tbuckley/cabot-search huggingface dataset:
QCOVID in Scotland: time to recalibrate our expectations?
Authors: Rishi K Gupta, Maarten van Smeden
Journal: Thorax (2021)

The field of prediction modelling has exploded during the COVID-19 pandemic, with countless studies seeking to derive and/or validate models to assist diagnosis of SARS-CoV-2 or to predict clinical outcomes of infection. While the vast majority of reports have been of a poor standard,1 there have been some examples of higher quality work, including the QCOVID prognostic model.2 Whereas most prediction models are intended to predict a single outcome, QCOVID seeks to predict the risk of acquiring and then either dying from or being hospitalised with SARS-CoV-2 in the general population. The model was originally derived using data from 6.1 million people in England during the first pandemic wave (January–April 2020) and showed promising performance in a recent analysis by the Office for National Statistics over a similar time period.3 QCOVID is implemented online,4 although stipulated for research rather than clinical use, and provides distinct probabilities of COVID-19 hospitalisation and COVID-19 mortality.

Simpson et al report an external validation of QCOVID using data from Scotland over two periods (1 March 2020 to 30 April 2020 and 1 May 2020 to 30 June 2020), designed to test the performance of the algorithms during time intervals that aligned with the original QCOVID derivation and temporal validation cohorts.5 The authors use a population-based approach, including data from primary care facilities covering an impressive 99% of the Scottish population. The data provided …
CC-92480 Enhances Cell-Autonomous Cytotoxicity through Blockade of G 2/M Transition When Combined with Bortezomib/Dexamethasone in Pre-Clinical Multiple Myeloma
Authors: Chad C Bjorklund, Michael Amatangelo, Jian Kang, Hsiling Chiu, Archana Mukhopadhyay, Krista Wollerman, Michael Pourdehnad, Patrick Hagner, Anjan Thakurta
Journal: Blood (2021)
COVID-19 Outcomes Among Participants in the NHLBI Myelodysplastic Syndromes (MDS) Natural History Study
Authors: Eric Padron, Donnie Hebert, Steven D. Gore, Nancy Gillis, Rami S. Komrokji, Wael Saber, Tareq Al Baghdadi, Jane Jijun Liu, Edward J. Gorak, Cecilia Lee, Christine Borchert, Steffanie H. Wilson, Jason Thompson, Mary Ellen Walker, Nancy L. DiFronzo, Amy E. DeZern, Mikkael A. Sekeres
Journal: Blood (2021)
SCRI-CAR19x22v2 T Cell Product Demonstrates Bispecific Activity in B-ALL
Authors: Colleen Annesley, Corinne Summers, Michael A. Pulsipher, Jodi L. Skiles, Amanda M. Li, Anant Vatsayan, Catherine Lindgren, Stephanie Mgebroff, Ashley Wilson, Wenjun Huang, Qian Vicky Wu, Josh Gustafson, Christopher Brown, Michael C. Jensen, Julie R. Park, Rebecca A Gardner
Journal: Blood (2021)
BRAF Fusions in Histiocytic Disorders: Frequency and Clinical Characteristics
Authors: Saurabh Zanwar, Jithma P. Abeykoon, Aldo A. Acosta-Medina, Aishwarya Ravindran, Karen Rech, Jonathan Schwartz, Nora Bennani, Mithun V. Shah, Diana Morlote, Gaurav Goyal, Ronald Go
Journal: Blood (2021)
Michael Rutter: the UK’s first professor of child psychiatry
Authors: John Illman
Journal: BMJ (2021)

Photo credit: Corbin O’Grady Studio/SPL

The so called father of child psychiatry, Michael Rutter (“Mike”) led the first research into psychiatric and physical disorders in children where researchers spoke directly to the children. The landmark Isle of Wight studies (1964-74) ridiculed the dogma that what children thought and said did not matter. Rutter, the genial author of more than 40 books and some 400 papers, insisted: “They do matter.”

In Fifteen Thousand Hours , the time most children were estimated to spend in school, he challenged the strategy of despair that had left many schools as little more than institutions of containment for disadvantaged children. In a three year urban study, he and his colleagues showed conclusively that schools could make a difference and that some were demonstrably better than others.

