tbuckley/cabot-search huggingface dataset:
Treatment of Acute Pain in Adults With Sickle Cell Disease in an Infusion Center Versus the Emergency Department
Authors: Sophie Lanzkron, Jane Little, Hang Wang, Joshua J. Field, J. Ryan Shows, Carlton Haywood, Mustapha Saheed, Marc Proudford, Derek Robertson, Adrienne Kincaid, Lorri Burgess, Charles Green, Rebecca Seufert, Jasmine Brooks, Allie Piehet, Brandi Griffin, Nicole Arnold, Steven Frymark, Marcus Wallace, Nebras Abu Al Hamayel, Chiung-Yu Huang, Jodi B. Segal, Ravi Varadhan
Journal: Annals of Internal Medicine (2021)

Patients with sickle cell disease (SCD) have vaso-occlusive crises (VOCs). Infusion centers (ICs) are alternatives to emergency department (ED) care and may improve patient outcomes.To assess whether care in ICs or EDs leads to better outcomes for the treatment of uncomplicated VOCs.Prospective cohort. (ClinicalTrials.gov: NCT02411396).4 U.S. sites, with recruitment between April 2015 and December 2016.Adults with SCD living within 60 miles of a study site.Participants were followed for 18 months after enrollment. Outcomes of interest were time to first dose of parenteral pain medication, whether pain reassessment was completed within 30 minutes after the first dose, and patient disposition on discharge from the acute care visit. Treatment effects for ICs versus EDs were estimated using a time-varying propensity score adjustment.Researchers enrolled 483 participants; the 269 who had acute care visits on weekdays are included in this report. With inverse probability of treatment-weighted adjustment, the mean time to first dose was 62 minutes in ICs and 132 minutes in EDs; the difference was 70 minutes (95% CI, 54 to 98 minutes; E-value, 2.8). The probability of pain reassessment within 30 minutes of the first dose of parenteral pain medication was 3.8 times greater (CI, 2.63 to 5.64 times greater; E-value, 4.7) in the IC than the ED. The probability that a participant's visit would end in admission to the hospital was smaller by a factor of 4 (0.25 [CI, 0.18 to 0.33]) with treatment in an IC versus an ED.The study was restricted to participants with uncomplicated VOCs.In adults with SCD having a VOC, treatment in an IC is associated with substantially better outcomes than treatment in an ED.Patient-Centered Outcomes Research Institute.
Impact of perioperative complications on length of hospitalizations, readmission rate and treatment failure after urethroplasty
Authors: M. Bandini, G. Barbagli, P.M. Joshi, R. Leni, G.O. Cirulli, G. Basile, S. Balò, F. Montorsi, S. Sansalone, A. Salonia, A. Briganti, D. Butnaru, S.B. Kulkarni, M. Lazzeri
Journal: European Urology (2021)
Genomic Signatures Supporting the Symbiosis and Formation of Chitinous Tube in the Deep-Sea Tubeworm <i>Paraescarpia echinospica</i>
Authors: Yanan Sun, Jin Sun, Yi Yang, Yi Lan, Jack Chi-Ho Ip, Wai Chuen Wong, Yick Hang Kwan, Yanjie Zhang, Zhuang Han, Jian-Wen Qiu, Pei-Yuan Qian
Journal: Molecular Biology and Evolution (2021)

