tbuckley/cabot-search huggingface dataset:
143P Efficacy and safety of the anti-PD-L1 monoclonal antibody Socazolimab in combination with carboplatin and etoposide for extensive-stage small cell lung cancer: Results from the phase Ib clinical trial
Authors: S. Lu, Z. Chen, Z. Li, Z. Zhou, Y. Yu, X. Ai, Y. Zhao, X. Niu, J. Cui, R. Guo, B.X. Li, X. Dai, Y. Li, M.S. Wong, R. Ng, Z. Zhao
Journal: Annals of Oncology (2022)
COVID-19 targets human adrenal glands
Authors: Waldemar Kanczkowski, Katja Evert, Marlena Stadtmüller, Martina Haberecker, Laura Laks, Lan-Sun Chen, Karl Frontzek, Jessica Pablik, Constanze Hantel, Felix Beuschlein, Thomas Kurth, Sven Gruber, Adriano Aguzzi, Zsuzsanna Varga, Stefan R Bornstein
Journal: The Lancet Diabetes & Endocrinology (2021)
Abstract P003: Blood Pressure, Antihypertensive Drugs, And Incident Frailty: The Multidomain Alzheimer Preventive Trial
Authors: Laure Rouch, Yves Rolland, Olivier Hanon, Jean-Sébastien Vidal, Philippe CESTAC, SALLERIN brigitte, Sandrine Andrieu, Bruno Vellas, Philipe de Souto Barreto
Journal: Circulation (2022)

Objectives: To examine the association of (1) high and low BP levels and (2) AH drug use with incident frailty. Study design: We conducted a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT). We included and followed-up for 5 years 1,394 non-frail community-dwelling participants aged ≥ 70 years. Main outcome measures: High BP was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg and low BP as systolic BP ≤ 110 mmHg and/or diastolic BP ≤ 70 mmHg. AH drugs were classified according to the Anatomical Therapeutic Chemical (ATC) code. Incident frailty was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses. Results: Low BP was associated with greater risk of frailty (HR = 1.43, 95% CI [1.07-1.92], p=0.02) after adjustment for age, sex, education, AH drug use, BMI, diabetes, ischemic heart disease, congestive heart failure, AF, stroke, MAPT randomization group, sit-to-stand chair test and pre-frailty. Participants with low BP and 2 AH drugs or more were those having the greatest risk. Neither high BP (HR = 0.84, 95% CI [0.63-1.22], p=0.24) nor AH drug use (HR = 1.21, 95% CI [0.89-1.64], p=0.22) were independently associated with incident frailty. Conclusions: Low BP could be used as a new marker for identifying older adults at higher risk of frailty. AH medications in older adults with low BP should be continuously reviewed to assure that their potential benefits outweigh potential risks.
Abstract MP67: Pre-pregnancy Cardiovascular Health And Stress Related To Severe Maternal Morbidity In Black And White Women
Authors: Janet M Catov, Baiyang Sun, Erica P Gunderson, Samantha Bryan, Marnie Bertolet, Cora E Lewis, Abbi Lane-cordova, Sadiya Khan, Stacy Beck
Journal: Circulation (2022)

