tbuckley/cabot-search huggingface dataset:
Abstract 14264: National Comparison of Hospital Market Share for Out-of-Hospital Cardiac Arrest and Elective Cardiac Surgery
Authors: David G Buckler, Ethan Abbott, Benjamin Abella, Brendan G Carr, Douglas Wiebe, alexis zebrowski
Journal: Circulation (2021)

Introduction: Competition in the healthcare market is a theoretical driver of innovation, cost-savings, and improved quality. When patients are treated for certain emergent conditions, such as out-of-hospital cardiac arrest (OHCA), individuals have less choice in their treating hospital. For patients undergoing elective cardiac valve replacement surgery (EVRS), hospital choice may reflect distinct referral patterns and preferences. Our objective was to compare hospital market share for different cardiac services, thus allowing for better understanding of the care landscape and target interventions to improve outcomes. Methods: Using age-eligible Medicare fee-for-service institutional claims, an emergency department (ED) treated OHCA cohort was identified via ICD-9/10 diagnosis codes and ED charges. EVRS, an inpatient referral procedure, were identified from in-patient summary claims using procedure codes. Market shares were built for each hospital by sequential addition of ZIP-code areas and calculating the hospital’s cumulative market share. Geographic market share areas were defined for each hospital at 90%, 25% and 10% cut-offs if present. Correlation between corresponding market shares and patient counts were assessed using Pearson’s r. Results: Between 1/2013 and 12/2015, we identified 206,162 EVRS claims and 222,018 OHCA claims. Median age was similar (77 vs 78 yrs), as was percent of female patient (43% vs 44%). Very few beneficiaries (0.38%) appeared in both cohorts. Many more hospitals cared for OHCA than EVRS (4482 vs 1170). More OHCA treating hospitals achieved a 25% market share (68% vs 57%) however, EVRS hospital with a 25% market share covered more population (420,294 vs 66,394) and had a greater client radius (21 vs 15 miles). Among the hospitals providing care to both cohorts, the cumulative market share and patient counts were positively correlated (r = 0.49 and 0.46 respectively, p&lt;0.001 for both). Conclusion: Despite many more hospitals providing care for OHCA, the market share for EVRS and OHCA trend together. This market trend, combined with the association of better outcomes with higher OHCA volume suggests that OHCA should be regionalized within markets to facilities that provide elective cardiac surgical procedures.
Abstract 11817: The Effect of Time to Treatment With Antiarrhythmic Drugs on Return of Spontaneous Circulation in Shock Refractory Out-of-Hospital Cardiac Arrest: A Secondary Analysis of the ALPS Randomized Controlled Trial
Authors: Mahbod Rahimi, Paul Dorian, Sheldon Cheskes, Gerald Lebovic, Steve Lin
Journal: Circulation (2021)

Purpose: The effects of amiodarone and lidocaine on the return of spontaneous circulation (ROSC), relative to time to treatment in out of hospital cardiac arrest (OHCA) patients is unknown. We conducted a post-hoc analysis of the Resuscitation Outcomes Consortium Amiodarone, Lidocaine, Placebo (ROC ALPS) randomized trial examining the association of time to treatment with ROSC at emergency department (ED) arrival. Method: In the ROC ALPS trial, adults with non-traumatic OHCA with initial VF/pVT after ≥ 1 shock were randomized to receive amiodarone, lidocaine or placebo. We used logistic regression to examine the association of time to treatment (911 call to study drug administration interval) with ROSC at ED arrival. Results: Overall, 1112 (36.7%) patients had ROSC at ED arrival. Time to treatment data were available for 2994 (99%) of the patients. The proportion of