Rutter was pivotal in the bitter nature versus nurture controversy dividing behaviour geneticists and psychosocial researchers. Reviewing Rutter’s highly acclaimed Genes and Behaviour—Nature-Nurture Interplay Explained in the British Journal of Psychiatry , Michael J Owen observed that as in many intellectual disputes, the flames had been fanned by evangelists on both sides.

Rutter’s knowledge, understanding, and formidable analytical approach, Owen wrote, probably made him one of the few people in the world who could have written such a book. “The problems and the issues are dissected and …
Deciphering the Individual Contribution of Absolute Neutrophil, Lymphocyte and Monocyte Counts to Thrombosis Risk in Patients with Myeloproliferative Neoplasms
Authors: Faiqa Farrukh, Paola Guglielmelli, Giuseppe Gaetano Loscocco, Animesh D. Pardanani, Curtis A. Hanson, Valerio De Stefano, Tiziano Barbui, Naseema Gangat, Alessandro M. Vannucchi, Ayalew Tefferi
Journal: Blood (2021)
Abstract 9213: Effect of Ai-Enabled Ecg Screening for Low Ef in Patients With Different Socioeconomic Status
Authors: Shaheen Kurani, Jonathan Inselman, David R Rushlow, Rozalina G McCoy, Thomas Thacher, Emma Behnken, Matthew Bernard, Steven L Rosas, Abdulla Akfaly, Artika Misra, Paul Molling, Joseph Krien, Randy Foss, Barbara Barry, Konstantinos Siontis, Suraj Kapa, Bernard J Gersh, Patricia A Pellikka, Francisco Lopez-jimenez, Zachi Attia, John D Halamka, Paul Friedman, Peter A Noseworthy, Xiaoxi Yao
Journal: Circulation (2021)

Introduction: Asymptomatic LV systolic dysfunction is often underdiagnosed, leading to missed opportunities for treatment. In a recently completed pragmatic RCT, an AI algorithm performed on the ECGs ordered as part of routine practice increased early diagnosis of low EF. The current study aimed to understand whether the effectiveness of the AI algorithm integrated into routine care differed by the socioeconomic status of the patient. Methods: The main findings of the RCT were previously published. Clinicians in the intervention group had access to AI results (i.e., a positive or negative screening result, with positive results indicating a high likelihood of low EF). When a positive result was found, clinicians in the intervention group received an alert that encouraged them to order TTE if considered clinically appropriate. Clinicians in the control group did not have access or received alerts. Area deprivation index (ADI) was used to measure area-level social determinants of health. This study included 16,992 patients (control 8,225; intervention: 8,767) who had ECG performed for any indications between 8/5/2019 and 3/31/2020, no prior HF, and a valid address to derive ADI. The primary endpoint was a new diagnosis of EF≤50% within 3 months. Results: The mean age was 60.5±17.6 y. AI increased the diagnosis of low EF in the overall cohort (OR 1.42 [1.13, 1.78], p=0.01). The magnitude of benefit was greater in patients with higher socioeconomic status, e.g., living in an area that is less deprived (OR 1.88 [1.16, 3.05]), with higher median income, lower poverty rate, higher education level, better housing conditions, and higher proportion of white-collar workers, although the interaction was not statistically significant (Figure). Conclusions: AI enables early diagnosis of low EF and the magnitude of benefit might be numerically greater in patients with higher socioeconomic status, possibly due to variations in access to or referral for subsequent testing.
<i>Ex Vivo</i> Drug Sensitivity Testing to Predict Response to Venetoclax + Azacitidine in Acute Myeloid Leukemia: Interim Results of the Prospective Multicenter Phase II Venex Trial
Authors: Heikki Kuusanmäki, Sari Kytölä, Ida Vänttinen, Amanda Ranta, Tanja Ruokoranta, Annasofia Holopainen, Sirpa Koskela, Milla E.L. Kuusisto, Kimmo Porkka, Riikka Räty, Imre Västrik, Krister Wennerberg, Caroline A. Heckman, Pia Ettala, Marja Pyörälä, Johanna Rimpiläinen, Timo Siitonen, Mika Kontro
Journal: Blood (2021)
RNA Binding Protein Syncrip Is Required for the Low-Output HSC By Sustaining Proteome Quality
Authors: Florisela Herrejon Chavez, Paolo Cifani, Alli Pine, Karen L Chu, Ersilia Barin, Alexandra Schurer, Hanzhi Luo, Diu T.T. Nguyen, Alex Kentsis, Christina Leslie, Michael G Kharas, Ly P Vu
Journal: Blood (2021)
A novel polypectomy technique: the “ropeway method” for resection of large pedunculated polyps
Authors: Daiki Nemoto, Yuki Nakajima, Yosuke Takahata, Kohei Suzuki, Masato Aizawa, Alan Kawarai Lefor, Kazutomo Togashi
Journal: Endoscopy (2021)