Vestimentiferan tubeworms are iconic animals that present as large habitat-forming chitinized tube bushes in deep-sea chemosynthetic ecosystems. They are gutless and depend entirely on their endosymbiotic sulfide-oxidizing chemoautotrophic bacteria for nutrition. Information on the genomes of several siboglinid endosymbionts has improved our understanding of their nutritional supplies. However, the interactions between tubeworms and their endosymbionts remain largely unclear due to a paucity of host genomes. Here, we report the chromosome-level genome of the vestimentiferan tubeworm Paraescarpia echinospica. We found that the genome has been remodeled to facilitate symbiosis through the expansion of gene families related to substrate transfer and innate immunity, suppression of apoptosis, regulation of lysosomal digestion, and protection against oxidative stress. Furthermore, the genome encodes a programmed cell death pathway that potentially controls the endosymbiont population. Our integrated genomic, transcriptomic, and proteomic analyses uncovered matrix proteins required for the formation of the chitinous tube and revealed gene family expansion and co-option as evolutionary mechanisms driving the acquisition of this unique supporting structure for deep-sea tubeworms. Overall, our study provides novel insights into the host's support system that has enabled tubeworms to establish symbiosis, thrive in deep-sea hot vents and cold seeps, and produce the unique chitinous tubes in the deep sea.
A Phase 1 Study Evaluating Rovalpituzumab Tesirine in Frontline Treatment of Patients With Extensive-Stage SCLC
Authors: Christine L. Hann, Timothy F. Burns, Afshin Dowlati, Daniel Morgensztern, Patrick J. Ward, Martina M. Koch, Chris Chen, Carrianne Ludwig, Maulik Patel, Halla Nimeiri, Philip Komarnitsky, D. Ross Camidge
Journal: Journal of Thoracic Oncology (2021)

Rovalpituzumab tesirine (Rova-T) is an antibody-drug conjugate targeting DLL3, a Notch pathway ligand highly expressed on SCLC cells. Rova-T was evaluated alone or in combination with platinum-based chemotherapy (cisplatin or carboplatin combined with etoposide [CE]) in frontline treatment of extensive-stage SCLC.One cycle of CE pre-enrollment was permitted (later mandated). The following four cohorts were enrolled: Rova-T monotherapy (0.3 mg/kg, every 6 [q6] wk × 2; cohort 1; n = 4); Rova-T induction (0.3 mg/kg, q6 wk × 2) followed by CE every 21 days (q21) × 4 (cohort 2; n = 5); Rova-T (0.1 or 0.2 mg/kg, q6 wk × 2) overlapping with CE q21 × 4 (cohort 3; n = 14); and Rova-T maintenance (0.3 mg/kg, q6 wk × 2) after CE q21 × 4 (cohort 4; n = 3).A total of 26 patients were dosed (cohort 3: 14; cohorts 1, 2, and 4 combined: 12). Median age was 66 years, and 73% had Eastern Cooperative Oncology Group performance status of 1. In cohort 3, seven patients (50%) had confirmed objective responses, with a median progression-free survival of 5.2 months and median overall survival of 10.3 months. Compared with cohorts 1, 2, and 4 combined, cohort 3 had lower frequency of some Rova-T-related adverse events of special interest, such as pleural effusion (0 versus 33%), pericardial effusion (0 versus 17%), ascites (0 versus 8%), peripheral edema (36% versus 42%), generalized edema (0 versus 8%), pneumonia (7% versus 25%), and hypoalbuminemia (0 versus 17%).Lower Rova-T doses may be associated with lower incidence of some Rova-T-related adverse events of special interest. Rova-T 0.2 mg/kg plus CE (cohort 3) was tolerable; however, there was no clear efficacy benefit of adding Rova-T to CE.
Assessing the effect of concomitant hormonal therapy on severe toxicity in patients treated with post-prostatectomy radiation therapy: Results from a large, multi-institutional study
Authors: N. Fossati, E. Mazzone, R.J. Karnes, S.A. Boorjian, G. Motterle, A. Bossi, T. Kumar, N. Di Muzio, C. Cozzarini, B. Noris Chiorda, G. Gandaglia, A. Stabile, V. Cucchiara, S. Scuderi, D. Robesti, D. Bartkowiak, S. Shariat, G. Goldner, S. Joniau, H. Van Poppel, C. Berghen, G. De Meerleer, F. Montorsi, T. Wiegel, A. Briganti
Journal: European Urology (2021)
Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination
Authors: Joana Barros-Martins, Swantje I. Hammerschmidt, Anne Cossmann, Ivan Odak, Metodi V. Stankov, Gema Morillas Ramos, Alexandra Dopfer-Jablonka, Annika Heidemann, Christiane Ritter, Michaela Friedrichsen, Christian Schultze-Florey, Inga Ravens, Stefanie Willenzon, Anja Bubke, Jasmin Ristenpart, Anika Janssen, George Ssebyatika, Günter Bernhardt, Jan Münch, Markus Hoffmann, Stefan Pöhlmann, Thomas Krey, Berislav Bošnjak, Reinhold Förster, Georg M. N. Behrens
Journal: Nature Medicine (2021)

