tbuckley/cabot-search huggingface dataset:
Type I interferon autoantibodies are associated with systemic immune alterations in patients with COVID-19
Authors: Monique G. P. van der Wijst, Sara E. Vazquez, George C. Hartoularos, Paul Bastard, Tianna Grant, Raymund Bueno, David S. Lee, John R. Greenland, Yang Sun, Richard Perez, Anton Ogorodnikov, Alyssa Ward, Sabrina A. Mann, Kara L. Lynch, Cassandra Yun, Diane V. Havlir, Gabriel Chamie, Carina Marquez, Bryan Greenhouse, Michail S. Lionakis, Philip J. Norris, Larry J. Dumont, Kathleen Kelly, Peng Zhang, Qian Zhang, Adrian Gervais, Tom Le Voyer, Alexander Whatley, Yichen Si, Ashley Byrne, Alexis J. Combes, Arjun Arkal Rao, Yun S. Song, Gabriela K. Fragiadakis, Kirsten Kangelaris, Carolyn S. Calfee, David J. Erle, Carolyn Hendrickson, Matthew F. Krummel, Prescott G. Woodruff, Charles R. Langelier, Jean-Laurent Casanova, Joseph L. Derisi, Mark S. Anderson, Chun Jimmie Ye
Journal: Science Translational Medicine (2021)

Neutralizing autoantibodies against type I interferons (IFNs) have been found in some patients with critical coronavirus disease 2019 (COVID-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the prevalence of these antibodies, their longitudinal dynamics across the disease severity scale, and their functional effects on circulating leukocytes remain unknown. Here, in 284 patients with COVID-19, we found type I IFN–specific autoantibodies in peripheral blood samples from 19% of patients with critical disease and 6% of patients with severe disease. We found no type I IFN autoantibodies in individuals with moderate disease. Longitudinal profiling of over 600,000 peripheral blood mononuclear cells using multiplexed single-cell epitope and transcriptome sequencing from 54 patients with COVID-19 and 26 non–COVID-19 controls revealed a lack of type I IFN–stimulated gene (ISG-I) responses in myeloid cells from patients with critical disease. This was especially evident in dendritic cell populations isolated from patients with critical disease producing type I IFN–specific autoantibodies. Moreover, we found elevated expression of the inhibitory receptor leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) on the surface of monocytes isolated from patients with critical disease early in the disease course. LAIR1 expression is inversely correlated with ISG-I expression response in patients with COVID-19 but is not expressed in healthy controls. The deficient ISG-I response observed in patients with critical COVID-19 with and without type I IFN–specific autoantibodies supports a unifying model for disease pathogenesis involving ISG-I suppression through convergent mechanisms.
25447 Baricitinib treatment results in clinically meaningful itch reduction and enhanced quality of life in patients with moderate-to-severe atopic dermatitis: Results from BREEZE-AD5
Authors: Shawn Kwatra, Seth Forman, Alma Cruz, Susan Ball, Amy DeLozier, Evangeline Pierce, Andrew Buchanan, Luna Sun, Yuxin Ding, Bruce Strober
Journal: Journal of the American Academy of Dermatology (2021)
Triple Therapy for Cystic Fibrosis <i>Phe508del</i>–Gating and –Residual Function Genotypes
Authors: Peter J. Barry, Marcus A. Mall, Antonio Álvarez, Carla Colombo, Karin M. de Winter-de Groot, Isabelle Fajac, Kimberly A. McBennett, Edward F. McKone, Bonnie W. Ramsey, Sivagurunathan Sutharsan, Jennifer L. Taylor-Cousar, Elizabeth Tullis, Neil Ahluwalia, Lucy S. Jun, Samuel M. Moskowitz, Valentin Prieto-Centurion, Simon Tian, David Waltz, Fengjuan Xuan, Yaohua Zhang, Steven M. Rowe, Deepika Polineni
Journal: New England Journal of Medicine (2021)

