tbuckley/cabot-search huggingface dataset:
Progression through return-to-sport and return-to-academics guidelines for concussion management and recovery in collegiate student athletes: findings from the Ivy League–Big Ten Epidemiology of Concussion Study
Authors: Douglas J Wiebe, Abigail C Bretzin, Bernadette A D'Alonzo
Journal: British Journal of Sports Medicine (2022)

Objective To examine the progression of collegiate student athletes through five stages of a return-to-activity protocol following sport-related concussion (SRC). Methods In a multisite prospective cohort study, we identified the frequency of initial 24–48 hours physical and cognitive rest, and the sequence of (1) symptom resolution and return to (2) exertion activity, (3) limited sport, (4) full sport and (5) full academics. In resulting profiles we estimated the likelihood of return to full sport ≤14 days or prolonged &gt;28 days and tested for variability based on timing of the stages. Results Among 1715 athletes with SRC (31.6% females), 67.9% had 24–48 hours initial physical and cognitive rest. The median was 6 days to return to full academics, 8 days to symptom resolution and 9 days to exertion. Three profiles emerged; all had the same sport-specific return progression, but varied in the relative timing of full academics. In unadjusted analyses, full academics as the first stage corresponded to the longest time to return to full sport, and initiating exertion the same day as symptom resolution resulted in the shortest time. In adjusted regression analyses, athletes initiating full academics while still symptomatic were 21.5% less likely (95% CI −27.4% to −15.5%) to return to full sport ≤14 days and, analogously, 19.1% more likely (95% CI 13.4% to 24.7%) to have prolonged return &gt;28 days. While additionally controlling for initial rest, sex, symptom count and concussion history, the likelihood of prolonged return &gt;28 days was 37.0% (95% CI 25.2% to 48.8%) in athletes initiating exertion considerably before symptoms resolved (ie, 7+ days), but only 3.6% (95% CI −1.4% to 8.6%) in athletes initiating exertion shortly before achieving symptom resolution (ie, 3–4 days). Conclusion We found evidence that sequential progressions were consistent with current recommendations including brief initial rest, and the initiation and relative timing of each stage impacted the final return-to-sport outcome.
Receipt of COVID-19 Booster Dose Among Fully Vaccinated Pregnant Individuals Aged 18 to 49 Years by Key Demographics
Authors: Hilda Razzaghi, Mehreen Meghani, Bradley Crane, Sascha Ellington, Allison L. Naleway, Stephanie A. Irving, Suchita A. Patel
Journal: JAMA (2022)

Ai-ris Y. Collier, MD; Katherine McMahan, MS; Jingyou Yu, PhD; Lisa H. Tostanoski, PhD; Ricardo Aguayo, BS; Jessica Ansel, NP; Abishek Chandrashekar, MS; Shivani Patel, BA; Esther Apraku Bondzie, BA; Daniel Sellers, BS; Julia Barrett, BS; Owen Sanborn, BS; Huahua Wan, MS; Aiquan Chang, BA; Tochi Anioke, BS; Joseph Nkolola, PhD; Connor Bradshaw, BS; Catherine Jacob-Dolan, BS; Jared Feldman, BS; Makda Gebre, MSc; Erica N. Borducchi, PhD; Jinyan Liu, PhD; Aaron G. Schmidt, PhD; Todd Suscovich, PhD; Caitlyn Linde, PhD; Galit Alter, PhD; Michele R. Hacker, ScD; Dan H. Barouch, MD, PhD
Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference
Authors: Anna Köttgen, Emilie Cornec-Le Gall, Jan Halbritter, Krzysztof Kiryluk, Andrew J. Mallett, Rulan S. Parekh, Hila Milo Rasouly, Matthew G. Sampson, Adrienne Tin, Corinne Antignac, Elisabet Ars, Carsten Bergmann, Anthony J. Bleyer, Detlef Bockenhauer, Olivier Devuyst, Jose C. Florez, Kevin J. Fowler, Nora Franceschini, Masafumi Fukagawa, Daniel P. Gale, Rasheed A. Gbadegesin, David B. Goldstein, Morgan E. Grams, Anna Greka, Oliver Gross, Lisa M. Guay-Woodford, Peter C. Harris, Julia Hoefele, Adriana M. Hung, Nine V.A.M. Knoers, Jeffrey B. Kopp, Matthias Kretzler, Matthew B. Lanktree, Beata S. Lipska-Ziętkiewicz, Kathleen Nicholls, Kandai Nozu, Akinlolu Ojo, Afshin Parsa, Cristian Pattaro, York Pei, Martin R. Pollak, Eugene P. Rhee, Simone Sanna-Cherchi, Judy Savige, John A. Sayer, Francesco Scolari, John R. Sedor, Xueling Sim, Stefan Somlo, Katalin Susztak, Bamidele O. Tayo, Roser Torra, Albertien M. van Eerde, André Weinstock, Cheryl A. Winkler, Matthias Wuttke, Hong Zhang, Jennifer M. King, Michael Cheung, Michel Jadoul, Wolfgang C. Winkelmayer, Ali G. Gharavi
Journal: Kidney International (2022)