Abstract Currently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca’s ChAdOx1-nCov-19 (ChAd) only in individuals older than 60 years, leaving millions of already ChAd-primed individuals with the decision to receive either a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School’s COVID-19 Contact Study cohort of healthcare professionals to monitor ChAd-primed immune responses before and 3 weeks after booster with ChAd ( n = 32) or BioNTech/Pfizer’s BNT162b2 ( n = 55). Although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4 + and CD8 + T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and P.1 variants of concern of severe acute respiratory syndrome coronavirus 2.
Abstract 2820: A human Claudin-3 monoclonal antibody as a potential multimodal theranostic probe in ovarian cancer
Authors: Sera Oh, Hobin Yang, Ho Rim Oh, Chul-Hee Lee, Young-Hwa Kim, Gi Jeong Cheon, Keon Wook Kang, Young Kee Shin, Hyewon Youn
Journal: Cancer Research (2021)

Abstract Introduction: Claudin-3 (CLDN3), a tight junction protein, regulates cell-to-cell interactions in epithelial or endothelial cell sheets. During tumorigenesis, epithelial cells are transformed and tumor cells proliferate through out-of-plane division, resulting in external exposure of CLDN3. This alteration of CLDN3 expression is associated with cancer progression, correlating with malignancy in various carcinomas. Since CLDN3 is particularly overexpressed in most ovarian cancers and used as an effective diagnostic marker, we tested the possibility of using a CLDN3-specific antibody as a novel imaging probe. Materials and Methods: After reducing the CLDN3 specific antibody to expose the -SH group, click chemistry was used to conjugate radioactive isotope 111In or fluorescent protein FNR648. Human ovarian cancer OVCAR-3 cells and human glioblastoma (U87MG) cells were used as CLDN3 positive and negative cells, respectively. Flow cytometry was used to measure the binding of CLDN3 IgG1 monoclonal antibody to theses cell lines. To establish xenograft model, OVCAR-3 cells were injected subcutaneously into the mice. 111In-labeled CLDN3 antibody (370 kBq/50 μl) was administered intravenously to mice with. After 24 hours, organs including tumor were excised and measured with a γ-counter. Images were acquired with IVIS and SPECT/CT. Results: The labeling efficiency of NOTA-111In or antibody-NOTA-111In was 98.52% or 100%, respectively. FNR648 labeled CLDN3 antibody was bound to the cell surface of OVCAR-3 at 83.4% and to U87MG at 5.7%, respectively. In OVCAR-3 tumor xenografted mice, mice injected with CLDN3 antibody showed 2.5-fold higher tumor uptake (20.4 ± 7.4% ID/g) than mice injected with human IgG (8.8 ± 2.6% ID/g) at 24 hour p.i. The fluorescence signal of CLDN3 antibody peaked at 24 hour p.i. Conclusion: We successfully conjugated radioisotope and fluorescent protein using the CLDN3 specific antibody. Since the specific binding of CLDN3 antibodies to OVCAR-3 tumors has been validated in a mouse model and diagnostic radionuclides can be replaced with therapeutic radionuclides, this human monoclonal antibody could be used as a useful theranostic probe. Citation Format: Sera Oh, Hobin Yang, Ho Rim Oh, Chul-Hee Lee, Young-Hwa Kim, Gi Jeong Cheon, Keon Wook Kang, Young Kee Shin, Hyewon Youn. A human Claudin-3 monoclonal antibody as a potential multimodal theranostic probe in ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2820.
A Pragmatic, Randomized Controlled Trial of Oral Antivirals for the Treatment of Chronic Hepatitis C: The PRIORITIZE Study
Authors: Mark S. Sulkowski, Juhi S. Moon, Kenneth E. Sherman, Giuseppe Morelli, Jama M. Darling, Andrew J. Muir, Mandana Khalili, Dawn A. Fishbein, Federico Hinestrosa, Mitchell L. Shiffman, Adrian Di Bisceglie, K. Rajender Reddy, Brian Pearlman, Anna S. Lok, Michael W. Fried, Paul W. Stewart, Joy Peter, Summer Wadsworth, Scott Kixmiller, Anquenette Sloan, Monika Vainorius, Patrick M. Horne, Larry Michael, Meichen Dong, Donna M. Evon, Jodi B. Segal, David R. Nelson
Journal: Hepatology (2021)