Pedunculated polyps at narrow or sharply bending areas in the colonic lumen can be challenging for endoscopic resection [1] [2] [3] [4] [5]. We report a newly invented technique, the “ropeway method,” to improve endoscopic resection of pedunculated polyps assisted by traction.
Abstract 9384: Evolocumab, a Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitor, Reduces Doxorubicin, Trastuzumab and Nivolumab Induced Cardiotoxicity Through Mtorc1 and Myd88 Related Pathways
Authors: Nicola Maurea, Martina Iovine, Simona Buccolo, Andrea Paccone, Francesca Cerrone, Vincenzo Quagliariello
Journal: Circulation (2021)

Introduction: The PCSK9 inhibitor evolocumab reduced low-density lipoprotein cholesterol and cardiovascular events in the FOURIER randomized clinical trial. Recent studies indicates the crucial involvement of PCSK9 in regulation of cardiac cell metabolism and survival. Doxorubicin and trastuzumab-induced cardiotoxicity still remains a clinically relevant problem in cancer patients. Patients treated with nivolumab experienced myocarditis, arrhythmia and heart failure; therefore finding new cardioprotective strategies in this patient cohort is a very important clinical need. Hypothesis: Considering the expression of PCSK9 in heart tissue and cardiomyocytes, we aimed to study the direct effects of evolocumab in cardiomyocytes during exposure to doxorubicin, trastuzumab and nivolumab Methods: Human fetal cardiomyocytes were exposed to subclinical concentration of doxorubicin, trastuzumab (both at 100 nM), nivolumab (200 nM) alone or in combination with evolocumab (50 nM) for 48h. After the incubation period, we performed the following analysis: cell viability, apoptosis and necrosis, lipid peroxidation and intracellular Ca 2+ concentration. Through ELISA method, we studied the expression of NLRP3 inflammasome, MyD88, mTORC1, nuclear NF-κB. Intracellular concentration of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF were also performed. Results: Evolocumab co-incubated with anticancer drugs increased significantly the cell viability from 38 to 58 % compared to doxorubicin, trasuzumab and nivolumab groups (p&lt;0,01 for all). Evolocumab downregulates MyD88, mTORC-1 and nuclear NF-kB with a significant reduction in IL-1α, IL-1β, IL17-α, G-CSF and GM-CSF (p&lt;0.05 vs doxorubicin, trasuzumab and nivolumab groups). Conclusions: The PCSK9 inhibitor evolocumab exerts cytoprotective effects on cardiomyocytes during exposure to doxorubicin, trastuzumab and anti PD-1 antibody nivolumab. This study open to new preclinical trials aimed to decrease cardiotoxicity during anticancer therapies.
Abstract 17189: Radiation-induced Accelerated Multi-valve Disease In A Patient With Subaortic Membrane
Authors: Mariana Garcia-Arango, Shravya Vinnakota, Hector R Villarraga
Journal: Circulation (2021)

