tbuckley/cabot-search huggingface dataset:
Covid-19 pneumonia in sickle cell anemia: A case report
Authors: K. Mills, C. Cohen
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Introduction Chronic medical illnesses can increase complications among patients with COVID19 infection. Sickle cell anemia is a chronic illness primarily found in persons of African descent, and COVID-19 has been found to disproportionately affect African Americans. However, there is scant data on the cohort of patients in which COVID-19 and Sickle cell anemia co-exist. Herein, we outline the hospital course of a 62-yearold woman with Hemoglobin (Hb) SS and COVID-19 infection. Case Presentation A 62-year-old woman with a history of Hemoglobin (Hb) SS complicated by avascular necrosis of the left shoulder presented to the emergency department with worsening shortness of breath for two days. She endorsed fevers, chills, cough, diarrhea and back pain similar to her sickle cell pain crises. She also revealed that she had tested positive for COVID-19 a week prior to presentation, after being exposed to a family member who was infected. On presentation, she was afebrile and normotensive but tachycardic, tachypneic, with initial oxygen saturation in the 70's which improved to 95-100% with high flow nasal canula (HFNC) 50% FiO2, 50 liters per minute. Initial labs revealed severe anemia (Hb 3.9, baseline 6.0), acute kidney injury, lactic acidosis, indirect hyperbilirubinemia, and elevated LDH. Chest X-ray showed bilateral multifocal consolidations. She was admitted to the medical intensive care unit for management of acute hypoxemic respiratory failure due to COVID pneumonia and acute chest syndrome. She received intravenous remdesivir, dexamethasone, ceftriaxone, and azithromycin. She underwent simple blood transfusion of 3 units packed red blood cells (PRBC), then a therapeutic RBC exchange transfusion. She was also on intravenous heparin, intravenous fluids and opioids. She was consented and enrolled in a lenzilumab trial. The patient clinically improved and was transferred to the intermediate care unit. Her supplementary oxygen was weaned down from HFNC to two liters per minute via nasal cannula. She was discharged with home oxygen, as well as outpatient follow up with sickle cell and primary care clinics. Discussion COVID-19 should be recognized as a new viral pathogen for acute chest syndrome. This patient had sickle cell pain, and COVID-19 screening should be considered among those presenting with painful crises during this pandemic to avoid overlooking a possible inciting factor. Exchange transfusion was utilized in this case;further case studies and clinical trials would aid clinicians in understanding appropriate management when these illnesses co-exist.
Serine hydroxymethyltransferase 2 expression promotes tumorigenesis in rhabdomyosarcoma with 12q13-q14 amplification
Authors: Thanh H. Nguyen, Prasantha L. Vemu, Gregory E. Hoy, Salah Boudjadi, Bishwanath Chatterjee, Jack F. Shern, Javed Khan, Wenyue Sun, Frederic G. Barr
Journal: Journal of Clinical Investigation (2021)

The 12q13-q14 chromosomal region is recurrently amplified in 25% of fusion-positive (FP) rhabdomyosarcoma (RMS) cases and is associated with a poor prognosis. To identify amplified oncogenes in FP RMS, we compared the size, gene composition, and expression of 12q13-q14 amplicons in FP RMS with those of other cancer categories (glioblastoma multiforme, lung adenocarcinoma, and liposarcoma) in which 12q13-q14 amplification frequently occurs. We uncovered a 0.2 Mb region that is commonly amplified across these cancers and includes CDK4 and 6 other genes that are overexpressed in amplicon-positive samples. Additionally, we identified a 0.5 Mb segment that is only recurrently amplified in FP RMS and includes 4 genes that are overexpressed in amplicon-positive RMS. Among these genes, only serine hydroxymethyltransferase 2 (SHMT2) was overexpressed at the protein level in an amplicon-positive RMS cell line. SHMT2 knockdown in amplicon-positive RMS cells suppressed growth, transformation, and tumorigenesis, whereas overexpression in amplicon-negative RMS cells promoted these phenotypes. High SHMT2 expression reduced sensitivity of FP RMS cells to SHIN1, a direct SHMT2 inhibitor, but sensitized cells to pemetrexed, an inhibitor of the folate cycle. In conclusion, our study demonstrates that SHMT2 contributes to tumorigenesis in FP RMS and that SHMT2 amplification predicts differential response to drugs targeting this metabolic pathway.
Unexpected impact of COVID-19 lockdown on spinal mobility and health perception in spondyloarthritis
Authors: Sophie De Mits, Ann-Sophie De Craemer, Liselotte Deroo, Thomas Renson, Filip E Van den Bosch, Philippe Carron, Dirk Elewaut
Journal: Annals of the Rheumatic Diseases (2021)

