tbuckley/cabot-search huggingface dataset:
A Biomarker Model to Distinguish Types of Myocardial Infarction and Injury
Authors: Johannes T. Neumann, Jessica Weimann, Nils A. Sörensen, Tau S. Hartikainen, Paul M. Haller, Jonas Lehmacher, Celine Brocks, Sophia Tenhaeff, Mahir Karakas, Thomas Renné, Stefan Blankenberg, Tanja Zeller, Dirk Westermann
Journal: Journal of the American College of Cardiology (2021)
Corrigendum to: Detecting Genetic Ancestry and Adaptation in the Taiwanese Han People
Authors: Yun-Hua Lo, Hsueh-Chien Cheng, Chia-Ni Hsiung, Show-Ling Yang, Han-Yu Wang, Chia-Wei Peng, Chun-Yu Chen, Kung-Ping Lin, Mei-Ling Kang, Chien-Hsiun Chen, Hou-Wei Chu, Chiao-Feng Lin, Mei-Hsuan Lee, Quintin Liu, Yoko Satta, Cheng-Jui Lin, Marie Lin, Shu-Miaw Chaw, Jun-Hun Loo, Chen-Yang Shen, Wen-Ya Ko
Journal: Molecular Biology and Evolution (2021)
Abstract 15390: Phosphodiesterase-3 Inhibitor Regulates Endothelial Autophagy and Re-Endothelialization in Experimental Models of a First-Generation mTOR Inhibitor-Eluting Stent
Authors: Shin-ichiro Hayashi, Etsuo Tsuchikane, Takeshi Suzuki, Osamu Kato, Yoshio Iwashima, Masatsugu Kishida, Fumiki Yoshihara, Takahiko Suzuki, Yuhei Kawano
Journal: Circulation (2018)

Introduction: Studies introduce impacts of antiproliferative drug-eluting stent (DES) in coronary heart disease, while attention has been focused on delayed arterial healing and late stent thrombos...
Prospective Feasibility Study with the Use of Losartan in COVID-19
Authors: Jeanwoo Yoo, Olena Bolotova, Imran Chaudhri, Nisha Nataraj, Haseena Sahib, Farrukh M. Koraishy, Sahar Ahmad, Michelle E. Bloom, Sandeep K. Mallipattu
Journal: Journal of the American Society of Nephrology (2020)

Yoo, Jeanwoo; Bolotova, Olena; Chaudhri, Imran; Nataraj, Nisha; Sahib, Haseena; Koraishy, Farrukh M.; Ahmad, Sahar; Bloom, Michelle E.; Mallipattu, Sandeep K. Author Information
27604 Response to baricitinib in the treatment of patients with early and late onset alopecia areata in the phase 2 portion of BRAVE-AA1 randomized controlled trial
Authors: Justin Ko, Janet Roberts, Maria Hordinsky, Susan Taylor, Arash Mostaghimi, Chiara Chiasserini, Yuxin Ding, Yun-Fei Chen, Wen-Shuo Wu, Yves Dutronc
Journal: Journal of the American Academy of Dermatology (2021)
LAG-3 expression on peripheral blood cells identifies patients with poorer outcomes after immune checkpoint blockade
Authors: Ronglai Shen, Michael A. Postow, Matthew Adamow, Arshi Arora, Margaret Hannum, Colleen Maher, Phillip Wong, Michael A. Curran, Travis J. Hollmann, Liwei Jia, Hikmat Al-Ahmadie, Niamh Keegan, Samuel A. Funt, Gopa Iyer, Jonathan E. Rosenberg, Dean F. Bajorin, Paul B. Chapman, Alexander N. Shoushtari, Allison S. Betof, Parisa Momtaz, Taha Merghoub, Jedd D. Wolchok, Katherine S. Panageas, Margaret K. Callahan
Journal: Science Translational Medicine (2021)

Peripheral blood LAG + CD8 + T cells are more commonly identified in immunotherapy-treated patients with cancer who have less favorable outcomes.
Neurofilament light and heterogeneity of disease progression in amyotrophic lateral sclerosis: development and validation of a prediction model to improve interventional trials
Authors: Simon Witzel, Felix Frauhammer, Petra Steinacker, David Devos, Pierre-François Pradat, Vincent Meininger, Steffen Halbgebauer, Patrick Oeckl, Joachim Schuster, Simon Anders, Johannes Dorst, Markus Otto, Albert C. Ludolph
Journal: Translational Neurodegeneration (2021)