Introduction: Severe maternal morbidity (SMM), unexpected complications of pregnancy with substantial consequences, are high in the U.S., contribute to maternal mortality, and racial disparities persist. Cardiovascular and psychosocial factors contribute to SMM, but pre-pregnancy risks are rarely studied. Hypothesis: Poor cardiovascular health (CVH) and adverse psychosocial stress before pregnancy contribute to SMM and racial disparities. Methods: Among 1,392 women in CARDIA (51% Black) with 2,372 post-enrollment births we characterized SMM using established criteria via delivery records (n=660 births) and self-reported hospitalizations &lt;6-weeks postpartum (hemorrhage, sepsis, cardiomyopathy, hysterectomy) and up to 1 year post-delivery (depression, domestic violence, overdose, cardiovascular). CVH before pregnancy was quantified (BP, BMI, smoking, glucose, cholesterol, diet, activity; lower score adverse) and stress was assessed at baseline as stressful life events (higher score adverse). Self-reported adverse pregnancy outcomes (APOs) were hypertensive disorders of pregnancy, preterm birth and gestational diabetes. Generalized linear mixed models related CVH and stress to risk of SMM birth, adjusted for race, age, education, parity, APOs; non-SMM births were the referent and models were stratified by race. Results: We identified 45 SMM births (1.9%; 1.7% Black, 1.9% White); 39% at delivery and 61% post-delivery. CVH was lower and stress was higher before SMM births (9.4 [2.3] vs. 10.4 [1.9] and 8.5 [4.7] vs. 7.0 [4.1], respectively, p&lt;0.01). Black but not White women with SMM were more likely to have poor pre-pregnancy CVH (p&lt;0.01; Figure). Higher stress was related to SMM in Black and White women (adjusted OR per SD 1.22 [95% CI 0.92, 1.61]. Better CVH was associated with lower SMM risk in Black but not White women (0.61 [0.48, 0.78] vs. 0.93 [0.72, 1.20]). Conclusion: Poor pre-pregnancy CVH is associated with risk of SMM in Black women, and stress may be associated with SMM risk regardless of race.
Microcarriers in application for cartilage tissue engineering: Recent progress and challenges
Authors: Sheng-Long Ding, Xin Liu, Xi-Yuan Zhao, Ke-Tao Wang, Wei Xiong, Zi-Li Gao, Cheng-Yi Sun, Min-Xuan Jia, Cheng Li, Qi Gu, Ming-Zhu Zhang
Journal: Bioactive Materials (2022)

Successful regeneration of cartilage tissue at a clinical scale has been a tremendous challenge in the past decades. Microcarriers (MCs), usually used for cell and drug delivery, have been studied broadly across a wide range of medical fields, especially the cartilage tissue engineering (TE). Notably, microcarrier systems provide an attractive method for regulating cell phenotype and microtissue maturations, they also serve as powerful injectable carriers and are combined with new technologies for cartilage regeneration. In this review, we introduced the typical methods to fabricate various types of microcarriers and discussed the appropriate materials for microcarriers. Furthermore, we highlighted recent progress of applications and general design principle for microcarriers. Finally, we summarized the current challenges and promising prospects of microcarrier-based systems for medical applications. Overall, this review provides comprehensive and systematic guidelines for the rational design and applications of microcarriers in cartilage TE.
Efficacy of Antibodies and Antiviral Drugs against Covid-19 Omicron Variant
Authors: Emi Takashita, Noriko Kinoshita, Seiya Yamayoshi, Yuko Sakai-Tagawa, Seiichiro Fujisaki, Mutsumi Ito, Kiyoko Iwatsuki-Horimoto, Shiho Chiba, Peter Halfmann, Hiroyuki Nagai, Makoto Saito, Eisuke Adachi, David Sullivan, Andrew Pekosz, Shinji Watanabe, Kenji Maeda, Masaki Imai, Hiroshi Yotsuyanagi, Hiroaki Mitsuya, Norio Ohmagari, Makoto Takeda, Hideki Hasegawa, Yoshihiro Kawaoka
Journal: New England Journal of Medicine (2022)

