tbuckley/cabot-search huggingface dataset:
The very early tumor regression rate and safety of anlotinib combined with sintilimab and chemotherapy for advanced non-small cell lung cancer without driver mutations.
Authors: Jian Jiang, Yuming Jia, Yue Ren, Ting Li, Lei-Ya Du, Mao-Qiong Jiang, Ye Qiu, Jie Chen, Jun Yan, Li Li
Journal: Journal of Clinical Oncology (2021)

e21090 Background: Unlike bevacizumab, anlotinib, which is also an anti-angiogenic drug, is indicated for lung squamous cell carcinoma(LSCC). A phase IB study showed that the first-line therapy with anlotinib and sintilimab for stage IIIB to IV NSCLC with negative driver genes has the objective response rate of 72.7%. Regardless of the PD-1 expression level, this combination method has consistent therapeutic benefit. According to the IMpower150 study, the four-drug combination therapy has a synergistic effect and prolong the survival time. It is necessary to further explore the efficacy and safety of anlotinib combined with sintilimab and chemotherapy for NSCLC without driver mutations. Methods: We retrospectively analyzed the patients of newly diagnosed unresectable stage IIIA-IVB NSCLC who received platinum-containing dual-drug chemotherapy combined with anlotinib and sintilimab in our hospital from January 2019 to December 2020. Patients receive at least one cycle of treatment, and the efficacy can be evaluated. The main observation indicators are the very early tumor regression rate and the safety. Results: This study included 11 patients with stage IIIA-IVB NSCLC with no driver mutations that were not resectable. Ten patients (90.9%) were male, with a median age of 65 years. The pathological types were LSCC (7, 63.6%), lung adenocarcinoma (3, 27.3%), and poor differentiated carcinoma (1, 9.1%). Six patients were with stage ⅢA-ⅢB, 4 patient with ⅢC-IVB. Eleven patients received an average of 1.63 cycles of treatment. In order to evaluate the efficacy of multi-drug combination therapy in a timely manner, and effectively avoid the risk of hemoptysis caused by anlotinib-induced pulmonary cavity, all patients were evaluated for efficacy after receiving one cycle of treatment. Eight patients achieved very early tumor regression (defined as tumor shrinkage ≥30% after receiving one cycle of treatment in the evaluation of efficacy), 2 patients achieved stable disease, and 1 patients achieved disease progression. The very early tumor regression rate was 72.7%. Three patients with locally advanced (ⅢA-ⅢB) NSCLC underwent radical R0 resection and the downstage rate reached 100%; 2 patients underwent radical radiotherapy. At the last follow-up time in February 2021, one patient died, the remaining patients were alive. No treatment-related grade 3-4 adverse reactions were observed. Conclusions: The high rate of very early tumor regressions in inoperable locally advanced NSCLC provided opportunities for radical surgery and radiotherapy in a short period of time. And the safety is satisfactory. Therefore, our research group has registered the prospective study of anlotinib combined with sintilimab and chemotherapy for the neoadjuvant downstage treatment of stage III NSCLC (Registration number: ChiCTR1900026631).