Multiple direct-acting antiviral (DAA) regimens are available to treat HCV genotype 1 infection. However, comparative effectiveness from randomized controlled trials of DAA regimens is unavailable.
Prognostic Impact of Morphological Cellularity in Early Assessment Bone Marrow Biopsy after 7+3 Induction in Patients with Acute Myeloid Leukemia
Authors: Fahrettin Covut, Divya Gupta, Raisa Pinto, Nina Dambrosio, Najla H El Jurdi, Masumi Ueda, Leland Metheny, Brenda W. Cooper, Paolo Caimi, Ehsan Malek, Folashade Otegbeye, Marcos De Lima, Ben K. Tomlinson
Journal: Blood (2017)
急性白血病に対する非血縁ドナー骨髄非破壊的造血幹細胞移植後のドナーIFNL4遺伝子型と非再発死亡率の関連:後ろ向きコホート研究【JST・京大機械翻訳】
Authors: Gadalla Shahinaz M, Wang Youjin, Wang Tao, Onabajo Olusegun O, Banday A Rouf, Obajemu Adeola, Karaesman Ezgi, Sucheston-Campbell Lara, Hahn Theresa, Sees Jennifer A, Spellman Stephen R, Lee Stephanie J, Katki Hormuzd A, Prokunina-Olsson Ludmila
Journal: The Lancet Haematology (2020)
Is it safe to omit systematic biopsies in addition to targeted MRI-ultrasound fusion biopsies in biopsy naïve men suspected for prostate cancer?
Authors: N.G. Alkema, F.J.S. Hoogeveen, E. Cauberg, L.P.W. Witte, M.F. Boomsma, M. Van ’T Veer-Ten Kate, E. De Boer, A.M. Hoogland, M.H. Blanker, M.G. Steffens
Journal: European Urology (2021)
Abstract 9657: Association Between Endothelial Function Measured by Enclosed Zone Flow-mediated Vasodilation and Cardiovascular Risk Factors
Authors: Masato Kajikawa, Haruka Morimoto, Haruki Hashimoto, Shogo Matsui, Tatsuya Maruhashi, Shinji Kishimoto, Yuji Takaeko, Takayuki Yamaji, Takahiro Harada, Takayuki Hidaka, Farina M Yusoff, Yasuki Kihara, Toshio Tsuji, Yukihito Higashi
Journal: Circulation (2019)

Introduction: Previously, we developed a new device for automatic measurement of flow-mediated vasodilation (FMD) using an oscillometric method. The name of this device is enclosed zone flow-mediat...
Nanopore metagenomic sequencing of influenza virus directly from respiratory samples: diagnosis, drug resistance and nosocomial transmission, United Kingdom, 2018/19 influenza season
Authors: Yifei Xu, Kuiama Lewandowski, Louise O Downs, James Kavanagh, Thomas Hender, Sheila Lumley, Katie Jeffery, Dona Foster, Nicholas D Sanderson, Ali Vaughan, Marcus Morgan, Richard Vipond, Miles Carroll, Timothy Peto, Derrick Crook, A Sarah Walker, Philippa C Matthews, Steven T Pullan
Journal: Eurosurveillance (2021)

