tbuckley/cabot-search huggingface dataset:
Johann Lucas Schoenlein (1793–1864): impact without publications
Authors: Bernhard Manger, Georg Schett, Gerd R Burmester
Journal: Annals of the Rheumatic Diseases (2020)

Johann Lucas Schoenlein was one of the most influential clinicians in Central Europe during the first half of the 19th century. However, today it is still not easy to retrace, how exactly he became such a celebrity, because with the exception of his doctoral thesis, all he published were two letters in a scientific journal, not even four pages in total.1 2 Until recently, almost all we knew came from manuscripts, books and letters of his students. Nonetheless, these documents speak out for him: One of them, the famous surgeon Theodor Billroth, wrote, “Those, who felt spiritually close to Schoenlein raved and became enthusiastic about him and, through him, about medicine”.3 Wilhelm Griesinger, one of the founders of clinical psychiatry, described his impressions as follows: “It seemed to me that he knew everything; and that he could do everything at the bedside!”.4 Within the last years, two parts of his bequest of scientific and private correspondence comprising more than 1500 letters and notes have been rediscovered by chance and meanwhile partially edited.5 6 This now allows a detailed insight into the life and scientific network of this clinician, about whom his most famous disciple, Rudolf Virchow said: “Thus he remained a colleague to his colleagues, a friend to his friends; thus he became a model of true humanity and liberality, in the correct classical sense of the word. Nothing human was foreign to him”.7 Virchows obituary, which is still the most detailed biography about Schoenlein, has also been translated into English.8

Schoenlein was born in 1793 as the only son of a rope maker in the romantic old Franconian city of Bamberg. After completing his medical education in Landshut and Wurzburg, he served as Professor and Head of Medicine at the …
<i>In</i>-Class Transition (<i>i</i>CT) from Parenteral Bortezomib to Oral Ixazomib Proteasome Inhibitor (PI) Therapy Increases the Feasibility of Long-Term PI Treatment and Benefit for Newly Diagnosed Multiple Myeloma (NDMM) Patients in an Outpatient Setting: Updated Real-World Results from the Community-Based United States (US) MM-6 Study
Authors: Saulius K. Girnius, Habte A. Yimer, Stephen J. Noga, Sudhir Manda, Roger M. Lyons, Kimberly Bogard, Presley Whidden, Dasha Cherepanov, Vickie Lu, Jack Aiello, Joshua R. Richter, Robert M. Rifkin
Journal: Blood (2020)
Airway immune mediator levels during asthma‐like symptoms in young children and their possible role in response to azithromycin
Authors: Christian J. Carlsson, Morten A. Rasmussen, Susanne B. Pedersen, Ni Wang, Jakob Stokholm, Bo L. Chawes, Klaus Bønnelykke, Hans Bisgaard
Journal: Allergy (2020)

Abstract Background Asthma‐like symptoms in young children are orchestrated by the local airway immune response, but current knowledge largely relies on in vitro airway models. Azithromycin has been shown to reduce the duration of episodes with asthma‐like symptoms, but efficacy may depend on the individual child's immune response. Objectives To investigate in vivo upper airway immune mediator levels during episodes with asthma‐like symptoms in young children and their ability to predict the clinical response to azithromycin treatment. Methods A total of 535 children aged 0‐3 years from the Copenhagen Prospective Studies of Asthma in Childhood‐2010 mother‐child cohort were examined for immune mediator levels in samples of nasal epithelial lining fluid during episodes with asthma‐like symptoms as well as in the asymptomatic state. In a sub‐study, children with recurrent asthma‐like symptoms were randomized to either a 3‐day course of oral azithromycin (10 mg/kg; n = 32) or placebo (n = 38). In the current study, we compared the pretreatment immune mediator levels with the clinical response to treatment with azithromycin in an exploratory post hoc analysis. Results The immune mediator concentrations during vs outside episodes were significantly upregulated for IFN‐ɣ (ratio 1.73), TNF‐α (ratio 2.05), IL‐1β (ratio 1.45), IL‐10 (ratio 1.97), while CCL22 (ratio 0.65) was downregulated. Low levels of TNF‐α and IL‐10 and high levels of CCL22 predicted better treatment response to azithromycin ( P ‐values &lt; .05). Conclusion Upper airway immune mediator levels were altered during episodes of asthma‐like symptoms, and levels of TNF‐α, CCL22, and IL‐10 may predict the response to azithromycin treatment.