PLCG1 is required for AML1-ETO leukemia stem cell self-renewal
Authors: Tina M. Schnoeder, Adrian Schwarzer, Ashok Kumar Jayavelu, Chen-Jen Hsu, Joanna Kirkpatrick, Konstanze Döhner, Florian Perner, Theresa Eifert, Nicolas Huber, Patricia Arreba-Tutusaus, Anna Dolnik, Salam A. Assi, Monica Nafria, Lu Jiang, Yu-Ting Dai, Zhu Chen, Sai-Juan Chen, Sophie G. Kellaway, Anetta Ptasinska, Elizabeth S. Ng, Edouard G. Stanley, Andrew G. Elefanty, Marcus Buschbeck, Holger Bierhoff, Steffen Brodt, Georg Matziolis, Klaus-Dieter Fischer, Andreas Hochhaus, Chun-Wei Chen, Olaf Heidenreich, Matthias Mann, Steven W. Lane, Lars Bullinger, Alessandro Ori, Björn von Eyss, Constanze Bonifer, Florian H. Heidel
Journal: Blood (2021)
TCT-129 Use of the PRECISE 3D-CT Morphological Classification for Percutaneous Closure Treatment Selection in Patients With Ventricular Septal Rupture
Authors: Eduardo Arias, Héctor González-Pacheco, Juan Sandoval-Jones, Enrique Berrios, Felix Damas de los Santos, Alexandra Arias, Hugo Rodríguez-Zanella, Julio Farjat Pasos, Moises Jimenez-Santos, Regina de la Mora Cervantes, José Antonio Arias-Godínez, Jorge Gaspar
Journal: Journal of the American College of Cardiology (2021)
In vitro and in vivo characterization of erythrosin B and derivatives against Zika virus
Authors: Zhong Li, Jimin Xu, Yuekun Lang, Xiangmeng Wu, Saiyang Hu, Subodh Kumar Samrat, Anil M. Tharappel, Lili Kuo, David Butler, Yongcheng Song, Qing-Yu Zhang, Jia Zhou, Hongmin Li
Journal: Acta Pharmaceutica Sinica B (2021)

Zika virus (ZIKV) causes significant human diseases without specific therapy. Previously we found erythrosin B, an FDA-approved food additive, inhibited viral NS2B-NS3 interactions, leading to inhibition of ZIKV infection in cell culture. In this study, we performed pharmacokinetic and in vivo studies to demonstrate the efficacy of erythrosin B against ZIKV in 3D mini-brain organoid and mouse models. Our results showed that erythrosin B is very effective in abolishing ZIKV replication in the 3D organoid model. Although pharmacokinetics studies indicated that erythrosin B had a low absorption profile, mice challenged by a lethal dose of ZIKV showed a significantly improved survival rate upon oral administration of erythrosin B, compared to vehicle control. Limited structure-activity relationship studies indicated that most analogs of erythrosin B with modifications on the xanthene ring led to loss or reduction of inhibitory activities towards viral NS2B-NS3 interactions, protease activity and antiviral efficacy. In contrast, introducing chlorine substitutions on the isobenzofuran ring led to slightly increased activities, suggesting that the isobenzofuran ring is well tolerated for modifications. Cytotoxicity studies indicated that all derivatives are nontoxic to human cells. Overall, our studies demonstrated erythrosin B is an effective antiviral against ZIKV both in vitro and in vivo.
Disease Progression Modeling for Economic Evaluation in Nonalcoholic Fatty Liver Disease—A Systematic Review
Authors: Lina Gruneau, Mattias Ekstedt, Stergios Kechagias, Martin Henriksson
Journal: Clinical Gastroenterology and Hepatology (2021)

Globally, 25% of people have nonalcoholic fatty liver disease (NAFLD), and, currently, there are no approved pharmacologic treatments for NAFLD. With a slow disease progression, long-term impact of pharmacologic treatments can be assessed only by complementing emerging clinical trial evidence with data from other sources in disease progression modeling. Although this modeling is crucial for economic evaluation studies assessing the clinical and economic consequences of new treatments, the approach to modeling the natural history of NAFLD differs in contemporary research. This systematic literature review investigated modeling of the natural history of NAFLD.A systematic literature review was conducted searching PubMed, Scopus, Cochrane, and the National Health Service Economic Evaluation Database to identify articles focusing on modeling of the natural history of NAFLD. Model structure and transition probabilities were extracted from included studies.Of the 28 articles identified, differences were seen in model structure and data input. Clear definitions of nonalcoholic steatohepatitis and NAFLD often were lacking; differences in the granularity of modeling fibrosis progression, the approach to disease regression, and modeling of advanced liver disease varied across studies. Observed transition probabilities for F0 to F1, F1 to F2, F2 to F3, and F3 to compensated cirrhosis varied between 0.059 to 0.095, 0.023 to 0.140, 0.018 to 0.070, and 0.040 to 0.118, respectively.The difference in disease progression modeling for seemingly similar models warrants further inquiry regarding how to model the natural course of NAFLD. Such differences may have a large impact when assessing the value of emerging pharmacologic treatments.