Background Influenza virus presents a considerable challenge to public health by causing seasonal epidemics and occasional pandemics. Nanopore metagenomic sequencing has the potential to be deployed for near-patient testing, providing rapid infection diagnosis, rationalising antimicrobial therapy, and supporting infection-control interventions. Aim To evaluate the applicability of this sequencing approach as a routine laboratory test for influenza in clinical settings. Methods We conducted Oxford Nanopore Technologies (Oxford, United Kingdom (UK)) metagenomic sequencing for 180 respiratory samples from a UK hospital during the 2018/19 influenza season, and compared results to routine molecular diagnostic standards (Xpert Xpress Flu/RSV assay; BioFire FilmArray Respiratory Panel 2 assay). We investigated drug resistance, genetic diversity, and nosocomial transmission using influenza sequence data. Results Compared to standard testing, Nanopore metagenomic sequencing was 83% (75/90) sensitive and 93% (84/90) specific for detecting influenza A viruses. Of 59 samples with haemagglutinin subtype determined, 40 were H1 and 19 H3. We identified an influenza A(H3N2) genome encoding the oseltamivir resistance S331R mutation in neuraminidase, potentially associated with an emerging distinct intra-subtype reassortant. Whole genome phylogeny refuted suspicions of a transmission cluster in a ward, but identified two other clusters that likely reflected nosocomial transmission, associated with a predominant community-circulating strain. We also detected other potentially pathogenic viruses and bacteria from the metagenome. Conclusion Nanopore metagenomic sequencing can detect the emergence of novel variants and drug resistance, providing timely insights into antimicrobial stewardship and vaccine design. Full genome generation can help investigate and manage nosocomial outbreaks.
Risk of bladder cancer death in patients younger than 50 with non-muscle-invasive and muscle-invasive bladder cancer
Authors: B. Russell, F. Leidberg, O. Hagberg, A. Ullén, K. Söderkvist, V. Ströck, F. Aljabery, T. Gårdmark, T. Jerlström, A. Sherif, L. Holmberg, R.T. Bryan, D. Enting, M. Van Hemelrijck
Journal: European Urology (2021)
Photobiomodulation Improves Memory in Mild Cognitive Impairment: Three Case Reports
Authors: Chan Agnes S, Lee TszLok, Sze Sophia, Hamblin Michael R
Journal: Alzheimers Disease & Dementia (2021)

Three patients (mean age = 62) received 18-sessions of PBM stimulation twice per week for nine weeks. Each patient was assessed with Rey- Osterrieth Complex Figure Test (Rey-O testing visual memory) and Hong Kong List Learning Test (HKLLT testing verbal memory), Clinical Dementia Rating Scale (CDR), Functional Activities Questionnaire (FAQ), Geriatric Anxiety Scale-10 Item Version (GAS-10) and Chinese Geriatric Depression Scale (CGDS) before and after PBM.
Abstract 1047: Dual targeting of CK2 and MTOR as a novel therapeutic approach for high-risk B-cell acute lymphoblastic leukemia
Authors: Chunhua Song, Zheng Ge, Yali Ding, Bihua Tan, Elanora Dovat, Yiping Yang, Chandrika Gowda, Sinisa Dovat
Journal: Cancer Research (2021)