A 69-year-old woman with history of right breast cancer status post lumpectomy and radiation (4.2 cGy) 18 months prior, presented with progressive NYHA class III dyspnea. TTE obtained prior to her cancer diagnosis was notable for normal LV size and wall thickness, a subaortic membrane with systolic mean Doppler gradient of 21 mmHg and a mildly thickened mitral valve without significant stenosis or regurgitation. On presentation, TTE was notable for severely increased concentric LV wall thickness (LV mass index 140 g/m 2 ), preserved ejection fraction, increased RV wall thickness, subaortic stenosis with systolic mean Doppler gradient 35 mmHg, moderate-severe aortic regurgitation, thickened mitral valve with posterior leaflet tethering and anterior leaflet override causing severe mitral regurgitation and moderate mitral stenosis (valve area 1.7 cm 2 by pressure half-time). She underwent a surgical intervention with septal myectomy, subaortic membrane resection, aortic root reconstruction, aortic and mitral valve replacement with bioprostheses. She did well post-operatively and had complete resolution of symptoms following cardiac rehabilitation. Radiation-induced valvular heart disease is linked to the total dose of radiation, use of sequential chemotherapy and time since irradiation, with a typical latency of 10-20 years. However, there is paucity of data regarding the influence of these variables in patients with pre-existing valve disease. This case illustrates dramatic acceleration of underlying aortic and mitral valve pathology in a patient with a subaortic membrane, 18 months after radiation. We also noted development of significant concentric LV hypertrophy that was disproportionate to the degree of obstruction across the sub-aortic membrane. Potential candidates for radiation therapy must be carefully screened for pre-existing valve disease, which should warrant increased vigilance and early screening for progressive valve disease.
Trends in Utilization of Stored Cryopreserved Autologous Peripheral Hematopoietic Cells (APBHC) Intended for a Second (or beyond) Autologous Hematopoietic Cell Transplantation (AHCT) in Patients with Multiple Myeloma (MM): A Single Center Experience
Authors: Farah Yassine, Mohamed A. Kharfan-Dabaja, Athanasios Tsalatsanis, Vivek Roy, Abba C. Zubair, Hemant S. Murthy, Ernesto Ayala, Madiha Iqbal, Taimur Sher, Sikander Ailawadhi, Ricardo D Parrondo
Journal: Blood (2021)
First-in-Human Study of WT1 Recombinant Protein Vaccination in Elderly Patients with AML in Remission: A Single-Center Experience
Authors: Stefanie Kreutmair, Dietmar Pfeifer, Miguel Waterhouse, Konstanze Döhner, Anna Frey, Justus Duyster, Anna Lena Illert, Michael Schmitt, Michael Lübbert
Journal: Blood (2021)
Hiding in the dark: pan-cancer characterization of expression and clinical relevance of CD40 to immune checkpoint blockade therapy
Authors: Chi Yan, Ann Richmond
Journal: Molecular Cancer (2021)

Highlights CD40 expression correlates with the type I anti-tumor response and better survival. Pan-cancer bioinformatics characterization reveals reduced CD40 expression in 11 cancer types, including RAS mut melanoma compared to nevi. RAS mutation correlates with reduced CD40 expression in malignant melanoma. CD40 expression is associated with better response to immune checkpoint blockade therapy in melanoma.
Abstract 11962: Early Diagnosis of Type-2 Cardio-renal Syndrome by Doppler Sonographic Evaluation of Renal Vasoconstriction
Authors: David Sacerdoti, Silvia Gaiani, Silvia Tonello, Enrica Franceschini, Paola Pesce, Paola Bizzotto, Giancarlo Bombonato, Cristiano Sarais, Massimo Bolognesi
Journal: Circulation (2012)

Renal failure of type-2 cardio-renal syndrome is due to renal hypoperfusion secondary to heart failure and is mediated by an imbalance between vasoconstrictors and vasodilators. The decrease in glo...
Sex Differences in the Pattern of Patient Referrals to Male and Female Surgeons
Authors: Fahima Dossa, Dan Zeltzer, Rinku Sutradhar, Andrea N. Simpson, Nancy N. Baxter
Journal: JAMA Surgery (2021)

