tbuckley/cabot-search huggingface dataset:
Gatekeeper Training and the Medical Community’s Fight Against Depression and Suicide—A Shared Burden
Authors: Kathleen C. Gallagher, Colleen E. Taylor
Journal: JAMA Surgery (2020)

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FT-4202, an Allosteric Activator of Pyruvate Kinase-R, Demonstrates Proof of Mechanism and Proof of Concept after a Single Dose and after Multiple Daily Doses in a Phase 1 Study of Patients with Sickle Cell Disease
Authors: R. Clark Brown, Kimberly Cruz, Theodosia A. Kalfa, Frans A. Kuypers, Santosh L. Saraf, Jeremie H. Estepp, Luke R. Smart, Punam Malik, Mark Lerman, Renae Mayer, Maria D. Ribadeneira, Sanjeev Forsyth, Patricia Schroeder, Eric Wu, Patrick Kelly, Marilyn J. Telen
Journal: Blood (2020)
YTHDF1-enhanced iron metabolism depends on TFRC m<sup>6</sup>A methylation
Authors: Jing Ye, Zhanggui Wang, Xiaozhen Chen, Xiaohua Jiang, Zhihuai Dong, Sunhong Hu, Wenya Li, Yuehui Liu, Bing Liao, Weidong Han, Jiaying Shen, Mang Xiao
Journal: Theranostics (2020)

Background: Among head and neck squamous cell carcinomas (HNSCCs), hypopharyngeal squamous cell carcinoma (HPSCC) has the worst prognosis. Iron metabolism, which plays a crucial role in tumor progression, is mainly regulated by alterations to genes and post-transcriptional processes. The recent discovery of the N6-methyladenosine (m6A) modification has expanded the realm of previously undiscovered post-transcriptional gene regulation mechanisms in eukaryotes. Many studies have demonstrated that m6A methylation represents a distinct layer of epigenetic deregulation in carcinogenesis and tumor proliferation. However, the status of m6A modification and iron metabolism in HPSCC remains unknown. Methods: Bioinformatics analysis, sample analysis, and transcriptome sequencing were performed to evaluate the correlation between m6A modification and iron metabolism. Iron metabolic and cell biological analyses were conducted to evaluate the effect of the m6A reader YTHDF1 on HPSCC proliferation and iron metabolism. Transcriptome-wide m6A-seq and RIP-seq data were mapped to explore the molecular mechanism of YTHDF1 function in HPSCC. Results: YTHDF1 was found to be closely associated with ferritin levels and intratumoral iron concentrations in HPSCC patients at Sir Run Run Shaw Hospital. YTHDF1 induced-HPSCC tumorigenesis depends on iron metabolism in vivo in vitro. Mechanistically, YTHDF1 methyltransferase domain interacts with the 3'UTR and 5'UTR of TRFC mRNA, then further positively regulates translation of m6A-modified TFRC mRNA. Gain-of-function and loss-of-function analyses validated the finding showing that TFRC is a crucial target gene for YTHDF1-mediated increases in iron metabolism. Conclusion: YTHDF1 enhanced TFRC expression in HPSCC through an m6A-dependent mechanism. From a therapeutic perspective, targeting YTHDF1 and TFRC-mediated iron metabolism may be a promising strategy for HPSCC.