Abstract Background Interventional trials in amyotrophic lateral sclerosis (ALS) suffer from the heterogeneity of the disease as it considerably reduces statistical power. We asked if blood neurofilament light chains (NfL) could be used to anticipate disease progression and increase trial power. Methods In 125 patients with ALS from three independent prospective studies—one observational study and two interventional trials—we developed and externally validated a multivariate linear model for predicting disease progression, measured by the monthly decrease of the ALS Functional Rating Scale Revised (ALSFRS-R) score. We trained the prediction model in the observational study and tested the predictive value of the following parameters assessed at diagnosis: NfL levels, sex, age, site of onset, body mass index, disease duration, ALSFRS-R score, and monthly ALSFRS-R score decrease since disease onset. We then applied the resulting model in the other two study cohorts to assess the actual utility for interventional trials. We analyzed the impact on trial power in mixed-effects models and compared the performance of the NfL model with two currently used predictive approaches, which anticipate disease progression using the ALSFRS-R decrease during a three-month observational period (lead-in) or since disease onset (ΔFRS). Results Among the parameters provided, the NfL levels ( P &lt; 0.001) and the interaction with site of onset ( P &lt; 0.01) contributed significantly to the prediction, forming a robust NfL prediction model ( R = 0.67). Model application in the trial cohorts confirmed its applicability and revealed superiority over lead-in and ΔFRS-based approaches. The NfL model improved statistical power by 61% and 22% (95% confidence intervals: 54%–66%, 7%–29%). Conclusion The use of the NfL-based prediction model to compensate for clinical heterogeneity in ALS could significantly increase the trial power. NCT00868166, registered March 23, 2009; NCT02306590, registered December 2, 2014.
Filamin C Cardiomyopathy Variants Cause Protein and Lysosome Accumulation
Authors: Radhika Agarwal, Joao A. Paulo, Christopher N. Toepfer, Jourdan K. Ewoldt, Subramanian Sundaram, Anant Chopra, Qi Zhang, Joshua Gorham, Steven R. DePalma, Christopher S. Chen, Steven P. Gygi, Christine E. Seidman, J.G. Seidman
Journal: Circulation Research (2021)

[Figure: see text].
Neuromodulation using ultra low frequency current waveform reversibly blocks axonal conduction and chronic pain
Authors: Martyn G. Jones, Evan R. Rogers, James P. Harris, Andrew Sullivan, D. Michael Ackermann, Marc Russo, Scott F. Lempka, Stephen B. McMahon
Journal: Science Translational Medicine (2021)

Nerve conduction and chronic pain are safely inhibited by an ultra low frequency current waveform.
Phase II study of durvalumab plus tremelimumab as therapy for patients with previously treated anti-PD-1/PD-L1 resistant stage IV squamous cell lung cancer (Lung-MAP substudy S1400F, NCT03373760)
Authors: Natasha B Leighl, Mary W Redman, Naiyer Rizvi, Fred R Hirsch, Philip C Mack, Lawrence H Schwartz, James L Wade, William J Irvin, Sreekanth C Reddy, Jeffrey Crawford, Jeffrey D Bradley, Thomas E Stinchcombe, Suresh S Ramalingam, Jieling Miao, Katherine Minichiello, Roy S Herbst, Vassiliki A Papadimitrakopoulou, Karen Kelly, David R Gandara
Journal: Journal for ImmunoTherapy of Cancer (2021)