<h3>Importance</h3> Studies have found that female surgeons have fewer opportunities to perform highly remunerated operations, a circumstance that contributes to the sex-based pay gap in surgery. Procedures performed by surgeons are, in part, determined by the referrals they receive. In the US and Canada, most practicing physicians who provide referrals are men. Whether there are sex-based differences in surgical referrals is unknown. <h3>Objective</h3> To examine whether physicians' referrals to surgeons are influenced by the sex of the referring physician and/or surgeon. <h3>Design, Setting, and Participants</h3> This cross-sectional, population-based study used administrative databases to identify outpatient referrals to surgeons in Ontario, Canada, from January 1, 1997, to December 31, 2016, with follow-up to December 31, 2018. Data analysis was performed from April 7, 2019, to May 14, 2021. <h3>Exposures</h3> Referring physician sex. <h3>Main Outcomes and Measures</h3> This study compared the proportion of referrals (overall and those referrals that led to surgery) made by male and female physicians to male and female surgeons to assess associations between surgeon, referring physician, or patient characteristics and referral decisions. Discrete choice modeling was used to examine the extent to which sex differences in referrals were associated with physicians' preferences for same-sex surgeons. <h3>Results</h3> A total of 39 710 784 referrals were made by 44 893 physicians (27 792 [61.9%] male) to 5660 surgeons (4389 [77.5%] male). Female patients made up a greater proportion of referrals to female surgeons than to male surgeons (76.8% vs 55.3%,<i>P</i> &lt; .001). Male surgeons accounted for 77.5% of all surgeons but received 87.1% of referrals from male physicians and 79.3% of referrals from female physicians. Female surgeons less commonly received procedural referrals than male surgeons (25.4% vs 33.0%,<i>P</i> &lt; .001). After adjusting for patient and referring physician characteristics, male physicians referred a greater proportion of patients to male surgeons than did female physicians; differences were greatest among referrals from other surgeons (rate ratio, 1.14; 95% CI, 1.13-1.16). Female physicians had a 1.6% (95% CI, 1.4%-1.9%) greater odds of same-sex referrals, whereas male physicians had a 32.0% (95% CI, 31.8%-32.2%) greater odds of same-sex referrals; differences did not attenuate over time. <h3>Conclusions and Relevance</h3> In this cross-sectional, population-based study, male physicians appeared to have referral preferences for male surgeons; this disparity is not narrowing over time or as more women enter surgery. Such preferences lead to lower volumes of and fewer operative referrals to female surgeons and are associated with sex-based inequities in medicine.
Instructive cartilage regeneration modalities with advanced therapeutic implantations under abnormal conditions
Authors: Zhonghan Wang, Hanxiang Le, Yanbing Wang, He Liu, Zuhao Li, Xiaoyu Yang, Chenyu Wang, Jianxun Ding, Xuesi Chen
Journal: Bioactive Materials (2021)

The development of interdisciplinary biomedical engineering brings significant breakthroughs to the field of cartilage regeneration. However, cartilage defects are considerably more complicated in clinical conditions, especially when injuries occur at specific sites (e.g., osteochondral tissue, growth plate, and weight-bearing area) or under inflammatory microenvironments (e.g., osteoarthritis and rheumatoid arthritis). Therapeutic implantations, including advanced scaffolds, developed growth factors, and various cells alone or in combination currently used to treat cartilage lesions, address cartilage regeneration under abnormal conditions. This review summarizes the strategies for cartilage regeneration at particular sites and pathological microenvironment regulation and discusses the challenges and opportunities for clinical transformation.
Deleting DNMT3A in CAR T cells prevents exhaustion and enhances antitumor activity
Authors: Brooke Prinzing, Caitlin C. Zebley, Christopher T. Petersen, Yiping Fan, Alejandro Allo Anido, Zhongzhen Yi, Phuong Nguyen, Haley Houke, Matthew Bell, Dalia Haydar, Charmaine Brown, Shannon K. Boi, Shanta Alli, Jeremy Chase Crawford, Janice M. Riberdy, Jeoungeun J. Park, Sheng Zhou, Mireya Paulina Velasquez, Chris DeRenzo, Cicera R. Lazzarotto, Shengdar Q. Tsai, Peter Vogel, Shondra M. Pruett-Miller, Deanna M. Langfitt, Stephen Gottschalk, Ben Youngblood, Giedre Krenciute
Journal: Science Translational Medicine (2021)