Numerous genes for monogenic kidney diseases with classical patterns of inheritance, as well as genes for complex kidney diseases that manifest in combination with environmental factors, have been discovered. Genetic findings are increasingly used to inform clinical management of nephropathies, and have led to improved diagnostics, disease surveillance, choice of therapy, and family counseling. All of these steps rely on accurate interpretation of genetic data, which can be outpaced by current rates of data collection. In March of 2021, Kidney Diseases: Improving Global Outcomes (KDIGO) held a Controversies Conference on "Genetics in Chronic Kidney Disease (CKD)" to review the current state of understanding of monogenic and complex (polygenic) kidney diseases, processes for applying genetic findings in clinical medicine, and use of genomics for defining and stratifying CKD. Given the important contribution of genetic variants to CKD, practitioners with CKD patients are advised to "think genetic," which specifically involves obtaining a family history, collecting detailed information on age of CKD onset, performing clinical examination for extrarenal symptoms, and considering genetic testing. To improve the use of genetics in nephrology, meeting participants advised developing an advanced training or subspecialty track for nephrologists, crafting guidelines for testing and treatment, and educating patients, students, and practitioners. Key areas of future research, including clinical interpretation of genome variation, electronic phenotyping, global representation, kidney-specific molecular data, polygenic scores, translational epidemiology, and open data resources, were also identified.
Using a smartphone application maintains physical activity following pulmonary rehabilitation in patients with COPD: a randomised controlled trial
Authors: Marc Spielmanns, Rainer Gloeckl, Inga Jarosch, Daniela Leitl, Tessa Schneeberger, Tobias Boeselt, Stephan Huber, Pawandeep Kaur-Bollinger, Bernhard Ulm, Claudia Mueller, Jonas Bjoerklund, Sabine Spielmanns, Wolfram Windisch, Anna-Maria Pekacka-Egli, Andreas Rembert Koczulla
Journal: Thorax (2022)

Background Evidence suggests that patients with COPD struggle to maintain improved physical activity (PA) after completing pulmonary rehabilitation (PR). Smartphone applications (apps) providing a comprehensive training programme have conferred healthy benefits. This study was conducted to determine whether regular usage of an app maintains PA following PR. Methods Patients with stage II–IV COPD were enrolled in a 6-month trial following PR. After the screening period, participants were randomised into the Kaia COPD app group (intervention group (IG)) or the control group (CG). The primary outcome was PA (daily steps), measured using an activity tracker. Secondary outcomes included the COPD Assessment Test (CAT), the Chronic Respiratory Disease Questionnaire (CRQ) and the 1 min Sit-to-Stand Test (STST). Results Sixty participants completed the study. The median steps from baseline to 6 months were significantly different between the groups, in favour of the IG (−105.3, IQR −1970.1 to 2105.8, vs CG −1173.0, IQR −3813.1 to –93.8; p=0.007). CAT was significantly decreased in the IG (15.1±8.6 vs 19.7±6.4, p=0.02), whereas the CRQ subdomains for dyspnoea (4.5±1.7 vs 3.7±1.3, p=0.033) and fatigue (4.5±1.4 vs 3.5±1.3, p=0.028) improved significantly in the IG. The STST at 6 months was not significant. Sleep duration and sleep efficiency showed no significant differences between the two groups at any time. Conclusions A comprehensive program by using the Kaia app following PR maintained PA and improved symptoms in patients with COPD at 6 months. The app might be an important accessory tool for enhanced COPD care. Trial registration number DRKS00017275.
68Ga-DOTATATE Uptake in Well-Differentiated Neuroendocrine Tumor of the External Auditory Canal
Authors: Özge Erol Fenercioğlu, Ediz Beyhan, Rahime Şahin, Mehmet Can Baloğlu, Tevfik Fikret Çermik
Journal: Clinical Nuclear Medicine (2022)