Introduction S1400F is a non-match substudy of Lung Cancer Master Protocol (Lung-MAP) evaluating the immunotherapy combination of durvalumab and tremelimumab to overcome resistance to anti-programmed death ligand 1 (PD-(L)1) therapy in patients with advanced squamous lung carcinoma (sq non-small-cell lung cancer (NSCLC)). Methods Patients with previously treated sqNSCLC with disease progression after anti-PD-(L)1 monotherapy, who did not qualify for any active molecularly targeted Lung-MAP substudies, were eligible. Patients received tremelimumab 75 mg plus durvalumab 1500 mg once every 28 days for four cycles then durvalumab alone every 28 days until disease progression. The primary endpoint was the objective response rate (RECIST V.1.1). Primary and acquired resistance cohorts, defined as disease progression within 24 weeks versus ≥24 weeks of starting prior anti-PD-(L)1 therapy, were analyzed separately and an interim analysis for futility was planned after 20 patients in each cohort were evaluable for response. Results A total of 58 eligible patients received drug, 28 with primary resistance and 30 with acquired resistance to anti-PD-(L)1 monotherapy. Grade ≥3 adverse events at least possibly related to treatment were seen in 20 (34%) patients. The response rate in the primary resistance cohort was 7% (95% CI 0% to 17%), with one complete and one partial response. No responses were seen in the acquired resistance cohort. In the primary and resistance cohorts the median progression-free survival was 2.0 months (95% CI 1.6 to 3.0) and 2.1 months (95% CI 1.6 to 3.2), respectively, and overall survival was 7.7 months (95% CI 4.0 to 12.0) and 7.6 months (95% CI 5.3 to 10.2), respectively. Conclusion Durvalumab plus tremelimumab had minimal activity in patients with advanced sqNSCLC progressing on prior anti-PD-1 therapy. Trial registration number NCT03373760 .
Alveolar macrophages rely on GM-CSF from alveolar epithelial type 2 cells before and after birth
Authors: Julia Gschwend, Samantha P.M. Sherman, Frederike Ridder, Xiaogang Feng, Hong-Erh Liang, Richard M. Locksley, Burkhard Becher, Christoph Schneider
Journal: The Journal of Experimental Medicine (2021)

Programs defining tissue-resident macrophage identity depend on local environmental cues. For alveolar macrophages (AMs), these signals are provided by immune and nonimmune cells and include GM-CSF (CSF2). However, evidence to functionally link components of this intercellular cross talk remains scarce. We thus developed new transgenic mice to profile pulmonary GM-CSF expression, which we detected in both immune cells, including group 2 innate lymphoid cells and γδ T cells, as well as AT2s. AMs were unaffected by constitutive deletion of hematopoietic Csf2 and basophil depletion. Instead, AT2 lineage-specific constitutive and inducible Csf2 deletion revealed the nonredundant function of AT2-derived GM-CSF in instructing AM fate, establishing the postnatal AM compartment, and maintaining AMs in adult lungs. This AT2-AM relationship begins during embryogenesis, where nascent AT2s timely induce GM-CSF expression to support the proliferation and differentiation of fetal monocytes contemporaneously seeding the tissue, and persists into adulthood, when epithelial GM-CSF remains restricted to AT2s.
Early toxicity and clinical outcomes after chimeric antigen receptor T-cell (CAR-T) therapy for lymphoma
Authors: Jonathan E Brammer, Zachary Braunstein, Aashish Katapadi, Kyle Porter, Michael Biersmith, Avirup Guha, Sumithira Vasu, Vedat O Yildiz, Sakima A Smith, Benjamin Buck, Devin Haddad, Richard Gumina, Basem M William, Sam Penza, Ayman Saad, Nathan Denlinger, Ajay Vallakati, Ragavendra Baliga, Raymond Benza, Philip Binkley, Lai Wei, Mason Mocarski, Steven M Devine, Samantha Jaglowski, Daniel Addison
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Chimeric antigen receptor T-cell (CAR-T) infusion is associated with early toxicity. Yet, whether early toxicity development holds ramifications for long-term outcomes is unknown. Methods From a large cohort of consecutive adult patients treated with CAR-T therapies for relapsed or refractory lymphomas from 2016 to 2019, we assessed progression-free survival (PFS), by toxicity development (cytokine release syndrome (CRS), neurotoxicity, or cardiotoxicity]. We also assessed the relationship of toxicity development to objective disease response, and overall survival (OS). Multivariable regression was utilized to evaluate relationships between standard clinical and laboratory measures and disease outcomes. Differences in outcomes, by toxicity status, were also assessed via 30-day landmark analysis. Furthermore, we assessed the effects of early anti-CRS toxicity therapy use (at ≤grade 2 toxicity) on maximum toxicity grade observed, and long-term disease outcomes (PFS and OS). Results Overall, from 102 CAR-T-treated patients, 90 were identified as treated with single-agent therapy, of which 88.9% developed toxicity (80 CRS, 41 neurotoxicity, and 17 cardiotoxicity), including 28.9% with high-grade (≥3) events. The most common manifestations were hypotension at 96.6% and fever at 94.8%. Among patients with cardiac events, there was a non-significant trend toward a higher prevalence of concurrent or preceding high-grade (≥3) CRS. 50.0% required tocilizumab or corticosteroids. The median time to toxicity was 3 days; high grade CRS development was associated with cardiac and neurotoxicity. In multivariable regression, accounting for disease severity and traditional predictors of disease response, moderate (maximum grade 2) CRS development was associated with higher complete response at 1 year (HR: 2.34; p=0.07), and longer PFS (HR: 0.41; p=0.02, in landmark analysis), and OS (HR: 0.43; p=0.03). Among those with CRS, relative blood pressure (HR: 2.25; p=0.004), respectively, also associated with improved PFS. There was no difference in disease outcomes, or maximum toxicity grade (CRS, neurotoxicity, or cardiotoxicity) observed, based on the presence or absence of the use of early CRS-directed therapies. Conclusions Among adult lymphoma patients, moderate toxicity manifest as grade 2 CRS after CAR-T infusion may associate with favorable clinical outcomes. Further studies are needed to confirm these findings.
26648 Real-world comparison of monotherapy and concomitant medication use with biologic therapies for psoriasis: Ixekizumab versus guselkumab
Authors: Andrew Blauvelt, Russel Burge, Bridget Charbonneau, William Malatestinic, Baojin Zhu, Fangyu Wang, Benjamin Lockshin
Journal: Journal of the American Academy of Dermatology (2021)
27462 Ex vivo efficacy of dermocosmetic containing peptides, salicylic acid, glycolic acid and vichy volcanic water in procollagen type I production
Authors: Claudia Marçal, Priscila Correia, José Euzébio Gonçalves Junior, Beatriz Sant’Anna, Delphine Kerob
Journal: Journal of the American Academy of Dermatology (2021)
Blood Pressure Limbo—How Low Can You Go?
Authors: Aishah Matar, John W. McEvoy
Journal: Diabetes Care (2021)

