tbuckley/cabot-search huggingface dataset:
Non–beta blocker enantiomers of propranolol and atenolol inhibit vasculogenesis in infantile hemangioma
Authors: Caroline T. Seebauer, Matthew S. Graus, None Lan Huang, Alex McCann, Jill Wylie-Sears, Frank Fontaine, Tara Karnezis, David Zurakowski, Steven J. Staffa, Frédéric Meunier, John B. Mulliken, Joyce Bischoff, Mathias Francois
Journal: Journal of Clinical Investigation (2021)

Propranolol and atenolol, current therapies for problematic infantile hemangioma (IH), are composed of R(+) and S(–) enantiomers: the R(+) enantiomer is largely devoid of beta blocker activity. We investigated the effect of R(+) enantiomers of propranolol and atenolol on the formation of IH-like blood vessels from hemangioma stem cells (HemSCs) in a murine xenograft model. Both R(+) enantiomers inhibited HemSC vessel formation in vivo. In vitro, similar to R(+) propranolol, both atenolol and its R(+) enantiomer inhibited HemSC to endothelial cell differentiation. As our previous work implicated the transcription factor sex-determining region Y (SRY) box transcription factor 18 (SOX18) in propranolol-mediated inhibition of HemSC to endothelial differentiation, we tested in parallel a known SOX18 small-molecule inhibitor (Sm4) and show that this compound inhibited HemSC vessel formation in vivo with efficacy similar to that seen with the R(+) enantiomers. We next examined how R(+) propranolol alters SOX18 transcriptional activity. Using a suite of biochemical, biophysical, and quantitative molecular imaging assays, we show that R(+) propranolol directly interfered with SOX18 target gene trans-activation, disrupted SOX18-chromatin binding dynamics, and reduced SOX18 dimer formation. We propose that the R(+) enantiomers of widely used beta blockers could be repurposed to increase the efficiency of current IH treatment and lower adverse associated side effects.
High Prevalence of Constitutional Mismatch Repair Deficiency in a Pediatric T-cell Lymphoblastic Lymphoma Cohort
Authors: Emma Kroeze, Dilys D. Weijers, Melanie M. Hagleitner, Hester A. de Groot-Kruseman, Marjolijn C. J. Jongmans, Roland P. Kuiper, Rob Pieters, Jules P. P. Meijerink, Jan L. C. Loeffen
Journal: HemaSphere (2021)

This study describes the clinical characteristics of a complete Dutch T-cell lymphoblastic lymphoma (T-LBL) cohort, including second primary malignancies and comorbidities. We show that over 10% of patients in this complete T-LBL cohort have been diagnosed with a cancer predisposition syndrome (CPS), consisting almost exclusively of constitutional mismatch repair deficiency (CMMRD). The clinical characteristics of sporadic T-LBL patients were compared with T-LBL patients that have been diagnosed with CMMRD. This shows that disease presentation is comparable but that disease localization in CMMRD patients might be more localized. The percentage of CPS seems reliable considering the completeness of the cohort of Dutch T-LBL patients and might even be an underestimation (possibility of undiagnosed CPS patients in cohort). As the frequency of an underlying predisposition syndrome among T-LBL patients may be underestimated at present, we advocate for screening all pediatric T-LBL patients for the presence of germline mutations in mismatch repair genes.
Biphasic versus monophasic manual blood culture bottles for low-resource settings: an in-vitro study
Authors: Sien Ombelet, Alessandra Natale, Jean-Baptiste Ronat, Thomas Kesteman, Olivier Vandenberg, Jan Jacobs, Liselotte Hardy
Journal: The Lancet Microbe (2021)