DNMT3A deletion preserves CAR T cell functionality during prolonged stimulation.
Abstract 9367: Predictors of Renal Function Improvement After Left Ventricular Assist Device Implantation in Moderate to Severe Chronic Kidney Disease
Authors: Rayhan Saiani, Ozan Unlu, Hector Sepulveda Alemany, Maria Pabon, Parag Goyal, Irina Sobol, Udhay Krishnan, Evelyn M Horn, Vesh Srivatana, Stuart Saal, Frank Liu, Maria G Karas
Journal: Circulation (2021)

Introduction: Renal dysfunction remains a relative contraindication to left ventricular assist device (LVAD) implantation due to postoperative morbidity and mortality in advanced stages of chronic kidney disease (CKD). However, correlates of early improvement and long-term durability of renal function have not been well elucidated in this population. Methods: We evaluated 113 consecutive patients who underwent LVAD implantation in our center from 2008 - 2019. Patients with pre-LVAD glomerular filtration rate (GFR) &lt; 60 mL/min (defined as the highest GFR reported within 30 days prior to implantation) were included. Demographic, clinical, echocardiographic, and hemodynamic data were collected during the index admission and up to two years after implantation. Results: Seventy-two patients met inclusion criteria (mean age 61 ± 12 years, male 88%, white 39%, nonischemic cardiomyopathy 60%, hypertension 61%, diabetes 47%, destination therapy 72%, HeartMate [HM] II 76%, HM3 24%). Forty-three patients (60%) had an increase and 26 (36%) had a &gt;25% improvement in GFR 3 months after implantation. The absence of proteinuria, defined as &gt;150 mg/day per a spot urine protein:creatinine ratio, was associated with &gt;25% improvement in GFR 3 months postoperatively (OR 3.85, 95% CI 1.24- 12.0, p = 0.02). No history of coronary artery disease, higher pre-implant albumin and hemoglobin levels, and shorter intra-operative bypass times were also associated with &gt;25% improvement in renal function at 3 months (all p &lt;0.05). Average GFR improved one month after LVAD implantation and remained stably improved for up to two years in patients with moderate to severe CKD (Figure). Conclusion: Early improvement in renal function appears to be durable for at least two years after LVAD implantation in patients with moderate to severe CKD. The absence of proteinuria, potentially reflecting a lack of intrinsic renal disease, may predict early improvement in renal function after LVAD implantation.
Estimating Selection Bias in Previous Monoclonal Gammopathy of Undetermined Significance Research - the Importance of Screening: Results from the Population-Based Screening Study Iceland Screens, Treats or Prevents Multiple Myeloma (iStopMM)
Authors: Aðalbjörg Ýr Sigurbergsdóttir, Sæmundur Rögnvaldsson, Sigrun Thorsteinsdottir, Ingigerdur Solveig Sverrisdottir, Gudrun Asta Sigurdardottir, Brynjar Vidarsson, Pall Torfi Onundarson, Bjarni Agnar Agnarsson, Margret Sigurdardottir, Ingunn Thorsteinsdottir, Isleifur Olafsson, Asdis Rosa Thordardottir, Gauti Kjartan Gislason, Andri Olafsson, Petros Kampanis, Malin Hultcrantz, Brian G.M. Durie, Stephen Harding, Ola Landgren, Thorvardur Jon Love, Sigurdur Y Kristinsson
Journal: Blood (2021)
Herpesvirus Infections of Intestinal Tract in the Patients with Intestinal Graft-Versus-Host Diseases: Laboratory Diagnosis Based on DNA Detection By Real-Time Quantitative PCR in Feces Samples
Authors: Ren Lin, Wenjun Liu, Fen Huang, Tingyue Luo, Wenjian Mo, Yingying Gu, Na Xu, Yuan Chang, Zhiping Fan, Xinquan Liang, Yuanbin Wu, Shunqing Wang, Jing Du, Liu Hui, Caixia Wang, Jing Sun, Qifa Liu
Journal: Blood (2021)