Venetoclax with azacitidine or decitabine in patients with newly diagnosed acute myeloid leukemia: Long term follow‐up from a phase 1b study
Authors: Daniel A. Pollyea, Keith Pratz, Anthony Letai, Brian A. Jonas, Andrew H. Wei, Vinod Pullarkat, Marina Konopleva, Michael J. Thirman, Martha Arellano, Pamela S. Becker, Brenda Chyla, Wan‐Jen Hong, Qi Jiang, Jalaja Potluri, Courtney D. DiNardo
Journal: American Journal of Hematology (2020)

This analysis represents the longest-term follow-up for patients with acute myeloid leukemia (AML) treated with 400 mg of venetoclax plus azacitidine or decitabine. Adults with newly diagnosed AML ineligible for intensive chemotherapy were enrolled in an open-label, non-randomized, multicenter phase 1b trial of venetoclax with azacitidine (AZA; 75 mg/m2 ; days 1-7) or decitabine (DEC; 20 mg/m2 ; days 1-5). Endpoints included safety, response rates (complete remission [CR], CR with incomplete blood count recovery [CRi]), response duration and overall survival (OS). The median follow-up time was 29 and 40 months for patients treated with venetoclax plus AZA and DEC combinations, respectively. Key Grade ≥ 3 AEs (AZA and DEC) were febrile neutropenia (39% and 65%), anemia (30% and 26%), thrombocytopenia (25% and 23%), and neutropenia (20% and 10%). The CR/CRi rate was 71% for venetoclax plus AZA and 74% for venetoclax plus DEC. The median duration of CR/CRi was 21.9 months and 15.0 months, and the median OS was 16.4 months and 16.2 months, for venetoclax plus AZA and DEC, respectively. These results support venetoclax plus hypomethylating agents as highly effective frontline AML therapies for patients unfit for intensive chemotherapy.
Abstract 421: Norepinephrine Catabolism Drives Cardiac Fibroblast Activation via Monoamine Oxidase Activity and Rage/β-adrenergic Signaling
Authors: Blake Monroe, Ethan J Anderson
Journal: Circulation Research (2020)

The mitochondrial enzyme monoamine oxidase A (MAO-A) plays an increasingly appreciated role in cardiac remodeling induced by diabetes and ischemic injury. Oxidative deamination of norepinephrine (NE) by MAO-A generates 3,4-dihydroxyphenylglycolaldehyde (DOPEGAL) and H 2 O 2 . Isolation and quantification of catechol-modified proteins from cardiac fibroblast lysate using an aminophenylboronic acid resin showed an MAO-dependent accumulation of catechol adducts in NE-treated cells (P&lt;0.05). Our lab has previously observed increased expression and activity of MAO in myocardium of diabetes patients compared with age-matched nondiabetic patients. Moreover, preliminary data suggest that catecholaldehydes and other biogenic aldehydes might contribute to the pathogenesis of cardiac fibrosis in diabetic cardiomyopathy via pro-fibrotic signaling mechanisms. We hypothesize that NE activates fibroblasts by both canonical pathways (i.e, adrenergic receptors) and by monoamine oxidase-mediated catabolism and activation of the receptor for advanced glycation endproducts (RAGE). Treatment of cardiac fibroblasts with NE (1 μM) resulted in accelerated proliferation, enhanced collagen I &amp; III secretion, robust increases in mitochondrial and total cellular ROS, and upregulated pro-fibrotic gene expression. These effects were abrogated by co-administration of RAGE antagonist FPS-ZM1, MAO inhibitors, β-blocker propranolol, and the aldehyde scavenger carnosine (P&lt;0.05). These findings suggest that NE (and other catecholamines) may influence extracellular matrix remodeling via multiple pathways, including adrenergic and also RAGE, via MAO-mediated catabolism.
Understanding, explaining, and utilizing medical artificial intelligence
Authors: Romain Cadario, Chiara Longoni, Carey K. Morewedge
Journal: Nature Human Behaviour (2021)

Medical artificial intelligence is cost-effective and scalable and often outperforms human providers, yet people are reluctant to use it. We show that resistance to the utilization of medical artificial intelligence is driven by both the subjective difficulty of understanding algorithms (the perception that they are a 'black box') and by an illusory subjective understanding of human medical decision-making. In five pre-registered experiments (1–3B: N = 2,699), we find that people exhibit an illusory understanding of human medical decision-making (study 1). This leads people to believe they better understand decisions made by human than algorithmic healthcare providers (studies 2A,B), which makes them more reluctant to utilize algorithmic than human providers (studies 3A,B). Fortunately, brief interventions that increase subjective understanding of algorithmic decision processes increase willingness to utilize algorithmic healthcare providers (studies 3A,B). A sixth study on Google Ads for an algorithmic skin cancer detection app finds that the effectiveness of such interventions generalizes to field settings (study 4: N = 14,013). Cadario et al. identify potential reasons underlying the resistance to use medical artificial intelligence and test interventions to overcome this resistance.