patients with ROSC at ED arrival decreased as time to drug administration increased, in amiodarone (OR 0.92, 95% CI 0.90-0.94 per min increase), lidocaine (OR 0.95, 95% CI: 0.93-0.96) and placebo (OR 0.95, 95% CI: 0.93-0.96) arms. The odds of ROSC at ED in the amiodarone group (versus placebo) changed in relation to the time of drug administration (OR 0.96, 95% CI: 0.93-0.99). With short times to drug administration, ROSC was higher in amiodarone versus placebo recipients, whereas ROSC was higher with placebo at later times. Comparing lidocaine to placebo, ROSC rate increased at all times (OR 1.29, 95% CI: 1.07-1.59); there was no time to drug administration effect (OR 1.00, 95% CI: 0.97-1.03). Among all patients, survival at hospital discharge was 21.0%, 24.4%, and 23.7% for placebo, amiodarone and lidocaine respectively. Conclusion: Amiodarone’s efficacy in restoring ROSC declined with longer duration of arrest, potentially due to its adverse hemodynamic effects. Overall, amiodarone and lidocaine had similar effects on mortality; in this study, ROSC at ED arrival trend did not reflect the overall survival rate
Characterization of Two Anti-P-Selectin Monoclonal Antibodies (mAbs): Crizanlizumab Shows Comparable or Stronger Effects Versus Inclacumab across Cell Adhesion Assays <i>in Vitro</i>
Authors: Tina Rubic-Schneider, Prithu Sundd, David Ledieu, Déborah Garcia, Jeannine Hehlen, Coline Burnet-Merlin, Benjamin Cochin de Billy, Barbara Greutmann, Frieder Krӧner, Mélanie Verneret, Andreas Bruederle, Xiufeng Gao, Maya Dajee
Journal: Blood (2021)
Sustained but Declining Humoral Immunity Against SARS-CoV-2 at 9 Months Postvaccination With BNT162b2: A Prospective Evaluation in 309 Healthy Individuals
Authors: Evangelos Terpos, Vangelis Karalis, Ioannis Ntanasis-Stathopoulos, Filia Apostolakou, Sentiljana Gumeni, Maria Gavriatopoulou, Dimitris Papadopoulos, Panagiotis Malandrakis, Eleni-Dimitra Papanagnou, Eleni Korompoki, Efstathios Kastritis, Ioannis Papassotiriou, Ioannis P. Trougakos, Meletios A. Dimopoulos
Journal: HemaSphere (2021)

The sustainability of coronavirus 19 (COVID-19) vaccine-induced immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical to be determined to inform public health decisions on vaccination programs and prevention measures against COVID-19. The aim of the present study was to prospectively evaluate the kinetics of neutralizing antibodies (NAbs) and anti-S-receptor binding domain (RBD IgGs) against SARS-CoV-2 after full vaccination with the BNT162b2 mRNA vaccine for up to 9 months in healthy individuals (NCT04743388). The assessments were performed at the following time points after the second vaccination: 2 weeks, 1 month, 3 months, 6 months, and 9 months. The measurements were performed with the GenScript’s cPassTM SARS-CoV-2 NAbs Detection Kit (GenScript, Inc.; Piscataway, NJ) and the Elecsys Anti-SARS-CoV-2 S assay (Roche Diagnostics GmbH; Mannheim, Germany). Three hundred nine participants with a median age of 48 years were included. A gradual decline in both NAbs and anti-S-RBD IgGs became evident from 2 weeks to 9 months postvaccination. Both NAbs and anti-S-RBD IgGs levels were significantly lower at 9 months compared with the previous timepoints. Interestingly, age was found to exert a statistically significant effect on NAbs elimination only during the first-trimester postvaccination, as older age was associated with a more rapid clearance of NAbs. Furthermore, simulation studies predicted that the median NAb value would fall from 66% at 9 months to 59% and 45% at 12 and 18 months postvaccination, respectively. This finding may reflect a declining degree of immune protection against COVID-19 and advocates for the administration of booster vaccine shots especially in areas with emerging outbreaks.
Analysis of COVID-19 Vaccine Type and Adverse Effects Following Vaccination
Authors: Alexis L. Beatty, Noah D. Peyser, Xochitl E. Butcher, Jennifer M. Cocohoba, Feng Lin, Jeffrey E. Olgin, Mark J. Pletcher, Gregory M. Marcus
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Little is known about the factors associated with COVID-19 vaccine adverse effects in a real-world population. <h3>Objective</h3> To evaluate factors potentially associated with participant-reported adverse effects after COVID-19 vaccination. <h3>Design, Setting, and Participants</h3> The COVID-19 Citizen Science Study, an online cohort study, includes adults aged 18 years and older with a smartphone or internet access. Participants complete daily, weekly, and monthly surveys on health and COVID-19–related events. This analysis includes participants who provided consent between March 26, 2020, and May 19, 2021, and received at least 1 COVID-19 vaccine dose. <h3>Exposures</h3> Participant-reported COVID-19 vaccination. <h3>Main Outcomes and Measures</h3> Participant-reported adverse effects and adverse effect severity. Candidate factors in multivariable logistic regression models included age, sex, race, ethnicity, subjective social status, prior COVID-19 infection, medical conditions, substance use, vaccine dose, and vaccine brand. <h3>Results</h3> The 19 586 participants had a median (IQR) age of 54 (38-66) years, and 13 420 (68.8%) were women. Allergic reaction or anaphylaxis was reported in 26 of 8680 participants (0.3%) after 1 dose of the BNT162b2 (Pfizer/BioNTech) or mRNA-1273 (Moderna) vaccine, 27 of 11 141 (0.2%) after 2 doses of the BNT162b2 or mRNA-1273 vaccine or 1 dose of the JNJ-78436735 (Johnson &amp; Johnson) vaccine. The strongest factors associated with adverse effects were vaccine dose (2 doses of BNT162b2 or mRNA-1273 or 1 dose of JNJ-78436735 vs 1 dose of BNT162b2 or mRNA-1273; odds ratio [OR], 3.10; 95% CI, 2.89-3.34;<i>P</i> &lt; .001), vaccine brand (mRNA-1273 vs BNT162b2, OR, 2.00; 95% CI, 1.86-2.15;<i>P</i> &lt; .001; JNJ-78436735 vs BNT162b2: OR, 0.64; 95% CI, 0.52-0.79;<i>P</i> &lt; .001), age (per 10 years: OR, 0.74; 95% CI, 0.72-0.76;<i>P</i> &lt; .001), female sex (OR, 1.65; 95% CI, 1.53-1.78;<i>P</i> &lt; .001), and having had COVID-19 before vaccination (OR, 2.17; 95% CI, 1.77-2.66;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> In this real-world cohort, serious COVID-19 vaccine adverse effects were rare and comparisons across brands could be made, revealing that full vaccination dose, vaccine brand, younger age, female sex, and having had COVID-19 before vaccination were associated with greater odds of adverse effects. Large digital cohort studies may provide a mechanism for independent postmarket surveillance of drugs and devices.
Safety and Immunogenicity of an Anti–Zika Virus DNA Vaccine
Authors: Pablo Tebas, Christine C. Roberts, Kar Muthumani, Emma L. Reuschel, Sagar B. Kudchodkar, Faraz I. Zaidi, Scott White, Amir S. Khan, Trina Racine, Hyeree Choi, Jean Boyer, Young K. Park, Sylvie Trottier, Celine Remigio, Diane Krieger, Susan E. Spruill, Mark Bagarazzi, Gary P. Kobinger, David B. Weiner, Joel N. Maslow
Journal: New England Journal of Medicine (2017)

Although Zika virus (ZIKV) infection is typically self-limiting, other associated complications such as congenital birth defects and the Guillain-Barré syndrome are well described. There are no approved vaccines against ZIKV infection.
circCHST15 is a novel prognostic biomarker that promotes clear cell renal cell carcinoma cell proliferation and metastasis through the miR-125a-5p/EIF4EBP1 axis
Authors: Cheng-Peng Gui, Bing Liao, Cheng-Gong Luo, Yu-Hang Chen, Lei Tan, Yi-Ming Tang, Jia-Ying Li, Yi Hou, Hong-De Song, Hai-Shan Lin, Quan-Hui Xu, Gao-Sheng Yao, Hao-Hua Yao, None Xi-Liu, Jun-Hang Luo, Jia-Zheng Cao, Jin-Huan Wei
Journal: Molecular Cancer (2021)

Abstract Background Circular RNAs (circRNAs) have been indicated as potentially critical mediators in various types of tumor progression, generally acting as microRNA (miRNA) sponges to regulate downstream gene expression. However, the aberrant expression profile and dysfunction of circRNAs in human clear cell renal cell carcinoma (ccRCC) need to be further investigated. This study mined key prognostic circRNAs and elucidates the potential role and molecular mechanism of circRNAs in regulating the proliferation and metastasis of ccRCC. Methods circCHST15 (hsa_circ_0020303) was identified by mining two circRNA microarrays from the Gene Expression Omnibus database and comparing matched tumor versus adjacent normal epithelial tissue pairs or matched primary versus metastatic tumor tissue pairs. These results were validated by quantitative real-time polymerase chain reaction and agarose gel electrophoresis. We demonstrated the biological effect of circCHST15 in ccRCC both in vitro and in vivo. To test the interaction between circCHST15 and miRNAs, we conducted a number of experiments, including RNA pull down assay, dual-luciferase reporter assay and fluorescence in situ hybridization. Results The expression of circCHST15 was higher in ccRCC tissues compared to healthy adjacent kidney tissue and higher in RCC cell lines compared to normal kidney cell lines. The level of circCHST15 was positively correlated with aggressive clinicopathological characteristics, and circCHST15 served as an independent prognostic indicator for overall survival and progression-free survival in patients with ccRCC after surgical resection. Our in vivo and in vitro data indicate that circCHST15 promotes the proliferation, migration, and invasion of ccRCC cells. Mechanistically, we found that circCHST15 directly interacts with miR-125a-5p and acts as a microRNA sponge to regulate EIF4EBP1 expression. Conclusions We found that sponging of miR-125a-5p to promote EIF4EBP1 expression is the underlying mechanism of hsa_circ_0020303-induced ccRCC progression. This prompts further investigation of circCHST15 as a potential prognostic biomarker and therapeutic target for ccRCC.
NCMP-21. IMMUNE-RELATED ACUTE MOTOR AXONAL NEUROPATHY: A SMALL CASE SERIES AND REVIEW OF THE LITERATURE
Authors: Yolanda Pina, Nam Tran, Neha Verma, Michael Vogelbaum, Peter Forsyth, Sepideh Mokhtari, Edwin Peguero
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Immunotherapy revolutionized cancer treatment in the past decade, with a significant increased survival in patients with solid tumors. However, immune checkpoint inhibitors (ICIs) have been associated with a growing number of neurotoxicities, some of which can be fatal if not recognized and treated promptly. Some of these neurotoxicities include very uncommon syndromes like Acute Motor Axonal Neuropathy (AMAN). Herein we present four oncological cases of patients who underwent immunotherapy and developed AMAN. METHODS Four patients were diagnosed with immune-related AMAN between 2017 and 2000 at H. Lee Moffitt Cancer Center. Patients were treated with standard of care. RESULTS We describe four oncological patients who developed a motor axonal neuropathy (i.e., AMAN) confirmed on nerve conduction studies following 2 cycles of immunotherapy, including a 28 year old woman with melanoma brain metastasis and a 50 year old woman with renal cell carcinoma both treated with ipilimumab and nivolumab, a 32 year old man with Hodgkin lymphoma who was treated with nivolumab and brentuximab, and a 77 year old woman with renal urothelial cancer who was treated with pembrolizumab and cabozantinib. All four patients were promptly recognized as having immune-related neurotoxicity (irNs), were promptly treated (i.e., high dose steroids +/- IVIG +/- other immunomodulators), and significantly improved and have remained stable. CONCLUSION This is the first case series of patients with AMAN following two cycles of immunotherapy, who were successfully treated. It is crucial to develop a better understanding of irNs, including those rare conditions that are difficult to diagnose and treat, as the utilization of these immunomodulating therapies continues to expand to include other solid malignancies. Neurologists should be involved early on in any case of suspected irN to assist in the management of these complicated patients and a swift work up should be initiated for timely diagnosis and treatment.
Unspliced XBP1 Counteracts β-Catenin to Inhibit Vascular Calcification
Authors: Liu Yang, Rongbo Dai, Hao Wu, Zeyu Cai, Nan Xie, Xu Zhang, Yicong Shen, Ze Gong, Yiting Jia, Fang Yu, Ying Zhao, Pinglan Lin, Chaoyang Ye, Yanhua Hu, Yi Fu, Qingbo Xu, Zhiqing Li, Wei Kong
Journal: Circulation Research (2021)

Vascular calcification is a prevalent complication in chronic kidney disease and contributes to increased cardiovascular morbidity and mortality. XBP1 (X-box binding protein 1), existing as the XBP1u (unspliced XBP1) and XBP1s (spliced XBP1) forms, is a key component of the endoplasmic reticulum stress involved in vascular diseases. However, whether XBP1u participates in the development of vascular calcification remains unclear.We aim to investigate the role of XBP1u in vascular calcification. XBP1u protein levels were reduced in high phosphate-induced calcified vascular smooth muscle cells, calcified aortas from mice with adenine diet-induced chronic renal failure, and calcified radial arteries from patients with chronic renal failure.Inhibition of XBP1u rather than XBP1s upregulated in the expression of the osteogenic markers Runx2 (runt-related transcription factor 2) and Msx2 (msh homeobox 2), and exacerbated high phosphate-induced vascular smooth muscle cell calcification, as verified by calcium deposition and Alizarin red S staining. In contrast, XBP1u overexpression in high phosphate-induced vascular smooth muscle cells significantly inhibited osteogenic differentiation and calcification. Consistently, smooth muscle cell-specific XBP1 deficiency in mice markedly aggravated the adenine diet- and 5/6 nephrectomy-induced vascular calcification compared with that in the control littermates. Further interactome analysis revealed that XBP1u is bound directly to β-catenin, a key regulator of vascular calcification, via amino acid (aa) 205-230 in its C-terminal degradation domain. XBP1u interacted with β-catenin to promote its ubiquitin-proteasomal degradation and thus inhibited β-catenin/TCF (T-cell factor)-mediated Runx2 and Msx2 transcription. Knockdown of β-catenin abolished the effect of XBP1u deficiency on vascular smooth muscle cell calcification, suggesting a β-catenin-mediated mechanism. Moreover, the degradation of β-catenin promoted by XBP1u was independent of GSK-3β (glycogen synthase kinase 3β)-involved destruction complex.Our study identified XBP1u as a novel endogenous inhibitor of vascular calcification by counteracting β-catenin and promoting its ubiquitin-proteasomal degradation, which represents a new regulatory pathway of β-catenin and a promising target for vascular calcification treatment.
155P Surufatinib plus toripalimab for second-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma, esophageal squamous cell carcinoma (ESCC) and neuroendocrine carcinoma (NEC): A multicenter, single-arm phase II study
Authors: M. Lu, X. Yu, Z. Chen, Y. Zhang, Z. Li, X. Zhang, F. Yin, F. Ye, Y. Cheng, L. Song, J. Xu, J. Zhou, H. Shi, P. Tan, S. Fan, W. Su, L. Shen
Journal: Annals of Oncology (2021)
Giving science the finger—is the second-to-fourth digit ratio (2D:4D) a biomarker of good luck? A cross sectional study
Authors: James M Smoliga, Lucas K Fogaca, Jessica S Siplon, Abigail A Goldburt, Franziska Jakobs
Journal: BMJ (2021)

To explore whether random chance, weak research methodology, or inappropriate reporting can lead to claims of statistically significant (yet, biologically meaningless) biomarker associations, using as a model the relation between a common surrogate of prenatal testosterone exposure, second-to-fourth digit ratio (2D:4D), and a random indicator of good luck.Cross sectional study.University sports performance laboratory in the United States. Data were collected from May 2015 to February 2017.176 adults (74 women, 102 men), including university students, faculty, and staff with no history of injuries, disease, or medical conditions that would affect digit length.2D:4D, body composition parameters potentially influenced by androgens (bone mineral content, bone mineral density, body fat percentage), and good luck (using poker hands from randomly selected playing cards as a surrogate).2D:4D significantly correlated with select body composition parameters (Spearman's rs range -0.26 to 0.23; P<0.05), but the correlations varied by sex, participant hand measured, and the method of measuring 2D:4D (by photocopy or radiography). However, the strongest correlation observed was between right hand 2D:4D in men measured by radiograph and poker hand rank (rs=0.28, P=0.004).Greater prenatal exposure to testosterone, as estimated by a lower 2D:4D, significantly increases good luck in adulthood, and also modulates body composition (albeit to a lesser degree). While these findings are consistent with a wealth of research reporting that 2D:4D is related to many seemingly disparate outcomes, they are not meant to provide confirmatory evidence that 2D:4D is a universal biomarker of nearly everything. Instead, the associations between 2D:4D and good luck are simply due to chance, and provide a "handy" example of the reproducibility crisis within medical and scientific research. Biologically sound hypotheses, pre-registration of trials, strong methodological and statistical analyses, transparent reporting of negative results, and unbiased interpretation of data are all necessary for biomarker studies and other areas of clinical research.
Editor's Note: Both TEAD-Binding and WW Domains Are Required for the Growth Stimulation and Oncogenic Transformation Activity of Yes-Associated Protein
Authors: Bin Zhao, Joungmok Kim, Xin Ye, Zhi-Chun Lai, Kun-Liang Guan
Journal: Cancer Research (2021)

The editors are publishing this note to alert readers to a concern about this article (1). The authors made the editors aware that two images were inadvertently duplicated in four panels of Fig. 3A. Specifically, the same image was used for the Vec and YAP-WT group on day 1 in 10% serum, and images including overlapping fields were used for the YAP-WT and YAP-W1W2 groups on day 0. Because of the length of time since publication of this article, original data are not available to correct the figures in this paper. The authors state they performed replicative experiments that supported the original findings, but that data was not part of the original study and has therefore not been introduced into the published article.