Hypertension is one of the leading causes of death worldwide (1). In 2019, 20.3% of all adult female deaths and 18.2% of all adult male deaths were attributed to high systolic blood pressure (SBP) globally (1). Population-based surveys from diverse settings have shown that many adults with high blood pressure (BP) are not appropriately diagnosed (2). This represents a failure of health systems, particularly when it is known that BP-lowering medications significantly reduce cardiovascular disease (CVD) events among hypertensive patients (3). Furthermore, those patients who are diagnosed are nonetheless often undertreated and not at the recommended BP target. Recent guidelines recommend lower BP targets than ever before, resulting in an increasingly urgent need to address the widespread undertreatment of hypertension.

For people on BP-lowering medication, the 2017 American College of Cardiology/American Heart Association guidelines for hypertension recommend targeting a BP goal of <130/80 mmHg for all hypertensive patients including patients with diabetes (4). The 2018 European Society of Cardiology guidelines recommend targeting a BP of <130/80 mmHg in most treated patients, as long as such treatment is well tolerated, and targeting an SBP in the range of 120–129 mmHg in patients <65 years of age (5). These more intensive treatment recommendations were informed by randomized clinical trial (RCT) data (6) but also by a wealth of epidemiologic data (7). However, the data informing BP targets for patients with diabetes are somewhat mixed, which contributed to the 2021 American Diabetes Association recommendation to use a CVD risk calculator prior to determining the appropriate BP target for individuals with diabetes. A target of <130/80 mmHg is reserved for patients with a 10-year CVD risk of ≥15%, while a target of <140/90 mmHg is advised for individuals at lower risk (8).