Impact of the New Definition of Metabolic Associated Fatty Liver Disease on the Epidemiology of the Disease
Authors: Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Jean Woo, Jill M. Abrigo, Carmen Ka-Man Chan, Sally She-Ting Shu, Julie Ka-Yu Leung, Angel Mei-Ling Chim, Alice Pik-Shan Kong, Grace Chung-Yan Lui, Henry Lik-Yuen Chan, Winnie Chiu-Wing Chu
Journal: Clinical Gastroenterology and Hepatology (2020)
HORIZON (OP-106): Melflufen Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma-Age Subgroup Analysis of Elderly Patients
Authors: Alessandra Larocca, Paul G. Richardson, Albert Oriol, Joan Blade Creixenti, Michele Cavo, Paula Rodríguez-Otero, Xavier Leleu, Maxim Norkin, Omar Nadeem, John W. Hiemenz, Hani Hassoun, Cyrille Touzeau, Adrián Alegre Amor, Agne Paner, Christopher Maisel, Amitabha Mazumder, Anastasios Raptis, Noemí Puig, Marcus Thuresson, Johan Harmenberg, Bengt Gustavsson, María-Victoria Mateos
Journal: Blood (2020)
<i>Modeling Acute Megakaryoblastic Leukemia of Down Syndrome Using Induced Pluripotent Stem Cells</i>
Authors: Brahim Arkoun, Virginie Dufour, Aurélie Siret, Stefania Mazzi, Yasmine Mammasse, Mathieu Vieira, Fabien Boudia, Elie Robert, Zakia Aid, Marie Cambot, Rachel Petermann, Sylvie Souquere, Philippe Rameau, Cyril Catelain, Romain Diot, Gérard Tachdjian, Najet Debili, Isabelle Plo, Hana Raslova, Sebastien Malinge, Eric Soler, Thomas Mercher, William Vainchenker
Journal: Blood (2020)
Association between physiological responses after exercise at low altitude and acute mountain sickness upon ascent is sex-dependent
Authors: Yang Shen, Yuan-Qi Yang, Chuan Liu, Jie Yang, Ji-Hang Zhang, Jun Jin, Hu Tan, Fang-Zheng-Yuan Yuan, Jing-Bin Ke, Chun-Yan He, Lai-Ping Zhang, Chen Zhang, Jie Yu, Lan Huang
Journal: Military Medical Research (2020)

Abstract Background Acute mountain sickness (AMS) is the mildest form of acute altitude illnesses, and consists of non-specific symptoms when unacclimatized persons ascend to elevation of ≥2500 m. Risk factors of AMS include: the altitude, individual susceptibility, ascending rate and degree of pre-acclimatization. In the current study, we examined whether physiological response at low altitude could predict the development of AMS. Methods A total of 111 healthy adult healthy volunteers participated in this trial; and 99 (67 men and 32 women) completed the entire study protocol. Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude (500 m). Heart rate, blood pressure (BP) and pulse oxygen saturation (SpO 2 ) were recorded prior to and during the last minute of exercise. The ascent from 500 m to 4100 m was completed in 2 days. AMS was defined as ≥3 points in a 4-item Lake Louise Score, with at least one point from headache wat 6–8 h after the ascent. Results Among the 99 assessable subjects, 47 (23 men and 24 women) developed AMS at 4100 m. In comparison to the subjects without AMS, those who developed AMS had lower proportion of men (48.9% vs. 84.6%, P &lt; 0.001), height (168.4 ± 5.9 vs. 171.3 ± 6.1 cm, P = 0.019), weight (62.0 ± 10.0 vs. 66.7 ± 8.6 kg, P = 0.014) and proportion of smokers (23.4% vs. 51.9%, P = 0.004). Multivariate regression analysis revealed the following independent risks for AMS: female sex (odds ratio ( OR ) =6.32, P &lt; 0.001), SpO 2 change upon exercise at low altitude ( OR = 0.63, P = 0.002) and systolic BP change after the ascent ( OR = 0.96, P = 0.029). Women had larger reduction in SpO 2 after the ascent, higher AMS percentage and absolute AMS score. Larger reduction of SpO 2 after exercise was associated with both AMS incidence ( P = 0.001) and AMS score ( P &lt; 0.001) in men but not in women. Conclusions Larger SpO 2 reduction after exercise at low altitude was an independent risk for AMS upon ascent. Such an association was more robust in men than in women. Trial registration Chinese Clinical Trial Registration, ChiCTR1900025728 . Registered 6 September 2019.