To the Editor: In November 2021, the B.1.1.529(omicron) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected in South Africa. 1 Since then, omicron has rapidly spread around the world.On November 26, 2021, the World Health Organization designated omicron as a variant of concern.The omicron variant was found to have at least 33 mutations (29 amino acid substitutions, 1 insertion of three amino acids, and 3 small deletions) in its spike (S) protein, as compared with early SARS-CoV-2 strains identified in Wuhan, China. 2 Notably, 15 of the 29 substitutions were in the receptorbinding domain of the S protein, which is the primary target for monoclonal antibody-based therapy.This finding suggests that the monoclonal antibodies that have been approved by the Food and Drug Administration (FDA) may be less effective against the omicron variant.Accordingly, we examined the neutralizing ability of FDA-approved and investigational therapeutic monoclonal antibodies (individually and in combination) against omicron and other variants of concern.Using a live-virus focus reduction neutralization assay (FRNT), we assessed the neutralizing activities of monoclonal antibodies against hCoV-19/Japan/NC928-2N/2021 (omicron; NC928), which was isolated from a traveler who arrived in Japan from Namibia; SARS-CoV-2/UT-NC002-1T/Human/2020/Tokyo (NC002), an early SARS-CoV-2 strain from February 2020; SARS-CoV-2/UT-HP127-1Nf/Human/2021/Tokyo (alpha; HP127); hCoV-19/USA/MD-HP01542/2021 (beta; HP01542); hCoV-19/Japan/TY7-503/2021 (gamma; TY7-503); and hCoV-19/USA/WI-UW-5250/ 2021 (delta; UW5250).Whole-genome sequencing analysis of the NC928 omicron virus stock revealed that the variant had the 15 substitutions
Inhibition of FGFR Reactivates IFNγ Signaling in Tumor Cells to Enhance the Combined Antitumor Activity of Lenvatinib with Anti-PD-1 Antibodies
Authors: Yusuke Adachi, Hiroshi Kamiyama, Kenji Ichikawa, Sayo Fukushima, Yoichi Ozawa, Shogo Yamaguchi, Satoshi Goda, Takayuki Kimura, Kotaro Kodama, Masahiro Matsuki, Saori Watanabe Miyano, Akira Yokoi, Yu Kato, Yasuhiro Funahashi
Journal: Cancer Research (2021)

Abstract Combination therapies consisting of immune checkpoint inhibitors plus anti-VEGF therapy show enhanced antitumor activity and are approved treatments for patients with renal cell carcinoma (RCC). The immunosuppressive roles of VEGF in the tumor microenvironment are well studied, but those of FGF/FGFR signaling remain largely unknown. Lenvatinib is a receptor tyrosine kinase inhibitor that targets both VEGFR and FGFR. Here, we examine the antitumor activity of anti-PD-1 mAb combined with either lenvatinib or axitinib, a VEGFR-selective inhibitor, in RCC. Both combination treatments showed greater antitumor activity and longer survival in mouse models versus either single agent treatment, whereas anti-PD-1 mAb plus lenvatinib had enhanced antitumor activity compared with anti-PD-1 mAb plus axitinib. Flow cytometry analysis showed that lenvatinib decreased the population of tumor-associated macrophages and increased that of IFNγ-positive CD8+ T cells. Activation of FGFR signaling inhibited the IFNγ-stimulated JAK/STAT signaling pathway and decreased expression of its target genes, including B2M, CXCL10, and PD-L1. Furthermore, inhibition of FGFR signaling by lenvatinib restored the tumor response to IFNγ stimulation in mouse and human RCC cell lines. These preclinical results reveal novel roles of tumor FGFR signaling in the regulation of cancer immunity through inhibition of the IFNγ pathway, and the inhibitory activity of lenvatinib against FGFRs likely contributes to the enhanced antitumor activity of combination treatment comprising lenvatinib plus anti-PD-1 mAb. Significance: FGFR pathway activation inhibits IFNγ signaling in tumor cells, and FGFR inhibition with lenvatinib enhances antitumor immunity and the activity of anti-PD-1 antibodies.
Seamless Genetic Recording of Transiently Activated Mesenchymal Gene Expression in Endothelial Cells During Cardiac Fibrosis
Authors: Shaohua Zhang, Yan Li, Xiuzhen Huang, Kuo Liu, Qing-Dong Wang, Alex F. Chen, Kun Sun, Kathy O. Lui, Bin Zhou
Journal: Circulation (2021)

Background: Cardiac fibrosis is a lethal outcome of excessive formation of myofibroblasts that are scar-forming cells accumulated after heart injury. It has been reported that cardiac endothelial cells (ECs) contribute to a substantial portion of myofibroblasts through endothelial to mesenchymal transition (EndoMT). Recent lineage tracing studies demonstrate that myofibroblasts are derived from the expansion of resident fibroblasts rather than from the transdifferentiation of ECs. However, it remains unknown whether ECs can transdifferentiate into myofibroblasts reversibly or EndoMT genes were just transiently activated in ECs during cardiac fibrosis. Methods: By using the dual recombination technology based on Cre-loxP and Dre-rox, we generated a genetic lineage tracing system for tracking EndoMT in cardiac ECs. We used it to examine if there is transiently activated mesenchymal gene expression in ECs during cardiac fibrosis. Activation of the broadly used marker gene in myofibroblasts, αSMA (α-smooth muscle actin), and the transcription factor that induces epithelial to mesenchymal transition, Zeb1 (zinc finger E-box–binding homeobox 1), was examined. Results: The genetic system enables continuous tracing of transcriptional activity of targeted genes in vivo. Our genetic fate mapping results revealed that a subset of cardiac ECs transiently expressed αSMA and Zeb1 during embryonic valve formation and transdifferentiated into mesenchymal cells through EndoMT. Nonetheless, they did not contribute to myofibroblasts, nor transiently expressed αSMA or Zeb1 after heart injury. Instead, expression of αSMA was activated in resident fibroblasts during cardiac fibrosis. Conclusions: Mesenchymal gene expression is activated in cardiac ECs through EndoMT in the developing heart, but ECs do not transdifferentiate into myofibroblasts, nor transiently express some known mesenchymal genes during homeostasis and fibrosis in the adult heart. Resident fibroblasts that are converted to myofibroblasts by activating mesenchymal gene expression are the major contributors to cardiac fibrosis.
Visual percepts evoked with an intracortical 96-channel microelectrode array inserted in human occipital cortex
Authors: Eduardo Fernández, Arantxa Alfaro, Cristina Soto-Sánchez, Pablo Gonzalez-Lopez, Antonio M. Lozano, Sebastian Peña, Maria Dolores Grima, Alfonso Rodil, Bernardeta Gómez, Xing Chen, Pieter R. Roelfsema, John D. Rolston, Tyler S. Davis, Richard A. Normann
Journal: Journal of Clinical Investigation (2021)

BACKGROUND. A long-held goal of vision therapy is to transfer information directly to the visual cortex of blind individuals, thereby restoring a rudimentary form of sight. However, no clinically available cortical visual prosthesis yet exists.
Abstract EP44: Longer Retirement Time Is Associated With Lower Left Ventricular Mass In Retired National Football League Players
Authors: Genevieve Smith, Camilo Fernandez Alonso, Gregory W Stewart
Journal: Circulation (2022)

Background: Increased left ventricular mass (LVM), a common structural phenomenon associated with athlete’s heart, has been reported to regress following cessation from systematic high-intensity training. However, information is limited on the interplay between length of retirement and LVM in former professional field-based athletes, a segment of the population in which both hypertension and obesity, factors generally associated with increased LVM, have been reported as highly prevalent. Thus, we aimed to explore this observation in a group of former National Football League (NFL) players. Methods: This complete-case analysis included 1,348 retired NFL players (aged 53.3 ± 12.8 years, 55.5% Black) that participated in the NFL’s Player Care Foundation comprehensive health screenings between 2015 and 2021. Years since retirement from professional American-style football (YrsRetired) was calculated as year of examination minus the last self-reported year playing for the NFL. Echocardiography was used to estimate LV mass, which was then indexed to height 2.7 (LVMI). LVMI was divided into quartiles and stepwise binary logistic regression models were fitted to assess the association of YrsRetired with the lowest quartile (Q1) of LVMI, after adjusting for traditional cardiometabolic risk factors, NFL career length, and playing position group (Model 1); cardiometabolic risk factors and playing position group (Model 2); or cardiometabolic risk factors only (Model 3). Results: The prevalence of hypertension and abdominal obesity in our sample was 75.1% and 57.1%, respectively. Mean retirement length was 24.8 ± 12.7 years (range: 1.0 - 59.0 years), and mean LVMI was 40.3 ± 9.7 g/m 2.7 . Increasing YrsRetired was independently associated with higher odds for LVMI Q1 (Model 2, odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.00-1.07, p= 0.04 ; Model 3, OR: 1.03, 95% CI: 1.00-1.07, p= 0.03). When adding NFL career length to the model, the association between YrsRetired and LVMI Q1 was attenuated (Model 1, p = 0.91). Conclusions: Longer retirement is associated with lower left ventricular mass in this group of retired NFL players. These findings suggest that regression of LVM following retirement from professional sport may be common in former NFL players, despite the high prevalence of hypertension and obesity reported in this population. Further, these findings imply that elite sports participation may have a potential buffering effect against hypertension and/or obesity-induced hemodynamic changes that increase LVM, which seem to particularly occur after retirement from professional sports. This potential instance may be impacted by professional career length.
In an Era of ctDNA, Is Metabolomics the New Kid on the Block?
Authors: Brian A. Van Tine, Costas A. Lyssiotis
Journal: Clinical Cancer Research (2022)

Summary Mass action drives the serum homeostasis of metabolites. Recent developments in biofluid metabolomics suggest the potential to harness these changes using small volumes of blood to diagnose, monitor, and risk stratify patients with cancer. This current study may represent a complementary technology to circulating tumor DNA detection. See related article by Larkin et al., p. 1651
Systemic sclerosis and COVID-19 vaccines: a SPIN Cohort study
Authors: Jessica K Gordon, Kimberly Showalter, Yin Wu, Linda Kwakkenbos, Marie-Eve Carrier, Richard S Henry, Nora Østbø, Julia Nordlund, Angelica Bourgeault, Mara Cañedo-Ayala, Andrea Carboni-Jiménez, Christopher P Denton, Luc Mouthon, Brett D Thombs, Robert F Spiera
Journal: The Lancet Rheumatology (2022)
Recent advances in nanotechnology for eradicating bacterial biofilm
Authors: Célia Sahli, Sergio E. Moya, John S. Lomas, Christine Gravier-Pelletier, Romain Briandet, Miryana Hémadi
Journal: Theranostics (2022)

Microorganisms grouped together into spatially-organized communities called biofilms, are the cause of dramatic chronic infections in plants, animals and humans. In this review, the characteristics of biofilms and their interactions with antimicrobials are first described. Limitations of antibiotic treatments are discussed, and state-of-the-art alternative approaches based on the use of polymer, lipid, organic, inorganic and hybrid nanoparticles are presented, highlighting recent achievements in the application of nanomaterials to the field of theranostics for the eradication of biofilm. The aim of this review is to present a complete vision of nanobiotechnology-based approaches for eradicating bacterial biofilms and fighting antimicrobial tolerance.
Abstract MP40: Associations Of Dietary Macronutrient And Fatty Class Composition With All-Cause And Cardiovascular Mortality: Data From National Health And Nutrition Examination Survey 1999-2014
Authors: Nicholas A Koemel, Alistair M Senior, David S Celermajer, Amanda Grech, Tim P Gill, David Raubenheimer, Stephen J Simpson, Michael R Skilton
Journal: Circulation (2022)

