast to clinical trials in humans, this experimental setup allowed vehicle- and replicate-controlled analyses on a patient–individual level deciphering substance-specific effects from natural disease progression. We found that eltrombopag effectively stimulated thrombopoiesis in MDS PDX without adversely affecting the patients’ clonal composition. In conclusion, our MDS PDX model is a useful tool for testing new therapeutic concepts in MDS preceding clinical trials.
Feasibility of cancer clinical trial enrollment goals based on cancer incidence.
Authors: George Nhat Tran, Matthew Harker, Karen Chiswell, Joseph M. Unger, Mark Fleury, Bradford Richard Hirsch, Kimberly Miller, Philip D'Almada, Sheri Tibbs, Yousuf Zafar
Journal: Journal of Clinical Oncology (2018)

20 Background: More than 20% of US clinical trials fail to accrue sufficient patients and terminate prematurely, impeding innovation and negating the valuable contributions of participating patients. The aim of this study is to estimate availability of patients for each trial opening in the national oncology clinical research portfolio to provide a benchmark for better understanding feasibility of clinical trial enrollment goals. Methods: The Database for Aggregate Analysis of ClinicalTrials.gov, up-to-date as of September 3, 2017, was used to identify actively-recruiting, interventional oncology trials at US sites. Observational studies were excluded as not all are registered. Trials were categorized via Medical Subject Headings or free text condition terms and sorted by cancer diagnosis. Trial slot availability was estimated between September 1, 2017, to August 31, 2018. Availability was estimated from total anticipated enrollment, assuming a constant recruitment rate. Estimates for studies with both foreign and US sites were pro-rated to calculate available enrollment in the US alone. The 2017 American Cancer Society cancer incidence estimates were used to approximate total US cancer diagnoses. Results: 4598 oncology trials were identified. Overall, an estimated 12.6 cancer patients are available for each clinical trial slot. The estimates by cancer diagnosis were: colorectal: 24.7 patients per trial slot; lung &amp; bronchus: 20.1; prostate: 17.6; breast (female): 13.8; leukemia 11.6; and brain &amp; other nervous system: 6.0. Conclusions: Across all diagnoses, 1 in 13 patients must enroll to meet accrual demands. This ratio varies by diagnosis. If cancer incidence is too low, trials with unrealistic accrual goals may be doomed at inception. In diagnoses with high disease burden, trial failure may be due to poor patient access or suboptimal design. [Table: see text]