Anti-CD19 CAR T-Cell (CNCT19) Infusion Following HDT/ASCT Is Safe and Effective in Patients with Relapsed/Refractory Large B-Cell Lymphoma
Authors: Wei Liu, Wenyang Huang, Ryu Lv, Shuhui Deng, Shuhua Yi, Huimin Liu, Lulu Lv, Lugui Qiu, Dehui Zou, Jianxiang Wang
Journal: Blood (2020)
Juntos en la pandemia de COVID-19 (together in the COVID-19 pandemic): health-care professionals and the Latinx community
Authors: Sandra E Zaeh, Kathleen R Page, Zackary D Berger, Laura Daly, Katherine Hartman Phillips, Tina Tolson, Michelle N Eakin, Panagis Galiatsatos, Emily Brigham
Journal: The Lancet Respiratory Medicine (2020)
Correspondence on ‘The use of tocilizumab and tofacitinib in patients with resolved hepatitis B infection: a case series’
Authors: Ryu Watanabe, Motomu Hashimoto, Akio Morinobu
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the article ‘The use of tocilizumab and tofacitinib in patients with resolved hepatitis B infection: a case series’ by Serling-Boyd et al .1 In this article, the authors conducted a retrospective study and examined the safety of tocilizumab (TCZ) and tofacitinib (TOF) in patients with resolved hepatitis B virus (HBV) infection defined as HB surface antigen (HBsAg)-negative, HB surface antibody (HBsAb)-positive and/or HB core antibody (HBcAb)-positive status. According to the authors, none of the patients developed HBV reactivation, leading to the conclusion that TCZ and TOF may be safely used in patients with resolved HBV infection.1 HBV reactivation can potentially cause de novo hepatitis B associated with a high mortality rate.2 Thus, this study is clinically relevant and reduces our anxiety regarding the management of HBV. However, we have several concerns about this report.

First, as acknowledged by the authors, it …
CST6 Is a Small Autocrine Molecule That Targets Myeloma Growth and Bone Destruction
Authors: Dongzheng Gai, Stewart JP, Xuxing Shen, Jin-Ran Chen, Can Li, Bailu Peng, Ya-Wei Qiang, Shmuel Yaccoby, Maurizio Zangari, Frits van Rhee, Guido J. Tricot, Lijuan Chen, John Shaughnessy, Fenghuang Zhan
Journal: Blood (2020)
Gut Microbiota Profiles of Treatment-Naïve Adult Acute Myeloid Leukemia Patientswith Neutropenic Fever during Intensive Chemotherapy
Authors: Thanawat Rattanathammethee, Pokpong Piriyakhuntorn, Sasinee Hantrakool, Chatree Chai-Adisaksopha, Ekarat Rattarittamrong, Adisak Tantiworawit, Lalita Norasetthada, Pimchanok Tuitemwong, Parameth Thiennimitr, Phinitphong Sarichai, Sarisa Na Pombejra
Journal: Blood (2020)
Does a Change in IPSS-R between Diagnosis and Transplant Have an Impact on Transplant Outcome in Patients with MDS? a Retrospective Analysis from the EBMT Chronic Malignancies Working Party
Authors: Christof Scheid, Dirk-Jan Eikema, Riitta Niittyvuopio, Johan Maertens, Jakob Passweg, Didier Blaise, Jennifer Byrne, Nicolaus Kröger, Martin Bornhäuser, Patrice Chevallier, Jean-Henri Bourhis, Jan J. Cornelissen, Henrik Sengeloev, Jürgen Finke, John A Snowden, Tobias Gedde-Dahl, Denis Guyotat, Urs Schanz, Amit Patel, Linda Koster, Liesbeth C. de Wreede, Patrick J Hayden, Francesco Onida, Marie Robin, Ibrahim Yakoub-Agha
Journal: Blood (2020)
SAT0083 Ultrasonographic evidence of intra-articular injections in the hip
Authors: E Qvistgaard, S Torp-Pedersen, H Kristoffersen, L Terslev, B Danneskiold-Samsøe, H Bliddal