Abstract A 38-year-old woman presented with a 4-month history of left-sided otalgia and otorrhea. Otoscopy revealed a mass in the left external auditory canal causing obliteration. A biopsy was taken, and the diagnosis was consistent with a well-differentiated neuroendocrine tumor. The patient was referred to our department for staging with 68 Ga-DOTATATE PET/CT. Increased radiopharmaceutical uptake was observed in the primary tumor and metastatic lymph nodes.
Longitudinal COVID-19-vaccination-induced antibody responses and Omicron neutralization in patients with lung cancer
Authors: Philip C Mack, Jorge E Gomez, Ananda M Rodilla, Juan Manuel Carreño, Chih-Yuan Hsu, Christian Rolfo, Noy Meshulami, Amy Moore, Rachel I Brody, Jennifer C King, Jacquelyn Treatman, Sooyun Lee, Ariel Raskin, Komal Srivastava, Charles R Gleason, Diego de Miguel-Perez, Johnstone Tcheou, Dominika Bielak, Rashmi Acharya, David E Gerber, Nicholas Rohs, Claudia I Henschke, David F Yankelevitz, Viviana Simon, John D Minna, Paul A Bunn, Adolfo García-Sastre, Florian Krammer, Yu Shyr, Fred R Hirsch
Journal: Cancer Cell (2022)
Sex Differences in Reported Adverse Drug Reactions to Angiotensin-Converting Enzyme Inhibitors
Authors: Sophie H. Bots, Michelle M. Schreuder, Jeanine E. Roeters van Lennep, Sarah Watson, Eugène van Puijenbroek, N. Charlotte Onland-Moret, Hester M. den Ruijter
Journal: JAMA Network Open (2022)

This cross-sectional study investigates differences by sex in reporting of adverse drug reactions associated with angiotensin-converting enzyme inhibitors combining global and prescription-corrected databases.
Extracellular Vesicles and Their Emerging Roles as Cellular Messengers in Endocrinology: An Endocrine Society Scientific Statement
Authors: Carlos Salomon, Saumya Das, Uta Erdbrügger, Raghu Kalluri, Sai Kiang Lim, Jerrold M Olefsky, Gregory E Rice, Susmita Sahoo, W Andy Tao, Pieter Vader, Qun Wang, Alissa M Weaver
Journal: Endocrine Reviews (2022)

Abstract During the last decade, there has been great interest in elucidating the biological role of extracellular vesicles (EVs), particularly, their hormone-like role in cell-to-cell communication. The field of endocrinology is uniquely placed to provide insight into the functions of EVs, which are secreted from all cells into biological fluids and carry endocrine signals to engage in paracellular and distal interactions. EVs are a heterogeneous population of membrane-bound vesicles of varying size, content, and bioactivity. EVs are specifically packaged with signaling molecules, including lipids, proteins, and nucleic acids, and are released via exocytosis into biofluid compartments. EVs regulate the activity of both proximal and distal target cells, including translational activity, metabolism, growth, and development. As such, EVs signaling represents an integral pathway mediating intercellular communication. Moreover, as the content of EVs is cell-type specific, it is a “fingerprint” of the releasing cell and its metabolic status. Recently, changes in the profile of EV and bioactivity have been described in several endocrine-related conditions including diabetes, obesity, cardiovascular diseases, and cancer. The goal of this statement is to highlight relevant aspects of EV research and their potential role in the field of endocrinology.
Donor plasmacytoid dendritic cells limit graft-versus-host disease through vasoactive intestinal polypeptide expression
Authors: Jingru Zhu, Yitong Wang, Jingxia Li, Pankoj Kumar Das, Hanwen Zhang, Tenzin Passang, Jian Ming Li, Tamas Nagy, Khanjan Gandhi, Sruthi Ravindranathan, Cynthia R. Giver, Mojibade Hassan, Yiwen Li, Alina Ulezko Antonova, Shuhua Wang, John D. Roback, Edmund K. Waller
Journal: Blood (2022)

Vasoactive intestinal polypeptide (VIP), an anti-inflammatory neuropeptide with pleiotropic cardiovascular effects, induces differentiation of hematopoietic stem cells into regulatory dendritic cells that limit graft-versus-host disease (GVHD) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. We have previously shown that donor plasmacytoid dendritic cells (pDCs) in bone marrow (BM) donor grafts limit the pathogenesis of GVHD. In this current study we show that murine and human pDCs express VIP, and that VIP-expressing pDCs limit T-cell activation and expansion using both in vivo and in vitro model systems. Using T cells or pDCs from transgenic luciferase+ donors in murine bone marrow transplantation (BMT), we show similar homing patterns of donor pDCs and T cells to the major sites for alloactivation of donor T cells: spleen and gut. Cotransplanting VIP-knockout (KO) pDCs with hematopoietic stem cells and T cells in major histocompatibility complex mismatched allogeneic BMT led to lower survival, higher GVHD scores, and more colon crypt cell apoptosis than transplanting wild-type pDCs. BMT recipients of VIP-KO pDCs had more T helper 1 polarized T cells, and higher plasma levels of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-α than recipients of wild-type pDCs. T cells from VIP-KO pDC recipients had increasing levels of bhlhe40 transcripts during the first 2 weeks posttransplant, and higher levels of CyclophilinA/Ppia transcripts at day 15 compared with T cells from recipients of wild-type pDCs. Collectively, these data indicate paracrine VIP synthesis by donor pDCs limits pathogenic T-cell inflammation, supporting a novel mechanism by which donor immune cells regulate T-cell activation and GVHD in allogeneic BMT.
Non-cleavable hinge enhances avidity and expansion of CAR-T cells for acute myeloid leukemia
Authors: Mark B. Leick, Harrison Silva, Irene Scarfò, Rebecca Larson, Bryan D. Choi, Amanda A. Bouffard, Kathleen Gallagher, Andrea Schmidts, Stefanie R. Bailey, Michael C. Kann, Max Jan, Marc Wehrli, Korneel Grauwet, Nora Horick, Matthew J. Frigault, Marcela V. Maus
Journal: Cancer Cell (2022)
Author Correction: A phase 1 trial of lipid-encapsulated mRNA encoding a monoclonal antibody with neutralizing activity against Chikungunya virus
Authors: Allison August, Husain Z. Attarwala, Sunny Himansu, Shiva Kalidindi, Sophia Lu, Rolando Pajon, Shu Han, Jean-Michel Lecerf, Joanne E. Tomassini, Marjie Hard, Leon M. Ptaszek, James E. Crowe, Tal Zaks
Journal: Nature Medicine (2022)

In the version of this article initially published, there were errors in the inset graph to Fig. 2a, where the inset had the graph lines and symbols for the 0.3 mg kg -1 and the 0.6 mg kg -1 switched, and the wrong data were shown for the 0.6 mg kg -1 in the inset.The labels and plots have been corrected in the HTML and PDF versions of the article.The original and corrected Fig 2a graphs are shown below.
SARS-CoV-2 Vaccination and Myocarditis in a Nordic Cohort Study of 23 Million Residents
Authors: Øystein Karlstad, Petteri Hovi, Anders Husby, Tommi Härkänen, Randi Marie Selmer, Nicklas Pihlström, Jørgen Vinsløv Hansen, Hanna Nohynek, Nina Gunnes, Anders Sundström, Jan Wohlfahrt, Tuomo A. Nieminen, Maria Grünewald, Hanne Løvdal Gulseth, Anders Hviid, Rickard Ljung
Journal: JAMA Cardiology (2022)

Reports of myocarditis after SARS-CoV-2 messenger RNA (mRNA) vaccination have emerged.
A 3D‐Bioprinted Multiple Myeloma Model (Adv. Healthcare Mater. 7/2022)
Authors: Di Wu, Zongyi Wang, Jun Li, Yan Song, Manuel Everardo Mondragon Perez, Zixuan Wang, Xia Cao, Changliang Cao, Sushila Maharjan, Kenneth C. Anderson, Dharminder Chauhan, Yu Shrike Zhang
Journal: Advanced Healthcare Materials (2022)

Coaxial Extrusion In article number 2100884 by Kenneth C. Anderson, Dharminder Chauhan, Yu Shrike Zhang, and co-workers, a high-content in vitro model of multiple myeloma is produced using a coaxial extrusion bioprinting method, allowing formation of a human bone marrow-like microenvironment featuring an outer mineral-containing sheath and an inner soft hydrogel-based core. The embedded myeloma cells reveal favorable characteristics of growth kinetics and drug responses, providing potential new insights for myeloma modeling, drug development, and personalizable therapy.
Cost-Accuracy Analysis of Chronic Obstructive Pulmonary Disease Screening in Low- and Middle-Income Countries
Authors: Sakshi Mohan, Maria Kathia Cárdenas, Federico Ricciardi, Trishul Siddharthan, Suzanne L. Pollard, Natalie A. Rykiel, William Checkley, John R. Hurst, Marta O. Soares, Patricia Alupo, Julie A. Barber, Maria Kathia Cárdenas, Ram K. Chandyo, William Checkley, Santa Kumar Das, Oscar Flores-Flores, John R. Hurst, Bruce Kirenga, J. Jaime Miranda, Sakshi Mohan, Suzanne L. Pollard, Shumonta A. Quaderi, Federico Ricciardi, Natalie A. Rykiel, Arun K. Sharma, Laxman Shrestha, Trishul Siddharthan, Marta O. Soares, Adaeze C. Wosu
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Cost-Accuracy Analysis of Chronic Obstructive Pulmonary Disease Screening in Low- and Middle-Income Countries." American Journal of Respiratory and Critical Care Medicine, 206(3), pp. 353–356
Body mass index associated with monoclonal gammopathy of undetermined significance (MGUS) progression in Olmsted County, Minnesota
Authors: Geffen Kleinstern, Dirk R. Larson, Cristine Allmer, Aaron D. Norman, Grace Muntifering, Jason Sinnwell, Alissa Visram, Vincent Rajkumar, Angela Dispenzieri, Robert A. Kyle, Susan L. Slager, Shaji Kumar, Celine M. Vachon
Journal: Blood Cancer Journal (2022)

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant clonal disorder that progresses to multiple myeloma (MM), or other plasma-cell or lymphoid disorders at a rate of 1%/year. We evaluate the contribution of body mass index (BMI) to MGUS progression beyond established clinical factors in a population-based study. We identified 594 MGUS through a population-based screening study in Olmsted County, Minnesota, between 1995 and 2003. Follow-up time was calculated from the date of MGUS to last follow-up, death, or progression to MM/another plasma-cell/lymphoid disorder. BMI (kg/m 2 &lt; 25/≥25) was measured close to screening date. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association of BMI ≥ 25 versus BMI &lt; 25 with MGUS progression and also evaluated the corresponding c-statistic and 95% CI to describe discrimination of the model for MGUS progression. Median follow-up was 10.5 years (range:0–25), while 465 patients died and 57 progressed and developed MM ( N = 39), AL amyloidosis ( N = 8), lymphoma ( N = 5), or Waldenstrom-macroglobulinemia ( N = 5). In univariate analyses, BMI ≥ 25 (HR = 2.14,CI:1.05–4.36, P = 0.04), non-IgG (HR = 2.84, CI:1.68–4.80, P = 0.0001), high monoclonal (M) protein (HR = 2.57, CI:1.50–4.42, P = 0.001), and abnormal free light chain ratio (FLC r ) (HR = 3.39, CI:1.98–5.82, P &lt; 0.0001) were associated with increased risk of MGUS progression, and were independently associated in a multivariable model (c-statistic = 0.75, CI:0.68–0.82). The BMI association was stronger among females (HR = 3.55, CI:1.06–11.9, P = 0.04) vs. males (HR = 1.39, CI:0.57–3.36, P = 0.47), although the interaction between BMI and sex was not significant ( P = 0.15). In conclusion, high BMI is a prognostic factor for MGUS progression, independent of isotype, M protein, and FLC r . This association may be stronger among females.
Re: Alterations in 18F-FDG PET/MRI and 15O-Water PET Brain Findings in Patients With Neurological Symptoms After COVID-19 Vaccination: A Pilot Study
Authors: Rujittika Mungmunpuntipantip, Viroj Wiwanitkit
Journal: Clinical Nuclear Medicine (2022)