BackgroundManual blood culture bottles (BCBs) are frequently used in low-resource settings. There are few BCB performance evaluations, especially evaluations comparing them with automated systems. We evaluated two manual BCBs (Bi-State BCB and BacT/ALERT BCB) and compared their yield and time to growth detection with those of automated BacT/ALERT system.MethodsBCBs were spiked in triplicate with 177 clinical isolates representing pathogens common in low-resource settings (19 bacterial and one yeast species) in adult and paediatric volumes, resulting in 1056 spiked BCBs per BCB system. Growth in manual BCBs was evaluated daily by visually inspecting the broth, agar slant, and, for BacT/ALERT BCB, colour change of the growth indicator. The primary outcomes were BCB yield (proportion of spiked BCB showing growth) and time to detection (proportion of positive BCB with growth detected on day 1 of incubation). 95% CI for yield and growth on day 1 were calculated using bootstrap method for clustered data using. Secondary outcomes were time to colony for all BCBs (defined as number of days between incubation and colony growth sufficient to use for further testing) and difference between time to detection in broth and on agar slant for the Bi-State BCBs.FindingsOverall yield was 95·9% (95% CI 93·9–98·0) for Bi-State BCB and 95·5% (93·3–97·8) for manual BacT/ALERT, versus 96·1% (94·0–98·1) for the automated BacT/ALERT system (p=0·61). Day 1 growth was present in 920 (90·8%) of 1013 positive Bi-State BCB and 757 (75·0%) of 1009 positive manual BacT/ALERT BCB, versus 1008 (99·3%) of 1015 automated bottles. On day 2, detection rates were 100% for BI-State BCB, 97·7% for manual BacT/ALERT BCB, and 100% for automated bottles. For Bi-State BCB, growth mostly occurred simultaneously in broth and slant (81·7%). Sufficient colony growth on the slant to perform further tests was present in only 44·1% of biphasic bottles on day 2 and 59·0% on day 3.InterpretationThe yield of manual BCB was comparable with the automated system, suggesting that manual blood culture systems are an acceptable alternative to automated systems in low-resource settings. Bi-State BCB outperformed manual BacT/ALERT bottles, but the agar slant did not allow earlier detection nor earlier colony growth. Time to detection for manual blood culture systems still lags that of automated systems, and research into innovative and affordable methods of growth detection in manual BCBs is encouraged.FundingMédecins Sans Frontières and Department of Economy, Science and Innovation of the Flemish Government.
Sequential Fludarabine, Ara-C, Etoposide (FLAV) Followed By Fludarabine/ Busulfan Reduced Toxicity Conditioning Is Safe and Effective Salvage for Adult Patients with Refractory Acute Myeloid Leukemia and High Risk Myelodysplasia
Authors: Ahmad S. Alotaibi, Shad Ahmed, Walid Rasheed, Marwan Shaheen, Nadiah Alobaidi, Ahmad Alnughmush, Amal Hejab, Taimoor Hussain, Ahmed Abdrabou, Haroon Alfadhil, Mostafa Saleh, Ahmed Bin Salman, Majed Altareb, Momen Nassani, Yazeed S Bajuaifer, Mohamed Isam Sharif, Emad Ghabashi, Shaykhah Alotaibi, Riad Youniss, Alfadel Alshaibani, Ali Alahmari, Saud Alhayli, Riad Elfakih, Feras Al Fraih, Amr Suleiman Hanbali, Fahad Alsharif, Naeem A. Chaudhri, Hazza Alzahrani, Fahed Almhareb, Mahmoud Aljurf, Syed O. Ahmed
Journal: Blood (2021)
Emerging nanoformulation strategies for phytocompounds and applications from drug delivery to phototherapy to imaging
Authors: Hwa Seung Han, Song Yi Koo, Ki Young Choi
Journal: Bioactive Materials (2021)