Abstract 436: Maternal Pregestational Diabetes Alters Fetal Gene Regulatory Program to Cause Spectrum of Congenital Heart Defects
Authors: Corrin Mansfield, Sathiyanarayanan Manivannan, Xinmin Zhang, Madhav K Kodigepalli, Vidu Garg, Madhumita Basu
Journal: Circulation Research (2020)

Maternal pre-gestational diabetes results in range of congenital malformations with significantpreponderance of congenital heart defects (CHD). We and others have previously demonstratedthat maternal high glucose (HG) acts as primary teratogen in diabetes and in combination withgenetic susceptibility loci, it increases the incidence of CHD ranging from mild ventricular septaldefects (VSD) to complex outflow tract (OFT) abnormalities. However, the underlying cellularand molecular basis of maternal HG dose-response on fetal cardiac development remainselusive. In this study, we have utilized Streptozotocin-induced murine model of maternal type1diabetes and demonstrated that spectrum of CHD in HG exposed developing embryos in utero ,is dose-dependent. We have performed histological analysis of hearts at embryonic (E) day 9.5,11.5, 13.5 and 15.5 exposed to different levels of maternal HG and compared them withuntreated normoglycemic controls. Analysis of E9.5, E11.5 and E13.5 embryos displayedtrabeculation and touchdown defects, thinning of right and left ventricular myocardium, VSD,OFT misalignment, double outlet right ventricle with increasing levels of maternal glucose.Whereas, E15.5 embryos exposed to maternal HG exhibited VSD, cardiac hypertrophy andhyper-trabeculation phenotypes in comparison to normoglycemic controls. To test cell-specificgene-regulatory program in response to hyperglycemia stress, we performed in vivo 10X singlecell transcriptomics and in vitro global RNA-sequencing on murine embryonic cell-lines culturedin normal and increasing doses of HG. RNA-seq analysis revealed differential gene expressionchanges associated with metabolic dysfunction, oxidative stress response, endothelial tomesenchymal transition, cardiomyocytes proliferation and impaired neural crest cell migration.Cardiomyocytes and endothelial cell proliferation (PHH3) and apoptosis (TUNEL) weremeasured using immunohistochemical analysis at E9.5-E15.5 embryonic hearts exposed tomaternal HG. In summary, more in-depth analysis of this study is warranted to indicate howmaternal intrauterine hyperglycemic environment disrupts the fine tuning of fetal cardiogenicgene/epigenetic program to cause CHD.