Figure 1 (A) Chest expansion in 65 patients with SpA was measured pre-lockdown (left panel), immediately after lockdown (middle panel) and 6 months after the pre-lockdown measurement (right panel).Significance (α=0.05) was determined using an ANOVA test for repeated measures.The grey boxes represent the mean, ***=p≤0.0001.(B) Standardised prospective follow-up of chest expansion in a nationwide cohort of patients with SpA (BeGIANT) over a period of 2 years, under stable established pharmacological therapy (n=202).Significance (α=0.05) was determined using an ANOVA test for repeated measures.Chest expansion at follow-up at month 12 (T1) at month 18 (T2) and at month 24 (T3).The grey boxes represent the mean.ANOVA, analysis of variance; ns, not significant; SpA, spondyloarthritis.
Genetic polymorphisms in interferon pathway and response to interferon treatment in hepatitis B patients: A pilot study
Authors: Jennifer K. King, Shiou-Hwei Yeh, Ming-Wei Lin, Chun-Jen Liu, Ming-Yang Lai, Jia-Horng Kao, Ding-Shinn Chen, Pei-Jer Chen
Journal: Hepatology (2002)

Interferon alfa (IEN-α) therapy remains a mainstay of treatment in active hepatitis B. However, sustained remission rates remain relatively low, and the search for factors important for response to therapy continues. Our study aimed to identify the host single nucleotide polymorphisms (SNPs) that predict IFN response in hepatitis B patients. We selected genes in the IFN pathway involved in antiviral and signaling activities and sequenced 22 SNPs for each of our 82 patients. Our results identified 2 SNPs in the antiviral pathway that may influence IFN response. One SNP in the regulatory region of the eIF-2α gene revealed A/G alleles. The rate of A/G heterozygotes is 22% in nonresponders (NR) and 2% in sustained responders (R), with an odds ratio (OR) of 12.82 (95% CI: 1.52-107.85, P = 0.009). After adjustment for age, sex, and HBV DNA level, the OR reaches 14.94 (95% CI: 1.45-153.71, P = 0.023). This marker revealed greater significance than HBV DNA levels (OR 5, 95% CI: 1.01-2.43, P = 0.033) as a marker for IFN response, suggesting its potential advantage over conventional predictors. In addition, borderline significance for the SNP in MxA gene promoter at nt -88 revealed G/T alleles, with the G/T heterozygote rate being 19% in nonresponders and 43% in sustained R ( P = 0.061), concurring with a previous study involving hepatitis C patients. In conclusion, this pilot identified SNPs as potential markers that could predict hepatitis B patient response. These observations may help guide future large-scale studies in examining host SNPs for their clinical utility in predicting IFN response. (Hepatology2002;36:1416-1424).
A Focus on “Bio” in Bio–Nanoscience: The Impact of Biological Factors on Nanomaterial Interactions
Authors: Christina Cortez‐Jugo, Ewa Czuba‐Wojnilowicz, Abigail Tan, Frank Caruso
Journal: Advanced Healthcare Materials (2021)