Introduction: There is a large body of evidence detailing the associations of individual macronutrients and fatty acids with all-cause and cardiovascular mortality. Studying nutrients in combination may provide additional information concerning complex associations and interactions. Hypothesis: We hypothesize that overall macronutrient and fat class composition are associated with all-cause and cardiovascular mortality. Methods: This analysis was undertaken using 24-hour food recall data from the National Health and Nutrition Examination Survey from years 1999-2014 (n = 36,138). Participants included both males and females ≥20 years of age (49.8 ± 18.4 years; 53% Female). All-cause (4764 deaths) and cardiovascular mortality (834 deaths) were obtained via linkage to the National Death Index. Associations of diet composition with mortality adjusting for age, sex, total energy intake, ethnicity, education level, household income, physical activity, alcohol intake, and smoking were assessed using 3-dimensional general additive Cox proportional hazard models of macronutrients (Protein; Carbohydrate; Fat) or fat classes (Polyunsaturated; Monounsaturated; Saturated). Response surfaces were generated on the survival function scale to aid interpretation. Results: There is a complex 3-way interactive non-linear association of macronutrient composition with both all-cause (Figure A-B) and cardiovascular mortality (both p &lt;0.001). Dietary fatty acid composition was associated with all-cause mortality (p &lt;0.001; Figure C-D), but there was no significant association for cardiovascular mortality (p = 0.09). In general, diets composed of moderate intake of all three macronutrients or low amounts of monounsaturated and polyunsaturated fat were associated with the highest risk of mortality. Conclusions: In conclusion, these findings indicate that associations between diet composition and mortality are more complex than previously understood with evidence of interactive and non-linear relationships.
Reply to R. Lakhotia et al
Authors: G.A. Amos Burke, Veronique Minard-Colin, Anne Aupérin, Sarah Alexander, Marta Pillon, Rafael Delgado, József Zsíros, Anne Uyttebroeck, Peggy Dartigues, Rodney R. Miles, Bernarda Kazanowska, Alan K. Chiang, Stéphanie Haouy, Catherine M. Bollard, Monika Csoka, Keith Wheatley, Donald A. Barkauskas, Peter C. Adamson, Gilles Vassal, Catherine Patte, Thomas G. Gross
Journal: Journal of Clinical Oncology (2022)

We thank Lakhotia et al 1 for their interest in our article. 2heir opening comment that dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) did not improve event-free survival (EFS) compared with historical controls treated with rituximab plus pediatric chemotherapy regimens is unfortunately incorrect as the historical controls for our study were all treated without rituximab.We have discussed this in our Discussion and suggested that DA-EPOCH without rituximab may be less effective than the historical pediatric regimens. 2khotia et al 1 raised the important point of dose intensity as a determinant of outcome in lymphoma and hypothesized that our finding of errors in dose escalation in at least one course in 29% of patients led to the observed lack of improvement with DA-EPOCH-R.Although this is certainly a plausible hypothesis, we do not think this is applicable for two main reasons.First, appropriately designed randomized trials are required to determine the impact of dose intensity on outcome for patients treated for non-Hodgkin lymphoma, 3 and to our knowledge, there has not been such a study for DA-EPOCH-R in primary mediastinal large B-cell lymphoma (PMLBL).Second, delivered dose intensity and its impact on outcome of DA-EPOCH-R have not been reported to date in any other study to our knowledge and so we do not agree that it is reasonable to suppose that the failures to escalate in at least one dose that we have reported contributed to the performance of DA-EPOCH that we observed.In addition, the EFS of patients correctly escalated in our study was 76.7% (95% CI, 59.1 to 88.2) which was inferior to that expected based on the National Cancer Institute (NCI) study, suggesting that factors other than dose intensity account for the poorer performance of DA-EPOCH-R in the pediatric setting.
The untapped potential of herpes zoster vaccination
Authors: Fiona Ecarnot, Jean-Pierre Michel
Journal: The Lancet Healthy Longevity (2022)

Herpes zoster infection corresponds to the reactivation of latent varicella-zoster virus, and is characterised by a vesicular dermatomal rash, which usually spontaneously resolves, but can result in persistent (>3 months) debilitating pain, known as postherpetic neuralgia. Two vaccines are available against herpes zoster, namely zoster vaccine live (ZVL) and a newer, recombinant zoster vaccine (RZV), available since 2017.