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In order to validate intra-articular medical treatment of osteoarthritis in the hip joints it is imperative to have documentation of the correct placement of the injection. Radiographic methods imply a radiation load, while ultrasound (US) is harmless. <h3>Objectives</h3> Our goal was to evaluate the use of US as guidance when performing injections in osteoarthritic hips using air as contrast medium.<sup>1–3</sup> <h3>Methods</h3> A total of 30 injections were given to 11 Patients with hip-osteoarthritis (ACR criteria)(Mean age 60 years (Range 44–86)). The femoral head and neck was scanned with a 8–13 MHz linear transducer. The probe was placed below the inguinal ligament in parallel with the axis of the femoral neck. Placement of a gauge 21 needle into the hip joint (anterior/inferior capsule below the femoral head) was monitored with a B mode (grey scale) scanning allowing a continuous visual guidance. Preceding the treatment, a small (0,5–2 ml) amount of atmospheric air was injected. <h3>Results</h3> The position of the needle was evident on the screen in all cases. The injections of air into the joint was demonstrated in 29 cases presenting a small hyperechoic brim inside the joint capsule. However, in one case in spite of a seemingly correct placement of the needle the hyperechoic air brim was clearly positioned outside the joint. Placement of the needle was subsequently corrected. Still picture of the setting as documentation revealed the presence of air without difficulty, however the needle tended to be less recognisable when not in motion. <h3>Conclusion</h3> The sole use of grey scale US as guidance device gives a good view of the intra-articular placement of a needle. However use of air as US contrast before an injection or aspiration, enhances the precision and allows photographic documentation of the set-up. <h3>References</h3> Carson BW, Wong A. Ultrasonographic guidance for injections of local steroids in the native hip. J Ultrasound Med. 1999;18(2):159–60 Bliddal H, Torp-Pedersen S. Use of small amounts of ultrasound guided air for injections. Ann Rheum Dis. 2000;59(12):926 Qvistgaard E, <i>et al</i>. Guidance by ultrasound of intra-articular injections of the knee and hip. submitted
Functional Genomics In Vivo Reveal Metabolic Dependencies of Pancreatic Cancer Cells
Authors: Xiphias Ge Zhu, Aleksey Chudnovskiy, Lou Baudrier, Benjamin Prizer, Yuyang Liu, Benjamin N. Ostendorf, Norihiro Yamaguchi, Abolfozl Arab, Bernardo Tavora, Rebecca Timson, Søren Heissel, Elisa de Stanchina, Henrik Molina, Gabriel D. Victora, Hani Goodarzi, Kıvanç Birsoy
Journal: Cell Metabolism (2020)
Abstract 11805: CT-based Virtual Heart and 12-lead ECG-based Automated VT Localization Method Identify Ablation Targets in a Patient Undergoing Intramural Ablation—A Case Study
Authors: Shijie Zhou, Eric Sung, Amir AbdelWahab, Adityo Prakosa, Konstantinos Aronis, Bohumil Milan Horacek, Ratika Parkash, Martin J Gardner, Chris Gray, Ciorsti J Macintyre, Jason Davis, John L Sapp, Natalia Trayanova
Journal: Circulation (2019)

Introduction: Infusion-needle catheter ablation of VT within deep intramural substrate requires accurate identification of appropriate targets. We have developed an automated method for localizing ...
Errors in Table
Authors: Lingkong Zeng, Tiantian Xiao, Wenhao Zhou
Journal: JAMA Pediatrics (2020)

Alfredo Tagarro, PhD, MD; Cristina Epalza, PhD, MD; Mar Santos, PhD, MD; Francisco José Sanz-Santaeufemia, PhD, MD; Enrique Otheo, PhD, MD; Cinta Moraleda, PhD, MD; Cristina Calvo, PhD, MD
Phase II Single-Arm "Window-of-Opportunity" Study of a Combination of Obinutuzumab and Venetoclax in Early Relapsed or Refractory Diffuse Large B-Cell Lymphoma (DLBCL) - First Results of the AGMT NHL15B Study
Authors: Ulrich Jaeger, Alexander Egle, Ingrid Simonitsch-Klupp, Sonja Heibl, Peter Neumeister, Ella Willenbacher, Florian Erlsbacher, Julian Larcher-Senn, Michael A. Fridrik, Richard Greil
Journal: Blood (2020)
Abstract 245: Cardiac Mitofusin-1 is Suppressed in Non-responding Patients With Heart Failure
Authors: Yung Ting Hsiao, Ippei Shimizu, Takayuki Wakasugi, Shuang Jiao, Tohru Watanabe, Takeshi Kashimura, Yohko Yoshida, Haruo Hanawa, Kazuyuki Ozaki, Tohru Minamino
Journal: Circulation Research (2020)

Background/Introduction: Mitochondria are dynamic regulators of cellular metabolism and homeostasis. The dysfunction of mitochondria has long been considered a major contributor to aging and age-related diseases. The prognosis of severe heart failure is still unacceptably poor and it is urgent to establish new therapies for this critical condition. Some patients with heart failure do not respond to established multidisciplinary treatment and they are classified as “non-responders”. The outcome is especially poor for non-responders, and underlying mechanisms are largely unknown. Purpose: Studies indicate mitochondrial dysfunction has causal roles for metabolic remodeling in the failing heart, but underlying mechanisms remain to be explored. This study tried to elucidate the role of Mitofusin-1 in a failing heart. Methods: We examined twenty-two heart failure patients who underwent endomyocardial biopsy of intraventricular septum. Patients were classified as non-responders when their left-ventricular (LV) ejection fraction did not show more than 10% improvement at remote phase after biopsy. Fourteen patients were classified as responders, and eight as non-responders. Electron microscopy, quantitative PCR, and immunofluorescence studies were performed to explore the biological processes or molecules involved in failure to respond. In addition to studies with cardiac tissue specific knockout mice, we also conducted functional in-vitro studies with neonatal rat ventricular myocytes. Results: Twenty-two patients with IDCM who underwent endomyocardial biopsy were enrolled in this study, including 14 responders and 8 non-responders. Transmission electron microscopy (EM) showed a significant reduction in mitochondrial size in cardiomyocytes of non-responders compared to responders. Quantitative PCR revealed that transcript of mitochondrial fusion protein, Mitofusin-1, was significantly reduced in non-responders. Studies with neonatal rat ventricular myocytes (NRVMs) indicated that the beta-1 adrenergic receptor-mediated signaling pathway induced microRNA-140 3p and 5p, which is negatively regulated Mitofusin-1 expression. Suppression of Mitofusin-1 resulted in a significant reduction in mitochondrial respiration of NRVMs. We generated left ventricular pressure overload model with thoracic aortic constriction (TAC) in cardiac specific Mitofusin-1 knockout model (c-Mfn1 KO). Systolic function was reduced in c-Mfn1 KO mice, and EM study showed an increase in dysfunctional mitochondria in the KO group subjected to TAC. Conclusions: Mitofusin-1 becomes a biomarker for non-responders with heart failure. In addition, our results suggest that therapies targeting mitochondrial dynamics and homeostasis would become next generation therapy for severe heart failure patients.