Bio-nanoscience research encompasses studies on the interactions of nanomaterials with biological structures or what is commonly referred to as the biointerface. Fundamental studies on the influence of nanomaterial properties, including size, shape, composition, and charge, on the interaction with the biointerface have been central in bio-nanoscience to assess nanomaterial efficacy and safety for a range of biomedical applications. However, the state of the cells, tissues, or biological models can also influence the behavior of nanomaterials at the biointerface and their intracellular processing. Focusing on the "bio" in bio-nano, this review discusses the impact of biological properties at the cellular, tissue, and whole organism level that influences nanomaterial behavior, including cell type, cell cycle, tumor physiology, and disease states. Understanding how the biological factors can be addressed or exploited to enhance nanomaterial accumulation and uptake can guide the design of better and suitable models to improve the outcomes of materials in nanomedicine.
Abstract 13132: The "Thrombosis-Bleeding Paradox" of Mechanical Circulatory Support: Shear Stress Promotes Platelet Prothrombosis and Microparticle Generation While Inducing Integrin αIIbβ3 Shedding and Decreased Aggregability
Authors: Yana Roka-Moiia, Daniel E Palomares, Joseph E Italiano, Jawaad Sheriff, Danny Bluestein, Marvin Slepian
Journal: Circulation (2019)

Introduction: Mechanical circulatory support (MCS) has emerged as a lifesaving therapy for patients with advanced and end-stage heart failure. Sadly, MCS therapy is limited by a paradoxical coagulo...
Danger perception and stress response through an olfactory sensor for the bacterial metabolite hydrogen sulfide
Authors: Kohei Koike, Seung-Jun Yoo, Katherin Bleymehl, Masayo Omura, Bolek Zapiec, Martina Pyrski, Thomas Blum, Mona Khan, Zhaodai Bai, Trese Leinders-Zufall, Peter Mombaerts, Frank Zufall
Journal: Neuron (2021)
Artemisinins Synergize with BCL2 Inhibitors By Reducing MCL1 Protein Levels in Leukemia Cells
Authors: Blake S Moses, Jennifer Fox, Xiaochun Chen, Samantha McCullough, Allison Kirkpatrick, Kalyani Kumar, Jeffrey W. Tyner, Gary H. Posner, Curt I. Civin
Journal: Blood (2017)
Abstract #1129: TIMP1 interactions with P75NTR in metastatic carcinoma and glioma cells
Authors: Mumtaz Rojiani, Steven Brem, Susan Murphy, Marguerite Obadia, Amyn Rojiani
Journal: Cancer Research (2009)

Abstract: Neurotrophins and their receptors including p75NTR have been described in the context of their physiologic interactions particularly during neuronal development, survival and neurite outgrowth. The role and functions of these molecules have expanded and now encompass a wide range of other activities, particularly within the domain of tumor biology. The expression of these molecules in tumors of nervous system origin such as glioma, neuroblastoma and medulloblastoma as well as in non-nervous system neoplasms such as melanoma, myeloma, papillary thyroid cancer, hepatocellular, prostate and lung carcinoma has been documented. Despite evidence of their expression in these neoplasms, their role remains unclear as both tumor promoting and tumor inhibitory functions of p75NTR, related to specific tumor types have been reported in vitro and in vivo. p75NTR has been implicated as a tumor and metastasis suppressor gene and in promoting apoptosis, particularly within the prostate. Also suggested was a role for -p75NTR in decreasing MMP2 and MMP9, with a simultaneous increase in TIMP1 expression and thus decreasing tumor kinetics. To examine the concomitant expression and possible interactions of p75NTR with TIMP1, we have used the H2009 lung carcinoma metastasis-derived cell line as well as the U251 glioma cell line. The TIMP1 overexpressing H2009 clone HB1 generated by transfection with TIMP1 overexpressing vector pBK-CMV- hTIMP-1, has previously been characterized in vitro and has been shown to be more aggressive in vivo. Using Western blots we have been able to demonstrate that TIMP1 overexpressing HB1 cells have a reduced expression of p75NTR when compared to the parent H2009 cells. U251 glioma cells transfected with the same vector have resulted in stable clones which have been similarly characterized. Colony formation assays performed on soft agar revealed that clones overexpressing TIMP-1 showed a far greater number of colony formation compared to U251. Similar experiments examining the effects of serum-free conditioned media from these cells on capillary network forming assays on Matrigel have also been examined. Although our preliminary data may appear contradictory to those seen in other model systems, it is well recognized that p75NTR activities are modulated by both the cell of origin as well as other interactions within the tumor microenvironment, particularly with molecules such as proteases and their inhibitors. Our data support a tumor inhibitory role for p75NTR in that TIMP1-overexpressing cells behaved more aggressively than the H2009 cells, possibly mediated by a decreased level of p75NTR. Additional studies to clarify the role of p75NTR in both carcinoma and glioma cell lines are ongoing. Supported by grant USAMRAA - RX4370802  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1129.
Association of Changes in Seasonal Respiratory Virus Activity and Ambulatory Antibiotic Prescriptions With the COVID-19 Pandemic
Authors: Alexander J. Lepak, Lindsay N. Taylor, Carolyn A. Stone, Lucas T. Schulz, Matthew C. Anderson, Barry C. Fox, Jonathan L. Temte
Journal: JAMA Internal Medicine (2021)

targeted survey, it was common for lactating examinees to report using test time to express breast milk or to experience physical symptoms.We propose that ABMS member boards have (1) an official lactation-specific examination accommodations policy, (2) policies readily available on ABMS member websites, (3) accommodation-request deadlines as close to the examination date as feasible, (4) accommodations for additional break time and frequency of breaks that meet the needs of examinees, and (5) guaranteed private space.Physicians should not be required to provide medical documentation that they are lactating.A limitation of this study is that we used social media to distribute a targeted convenience survey.We are therefore unable to assess response rate or determine whether respondents are representative.Lactating physicians face unique challenges when preparing and sitting for board examinations.We propose that all ABMS member boards have clear, adequate, and easily accessible lactation-specific examination accommodation policies that address the needs of lactating female physicians.
Abstract 417: The Prognostic Value of Lactate in Cardiac Intensive Care Unit Patients With and Without Cardiac Arrest
Authors: Barry Burstein, Saraschandra Vallabhajosyula, Bradley Ternus, Kianoush Kashani, Gregory W Barsness, Jacob C Jentzer
Journal: Circulation (2019)