Private Academic Consultant, Bangkok, Thailand [email protected] Dr DY Patil University, Pune, India. Conflicts of interest and sources of funding: none declared.
Leveraging epigenomic patterns to resolve the heterogeneity and origins of CNS germ cell tumors
Authors: Srinidhi Varadharajan, Stephen C Mack
Journal: Neuro-Oncology (2022)

Germ cell tumors (GCTs) are a heterogeneous group of tumors of germ cells, primarily occurring in gonads, however, about one-third of GCTs can also occur in extragonadal sites. Although significant strides have been made in studying this group of tumors, a clear understanding of the underlying molecular pathogenesis is still lacking. Central nervous system (CNS) GCTs are relatively rare tumors predominantly occurring in young and adolescent males, with a considerable geographical variation in incidence.1 CNS GCTs are classified into two major groups, germinomas and non-germinomatous germ cell tumors (NGGCTs). The latter is a heterogenous group consisting of subtypes, including yolk sac tumors, embryonal carcinomas, choriocarcinomas, and teratomas, often occurring as mixed GCTs. Germinomas account for up to ~65% of the CNS GCT and are extremely sensitive to chemotherapy and radiation.1 In contrast, NGGCTs require intense chemotherapy and radiation, and sometimes surgical resection. Distinct epigenetic programs in these subgroups may underscore disparate molecular underpinnings, clinical outcomes, and response to therapy.
The brain in pediatric critical care: unique aspects of assessment, monitoring, investigations, and follow-up
Authors: Kate L. Brown, Shruti Agrawal, Matthew P. Kirschen, Chani Traube, Alexis Topjian, Ronit Pressler, Cecil D. Hahn, Barnaby R. Scholefield, Hari Krishnan Kanthimathinathan, Aparna Hoskote, Felice D’Arco, Melania Bembea, Joseph C. Manning, Maayke Hunfeld, Corinne Buysse, Robert C. Tasker
Journal: Intensive Care Medicine (2022)
PET/CT Imaging of Hemorrhagic Pseudotumor Arising From Treated Plasmacytoma
Authors: Jameson L. Cumsky, Ba Duong Nguyen
Journal: Clinical Nuclear Medicine (2022)

Abstract Hemorrhagic pseudotumor occurs in approximately 1% to 2% of patients with hemophilia. This lesion is exceptionally rare in nonhemophiliac individuals. The authors present a case of treated right ischial plasmacytoma with a progressively enlarging expansile hemorrhagic pseudotumor, documented on 18 F-FDG PET/CT and MRI and confirmed by histology.
Superiority of 11C-Choline PET/CT in the Delineation of a Rare Intracranial Diffuse Embryonic Tumor
Authors: Ye Dong, Wenlan Zhou, Yanjiang Han, Hubing Wu
Journal: Clinical Nuclear Medicine (2022)

Intracranial diffuse embryonal tumor in the adult is rare. We report a young woman with a diffuse embryonal malignancy in the saddle area, which was depicted well by 11 C-choline PET/CT, superior to 18 F-FDG PET/CT and contrast-enhanced MRI. Under the guiding of 11 C-choline PET/CT, the biopsy was successfully performed and the diagnosis was established. This case highlights that 11 C-chione PET/CT may be useful to diagnose and delineate the intracranial diffuse embryonic tumors.
Shall We Dance: Evolving Partnerships of Targeted Therapies for AML
Authors: Alexander E. Perl, Paresh Vyas
Journal: Clinical Cancer Research (2022)

Summary Two publications detailing the clinical outcomes of patients with acute myeloid leukemia and mutations in IDH1, IDH2, or FLT3 who received initial therapy with venetoclax and azacitidine provide new insights into risk stratification and set the stage for future trials integrating molecularly targeted therapy with this new standard regimen. See related articles by Konopleva et al., p. 2744 and Pollyea et al., p. 2753