Three-Dimensional Visualization of Hypoxia-Induced Pulmonary Vascular Remodeling in Mice
Authors: Takayuki Fujiwara, Norifumi Takeda, Hironori Hara, Satoshi Ishii, Genri Numata, Hiroyuki Tokiwa, Sonoko Maemura, Takaaki Suzuki, Hiroshi Takiguchi, Yoshiaki Kubota, Kinya Seo, Asuka Sakata, Seitaro Nomura, Masaru Hatano, Kazutaka Ueda, Mutsuo Harada, Haruhiro Toko, Eiki Takimoto, Hiroshi Akazawa, Satoshi Nishimura, Issei Komuro
Journal: Circulation (2021)
TCT-244 Impact of Patient-Reported Preprocedural Physical and Mental Health on 10-Year Mortality After Percutaneous or Surgical Coronary Revascularization
Authors: Masafumi Ono, Patrick Serruys, Scot Garg, Hideyuki Kawashima, Chao Gao, Hironori Hara, Mattia Lunardi, Rutao Wang, Neil O’Leary, Michael Mack, David Holmes, Marie-Claude Morice, Pieter Kappetein, Daniel Thuijs, Thilo Noack, Friedrich-Wilhelm Mohr, Piroze Davierwala, John Spertus, Yoshinobu Onuma
Journal: Journal of the American College of Cardiology (2021)
Citrullination Was Introduced into Animals by Horizontal Gene Transfer from Cyanobacteria
Authors: Thomas F M Cummings, Kevin Gori, Luis Sanchez-Pulido, Gavriil Gavriilidis, David Moi, Abigail R Wilson, Elizabeth Murchison, Christophe Dessimoz, Chris P Ponting, Maria A Christophorou
Journal: Molecular Biology and Evolution (2021)

Abstract Protein posttranslational modifications add great sophistication to biological systems. Citrullination, a key regulatory mechanism in human physiology and pathophysiology, is enigmatic from an evolutionary perspective. Although the citrullinating enzymes peptidylarginine deiminases (PADIs) are ubiquitous across vertebrates, they are absent from yeast, worms, and flies. Based on this distribution PADIs were proposed to have been horizontally transferred, but this has been contested. Here, we map the evolutionary trajectory of PADIs into the animal lineage. We present strong phylogenetic support for a clade encompassing animal and cyanobacterial PADIs that excludes fungal and other bacterial homologs. The animal and cyanobacterial PADI proteins share functionally relevant primary and tertiary synapomorphic sequences that are distinct from a second PADI type present in fungi and actinobacteria. Molecular clock calculations and sequence divergence analyses using the fossil record estimate the last common ancestor of the cyanobacterial and animal PADIs to be less than 1 billion years old. Additionally, under an assumption of vertical descent, PADI sequence change during this evolutionary time frame is anachronistically low, even when compared with products of likely endosymbiont gene transfer, mitochondrial proteins, and some of the most highly conserved sequences in life. The consilience of evidence indicates that PADIs were introduced from cyanobacteria into animals by horizontal gene transfer (HGT). The ancestral cyanobacterial PADI is enzymatically active and can citrullinate eukaryotic proteins, suggesting that the PADI HGT event introduced a new catalytic capability into the regulatory repertoire of animals. This study reveals the unusual evolution of a pleiotropic protein modification.