Over thousands of years, natural bioactive compounds derived from plants (bioactive phytocompounds, BPCs) have been used worldwide to address human health issues. Today, they are a significant resource for drug discovery in the development of modern medicines. Although many BPCs have promising biological activities, most of them cannot be effectively utilized in drugs for therapeutic applications because of their inherent limitations of low solubility, structural instability, short half-life, poor bioavailability, and non-specific distribution to organs. Researchers have utilized emerging nanoformulation (NF) technologies to overcome these limitations as they have demonstrated great potential to improve the solubility, stability, and pharmacokinetic and pharmacodynamic characteristics of BPCs. This review exemplifies NF strategies for resolving the issues associated with BPCs and summarizes recent advances in their preclinical and clinical applications for imaging and therapy. This review also highlights how innovative NF technologies play a leading role in next-generation BPC-based drug development for extended therapeutic applications. Finally, this review discusses the opportunities to take BPCs with meaningful clinical impact from bench to bedside and extend the patent life of BPC-based medicines with new formulations or application to new adjacent diseases beyond the primary drug indications.
Correction: A Randomized Trial of Combined PD-L1 and CTLA-4 Inhibition with Targeted Low-dose or Hypofractionated Radiation for Patients with Metastatic Colorectal Cancer
Authors: Arta M. Monjazeb, Anita Giobbie-Hurder, Ana Lako, Emily M. Thrash, Ryan C. Brennick, Katrina Z. Kao, Claire Manuszak, Ryan D. Gentzler, Anteneh Tesfaye, Salma K. Jabbour, Olatunji B. Alese, Osama E. Rahma, James M. Cleary, Elad Sharon, Harvey J. Mamon, May Cho, Howard Streicher, Helen X. Chen, Mansoor M. Ahmed, Adrian Mariño-Enríquez, Seunghee Kim-Schulze, Sacha Gnjatic, Emanual Maverakis, Alina I. Marusina, Alexander A. Merleev, Mariano Severgnini, Kathleen L. Pfaff, James Lindsay, Jason L. Weirather, Srinika Ranasinghe, Alexander Spektor, Scott J. Rodig, F. Stephen Hodi, Jonathan D. Schoenfeld
Journal: Clinical Cancer Research (2021)

In the original version of this article (1), the name of the thirty-third author, F. Stephen Hodi, is incorrect. The name has been corrected in the latest online HTML and PDF versions of the article. The authors regret this error.
Abstract 12327: Intravenous Waveform Analysis Correlates With Volume Status in Resuscitation in In-Vivo Rat Model
Authors: Matthew Barajas, Matthias L Riess, Franz J Baudenbacher, Matthew Hampton, zhu li, Susan Eagle
Journal: Circulation (2021)

Introduction: Current volume status markers under-perform. Dynamic markers demonstrate improved outcomes in goal directed fluid therapy but maintain validity in a narrow range of clinical parameters. In addition, they assess volume responsiveness over total volume status. Repeated echo assessments may be infeasible. Hypothesis: Intravenous waveform analysis-derived F1 more closely models volume status than current markers in a rat resuscitation model. Methods: Seven Sprague Dawley rats were anesthetized and mechanically ventilated. Pressure transductions occurred via cannulation of the right femoral vein, left femoral artery and right internal jugular vein. Hemorrhage and resuscitation occurred via the left femoral vein. Heparinized rats were bled to 80% of the estimated blood volume (EBV) then resuscitated with their own whole blood in increments of 2% of the EBV until euvolemia was reached. Cardiac output (CO) and left ventricular end diastolic area (LVEDA) were calculated with echocardiography. Fast Fourier transform was performed on venous waveforms to obtain the heart rate linked F1 amplitude. Pearson’s correlation coefficients were compared using Fisher’s Z transformation. Mixed effects modeling goodness-of-fit was assessed with Akaike information criterion (AIC). Significance was set at p=.05. Results: F1 had the strongest correlation with volume status, r= .70, followed by CO, r=.55, LVEDA, r=.55, mean arterial pressure (MAP), r=.50, central venous pressure r= -.02, and pulse pressure variation (PPV), r=.01. When compared, F1 rho was significantly greater than that of all variables except CO and LVEDA, p=.09 and p=.07, respectively. In mixed effects regression, F1 displayed the most significant AIC, -274, followed by CO at -239. Conclusions: The novel marker F1 is strongly correlated with volume status during whole blood resuscitation. F1 may be superior to current markers for directing volume resuscitation therapy.
Abstract 13434: Chronic Total Occlusions in Refractory Cardiac Arrest Patients
Authors: Ales Kral, Jan Belohlavek, Daniel Rob, Jana Smalcova
Journal: Circulation (2021)