The Impact of ABO Blood Group on Clinical Outcomes and Susceptibility in COVID-19: A Retrospective Population Study of 3305 Patients
Authors: Waleed Alduaij, Sarah Al-Youha, Ahmad Al-Serri, Sulaiman Almazeedi, Mohannad Al-Haddad, Mohammad H Jamal, Salman Al-Sabah
Journal: Blood (2020)
SAT0147 Correlation between fibromyalgia impact questionnaire (fiq) and clinical symptoms in fibromyalgia
Authors: A Gür, M Karakoç, K Nas, R Çevik, AJ Saraç, F Erdogan
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Several well established instruments are available to measure health status and functional disability in persons with rheumatic diseases. Although both instruments are reliable and valid for several rheumatic disease groups, no formal psychometric testing of instruments have been reported for the population with fibromyalgia. <h3>Objectives</h3> The study was designed to investigate the correlation between Fibromyalgia Impact Questionnaire (FIQ) and clinical symptoms, Health Assessment Questionnaire (HAQ) in patients with fibromyalgia in Turkey. <h3>Methods</h3> FIQ is an assessment and evaluation instrument developed to measure physical functioning, work status, depression, anxiety, sleep, pain, stiffness, fatigue, and well being of fibromyalgia patients. We administered the FIQ and HAQ to 64 patients with fibromiyalgia and 48 healthy persons. Severity of relevant clinical symptoms (pain, fatigue, sleep disturbance, morning stiffness, muscle spasm, number of tender points, sensitivity of trigger points) were assessed. <h3>Results</h3> The mean age of the patients and healthy group were 27,98+7,23 and 28,75+5,67, respectively (p &gt; 0.05). Disease duration was 4,09+3,42 years. Correlation between FIQ and HAQ scores were rho = 0.46 (p &lt; 0.01). Significant correlations were obtained between the FIQ scores and severity of clinical symptoms (morning stiffness r = 0.42 (p &lt; 0.01), fatigue r = 0.26 (p &lt; 0.05), pain r = 0.67 (p &lt; 0.01), sensitivity r = 0.25 (p &lt; 0.05)). In addition, significant correlations were obtained between the HAQ scores and number of tender points r = 0.28 (p &lt; 0.05), morning stiffness r = 0.28 (p &lt; 0.05), pain r = 0.37 (p &lt; 0.01). <h3>Conclusion</h3> In conclusion, the FIQ is a reliable and valid instrument for measuring functional disability in Turkish patients with fibromiyalgia. In addition, our study suggest that FIQ is more significant than HAQ in correlations with clinical symptoms in patients with fibromiyalgia.
Abstract 404: Acute Knock-down of Cardiac Peroxisome Proliferator Activated Receptor α Does Not Impair Cardiac Function
Authors: Natasha Fillmore, Junhui Sun, Danielle Springer, Elizabeth Murphy
Journal: Circulation Research (2020)

Alterations in glucose and fatty acid metabolism are believed to contribute to the development of heart failure. Peroxisome Proliferator Activated Receptor α (PPARα) is a transcription factor that regulates fatty acid metabolism and is frequently reported to be reduced in heart failure. However, it is controversial whether this decline in PPARα mediates the development of cardiac hypertrophy and heart failure. To improve our understanding of the role of cardiac PPARα we generated a tamoxifen inducible cardiac-specific PPARα knockout mouse (cPPAR -/- ). Control (Mer-Cre-Mer and Flox -/- ) mice and cPPAR -/- (Mer-Cre-Mer and Flox +/+ ) mice were treated with tamoxifen at ~2.5 months and were studied 5 weeks after treatment. We verified loss of cardiac PPARα using western blot. cPPAR -/- mice appear healthy with normal body weight gain and survival. To examine the impact of cardiac deletion of PPARα on cardiac function we performed echocardiography on control and cPPAR -/- . There was no reduction in systolic function between control and cPPAR -/- mice. Ejection fraction (Control, 56.3±0.9; cPPAR -/- , 59.7±0.1) and fractional shortening (Control, 29.1±0.5; cPPAR -/- , 31.5±0.1) were similar in cPPAR -/- compared to control hearts. Interestingly however, baseline heart rate was significantly lower in cPPAR -/- versus control mice (Control, 531.3±18.3; cPPAR -/- , 459.8±2.9 bpm). In addition to having normal cardiac function, heart weights were similar between control and cPPAR -/- mice. Overall, these data indicate that an acute reduction in myocardial PPARα per se does not cause cardiac dysfunction. However these data do not exclude the possibility that loss of PPARα could drive cardiac pathology in the context of other signals.
Factors Associated with High Healthcare Utilization at the End-of-Life (EOL) for Patients with Acute Myeloid Leukemia
Authors: Dagny M. Vaughn, P. Connor Johnson, Annemarie D. Jagielo, Matthew J. Reynolds, Alison R. Kavanaugh, Jason A. Webb, Amir T. Fathi, Gabriela S. Hobbs, Andrew M. Brunner, Nina R. O'Connor, Selina M. Luger, Bhavana Bhatnagar, Thomas W. LeBlanc, Areej El-Jawahri
Journal: Blood (2020)
Manual Partial Exchange Transfusion a Cost Effective Life Saving Intervention in Sickle Cell Crisis: Single Centre Retrospective Data Analysis
Authors: Seema S. Bhatwadekar, Shubhangi Vishwas Deshpande, Shweta Vikas Khadse, Bijal Shah, Devenkumar Desai, Devashri Jani, Pina Vasoya, Ujjwala Lakhmapurkar, Saloni Shah, Aangi Jayesh Shah
Journal: Blood (2020)
High Incidence of Venous Thromboembolism in Patients with Chronic Graft-Versus-Host Disease
Authors: Najla El Jurdi, Heba Elhusseini, Todd E. DeFor, Grigori Okoev, Aleksandr Lazaryan, John Rogosheske, Kristen Weiler, Veronika Bachanova, Brian C. Betts, Bruce R. Blazar, Claudio G. Brunstein, Fiona He, Shernan G Holtan, Murali Janakiram, Radhika Gangaraju, Joseph E. Maakaron, Margaret L. MacMillan, Armin Rashidi, Erica D. Warlick, Smita Bhatia, Joan D. Beckman, Gregory M Vercellotti, Daniel J. Weisdorf, Mukta Arora
Journal: Blood (2020)
Radiological assessment schedule for high-grade glioma patients during the surveillance period using parametric modeling
Authors: So Young Ji, Jongjin Lee, Joo Ho Lee, Soon-Tae Lee, Jae Kyung Won, Jin Wook Kim, Yong Hwy Kim, Tae Min Kim, Seung Hong Choi, Sung-Hye Park, Yongdai Kim, Chul-Kee Park
Journal: Neuro-Oncology (2020)

An optimal radiological surveillance plan is crucial for high-grade glioma (HGG) patients, which is determined arbitrarily in daily clinical practice. We propose the radiological assessment schedule using a parametric model of standardized progression-free survival (PFS) curves.A total of 277 HGG patients (178 glioblastoma [GBM] and 99 anaplastic astrocytoma [AA]) from a single institute who completed the standard treatment protocol were enrolled in this cohort study and retrospectively analyzed. The patients were stratified into each layered risk group by genetic signatures and residual mass or through recursive partitioning analysis. PFS curves were estimated using the piecewise exponential survival model. The criterion of a 10% progression rate among the remaining patients at each observation period was used to determine the optimal radiological assessment time point.The optimal follow-up intervals for MRI evaluations of isocitrate dehydrogenase (IDH) wild-type GBM was every 7.4 weeks until 120 weeks after the end of standard treatment, followed by a 22-week inflection period and every 27.6 weeks thereafter. For the IDH mutated GBM, scans every 13.2 weeks until 151 weeks are recommended. The optimal follow-up intervals were every 22.8 weeks for IDH wild-type AA, and 41.2 weeks for IDH mutated AA until 241 weeks. Tailored radiological assessment schedules were suggested for each layered risk group of the GBM and the AA patients.The optimal schedule of radiological assessments for each layered risk group of patients with HGG could be determined from the parametric model of PFS.
Abstract MP150: Inositol 1,4,5-trisphosphate Receptors Selectively Regulate Detrimental Cardiac Fibrosis by Modulating ER-phagy
Authors: Gaetano Santulli, Marco Morelli, Xujun Wang, John Ferrante, Jessica Gambardella
Journal: Circulation Research (2020)

Background: Therapeutic strategies that specifically target excessive post-ischemic cardiac fibrosis are lacking but desperately needed; thus, it is critical to understand the molecular mechanisms underlying these processes. Genome-wide association studies have revealed an association between inositol 1,4,5-trisphosphate receptors (IP3Rs) and ischemic heart disease. However, experimental studies examining the exact role of IP3Rs in post-ischemic cardiac fibrosis are missing. Aim: We hypothesize that IP3Rs play a key role in the regulation of cardiac myofibroblasts (myoFBs) in healing the infarcted heart after myocardial infarction (MI). Methods: We performed an integrated set of in vivo, ex vivo , and in vitro experiments aiming at identifying the functional role of cardiac myoFB IP3Rs in post-ischemic cardiac remodeling. We generated cardiac myo-FB-specific Triple IP3R knock-out (IP3R TKO ) mice ( Cre/lox recombination technique; Promoter: Periostin ), allowing us to overcome the difficulties encountered following the KO or KD of a single (of the three existent) IP3Rs, a strategy that has been shown to induce compensatory upregulation of the other isoforms. Results: After MI, IP3Rs are significantly upregulated in myoFBs of the remote regions but not in the scar area. IP3R TKO mice display a significantly reduced interstitial cardiac fibrosis and a markedly attenuated myocardial dysfunction following MI compared with control IP3R flox or Periostin Cre littermates. Moreover, FBs lacking IP3Rs exhibit significantly reduced migratory and secretory capacities, a finding confirmed both in murine and human FBs. Mechanistically, we show that IP3Rs modulate endoplasmic reticulum autophagy (ER-phagy) in primary isolated myoFBs following ischemic injury. Conclusions: Taken together, our findings indicate for the first time that IP3Rs are essential for the regulation of post-ischemic cardiac fibrosis.
Outcomes of Patients with Multiple Myeloma Who Received VRD Induction, Autologous Hematopoietic Cell Transplantation and Lenalidomide Maintenance
Authors: Mahmoud R. Gaballa, Taha Al-Juhaishi, Qaiser Bashir, Samer A. Srour, Neeraj Saini, Jeremy Ramdial, Yago Nieto, Regan Murphy, Hans C. Lee, Krina K. Patel, Partow Kebriaei, Sheeba K. Thomas, Donna M. Weber, Robert Z. Orlowski, Richard E. Champlin, Muzaffar H. Qazilbash
Journal: Blood (2020)
Quality of Outpatient Depression Treatment in Patients With Comorbid Substance Use Disorder
Authors: Lara N. Coughlin, Paul Pfeiffer, Dara Ganoczy, Lewei A. Lin
Journal: American Journal of Psychiatry (2020)

Clinical practice guidelines recommend concurrent treatment of co-occurring depression and substance use disorders; however, the degree to which patients with substance use disorders receive guideline-concordant treatment for depression is unknown. The authors investigated the provision of guideline-concordant depression treatment to patients with and without substance use disorders in a large integrated health care system.
Glycoside Residues on Platelet's Surface Regulate Platelet Function, Apoptosis and Binding of Coagulation Complexes in Patients with Immune Thrombocytopaenia
Authors: Nora V. Butta, María Teresa Alvarez Román, Elena Monzón Manzano, Paula Acuña, Mónica Martín, María Isabel Rivas Pollmar, Raul Justo Sanz, Elena G Arias-Salgado, Sara García Barcenilla, Tamara Cebanu, Elena González Zorrilla, Miguel A Canales, Victor Jimenez-Yuste
Journal: Blood (2020)
Lineage-Independent Tumors in Bilateral Neuroblastoma
Authors: Tim H.H. Coorens, Sarah J. Farndon, Thomas J. Mitchell, Neha Jain, Sangjin Lee, Michael Hubank, Neil Sebire, John Anderson, Sam Behjati
Journal: New England Journal of Medicine (2020)

Summ a r yChildhood tumors that occur synchronously in different anatomical sites usually represent metastatic disease.However, such tumors can be independent neoplasms.We investigated whether cases of bilateral neuroblastoma represented independent tumors in two children with pathogenic germline mutations by genotyping somatic mutations shared between tumors and blood.Our results suggested that in both children, the lineages that had given rise to the tumors had segregated within the first cell divisions of the zygote, without being preceded by a common premalignant clone.In one patient, the tumors had parallel evolution, including distinct second hits in SMARCA4, a putative predisposition gene for neuroblastoma.These findings portray cases of bilateral neuroblastoma as having independent lesions mediated by a germline predisposition.(Funded by Children with Cancer UK and Wellcome.