Introduction: Lactate is a known prognostic marker in critically ill patients, including patients with shock and cardiac arrest (CA). We sought to describe the association between admission lactate and hospital mortality in cardiac intensive care unit (CICU) patients, particularly those with CA. Methods: We retrospectively evaluated adult patients admitted to a tertiary care CICU from January 1, 2007, to April 30, 2018, with measured lactate on admission. We examined hospital mortality as a function of admission lactate level in patients with and without CA. Multivariable logistic regression was used to determine predictors of hospital mortality in the overall cohort, after adjustment for clinical characteristics, therapies, and illness severity. Results: We included 3,042 patients with a median age of 70 years (IQR 60-80), including 40.5% (n=1,233) females. There were 789 patients (26.1%) with a diagnosis of CA. The median APACHE-4 predicted mortality was 24.2% (IQR 10.9-50.7), and 50.8% (n=1546) were treated with vasoactive infusions. The median lactate on admission was 1.8 mmol/L (IQR 1.1-3.0). CICU mortality occurred in 478 (15.7%) patients) and hospital mortality occurred in 706 (23.2%) patients. Hospital mortality rose progressively as a function of admission lactate ( Figure ). On univariable analysis, lactate was associated with increased hospital mortality among the overall cohort (OR 1.36, CI 1.31-1.42, P &lt; .001; AUROC 0.71), patients with CA (OR 1.33 (95% CI 1.25-1.41, P &lt; .01; AUROC 0.73), and patients without CA (OR 1.27, CI 1.21-1.34, P &lt; .01; AUROC 0.64). On multivariable analysis, lactate was one of the most significant predictors of hospital mortality (adjusted OR 1.13 per mmol/L, 95% CI 1.08-1.18, P &lt; .001). Conclusions: Admission lactate levels are strongly associated with increased hospital mortality among CICU patients, especially those with CA. The prognostic value of lactate levels may help inform clinicians caring for CICU patients.
Humanized CD19-Targeted Chimeric Antigen Receptor (CAR) T Cells in CAR-Naive and CAR-Exposed Children and Young Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia
Authors: Regina M. Myers, Yimei Li, Allison Barz Leahy, David M. Barrett, David T. Teachey, Colleen Callahan, Christina C. Fasano, Susan R. Rheingold, Amanda DiNofia, Lisa Wray, Richard Aplenc, Diane Baniewicz, Hongyan Liu, Pamela A. Shaw, Edward Pequignot, Kelly D. Getz, Jennifer L. Brogdon, Andrew D. Fesnak, Donald L. Siegel, Megan M. Davis, Chelsie Bartoszek, Simon F. Lacey, Elizabeth O. Hexner, Anne Chew, Gerald B. Wertheim, Bruce L. Levine, Carl H. June, Stephan A. Grupp, Shannon L. Maude
Journal: Journal of Clinical Oncology (2021)

PURPOSE CD19-targeted chimeric antigen receptor (CAR)–modified T cells demonstrate unprecedented responses in B-cell acute lymphoblastic leukemia (B-ALL); however, relapse remains a substantial challenge. Short CAR T-cell persistence contributes to this risk; therefore, strategies to improve persistence are needed. METHODS We conducted a pilot clinical trial of a humanized CD19 CAR T-cell product (huCART19) in children and young adults with relapsed or refractory B-ALL (n = 72) or B-lymphoblastic lymphoma (n = 2), treated in two cohorts: with (retreatment, n = 33) or without (CAR-naive, n = 41) prior CAR exposure. Patients were monitored for toxicity, response, and persistence of huCART19. RESULTS Seventy-four patients 1-29 years of age received huCART19. Cytokine release syndrome developed in 62 (84%) patients and was grade 4 in five (6.8%). Neurologic toxicities were reported in 29 (39%), three (4%) grade 3 or 4, and fully resolved in all cases. The overall response rate at 1 month after infusion was 98% (100% in B-ALL) in the CAR-naive cohort and 64% in the retreatment cohort. At 6 months, the probability of losing huCART19 persistence was 27% (95% CI, 14 to 41) for CAR-naive and 48% (95% CI, 30 to 64) for retreatment patients, whereas the incidence of B-cell recovery was 15% (95% CI, 6 to 28) and 58% (95% CI, 33 to 77), respectively. Relapse-free survival at 12 and 24 months, respectively, was 84% (95% CI, 72 to 97) and 74% (95% CI, 60 to 90) in CAR-naive and 74% (95% CI, 56 to 97) and 58% (95% CI, 37 to 90) in retreatment cohorts. CONCLUSION HuCART19 achieved durable remissions with long-term persistence in children and young adults with relapsed or refractory B-ALL, including after failure of prior CAR T-cell therapy.
Benefits and risks associated with different uses of the COVID-19 vaccine Vaxzevria: a modelling study, France, May to September 2021
Authors: Cécile Tran Kiem, Alessio Andronico, Paolo Bosetti, Juliette Paireau, Lise Alter, Pierre-Yves Boëlle, Arnaud Fontanet, Daniel Lévy-Bruhl, Simon Cauchemez
Journal: Eurosurveillance (2021)

Thrombosis with thrombocytopenia (TTS) has been identified as a rare adverse event following COVID-19 vaccination with Vaxzevria. We modelled the benefits and risks of Vaxzevria distribution from May to September 2021 in metropolitan France where other vaccines are available, considering French hospitalisation data and European data on TTS. Across different scenarios, benefits of Vaxzevria distribution in people 55 years and older exceeded the risk of death from COVID-19. In young adults, risks were at least of similar magnitude as benefits.
The dawn of the omics era in human precision-cut lung slices
Authors: John Stegmayr, Darcy E. Wagner
Journal: European Respiratory Journal (2021)

<b>New techniques permit the use of multiple omics and advanced imaging technologies with human precision-cut lung slices (PCLS) to allow for more objective and comprehensive molecular analysis to bring PCLS closer to the era of precision medicine</b>https://bit.ly/3deBjx2
Rituximab Maintenance Versus Observation After Immunochemotherapy (R-CHOP, R-MCP, and R-FCM) in Untreated Follicular Lymphoma Patients: A Randomized Trial of the Ostdeutsche Studiengruppe Hämatologie und Onkologie and the German Low-Grade Lymphoma Study Group
Authors: Carsten Hirt, Eva Hoster, Michael Unterhalt, Mathias Hänel, Gabriele Prange-Krex, Roswitha Forstpointner, Axel Florschütz, Ullrich Graeven, Norbert Frickhofen, Gerald Wulf, Eva Lengfelder, Christian Lerchenmüller, Rudolf Schlag, Judith Dierlamm, Ludwig Fischer von Weikersthal, Asima Ahmed, Hanns-Detlev Harich, Andreas Rosenwald, Wolfram Klapper, Martin Dreyling, Wolfgang Hiddemann, Michael Herold
Journal: HemaSphere (2021)

The German study groups, the German Low-Grade Lymphoma Study Group (GLSG) and Ostdeutsche Studiengruppe Hämatologie und Onkologie (OSHO), initiated in 2007 a double randomized trial to investigate efficacy and safety of rituximab maintenance versus observation in remission after randomly assigned induction treatment in the first-line follicular lymphoma. Previously untreated patients with stage II–IV follicular lymphoma in need of therapy were randomized to receive 6 cycles of R-CHOP, R-MCP, or R-FCM. Responding patients were subsequently randomized to 2 years rituximab maintenance or observation, stratified by type of immunochemotherapy, quality of remission, and Follicular Lymphoma International Prognostic Index (FLIPI). Recruitment was stopped in 2011 after the PRIMA results had been published. Median age of the 206 recruited patients was 66 years (range, 24–86), and (FLIPI) was low in 13%, intermediate in 28%, and high in 60%. High and comparable overall response rates were observed after R-CHOP (88%), R-MCP (89%), and R-FCM (91%). Rituximab maintenance substantially prolonged progression-free survival (PFS) in comparison to observation in remission (hazard ratio 0.39, P = 0.0064). In the rituximab maintenance group, the 3-year PFS was 89% compared with 69% in the observation group. No differences in overall survival were observed for maintenance vs. observation (hazard ratio 1.04, 95% confidence interval 0.32–3.43, P = 0.95). In this randomized trial, 2 years of rituximab maintenance was associated with significantly prolonged PFS in comparison to observation after response to first-line immunochemotherapy in follicular lymphoma. Our data represent an independent confirmation of the PRIMA trial results. (Clinical Trial EudraCT Number: 2005-005473-29, 2006-09-26)
Richter's transformation in the heart
Authors: Andrea Marra, Francesco Adamo, Stefano Baldoni, Maria Elena Laurenti, Michele Giansanti, Stefano Pasquino, Barbara Bigerna, Daniele Sorcini, Arianna Stella, Valerio Guarente, Roberto Limongello, Vincenzo Perriello, Giovanni Martino, Stefano Ascani, Brunangelo Falini, Paolo Sportoletti
Journal: The Lancet Oncology (2021)