Abstract Genomic defect and Casein Kinase II-mediated hyper-phosphorylation of Ikaros tumor suppressor cause the loss of function of Ikaros, and Ikaros dysfunction is characteristics of high-risk B-cell acute lymphoblastic leukemia (HR B-ALL) with poor prognosis. The increased activation of the PI3K/AKT/mTOR pathway is also observed in HR B-ALL and identifies mTOR as an attractive therapeutic target in HR B-ALL. Here, we report that Ikaros represses MTOR transcription and Ikaros' ability to repress MTOR in leukemia is impaired by oncogenic CK2 kinase. Treatment with the CK2 inhibitor, CX-4945, enhances Ikaros activity as a repressor of MTOR, resulting in reduced expression of MTOR in HR B-ALL. Thus, we designed a novel therapeutic approach that implements dual targeting of mTOR: direct inhibition of the mTOR protein (with rapamycin), in combination with Ikaros-mediated transcriptional repression of the MTOR gene (using the CK2 inhibitor, CX-4945). Combination treatment with rapamycin and CX-4945 shows synergistic therapeutic effects in vitro and in patient-derived xenografts from HR B-ALL. These data suggest that such therapy has the potential to reduce the death rate in HR B-ALL. The dual targeting of oncogene transcription, combined with inhibition of the corresponding oncoprotein provides a paradigm for a novel precision medicine approach for treating hematological malignancies. Citation Format: Chunhua Song, Zheng Ge, Yali Ding, Bihua Tan, Elanora Dovat, Yiping Yang, Chandrika Gowda, Sinisa Dovat. Dual targeting of CK2 and MTOR as a novel therapeutic approach for high-risk B-cell acute lymphoblastic leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1047.
Artificial intelligence 3D augmented reality guided biopsy during robotic prostatectomy: A new way to reduce the positive surgical margin rate
Authors: F. Porpiglia, E. Checcucci, D. Amparore, S. De Cillis, G. Volpi, F. Massa, E. Bollito, P. Piazzolla, A. Bellin, M. Manfredi, E. Vezzetti, C. Fiori
Journal: European Urology (2021)
Abstract 1820: Uncovering mechanisms of immune evasion in a novel immunogenic model of KRAS-mutant lung cancer
Authors: Jesse Boumelha, Sophie de Carné, Edurne Mugarza, Pablo Romero-Clavijo, Miriam Molina-Arcas, Julian Downward
Journal: Cancer Research (2021)

Abstract Oncogenic KRAS mutations drive tumourigenesis in 30% of non-small cell lung cancer (NSCLC). Despite much effort, targeted therapies that aim to directly inhibit signalling pathways downstream of KRAS have limited clinical benefits for NSCLC patients, but the recent approval of PD-1/PD-L1 antibodies has led to striking durable responses. However, only a fraction of patients respond and therefore a deeper understanding of the mechanisms that drive immune evasion are required in order to broaden the clinical efficacy of immunotherapy. Increasing evidence suggests that oncogenic signalling pathways greatly influence the tumour immune landscape to impair anti-tumour immune responses. We therefore aim to understand the mechanisms by which KRAS signalling mediates immune evasion in lung cancer. Current mouse models of KRAS-mutant lung cancer are poorly immunogenic, limiting investigations into tumour-immune interactions. To overcome this, we generated a novel transplantable KRAS-mutant lung cancer model, KPAR1.3, which triggers spontaneous anti-tumour immune responses and is sensitive to immune checkpoint blockade. To identify mechanisms of immune evasion we carried out an in vivo pooled CRISPR-Cas9 screen targeting 240 KRAS-regulated genes using this novel immunogenic model. This identified a number of genes that increased sensitivity or caused resistance to anti-tumour immune responses. As an alternative approach we utilised the recently developed class of mutant-specific KRAS-G12C inhibitors to assess the impact of inhibiting KRAS signalling on anti-tumour immune responses in KPAR1.3 tumours. KRAS-inhibition stimulated adaptive immunity in vivo, which contributed to the response of KPAR1.3 tumours in immune-competent mice. Together these data suggest that targeting KRAS, or KRAS-driven mechanisms of immune evasion, could broaden the clinical efficacy of immunotherapy in KRAS-mutant NSCLC. Citation Format: Jesse Boumelha, Sophie de Carné, Edurne Mugarza, Pablo Romero-Clavijo, Miriam Molina-Arcas, Julian Downward. Uncovering mechanisms of immune evasion in a novel immunogenic model of KRAS-mutant lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1820.