Risk Factors for Severe Form of COVID-19 after Allogeneic Hematopoietic Stem Cell Transplantation: A SFGM-TC Multicentre Cohort Study
Authors: Alienor Xhaard, Constance Xhaard, Maud D'Aveni, Hélène Salvator, Marie-Laure Chabi-Charvillat, Tereza Coman, Yves Beguin, Yves Chalandon, Xavier Poire, Michael Loschi, Catherine Paillard, Bénédicte Bruno, Patrice Ceballos, Jean-Hugues Dalle, Karin Bilger, Jacques-Olivier Bay, Marie Robin, Stephanie N'guyen-Quoc, Marie Thérèse Rubio
Journal: Blood (2020)
Mesophasic organization of GABAA receptors in hippocampal inhibitory synapses
Authors: Yun-Tao Liu, Chang-Lu Tao, Xiaokang Zhang, Wenjun Xia, Dong-Qing Shi, Lei Qi, Cheng Xu, Rong Sun, Xiao-Wei Li, Pak-Ming Lau, Z. Hong Zhou, Guo-Qiang Bi
Journal: Nature Neuroscience (2020)
Hyperglycemia cooperates with Tet2 heterozygosity to induce leukemia driven by proinflammatory cytokine–induced lncRNA Morrbid
Authors: Zhigang Cai, Xiaoyu Lu, Chi Zhang, Sai Nelanuthala, Fabiola Aguilera, Abigail Hadley, Baskar Ramdas, Fang Fang, Kenneth Nephew, Jonathan J. Kotzin, Adam Williams, Jorge Henao-Mejia, Laura Haneline, Reuben Kapur
Journal: Journal of Clinical Investigation (2020)

Diabetes mellitus (DM) is a risk factor for cancer. The role of DM-induced hyperglycemic (HG) stress in blood cancer is poorly understood. Epidemiologic studies show that individuals with DM are more likely to have a higher rate of mutations in genes found in pre-leukemic hematopoietic stem and progenitor cells (pre-LHSPCs) including TET2. TET2-mutant pre-LHSPCs require additional hits to evolve into full-blown leukemia and/or an aggressive myeloproliferative neoplasm (MPN). Intrinsic mutations have been shown to cooperate with Tet2 to promote leukemic transformation. However, the extrinsic factors are poorly understood. Using a mouse model carrying Tet2 haploinsufficiency to mimic the human pre-LHSPC condition and HG stress, in the form of an Ins2Akita/+ mutation, which induces hyperglycemia and type 1 DM, we show that the compound mutant mice developed a lethal form of MPN and/or acute myeloid leukemia (AML). RNA-Seq revealed that this was due in part to upregulation of proinflammatory pathways, thereby generating a feed-forward loop, including expression of the antiapoptotic, long noncoding RNA (lncRNA) Morrbid. Loss of Morrbid in the compound mutants rescued the lethality and mitigated MPN/AML. We describe a mouse model for age-dependent MPN/AML and suggest that hyperglycemia acts as an environmental driver for myeloid neoplasms, which could be prevented by reducing expression levels of the inflammation-related lncRNA Morrbid.
Pure Pathologic Response Is Associated with Improved Overall Survival in Patients with Advanced Systemic Mastocytosis Receiving Avapritinib in the Phase I EXPLORER Study
Authors: Jason Gotlib, Deepti H. Radia, Tracy I. George, William A Robinson, Albert T. Quiery, Mark W. Drummond, Prithviraj Bose, Elizabeth O. Hexner, Elliott F. Winton, Hans-Peter Horny, Meera Tugnait, Oleg Schmidt-Kittler, Erica K. Evans, Hui-Min Lin, Brenton G. Mar, Michael W. Deininger, Daniel J. DeAngelo
Journal: Blood (2020)