Analysis of the Effectiveness of the Ad26.COV2.S Adenoviral Vector Vaccine for Preventing COVID-19
Authors: Juan Corchado-Garcia, David Zemmour, Travis Hughes, Hari Bandi, Tudor Cristea-Platon, Patrick Lenehan, Colin Pawlowski, Sairam Bade, John C. O’Horo, Gregory J. Gores, Amy W. Williams, Andrew D. Badley, John Halamka, Abinash Virk, Melanie D. Swift, Tyler Wagner, Venky Soundararajan
Journal: JAMA Network Open (2021)

Continuous assessment of the effectiveness and safety of the US Food and Drug Administration-authorized SARS-CoV-2 vaccines is critical to amplify transparency, build public trust, and ultimately improve overall health outcomes.To evaluate the effectiveness of the Johnson & Johnson Ad26.COV2.S vaccine for preventing SARS-CoV-2 infection.This comparative effectiveness research study used large-scale longitudinal curation of electronic health records from the multistate Mayo Clinic Health System (Minnesota, Arizona, Florida, Wisconsin, and Iowa) to identify vaccinated and unvaccinated adults between February 27 and July 22, 2021. The unvaccinated cohort was matched on a propensity score derived from age, sex, zip code, race, ethnicity, and previous number of SARS-CoV-2 polymerase chain reaction tests. The final study cohort consisted of 8889 patients in the vaccinated group and 88 898 unvaccinated matched patients.Single dose of the Ad26.COV2.S vaccine.The incidence rate ratio of SARS-CoV-2 infection in the vaccinated vs unvaccinated control cohorts, measured by SARS-CoV-2 polymerase chain reaction testing.The study was composed of 8889 vaccinated patients (4491 men [50.5%]; mean [SD] age, 52.4 [16.9] years) and 88 898 unvaccinated patients (44 748 men [50.3%]; mean [SD] age, 51.7 [16.7] years). The incidence rate ratio of SARS-CoV-2 infection in the vaccinated vs unvaccinated control cohorts was 0.26 (95% CI, 0.20-0.34) (60 of 8889 vaccinated patients vs 2236 of 88 898 unvaccinated individuals), which corresponds to an effectiveness of 73.6% (95% CI, 65.9%-79.9%) and a 3.73-fold reduction in SARS-CoV-2 infections.This study's findings are consistent with the clinical trial-reported efficacy of Ad26.COV2.S and the first retrospective analysis, suggesting that the vaccine is effective at reducing SARS-CoV-2 infection, even with the spread of variants such as Alpha or Delta that were not present in the original studies, and reaffirm the urgent need to continue mass vaccination efforts globally.
Correspondence on “Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial” by Molto <i>et al</i>
Authors: Uta Kiltz, Juergen Braun
Journal: Annals of the Rheumatic Diseases (2021)

With great interest, we read the results of the tight control in spondyloarthritis (TICOSPA) study1 in which a tight-control/treat-to-target strategy (T2T) was compared with usual care in patients with axial spondyloarthritis (axSpA). In this study which was the first ever to use a T2T strategy in axSpA, a main outcome parameter was used that had never been used before: the percentage of patients with a ≥30% improvement on the ‘Assessment of spondyloarthritis international society (ASAS)-Health Index (ASAS-HI), and other conventional efficacy outcomes were also recorded.1 As recently explained, one important reasons to use the ASAS HI in TICOSPA as primary endpoint was to avoid circular reasoning, for example, using the same items for inclusion and outcome.2

The aim of this correspondence is not to discuss the strategy used in the trial since this has been done in a recent editorial but to discuss the use of this outcome parameter which represents a tool that has been developed over many years with >2000 patients and a major input from patients. This is also documented by the fact that 5 items out of the 17 in the ASAS HI were proposed by patients with ankylosing spondylitis (AS) and they are not part of any other tool that has been …
Structural and allergenic properties of the fatty acid binding protein from shrimp <i>Litopenaeus vannamei</i>
Authors: Marlon Múnera, Dalgys Martínez, Judith Wortmann, Josefina Zakzuk, Walter Keller, Luis Caraballo, Leonardo Puerta
Journal: Allergy (2021)

The shrimp Litopenaeus vannamei is an important source of food allergens but its allergenic repertoire is poorly characterized. Cross-reactivity between crustacean and mites has been reported, with tropomyosin, the most relevant allergen involved. The aim of this study was to investigate the structural and immunological properties of a recombinant Fatty Acid Binding Protein (FABP) family from L. vannamei (LvFABP).ELISA, skin prick test (SPT) and basophil activation assays were performed to determine IgE reactivity and allergenic activity of LvFABP. LC-MS/MS and Circular Dichroism experiments were done for structural analysis. B-cell epitope mapping with overlapping peptides, and cross-inhibition studies using human sera were done to identify antigenic regions and cross-reactivity.The recombinant LvFABP bound serum IgE from 27% of 36 shrimp allergic patients and showed allergenic activity when tested for basophil activation and SPT in a selected number of them. CD-spectroscopy of LvFABP revealed that the protein is folded with a secondary structure composed of mainly β-strands and a smaller fraction of α helices. This is consistent with molecular modelling results, which exhibit a typical β barrel fold with two α-helices and ten β-strands. Epitope mapping identified two IgE-binding antigenic regions and inhibition assays found high cross-reactivity between LvFABP and Blo t 13, mediated by the antigenic region involving amino acids 54 to 72.Our results show that LvFABP is a shrimp allergen that cross reacts with the house dust mite allergen Blo t 13 and has allergenic activity, which suggest that it could be clinically relevant in case of shellfish allergy. This new allergen, named Lit v 13, will also help to understand basic mechanisms of sensitization to shrimp.