These different guideline recommendations reflect the ongoing uncertainty in the balance …
Translation of a spinal bone cement product from bench to bedside
Authors: Fei Feng, Mengmeng Chen, Xuan Wang, Hongwei Zhang, Hongtao Nie, Hai Tang
Journal: Bioactive Materials (2021)

Spinal acrylic bone cements (ABCs) are used clinically for percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) to treat osteoporotic vertebral compression fractures. Product translation of spinal ABC products followed the design control processes including design verification and validation. The bench to bedside translation of the first Chinese spinal ABC product (Alliment®, namely Alliment Cement) approved by National Medical Products Administration of China was investigated and another commercial product served as the control (Osteopal®V, namely Osteopal V Cement). Results of non-clinical bench performance verification tests of compression, bending and monomer release showed that the newly marketed Alliment Cement is similar to the Osteopal V Cement with properties of both meeting the criteria specified by standards. The Alliment Cement demonstrated good biocompatibility during the 26 weeks' bone implantation test. Porcine cadaver validation tests further revealed that the Alliment Cement satisfied the needs for both PVP and PKP procedures. A post-approval, retrospective clinical investigation further demonstrated the safety and efficacy of the Alliment Cement, with a significant reduction of pain and the improved stability of the fractured vertebral bodies. A successful translation of biomaterial medical products needs close collaborations among academia, industry, healthcare professionals and regulatory agencies.
27832 Impact of facial and truncal acne on quality of life (QoL) in female adults: A multicountry population-based survey
Authors: Brigitte Dréno, Stefan Beissert, Fran E. Cook-Bolden, Rajeev Chavda, Julie C. Harper, Adelaide A. Hebert, Edward Lain, Alison Layton, Marco Rocha, Jonathan S. Weiss, Jerry K.L. Tan
Journal: Journal of the American Academy of Dermatology (2021)
Multifunctional SGQDs-CORM@HA nanosheets for bacterial eradication through cascade-activated “nanoknife” effect and photodynamic/CO gas therapy
Authors: Jiahui Liu, Rong Sheng Li, Mengting He, Zhigang Xu, Li Qun Xu, Yuejun Kang, Peng Xue
Journal: Biomaterials (2021)
Reply to Krishna and Jain
Authors: Mohammad Al-Haddad, Michael B. Wallace
Journal: Endoscopy (2021)

See also: Comments on: “Fine-needle aspiration of pancreatic cystic lesions: a randomized study with long-term follow-up comparing standard and flexible needles”Endoscopy 2021; 53(09): 987-987DOI: 10.1055/a-1425-5322
Dual Inhibition of FLT3 and AXL by Gilteritinib Overcomes Hematopoietic Niche-Driven Resistance Mechanisms in <i>FLT3</i>-ITD Acute Myeloid Leukemia
Authors: Pierre-Yves Dumas, Arnaud Villacreces, Amélie V. Guitart, Ali El-habhab, Layal Massara, Olivier Mansier, Audrey Bidet, Delphine Martineau, Solene Fernandez, Thibaut Leguay, Arnaud Pigneux, Isabelle Vigon, Jean-Max Pasquet, Vanessa Desplat
Journal: Clinical Cancer Research (2021)

Abstract Purpose: AXL has been shown to play a pivotal role in the selective response of FLT3-ITD acute myeloid leukemia (AML) cells to FLT3 tyrosine kinase inhibitors (TKI), particularly within the bone marrow microenvironment. Experimental Design: Herein, we compared the effect of dual FLT3/AXL-TKI gilteritinib with quizartinib through in vitro models mimicking hematopoietic niche conditions, ex vivo in primary AML blasts, and in vivo with dosing regimens allowing plasma concentration close to those used in clinical trials. Results: We observed that gilteritinib maintained a stronger proapoptotic effect in hypoxia and coculture with bone marrow stromal cells compared with quizartinib, linked to a dose-dependent inhibition of AXL phosphorylation. In vivo, use of the MV4–11 cell line with hematopoietic engraftment demonstrated that gilteritinib was more effective than quizartinib at targeting leukemic cells in bone marrow. Finally, FLT3-ITD AML patient-derived xenografts revealed that this effect was particularly reproducible in FLT3-ITD AML with high allelic ratio in primary and secondary xenograft. Moreover, gilteritinib and quizartinib displayed close toxicity profile on normal murine hematopoiesis, particularly at steady state. Conclusions: Overall, these findings suggest that gilteritinib as a single agent, compared with quizartinib, is more likely to reach leukemic cells in their protective microenvironment, particularly AML clones highly dependent on FLT3-ITD signaling.
Tuberculosis incidence and mortality in people living with human immunodeficiency virus: a Danish nationwide cohort study
Authors: Raquel Martin-Iguacel, Josep M. Llibre, Court Pedersen, Niels Obel, Nina Breinholt Stærke, Johanna Åhsberg, Iben Ørsted, Inge Holden, Gitte Kronborg, Rajesh Mohey, Line Dahlerup Rasmussen, Isik Somuncu Johansen
Journal: Clinical Microbiology and Infection (2021)