Elexacaftor–tezacaftor–ivacaftor is a small-molecule cystic fibrosis transmembrane conductance regulator (CFTR) modulator regimen shown to be efficacious in patients with at least one Phe508del allele, which indicates that this combination can modulate a single Phe508del allele. In patients whose other CFTR allele contains a gating or residual function mutation that is already effectively treated with previous CFTR modulators (ivacaftor or tezacaftor–ivacaftor), the potential for additional benefit from restoring Phe508del CFTR protein function is unclear.
The clinical outcomes and genomic landscapes of acute lymphoblastic leukemia patients with <scp>E2A‐PBX1</scp>: A 10‐year retrospective study
Authors: Biqi Zhou, Xinran Chu, Hong Tian, Tianhui Liu, Hong Liu, Wei Gao, Suning Chen, Shaoyan Hu, Depei Wu, Yang Xu
Journal: American Journal of Hematology (2021)

The clinical outcomes and genomic features of E2A-PBX1 (TCF3-PBX1)-positive B-cell acute lymphoblastic leukemia (B-ALL) patients remain unclear. A total of 137 patients carrying E2A-PBX1 among 3164 B-ALL patients between 2009 and 2019 were retrospectively analyzed. The 5-year overall survival (OS) and disease-free survival (DFS) rates of the whole cohort were 68.6% and 61.0%, respectively. Age [DFS, p = 0.037; cumulative incidence of relapse (CIR), p = 0.005] and the level of minimal residual disease (MRD) after induction chemotherapy (OS, p = 0.020; DFS, p = 0.002; CIR, p = 0.006) were independent risk factors. In adolescents/adults, allogeneic hematopoietic stem cell transplantation (allo-HSCT) at first complete remission (CR1) significantly improved the 5-year prognosis (OS, p < 0.001; DFS, p < 0.001; CIR, p < 0.001). Haploidentical HSCT decreased the CIR compared with human leukocyte antigen-matched HSCT in adolescents/adults (p = 0.017). Mutations in PBX1, PAX5, CTCF and SETD2, amplification of AKT3, and deletion of CDKN2A/B were common in the total cohort, while transcriptome differences were found in the cell cycle, nerve growth factor (NGF) signaling pathway and transcriptional regulation by TP53 between adolescents/adults and children. Patients with multiple subclones at diagnosis tended to have unfavorable 3-year prognoses (DFS, p = 0.010; CIR, p = 0.021). Leukemia clones with DNA repair gene mutations showed aggressive and treatment-refractory phenotypes in this subtype of ALL. Our study indicated that age, the level of MRD and DNA repair gene mutations were associated with E2A-PBX1-positive B-ALL outcomes. Allo-HSCT, especially haploidentical HSCT, could improve the prognosis of adolescent/adult patients.
27476 Increased benefit of secukinumab vs ustekinumab in patients with psoriasis regardless of previous systemic psoriasis therapy: Pooled analysis of the phase 3 CLEAR and CLARITY trials
Authors: Andrew Blauvelt, Stephen Tyring, Jerry Bagel, Elizabeth Nguyen, Xiangyi Meng, Torben Kasparek, Mark Lebwohl
Journal: Journal of the American Academy of Dermatology (2021)
結節性リンパ球優位型ホジキンリンパ腫の変異体組織像が予後に及ぼす影響: ドイツホジキン研究グループ(GHSG)の報告
Authors: Hartmann Sylvia, A Eichenauer Dennis, Plutschow Annette, Mottok Anja, Bob Roshanak, Koch Karoline, Bernd Heinz-Wolfram, Cogliatti Sergio, Hummel Michael, C Feller Alfred, Ott German, Moller Peter, Rosenwald Andreas, Stein Harald, Hansmann Martin-Leo, Engert Andreas, Klapper Wolfram
Journal: Blood (2013)
Extracellular vesicles derived from mesenchymal stem/stromal cells: The regenerative impact in liver diseases
Authors: Adriana Psaraki, Lydia Ntari, Christos Karakostas, Despoina Korrou‐Karava, Maria G. Roubelakis
Journal: Hepatology (2021)

Liver dysfunctions are classified into acute and chronic diseases, which comprise a heterogeneous group of pathological features and a high mortality rate. Liver transplantation remains the gold-standard therapy for most liver diseases, with concomitant limitations related to donor organ shortage and lifelong immunosuppressive therapy. A concept in liver therapy intends to overcome these limitations based on the secreted extracellular vesicles (EVs; microvesicles and exosomes) by mesenchymal stem/stromal cells (MSCs). A significant number of studies have shown that factors released by MSCs could induce liver repair and ameliorate systemic inflammation through paracrine effects. It is well known that this paracrine action is based not only on the secretion of cytokines and growth factors but also on EVs, which regulate pathways associated with inflammation, hepatic fibrosis, integrin-linked protein kinase signaling, and apoptosis. Herein, we extensively discuss the differential effects of MSC-EVs on different liver diseases and on cellular and animal models and address the complex molecular mechanisms involved in the therapeutic potential of EVs. In addition, we cover the crucial information regarding the type of molecules contained in MSC-EVs that can be effective in the context of liver diseases. In conclusion, outcomes on MSC-EV-mediated therapy are expected to lead to an innovative, cell-free, noninvasive, less immunogenic, and nontoxic alternative strategy for liver treatment and to provide important mechanistic information on the reparative function of liver cells.
Trends in Funding and Acquisition of Surgical Practices by Private Equity Firms in the US From 2000 to 2020
Authors: Jessica I. Billig, Sandra V. Kotsis, Kevin C. Chung
Journal: JAMA Surgery (2021)

OR, 0.38; 95% CI, 0.35-0.41; P < .001). Similarly, surgery performed by a surgeon who used high-dose mannitol prepublication was also associated with a smaller decrease in the odds of mannitol administration (OR, 0.43; 95% CI, 0.39-0.47;P < .001)vs surgeons who used low-dose mannitol (OR, 0.29; 95% CI, 0.26-0.33;P < .001).No temporal changes were observed in the overall use of minimally invasive surgery, rate of partial vs radical nephrectomy, and use of intraoperative ultrasonography.Discussion | Following RCT publication, there was a rapid decrease in mannitol use for partial nephrectomy.This suggests an eagerness (particularly among academic, highvolume surgeons) to practice evidence-based medicine.Surgeons whose practice did not align with study protocols were less likely to change, perhaps reflecting the generalizability of the trial's design.Whether the publication was associated with use of mannitol in kidney transplant or cardiac surgery, where therapeutic benefits may differ, is an area of interest.As a limitation, distinction cannot be made between surgeons who were not aware of the RCT vs those who disagreed with its conclusions.Given absence of detailed information on kidney function, assessment of the trial's association with individual patient outcomes is limited.That considered, surgical RCTs are rare, and few studies have estimated their association with nationwide practice.Here we show the broad, rapid real-world surgical practice response to a prominent surgical RCT.
Diagnostic usefulness of subgenomic RNA detection of viable SARS-CoV-2 in patients with COVID-19
Authors: Ji Yeun Kim, Joon-Yong Bae, Seongman Bae, Hye Hee Cha, Ji-Soo Kwon, Mi Hyun Suh, Hyun Jung Lee, Jiwon Jung, Min Jae Kim, Chunguang Cui, Heedo Park, Jungmin Lee, Man-Seong Park, Sung-Han Kim
Journal: Clinical Microbiology and Infection (2021)
27620 Effects of ruxolitinib cream in patients with atopic dermatitis with baseline body surface area ≥10% and Eczema Area and Severity Index score ≥16: Pooled results from two phase 3 studies
Authors: Eric L. Simpson, Leon Kircik, Andrew Blauvelt, Michael E. Kuligowski, May E. Venturanza, Kang Sun, Lawrence F. Eichenfield
Journal: Journal of the American Academy of Dermatology (2021)
LINC01140 promotes the progression and tumor immune escape in lung cancer by sponging multiple microRNAs
Authors: Rongmu Xia, Guojun Geng, Xiuyi Yu, Zhong Xu, Jing Guo, Hongming Liu, Ning Li, Ziyan Li, Yingli Li, Xiaofang Dai, Qicong Luo, Jie Jiang, Yanjun Mi
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Long intergenic non-protein coding RNA 1140 (LINC01140), a long non-coding RNA, is highly expressed in various cancers; however, its biological functions in lung cancer (LC) progression and immune escape are still unclear. Methods Here, to elucidate LINC01140 function, 79 paired LC and paracancerous tissues were collected. LINC01140 expression levels were determined using fluorescence in situ hybridization and qPCR analysis. Cell counting kit-8 (CCK-8) assay and transwell assays were performed. The interaction between microRNAs (miRNAs) and LINC01140 was confirmed using an RNA immunoprecipitation assay. Cytokine-induced killer (CIK) cell phenotypes were analyzed by flow cytometry. Cytokine secretion levels were determined by ELISA. CIK cytotoxicity was assessed by measuring lactate dehydrogenase release. Besides, xenograft tumor mouse models were used to unveil the in vivo function of LINC01140. Results We found that LINC01140 was highly expressed in human LC tissues and cell lines. High LINC01140 levels were associated with poor survival in patients with LC. LINC01140 upregulation promoted the proliferation, migration, and invasion of LC cells through direct interaction with miR-33a-5p and miR-33b-5p, thereby contributing to c-Myc expression and also inhibited cisplatin-induced cell apoptosis. In subcutaneous tumor xenograft mice, LINC01140 knockdown markedly reduced tumor growth and lung metastasis. Additionally, LINC01140 directly repressed miR-377-3 p and miR-155-5 p expression levels, resulting in the upregulation of their common downstream target programmed death-ligand 1 (PD-L1), a crucial target in LC immunotherapy. Notably, we proved that LINC01140 knockdown, along with CIK administration, suppressed the growth of subcutaneous LC xenografts by decreasing PD-L1 expression in severe combined immunodeficient mice. Conclusions Taken together, LINC01140 overexpression protects c-Myc and PD-L1 mRNA from miRNA-mediated inhibition and contributes to the proliferation, migration, invasion, and immune escape of LC cells. These results provide a theoretical basis that LINC01140 is a promising target for LC treatment.
Is the Sokal or EUTOS long-term survival (ELTS) score a better predictor of responses and outcomes in persons with chronic myeloid leukemia receiving tyrosine-kinase inhibitors?
Authors: Xiao-Shuai Zhang, Robert Peter Gale, Xiao-Jun Huang, Qian Jiang
Journal: Leukemia (2021)

Abstract Data from 1661 consecutive subjects with chronic-phase chronic myeloid leukemia (CML) receiving initial imatinib ( n = 1379) or a 2 nd -generation tyrosine-kinase inhibitor (2G-TKI; n = 282) were interrogated to determine whether the Sokal or European Treatment and Outcome Study for CML (EUTOS) long-term survival (ELTS) scores were more accurate responses and outcome predictors. Both scores predicted probabilities of achieving complete cytogenetic response (CCyR), major molecular response (MMR), failure- and progression-free survivals (FFS, PFS), and survival in all subjects and those receiving imatinib therapy. However, the ELTS score was a better predictor of MR 4 , MR 4.5 , and CML-related survival than the Sokal score. In subjects receiving 2G-TKI therapy, only the ELTS score accurately predicted probabilities of CCyR, MMR, MR 4 , FFS, and PFS. In the propensity score matching, subjects classified as intermediate risk by the ELTS score receiving a 2G-TKI had better responses ( p &lt; 0.001~0.061), FFS ( p = 0.002), and PFS ( p = 0.03) but not survival. Our data suggest better overall prediction accuracy for the ELTS score compared with the Sokal score in CML patients, especially those receiving 2G-TKIs. People identified as intermediate risk by the ELTS score may benefit more from initial 2G-TKI therapy in achieving surrogate endpoints but not survival, especially when a briefer interval to stopping TKI therapy is the therapy objective.
Abstract 055: Statins Raise Glucose Preferentially among Men Who are Older and at Greater Metabolic Risk
Authors: Beatrice A Golomb, Sabrina Koperski, Halbert L White
Journal: Circulation (2012)

Background: Several major statin trials have shown increased incident diabetes and/or modest average elevations in HbA1C (e.g. PROVE-IT, JUPITER) with statins, though average effects on glucose are small: There may be a vulnerable subset. Hypothesis: We hypothesized that advancing age and metabolic status would condition the rise in glucose on statins. Design: Sex-stratified randomized double-blind placebo-controlled trial of simvastatin 20mg, pravastatin 40mg or placebo for 6 months. We assessed glucose-change (from baseline to 6-months) on statins relative to placebo, as a function of age and metabolic markers (HDL30, SBP&gt;130, triglycerides&gt;130, glucose&gt;100) in men (N=692). Analysis: Regression of statin-vs-placebo on glucose change was performed for subjects without and with metabolic markers. The effect of the number of metabolic markers present on the rise in glucose due to statins was examined, as measured by the interaction term of statins x #-metabolic-markers, as a function of age. Robust standard errors were used. Results: Statins showed little effect on glucose overall. Glucose elevation due to statins emerged in the presence of each metabolic marker (Table 1A), and increased with number of metabolic markers for both simvastatin and pravastatin in older age (Table 1B). Conclusion: Statins increase glucose particularly among persons who are older and have greater existing metabolic load.
Abstract 16472: Novel H2S Prodrug, SG1002, Attenuates Adverse Left Ventricular Remodeling Following Myocardial Infarction via Induction of Pro-Angiogenic microRNA-126
Authors: Om Evani, Teja Devarakonda, Adolfo G Mauro, Chad Cain, Fadi N Salloum
Journal: Circulation (2018)

Background: The protective effects of exogenous hydrogen sulfide (H2S) administration have been shown in ischemic heart failure and pressure overload-induced cardiomyopathy. However, current formul...
Shared decision making: an ideal and an art
Authors: Jan Matthys
Journal: BMJ (2021)

Shared decision making (SDM) consists of communication, collaboration, aspects of evidence based medicine, and relationship building-all based on the principle of the autonomy of the patient.It is a complex process with each consultation unique. 1 SDM, therefore, remains an ideal.This explains why it is uncertain whether any interventions for increasing the use of SDM by healthcare professionals are effective because the certainty of the evidence is low or very low. 2 National Institute for Health and Care Excellence recommendations are mostly based on moderate to very low randomised controlled trial evidence. 3 The Calgary-Cambridge consultation model used in undergraduate teaching has been honed by experts over many years.But it comprises 73 items-too long always to be helpful in a short interaction between doctor and patient. 4 The identification and eliciting of patients' ideas, concerns, and expectations (ICE) are key competencies for GPs in SDM.For more than 20 years the ICE acronym has helped me in my practice. 5 I like to compare my job as a GP with the work of the Flemish painter Jan van Eyck.In his time, Van Eyck had a revolutionary optics knowledge of the behaviour and properties of light, including its interactions with matter.In his portrait of Arnolfini 6 a convex mirror is placed like an eye in the centre of the composition, compressing and expanding the space at the same time.It is my job as a doctor to reveal, try to mirror, compress or expand the ideas, concerns, and expectations of my patients.This is a requisite for SDM.The literature on SDM is exploding and sharing decisions remains an art.Although I am not a gifted artist-painter with an incredible technique, I may practise the healing art of medicine.
Prevalence Trend of Myopia after Promoting Eye Care in Preschoolers
Authors: Yu-Chieh Yang, Nai-Wei Hsu, Chiao-Yu Wang, Mong-Ping Shyong, Der-Chong Tsai
Journal: Ophthalmology (2021)

To report the prevalence of preschool myopia after implementing a policy intervention promoting outdoor activities and the secular trend of myopia before and during the coronavirus disease 2019 (COVID-19) pandemic in a Taiwan preschool population.Repeated countywide population-based, cross-sectional surveys based on the Yilan Myopia Prevention and Vision Improvement Program (YMVIP).Among 23 930 kindergarteners 5 to 6 years of age from 7 school-year cohorts in Yilan County from 2014 through 2020, a total of 21 761 children (90.9%) were included for analysis.Since launching the YMVIP in August 2014, myopia prevention strategies, such as increasing outdoor activities (2 hours/weekday), have been promoted in all kindergartens, and countywide school-based eye examinations, including cycloplegic autorefraction, and caregiver-administered questionnaires have been carried out annually for all participants.The prevalence of myopia (spherical equivalent, ≤ -0.5 D in either eye) in each of the 7 school-year cohorts of preschoolers 5 to 6 years of age.The prevalence of myopia continuously decreased for 2 years after implementing the YMVIP: 2014 cohort, 15.5% (95% confidence interval [CI], 14.2%-16.8%); 2015 cohort, 13.5% (95% CI, 12.3%-14.7%); and 2016 cohort, 8.4% (95% CI, 7.4%-9.4%). Subsequent cohorts were exposed maximally to these school-based myopia prevention strategies, and the prevalence of myopia remained relatively stable, between 8.5% and 10.3%, even during the COVID-19 pandemic. Multivariate logistic regression analysis showed a dose-dependent association between the duration of exposure to preventive strategies and the prevalence of myopia (up to 1-year YMVIP exposure, odds ratio, 0.86 [95% CI, 0.74-0.99]; up to 2-year YMVIP exposure, odds ratio, 0.56 [95% CI, 0.50-0.63]) after controlling other myopigenic factors.This population-based evidence showed high prevalence of preschool myopia and an L-shaped decline after introducing strategies to promote outdoor activities in kindergartens. With undisrupted school-based preventive strategies, the prevalence of myopia can be kept stable, even during the COVID-19 pandemic.
T-follicular helper cell expansion and chronic T-cell activation are characteristic immune anomalies in Evans syndrome
Authors: Deepak Kumar, Chengyu Prince, Carolyn M. Bennett, Michael Briones, Laura Lucas, Athena Russell, Kiran Patel, Satheesh Chonat, Sara Graciaa, Holly Edington, Michael H. White, Lisa Kobrynski, Manar Abdalgani, Suhag Parikh, Sharat Chandra, Jack Bleesing, Rebecca Marsh, Sunita Park, Edmund K. Waller, Sampath Prahalad, Shanmuganathan Chandrakasan
Journal: Blood (2021)
26691 Rapid and concurrent improvements in the signs and symptoms of atopic dermatitis with baricitinib in the phase 3 study, BREEZE-AD5
Authors: Peter Lio, Jennifer Soung, Jennifer Cather, Marta Casillas, Yuxin Ding, Amy M. De Lozier, Yun-Fei Chen, Eric Simpson
Journal: Journal of the American Academy of Dermatology (2021)
CHK yourself, before you wreck yourself: targeting the DNA damage response in secondary pulmonary hypertension
Authors: Andrew Bryant, Vinicio de Jesus Perez
Journal: Thorax (2021)

Despite the debilitating and lethal nature of pulmonary hypertension (PH) secondary to interstitial lung disease (group 3 PH),1 research into the treatment of this unique category of vasculopathy remains in a relatively nascent stage compared with that of pulmonary arterial hypertension (PAH, group 1). A clue to uncovering the underlying pathophysiology of this particular subtype of group 3 PH, however, may be found in overlapping interest in the DNA damage response (DDR) shared by both pulmonary fibrosis and PH researchers.2 Primarily a pathway dedicated to preventing DNA damage to cellular progeny, the DDR functions via a complex network of cell cycle checkpoint signalling and DNA repair mechanisms. In the context of malignancy, these non-redundant pathways can be exploited by dependent cancerous cells to thwart apoptosis, thus promoting survival and eventual metastasis.

Therapeutically, a key target of the DDR is the family of checkpoint kinases: CHK1 primarily affecting the prevention of DNA damage being replicated (resulting in G1/S-phase cell cycle arrest), and CHK2 mediating transmission to the next generation of cells (a G2/M-phase checkpoint).3 While there are examples of CHK regulation related to end-organ fibrosis, to date, there is a dearth of literature describing the role of CHK in lung fibrosis. …
A Call for Improved Breast Cancer Screening Strategies, Not Only for Women With Dense Breasts
Authors: Christiane K. Kuhl
Journal: JAMA Network Open (2021)

Narumi Harada-Shoji, MD, PhD; Akihiko Suzuki, MD, PhD; Takanori Ishida, MD, PhD; Ying-Fang Zheng, MD, PhD; Yoko Narikawa-Shiono, PhD; Akiko Sato-Tadano, MD, PhD; Rie Ohta; Noriaki Ohuchi, MD, PhD