Evaluation of Hypofractionated Radiation Therapy Use and Patient-Reported Outcomes in Men With Nonmetastatic Prostate Cancer in Australia and New Zealand
Authors: David I. Pryor, Jarad M. Martin, Jeremy L. Millar, Heather Day, Wee Loon Ong, Marketa Skala, Liesel M. FitzGerald, Benjamin Hindson, Braden Higgs, Michael E. O’Callaghan, Farhan Syed, Amy J. Hayden, Sandra L. Turner, Nathan Papa
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Randomized clinical trials in prostate cancer have reported noninferior outcomes for hypofractionated radiation therapy (HRT) compared with conventional RT (CRT); however, uptake of HRT across jurisdictions is variable. <h3>Objective</h3> To evaluate the use of HRT vs CRT in men with nonmetastatic prostate cancer and compare patient-reported outcomes (PROs) at a population level. <h3>Design, Setting, and Participants</h3> Registry-based cohort study from the Australian and New Zealand Prostate Cancer Outcomes Registry (PCOR-ANZ). Participants were men with nonmetastatic prostate cancer treated with primary RT (excluding brachytherapy) from January 2016 to December 2019. Data were analyzed in March 2021. <h3>Exposures</h3> HRT defined as 2.5 to 3.3 Gy and CRT defined as 1.7 to 2.3 Gy per fraction. <h3>Main Outcomes and Measures</h3> Temporal trends and institutional, clinicopathological, and sociodemographic factors associated with use of HRT were analyzed. PROs were assessed 12 months following RT using the Expanded Prostate Cancer Index Composite (EPIC)–26 Short Form questionnaire. Differences in PROs were analyzed by adjusting for age and National Comprehensive Cancer Network risk category. <h3>Results</h3> Of 8305 men identified as receiving primary RT, 6368 met the inclusion criteria for CRT (n = 4482) and HRT (n = 1886). The median age was 73.1 years (IQR, 68.2-77.3 years), 2.6% (168) had low risk, 45.7% (2911) had intermediate risk, 44.5% (2836) had high-/very high–risk, and 7.1% (453) had regional nodal disease. Use of HRT increased from 2.1% (9 of 435) in the first half of 2016 to 52.7% (539 of 1023) in the second half of 2019, with lower uptake in the high-/very high–risk (1.9% [4 of 215] to 42.4% [181 of 427]) compared with the intermediate-risk group (2.2% [4 of 185] to 67.6% [325 of 481]) (odds ratio, 0.26; 95% CI, 0.15-0.45). Substantial variability in the use of HRT for intermediate-risk disease remained at the institutional level (median 53.3%; range, 0%-100%) and clinician level (median 57.9%; range, 0%-100%) in the last 2 years of the study period. There were no clinically significant differences across EPIC-26 urinary and bowel functional domains or bother scores. <h3>Conclusions and Relevance</h3> In this cohort study, use of HRT for prostate cancer increased substantially from 2016. This population-level data demonstrated clinically equivalent PROs and supports the continued implementation of HRT into routine practice. The wide variation in practice observed at the jurisdictional, institutional, and clinician level provides stakeholders with information that may be useful in targeting implementation strategies and benchmarking services.