Introduction: Coronary artery disease (CAD) is the most frequent cause of cardiac arrest (CA) in adults. Coronary chronic total occlusions (CTOs) are associated with an increased risk CA and predict future malignant arrhythmias in CA survivors. Nevertheless, the prevalence of CTOs in patients with CA and especially refractory CA is poorly characterized. We sought to evaluate the frequency and characteristics of CTOs in refractory CA patients included in the Prague-OHCA study. Methods: From 256 patients with refractory CA randomized in the Prague-OHCA study, coronary angiography (CAG) was performed in 181 subjects. Of the 128 patients with significant CAD (defined as more than 50% diameter stenosis in at least one major coronary vessel), 14 had a different primary cause of CA, leading to a study cohort of 114 patients with CAD as the primary cause of CA. 41 patients had at least one coronary CTO, whereas 73 patients had significant CAD without CTOs. Clinical, angiographic parameters, initial management and outcome was compared between the CTO and non-CTO groups. Results: Patients in the CTO cohort were older (59 ±12 versus 54 ±11 years, p = 0.015) and had shorter CA durations (45 ± 25 versus 55 ± 24 minutes, p = 0.03) as compared to patients in the non-CTO cohort. The CTO cohort presented less frequently with an acute coronary syndrome (ACS) (51 versus 89%, p &lt; 0.0001) and had a higher prevalence of multi-vessel disease (89 versus 51%, p &lt; 0.0001), as compared to the non-CTO cohort. Acute index PCI was performed less frequently in the CTO group (61 versus 86%, p = 0.002). Patients in the CTO group experienced more frequent neurologic recovery (51 versus 32%, p = 0.04), whereas cardiac recovery (63 versus 51%, p = 0.19) and six month mortality (51 versus 59%, p = 0.43) did not differ between the CTO and non-CTO group. Conclusions: CTOs represent a frequent cause of refractory CA. Patients with refractory CA due to CTOs were older with a high prevalence of multi-vessel disease and presented less frequently with an ACS, as compared to patients with significant CAD without CTOs. The observed more frequent neurologic recovery in the CTO cohort is presumably due to shorter CA durations in these patients. Mid- and long-term prognosis did not differ between the CTO and non-CTO cohort.
Preliminary Safety and Efficacy Results from Precizn-1: An Ongoing Phase 1/2 Study on Zinc Finger Nuclease-Modified Autologous CD34+ HSPCs for Sickle Cell Disease (SCD)
Authors: Asif Alavi, Lakshmanan Krishnamurti, Mehrdad Abedi, Isobelle Galeon, David Reiner, Sharon E Smith, Lin Wang, Anne Ramezi, Pablo Rendo, Mark C. Walters
Journal: Blood (2021)
Efficacy of rFVIIIFc for First-Time Immune Tolerance Induction (ITI) Therapy: Final Results from the Global, Prospective VerITI-8 Study
Authors: Lynn Malec, An Van Damme, Anthony Chan, Mariya Spasova, Nisha Jain, Charlotte Sensinger, Jennifer Dumont, Stefan Lethagen, Manuel Carcao, Flora Peyvandi
Journal: Blood (2021)
Lack of Specificity of Neonatal Intracranial Paraventricular Calcifications
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Journal of Clinical Investigation in the time of COVID-19
Authors: Arturo Casadevall, Sarah Jackson, Gregg L. Semenza, Gordon F. Tomaselli, Rexford S. Ahima
Journal: Journal of Clinical Investigation (2021)

In this editorial, we describe the experience of the JCI editors during the COVID-19 pandemic. Our goal is to share how we operated during the pandemic, recount how the JCI contributed to the response, highlight some of the major papers we published on SARS-CoV-2 and COVID-19, and impart our insights in the hope that these are helpful to journal editors that may need to deal with similar types of crises in the future.
Schools: still a gaping hole in the English covid strategy
Authors: Christina Pagel, Adam Squires
Journal: BMJ (2021)