To explore changes over time in the epidemiology of tuberculosis (TB) in Denmark in people living with human immunodeficiency virus (HIV) (PLWH).In this nationwide, population-based cohort study we included all adult PLWH from the Danish HIV Cohort Study (1995-2017) without previous TB. We estimated TB incidence rate (IR), all-cause mortality rate (MR), associated risk and prognostic factors using Poisson regression.Among 6982 PLWH (73 596 person-years (PY)), we observed 217 TB events (IR 2.9/1000 PY, 95% CI 2.6-3.4: IR 6.7, 95% CI 5.7-7.9 among migrants and IR 1.4, 95% CI 1.1-1.7 among Danish-born individuals; p < 0.001). The IR of concomitant HIV/TB remained high and unchanged over time. The IR of TB diagnosed >3 months after HIV diagnosis declined with calendar time, longer time from HIV diagnosis, and CD4 cell recovery. Independent TB risk factors were African/Asian/Greenland origin (adjusted incidence rate ratio (aIRR) 5.2, 95% CI 3.5-7.6, aIRR 6.5, 95% CI 4.2-10.0, aIRR 7.0, 95% CI 3.4-14.6, respectively), illicit drug use (aIRR 6.9, 95% CI 4.2-11.2), CD4 <200 cells/μL (aIRR 2.7, 95% CI 2.0-3.6) and not receiving antiretroviral therapy (aIRR 3.7, 95% CI 2.5-5.3). Fifty-five patients died (MR 27.9/1000 PY, 95% CI 21.4-36.3), with no improvement in mortality over time. Mortality prognostic factors were Danish-origin (adjusted mortality rate ratio (aMRR) 2.3, 95% CI 1.3-4.3), social burden (aMRR 3.9, 95% CI 2.2-7.0), CD4 <100 cells/μL at TB diagnosis (aMRR 2.6, 95% CI 1.3-4.9), TB diagnosed >3 months after HIV versus concomitant diagnosis (aMRR 4.3, 95% CI 2.2-8.7) and disseminated TB (aMRR 3.3, 95% CI 1.1-9.9).Late HIV presentation with concomitant TB remains a challenge. Declining TB rates in PLWH were observed over time and with CD4 recovery, highlighting the importance of early and successful antiretroviral therapy. However, MR remained high. Our findings highlight the importance of HIV and TB screening strategies and treatment of latent TB in high-risk groups.
The extracellular innate-immune effector HMGB1 limits pathogenic bacterial biofilm proliferation
Authors: Aishwarya Devaraj, Laura A. Novotny, Frank H. Robledo-Avila, John R. Buzzo, Lauren Mashburn-Warren, Joseph A. Jurcisek, Natalia O. Tjokro, Santiago Partida-Sanchez, Lauren O. Bakaletz, Steven D. Goodman
Journal: Journal of Clinical Investigation (2021)

Herein, we describe an extracellular function of the vertebrate high-mobility group box 1 protein (HMGB1) in the proliferation of bacterial biofilms. Within host cells, HMGB1 functions as a DNA architectural protein, similar to the ubiquitous DNABII family of bacterial proteins; despite that, these proteins share no amino acid sequence identity. Extracellularly, HMGB1 induces a proinflammatory immune response, whereas the DNABII proteins stabilize the extracellular DNA-dependent matrix that maintains bacterial biofilms. We showed that when both proteins converged on extracellular DNA within bacterial biofilms, HMGB1, unlike the DNABII proteins, disrupted biofilms both in vitro (including the high-priority ESKAPEE pathogens) and in vivo in 2 distinct animal models, albeit with induction of a strong inflammatory response that we attenuated by a single engineered amino acid change. We propose a model where extracellular HMGB1 balances the degree of induced inflammation and biofilm containment without excessive release of biofilm-resident bacteria.