TCT-442 HV Electrophysiology Study in QRS Prolongation After TAVR: Experience of a Center
Authors: Carlos Arellano Serrano, Paula Vela Martin, Arturo Garcia-Touchard, Jose Antonio Fernandez Diaz, Maria Del Trigo, Victor Castro, Eusebio García-Izquierdo, Ignacio Fernández Lozano, Javier Segovia-Cubero, Juan Francisco Oteo Dominguez
Journal: Journal of the American College of Cardiology (2021)
Whole-genome landscape of adult T-cell leukemia/lymphoma
Authors: Yasunori Kogure, Takuro Kameda, Junji Koya, Makoto Yoshimitsu, Kisato Nosaka, Jun-ichirou Yasunaga, Yoshitaka Imaizumi, Mizuki Watanabe, Yuki Saito, Yuta Ito, Marni B. McClure, Mariko Tabata, Sumito Shingaki, Kota Yoshifuji, Kenichi Chiba, Ai Okada, Nobuyuki Kakiuchi, Yasuhito Nannya, Ayako Kamiunten, Yuki Tahira, Keiichi Akizuki, Masaaki Sekine, Kotaro Shide, Tomonori Hidaka, Yoko Kubuki, Akira Kitanaka, Michihiro Hidaka, Nobuaki Nakano, Atae Utsunomiya, R. Alejandro Sica, Ana Acuna-Villaorduna, Murali Janakiram, Urvi Shah, Juan Carlos Ramos, Tatsuhiro Shibata, Kengo Takeuchi, Akifumi Takaori-Kondo, Yasushi Miyazaki, Masao Matsuoka, Kenji Ishitsuka, Yuichi Shiraishi, Satoru Miyano, Seishi Ogawa, B. Hilda Ye, Kazuya Shimoda, Keisuke Kataoka
Journal: Blood (2021)
A Randomized Open Label Pilot Study of <i>Clostridium Butyricum</i> Miyairi 588 (CBM588) in Recipients of Allogeneic Hematopoietic Cell Transplantation
Authors: Karamjeet S. Sandhu, Dongyun Yang, Sally Mokhtari, Sanjeet S Dadwal, Vinod A. Pullarkat, Monzr M. Al Malki, Thai Cao, Ricardo Spielberger, Amandeep Salhotra, Haris Ali, Andrew S. Artz, Anthony S. Stein, Myo Htut, Elizabeth Budde, Leslie L. Popplewell, Harry Xu, Lauren Reining, Lucy Y Ghoda, Ibrahim Aldoss, Guido Marcucci, Stephen J Forman, Sarah Highlander, Ryotaro Nakamura
Journal: Blood (2021)
TCT-4 Prognosis and Medical Cost of Measuring Fractional Flow Reserve in Percutaneous Coronary Intervention
Authors: David Hong, Seung Hun Lee, Doosup Shin, Ki Hong Choi, Hyun Kuk Kim, Taek Kyu Park, Jeong Hoon Yang, Young Bin Song, Joo-Yong Hahn, Seung-Hyuck Choi, Hyeon-Cheol Gwon, Joo Myung Lee
Journal: Journal of the American College of Cardiology (2021)
TCT-257 In-Patient Outcome Comparison of Patients With Acute Coronary Syndrome Undergoing PCI or CABG and Heparin-Induced Thrombocytopenia: A Nationwide Inpatient Sample Database Analysis
Authors: Neel Patel, Birendra Amgai, Adrija Hajra, Sagar Ranka, Sandipan Chakraborty, Dhrubajyoti Bandyopadhyay, Zeel Patel, Soniya Koirala, Madhu Reddy, Wilbert Aronow, Samir Pancholy
Journal: Journal of the American College of Cardiology (2021)
Improvement in Exercise Capacity by Exercise Training is Associated with Favorable Outcome in Advanced Heart Failure with High BNP Level
Authors: Nakanishi Michio, Nakao Kazuhiro, Kumasaka Reon, Arakawa Tetsuo, Ohhara Takahiro, Fukui Shigefumi, Yanase Masanobu, Noguchi Teruo, Yasuda Satoshi, Goto Yoichi
Journal: Circulation (2015)