In August, one of us (CP) wrote about schools being the gaping hole in the English covid strategy.This was written in the face of the highly transmissible delta covid-19 variant. 1 Three failings were identified: delayed vaccination of 12-15 year olds; lack of public health measures in schools such as masks and ventilation; and continued high community transmission leaving schools vulnerable.So what happened?And what needs to happen next?
Chronic electrical stimulation of peripheral nerves via deep-red light transduced by an implanted organic photocapacitor
Authors: Malin Silverå Ejneby, Marie Jakešová, Jose J. Ferrero, Ludovico Migliaccio, Ihor Sahalianov, Zifang Zhao, Magnus Berggren, Dion Khodagholy, Vedran Đerek, Jennifer N. Gelinas, Eric Daniel Głowacki
Journal: Nature Biomedical Engineering (2021)
Pyoderma Gangrenosum
Authors: Yi-Li Hou, Chih-Hung Lee
Journal: JAMA Dermatology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
<i>Notes from the Field:</i> COVID-19–Associated Mucormycosis — Arkansas, July–September 2021
Authors: Theresa M. Dulski, Megan DeLong, Kelley Garner, Naveen Patil, Michael J. Cima, Laura Rothfeldt, Trent Gulley, Austin Porter, Keyur S. Vyas, Hazel K. Liverett, Mitsuru Toda, Jeremy A.W. Gold, Atul Kothari
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

During September 17-24, 2021, three clinicians independently notified the Arkansas Department of Health (ADH) of multiple patients with mucormycosis after a recent diagnosis of COVID-19.To provide data to guide clinical and public health practice, ADH coordinated a statewide call on October 11, 2021 to infection preventionists for COVID-19-associated mucormycosis cases.Mucormycosis is an uncommon but severe invasive fungal infection caused by molds in the order Mucorales.Mucormycosis typically affects persons with immunocompromising conditions such as a hematologic malignancy, stem cell or solid organ transplantation, or uncontrolled diabetes (1).The emergence of COVID-19-associated mucormycosis has been described in other parts of the world, particularly in India, but has been infrequently reported in the United States (2-4).COVID-19 might increase mucormycosis risk because of COVID-19-induced immune dysregulation or associated treatments such as corticosteroids and immunomodulatory drugs (e.g., tocilizumab or baricitinib) that impair host defenses against molds (5).A case of mucormycosis was defined as laboratory identification of Mucorales by culture, histopathology, or polymerase chain reaction in a patient with a clinical diagnosis of invasive mucormycosis.† Cases were considered COVID-19-associated if the patient received a positive reverse transcription-polymerase chain reaction or antigen test result for SARS-CoV-2 (the virus that causes COVID-19) during the 60 days preceding the mucormycosis diagnosis.Cases were reported to ADH using a standardized case report form, medical records, or oral report.Data were stored using * These authors contributed equally to this report.† Signs and symptoms of mucormycosis vary by the affected body site.Rhinoorbital-cerebral mucormycosis signs and symptoms frequently include fever, unilateral facial swelling, headache, sinus congestion, vision loss, proptosis, and necrotic lesions of the nasal bridge or palate.Cutaneous mucormycosis signs and symptoms frequently include fever, blisters or ulcers that become necrotic, and pain, erythema, or swelling around the wound.Pulmonary mucormycosis signs and symptoms frequently include fever, cough, chest pain, and shortness of breath.Gastrointestinal mucormycosis signs and symptoms frequently include fever, abdominal pain, nausea, vomiting, and gastrointestinal bleeding.https://www.cdc.gov/fungal/
Re: Luke Harper, T. Blanc, M. Peycelon, et al. Circumcision and Risk of Febrile Urinary Tract Infection in Boys with Posterior Urethral Valves: Result of the CIRCUP Randomized Trial. Eur Urol. 2022;81:64–72
Authors: Deepansh Dalela, Kristina Suson
Journal: European Urology (2021)
Editorial Board
Authors: Clarence Loeb, Arthur Proetz, William Wherry, William Benedict, W Morrison, Stanley Truhlsen, Paul Henkind, Paul Lichter, Donald Minckler, Andrew Schachat, George Bartley, Stephen Mcleod, San Francisco, Daniel Albert, Creig Hoyt, Emily Chew, Henry Jampel, Bennie Jeng, Susan Vitale, Anita Bethesda, San Agarwal, Ike Francisco, Tin Aung, Balwantray Chauhan, Michael Chiang, Laura Downie, Anat Galor
Journal: Ophthalmology (2021)
Preterm Delivery Is a Long-term Hypertension Risk Factor
Authors: Anita Slomski
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal