tbuckley/cabot-search huggingface dataset:
Identification of novel biomarkers to distinguish bradykinin‐mediated angioedema from mast cell‐/histamine‐mediated angioedema
Authors: Gesa Bindke, Manuela Gehring, Dorothea Wieczorek, Alexander Kapp, Timo Buhl, Bettina Wedi
Journal: Allergy (2021)

The pathophysiology of the underlying paroxysmal permeability disturbances in angioedema (AE) is not well understood.To identify clinical and laboratory parameters specific for a certain AE subtype, 40 AE patients were prospectively enrolled: 15 hereditary (HAE), 13 ACE-inhibitor induced (ACE-AE), and 12 mast cell-mediated without wheals in chronic spontaneous urticaria (CSU-AE). Ten healthy subjects served as controls. Serum levels of markers indicating activation of the ficolin-lectin pathway, of endothelial cells, or those indicating impairment of vascular integrity or inflammation were assessed by enzyme-linked immunosorbent assay.New routine clinical diagnostic criteria could not be identified, not even for distinguishing bradykinin-mediated (BK-) AE (ie, HAE and ACE-AE) from mast cell-/histamine-mediated CSU-AE. However, FAP-α and tPA were significantly increased in all AE compared to controls. In HAE, FAP- α, tPA, uPAR, pentraxin-3, Tie-2, sE-selectin, and VE-cadherin were significantly increased compared to controls. In HAE compared to CSU-AE and ACE-AE, sE-Selectin, Tie-2, and VE-Cadherin were significantly increased, whereas for Ang-2 the difference was significant compared to CSU-AE only. Tie-2 correlated strongly negatively with C4, C1-INH activity, and C1-INH function.This study is the first to compare HAE, ACE-AE, and CSU-AE. Although significance is limited by small sample size, Tie-2 was identified as a new promising biomarker candidate for HAE. FAP- α and tPA might serve as a marker for AE in general, whereas sE-selectin and Ang-2 were increased in BK-AE only. Our results add information to the role of endothelial dysfunction and serine proteases in different AE subtypes.
P30-6 A retrospective study of antiemetic therapies to prevent carboplatin-induced nausea and vomiting in lung cancer
Authors: Akinori Uesugi, Erina Takabe, Syota Hatano, Takashi Yoshida, Takaaki Kiuchi, Youichi Kudo, Takeshi Kawanobe, Ryoji Kato
Journal: Annals of Oncology (2021)
Mitigating Detrimental Influences of Ambient Air Collection of Bone Marrow By Hypoxic Collection Results in Detection of Functionally Enhanced Aged Mouse Hematopoiesis: Reflecting Stem Cell Expression Levels of CXCR4, CCR5 and ROS
Authors: Maegan Capitano, Scott Cooper, Bin Guo, Jing Zhang, Xinxin Huang, Qingchun Cai, Heather A. O'Leary, Hui Lin Chua, Artur Plett, Christie M. Orschell, Hal E. Broxmeyer
Journal: Blood (2017)
North American Practice-Based Recommendations for Transjugular Intrahepatic Portosystemic Shunts in Portal Hypertension
Authors: Justin R. Boike, Bartley G. Thornburg, Sumeet K. Asrani, Michael B. Fallon, Brett E. Fortune, Manhal J. Izzy, Elizabeth C. Verna, Juan G. Abraldes, Andrew S. Allegretti, Jasmohan S. Bajaj, Scott W. Biggins, Michael D. Darcy, Maryjane A. Farr, Khashayar Farsad, Guadalupe Garcia-Tsao, Shelley A. Hall, Caroline C. Jadlowiec, Michael J. Krowka, Jeanne Laberge, Edward W. Lee, David C. Mulligan, Mitra K. Nadim, Patrick G. Northup, Riad Salem, Joseph J. Shatzel, Cathryn J. Shaw, Douglas A. Simonetto, Jonathan Susman, K. Pallav Kolli, Lisa B. VanWagner
Journal: Clinical Gastroenterology and Hepatology (2021)

Complications of portal hypertension, including ascites, gastrointestinal bleeding, hepatic hydrothorax, and hepatic encephalopathy, are associated with significant morbidity and mortality. Despite few high-quality randomized controlled trials to guide therapeutic decisions, transjugular intrahepatic portosystemic shunt (TIPS) creation has emerged as a crucial therapeutic option to treat complications of portal hypertension. In North America, the decision to perform TIPS involves gastroenterologists, hepatologists, and interventional radiologists, but TIPS creation is performed by interventional radiologists. This is in contrast to other parts of the world where TIPS creation is performed primarily by hepatologists. Thus, the successful use of TIPS in North America is dependent on a multidisciplinary approach and technical expertise, so as to optimize outcomes. Recently, new procedural techniques, TIPS stent technology, and indications for TIPS have emerged. As a result, practices and outcomes vary greatly across institutions and significant knowledge gaps exist. In this consensus statement, the Advancing Liver Therapeutic Approaches group critically reviews the application of TIPS in the management of portal hypertension. Advancing Liver Therapeutic Approaches convened a multidisciplinary group of North American experts from hepatology, interventional radiology, transplant surgery, nephrology, cardiology, pulmonology, and hematology to critically review existing literature and develop practice-based recommendations for the use of TIPS in patients with any cause of portal hypertension in terms of candidate selection, procedural best practices and, post-TIPS management; and to develop areas of consensus for TIPS indications and the prevention of complications. Finally, future research directions are identified related to TIPS for the management of portal hypertension.
MO33-1 Trends in chemotherapy at our hospital and department under the COVID-19 pandemic
Authors: Akihiko Kageyama, Shinichiro Makino, An Ohigashi, Taichi Tamura, Yuka Morita, Shohei Nakamura, Yu Yagi, Yusuke Kanemasa, Tatsu Shimoyama, Yasushi Omuro
Journal: Annals of Oncology (2021)
MO4-4 Osimertinib is associated with type II cancer therapy-related cardiac dysfunction
Authors: Kei Kunimasa, Toru Oka, Satoshi Hara, Noriyuki Yamada, Satoshi Oizumi, Yoshihiro Miyashita, Hayato Kawachi, Takahisa Kawamura, Takako Inoue, Hanako Kuhara, Motohiro Tamiya, Kazumi Nishino, Takashi Matsunaga, Fumio Imamura, Masashi Fujita, Toru Kumagai
Journal: Annals of Oncology (2021)
Emerging therapies for relapsed/refractory multiple myeloma: CAR-T and beyond
Authors: Christopher T. Su, J. Christine Ye
Journal: Journal of Hematology & Oncology (2021)

The pace of innovation of multiple myeloma therapy in recent years is remarkable with the advent of monoclonal antibodies and the approval of novel agents with new mechanisms of action. Emerging therapies are on the horizon for clinical approval with significant implications in extending patient survival and advancing closer to the goal of a cure, especially in areas of immunotherapy such as chimeric antigen receptor T cells, bispecific T cell engager antibodies, antibody drug conjugates, newer generations of monoclonal antibodies, and small molecule inhibitor and modulators. This review provides an update of current myeloma therapeutics in active preclinical and early clinical development and discusses the mechanism of action of several classes of novel therapeutics.
事前曝露予防の候補を同定するための自動化HIV予測アルゴリズムの開発と検証:モデリング研究【JST・京大機械翻訳】
Authors: Krakower Douglas S, Gruber Susan, Hsu Katherine, Menchaca John T, Maro Judith C, Kruskal Benjamin A, Wilson Ira B, Mayer Kenneth H, Klompas Michael
Journal: The Lancet HIV (2019)
<i>QuickStats:</i> Percentage* of Adults Aged ≥18 Years with Diagnosed Chronic Obstructive Pulmonary Disease,† by Urbanization Level§ and Age Group — National Health Interview Survey, United States, 2019¶
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

In 2019, the percentage of adults aged â¥18 years with diagnosed chronic obstructive pulmonary disease (COPD) was higher among those living in nonmetropolitan areas (8%) than among those living in metropolitan areas (4%).
ATM/NEMO signaling modulates the expression of PD-L1 following docetaxel chemotherapy in prostate cancer
Authors: Zongren Wang, Xueling Zhang, Wuguo Li, Qiao Su, Zhaoyang Huang, Xinyao Zhang, Haiqi Chen, Chengqiang Mo, Bin Huang, Wei Ou, Junxing Chen, Guangyin Zhao, Lingwu Chen, Lan Shao
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The efficacy of docetaxel-based chemotherapy is limited by the development of drug resistance. Recent studies demonstrated the efficacy of anti-programmed death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) immunotherapies in metastatic prostate cancer. The ataxia telangiectasia mutation (ATM) protein plays a crucial role in maintaining genome stability and function of mitosis. Here, we aimed to determine whether PD-1/PD-L1 signaling contributes to the resistance to DTX and to elucidate the mechanism underlying DTX-induced PD-L1 expression. Methods In this retrospective study, PD-L1 expression was analyzed in 33 tumor tissue samples from prostate cancer patients. Prostate cell lines were used to perform functional assays and examine underlying mechanisms in vitro. A fully mouse prostate cancer model and a humanized chimeric mouse bearing human prostate tumors and peripheral blood mononuclear cells were used for in vivo assays. Results We have shown that DTX, a chemotherapeutic drug which causing microtubule interference, could significantly induce the expression of PD-L1 in prostate cancer cells. This effect is blocked by the inhibition of ATM, suggesting that it plays an essential role in PD-L1 expression upregulated by DTX. Mechanistic studies have shown that ATM activity in cancer cells enhances the stability of the NF-κB essential modulator (NEMO), which leading to an increase in the NF-κB activity and PD-L1 expression. Using the mouse model, it was further demonstrated that a combination of ATM and NEMO inhibitors along with DTX augmented the antitumor efficacy of chemotherapy, which are comparable to that of PD-L1 antibody. Conclusions Our findings have revealed that a previously unrecognized ATM-NEMO signaling which induced by DTX is capable of suppressing tumor immunity by activating the expression of PD-L1, suggesting that the ATM-NEMO-NF-κB axis can be exploited to restore the immune balance and overcome cancer resistance triggered by DTX. Graphic Abstract : supplementary file 1
Functional Evolution of a Bark Beetle Odorant Receptor Clade Detecting Monoterpenoids of Different Ecological Origins
Authors: Xiao-Qing Hou, Jothi Kumar Yuvaraj, Rebecca E Roberts, Dan-Dan Zhang, C Rikard Unelius, Christer Löfstedt, Martin N Andersson
Journal: Molecular Biology and Evolution (2021)

Insects detect odors using an array of odorant receptors (ORs), which may expand through gene duplication. How and which new functions may evolve among related ORs within a species remain poorly investigated. We addressed this question by functionally characterizing ORs from the Eurasian spruce bark beetle Ips typographus, in which physiological and behavioral responses to pheromones, volatiles from host and nonhost trees, and fungal symbionts are well described. In contrast, knowledge of OR function is restricted to two receptors detecting the pheromone compounds (S)-(-)-ipsenol (ItypOR46) and (R)-(-)-ipsdienol (ItypOR49). These receptors belong to an Ips-specific OR-lineage comprising seven ItypORs. To gain insight into the functional evolution of related ORs, we characterized the five remaining ORs in this clade using Xenopus oocytes. Two receptors responded primarily to the host tree monoterpenes (+)-3-carene (ItypOR25) and p-cymene (ItypOR27). Two receptors responded to oxygenated monoterpenoids produced in larger relative amounts by the beetle-associated fungi, with ItypOR23 specific for (+)-trans-(1R, 4S)-4-thujanol, and ItypOR29 responding to (+)-isopinocamphone and similar ketones. ItypOR28 responded to the pheromone E-myrcenol from the competitor Ips duplicatus. Overall, the OR responses match well with those of previously characterized olfactory sensory neuron classes except that neurons detecting E-myrcenol have not been identified. The characterized ORs are under strong purifying selection and demonstrate a shared functional property in that they all primarily respond to monoterpenoids. The variation in functional groups among OR ligands and their diverse ecological origins suggest that neofunctionalization has occurred early in the evolution of this OR-lineage following gene duplication.
Performance of the model for end-stage liver disease score for mortality prediction and the potential role of etiology
Authors: Gennaro D’Amico, Luigi Maruzzelli, Aldo Airoldi, Ioannis Petridis, Giulia Tosetti, Antonio Rampoldi, Mario D’Amico, Roberto Miraglia, Stella De Nicola, Vincenzo La Mura, Marco Solcia, Riccardo Volpes, Giovanni Perricone, Cristiano Sgrazzutti, Angelo Vanzulli, Massimo Primignani, Angelo Luca, Giuseppe Malizia, Alessandro Federico, Marcello Dallio, Angelo Andriulli, Angelo Iacobellis, Luigi Addario, Matteo Garcovich, Antonio Gasbarrini, Luchino Chessa, Francesco Salerno, Giulia Gobbo, Manuela Merli, Lorenzo Ridola, Gianluca Svegliati Baroni, Giuseppe Tarantino, Nicola Caporaso, Filomena Morisco, Pietro Pozzoni, Agostino Colli, Luca Saverio Belli
Journal: Journal of Hepatology (2021)
Abstract 8900: Urinary β2-Microglobulin-Creatinine ratio is Associated with High Risk in Chronic Heart Failure Patients
Authors: Yoichiro Otaki, Hiroki Takahashi, Tetsu Watanabe, Tetsuro Shishido, Akira Funayama, Shinpei Kadowaki, Taro Narumi, Shunsuke Netsu, Shintaro Honda, Hiromasa Hasegawa, Mitusnori Ishino, Satoshi Nishiyama, Takanori Arimoto, Takehiko Miyashita, Takuya Miyamoto, Isao Kubota
Journal: Circulation (2011)

Background It has been reported that renal dysfunction has strong association with clinical outcomes in chronic heart failure (CHF) patients. Recent study demonstrated that several urinary markers ...
Danse macabre on “freedom day”
Authors: Alison Shepherd
Journal: BMJ (2021)

Alberto Pezzali/AP/Shutterstock

Clubbers at London’s Piano Works mark the lifting of all remaining covid restrictions in England on 19 July. The nightclub was one of many venues across the country that opened for the first time since March 2020.

The UK is forecast to soon have more new SARS-CoV-2 …
Cross-reactive antibodies against human coronaviruses and the animal coronavirome suggest diagnostics for future zoonotic spillovers
Authors: Shelley Klompus, Sigal Leviatan, Thomas Vogl, Roei D. Mazor, Iris N. Kalka, Liat Stoler-Barak, Nachum Nathan, Ayelet Peres, Lihee Moss, Anastasia Godneva, Sharon Kagan Ben Tikva, Eilat Shinar, Hadas Cohen-Dvashi, Ronen Gabizon, Nir London, Ron Diskin, Gur Yaari, Adina Weinberger, Ziv Shulman, Eran Segal
Journal: Science Immunology (2021)

The spillover of animal coronaviruses (aCoVs) to humans has caused SARS, MERS, and COVID-19. While antibody responses displaying cross-reactivity between SARS-CoV-2 and seasonal/common cold human coronaviruses (hCoVs) have been reported, potential cross-reactivity with aCoVs and the diagnostic implications are incompletely understood. Here, we probed for antibody binding against all seven hCoVs and 49 aCoVs represented as 12,924 peptides within a phage-displayed antigen library. Antibody repertoires of 269 recovered COVID-19 patients showed distinct changes compared to 260 unexposed pre-pandemic controls, not limited to binding of SARS-CoV-2 antigens but including binding to antigens from hCoVs and aCoVs with shared motifs to SARS-CoV-2. We isolated broadly reactive monoclonal antibodies from recovered COVID-19 patients that bind a shared motif of SARS-CoV-2, hCoV-OC43, hCoV-HKU1, and several aCoVs, demonstrating that interspecies cross-reactivity can be mediated by a single immunoglobulin. Employing antibody binding data against the entire CoV antigen library allowed accurate discrimination of recovered COVID-19 patients from unexposed individuals by machine learning. Leaving out SARS-CoV-2 antigens and relying solely on antibody binding to other hCoVs and aCoVs achieved equally accurate detection of SARS-CoV-2 infection. The ability to detect SARS-CoV-2 infection without knowledge of its unique antigens solely from cross-reactive antibody responses against other hCoVs and aCoVs suggests a potential diagnostic strategy for the early stage of future pandemics. Creating regularly updated antigen libraries representing the animal coronavirome can provide the basis for a serological assay already poised to identify infected individuals following a future zoonotic transmission event.
Abstract 2073: Use of Diastolic Tissue Velocity and Standard Parameters to Assess Treatment Response in Subclinical Myocardial Disease - A Randomized Trial of Lifestyle Intervention in Type 2 Diabetes
Authors: Matthew D Hordern, Louise M Smith, Leanne Short, Melodie Downey, Johannes B Prins, Jeff S Coombes, Thomas H Marwick
Journal: Circulation (2007)

Background. Myocardial dysfunction is common in type 2 diabetes (T2DM), but the best markers of treatment response are undefined. We sought the effects of a 1 year lifestyle intervention (LI) on myocardial function and left ventricular (LV) characteristics, and to determine the predictors of this improvement. Methods. Pts with uncomplicated T2DM (223), no known cardiac disease and a negative stress echo were randomized into usual care (n=112) or LI groups (n=111). The LI involved individualized home-based training (150min/wk of moderate exercise) and caloric restriction. Myocardial function (diastolic (E′) tissue velocity, strain and strain rate), LV characteristics (EF, E/A, LVMI and E/E′), metabolic control (HbA 1c , blood glucose, insulin resistance (HOMA), BMI, fat mass) and VO 2max were assessed at baseline and follow-up in 159 pts (LI n=74) who remained in the study for 1 year. Results. Compared with usual care, LI was associated with significant (p&lt;0.05) increases in E′ but not in strain, strain rate, EF, E/A, LVMI and E/E′ (Table ). Changes in E′ tissue velocity were significantly correlated with baseline E′ (r=−0.59, p&lt;0.01), baseline metabolic status (BMI (r=0.23, p&lt;0.01), insulin (r=0.22, p&lt;0.01), HDL (r=−0.18, p&lt;0.03)) and metabolic improvement (BMI (r=−0.17, p&lt;0.04), insulin (r=−0.22, p&lt;0.01), HbA 1c (r=−0.24, p&lt;0.01) and HOMA (r=−0.24, p&lt;0.01)). Multivariate analysis revealed that age (beta=−0.33, p&lt;0.01), baseline E′ (beta=−0.68, p&lt;0.01) and changes in HbA 1c (beta=−0.21, p&lt;0.01) were independent predictors of changes in E′ and together accounted for 52% of the change in E′ (p&lt;0.01). Conclusions. Diastolic myocardial properties, but not systolic deformation or standard LV characteristics respond to a 1 year individualized lifestyle intervention in T2DM. Improved diastolic myocardial function were associated with poor metabolic and myocardial health at baseline and greater improvements in metabolism over the intervention period. Comparison between Intervention and Control Groups
Refining Convergent Rate Analysis with Topology in Mammalian Longevity and Marine Transitions
Authors: Stephen Treaster, Jacob M Daane, Matthew P Harris
Journal: Molecular Biology and Evolution (2021)

Abstract The quest to map the genetic foundations of phenotypes has been empowered by the modern diversity, quality, and availability of genomic resources. Despite these expanding resources, the abundance of variation within lineages makes it challenging to associate genetic change to specific phenotypes, without an a priori means of isolating the changes from background genomic variation. Evolution provides this means through convergence—that is, the shared variation that may result from replicate evolutionary experiments across independent trait occurrences. To leverage these opportunities, we developed TRACCER: Topologically Ranked Analysis of Convergence via Comparative Evolutionary Rates. Compared to current methods, this software empowers rate convergence analysis by factoring in topological relationships, because genetic variation between phylogenetically proximate trait changes is more likely to be facilitating the trait. Comparisons are performed not with singular branches, but with the complete paths to the most recent common ancestor for each pair of lineages. This ensures that comparisons represent a single context diverging over the same timeframe while obviating the problematic requirement of assigning ancestral states. We applied TRACCER to two case studies: mammalian transitions to marine environments, an unambiguous collection of traits that have independently evolved three times; and the evolution of mammalian longevity, a less delineated trait but with more instances to compare. By factoring in topology, TRACCER identifies highly significant, convergent genetic signals, with important incongruities and statistical resolution when compared to existing approaches. These improvements in sensitivity and specificity of convergence analysis generate refined targets for downstream validation and identification of genotype–phenotype relationships.
Mechanistic Insights of Empagliflozin in Nondiabetic Patients With HFrEF
Authors: Juan Antonio Requena-Ibáñez, Carlos G Santos-Gallego, Anderly Rodriguez-Cordero, Ariana P Vargas-Delgado, Donna Mancini, Samantha Sartori, Farah Atallah-Lajam, Chiara Giannarelli, Frank Macaluso, Anuradha Lala, Javier Sanz, Valentin Fuster, Juan José Badimon
Journal: JACC Heart Failure (2021)
Abstract 15620: Persistence and Survival of Rat Neonatal Cardiomyocytes after Injection into Infarcted Syngeneic Hearts Depends on their Purity and Is Improved by Co-Injection of Mesenchymal Bone-Marrow Cells
Authors: Benjamin Krausgrill, Simon Oeckenpöhler, Martina Maaβ, Martin Raths, Dennis Ladage, Marcel Halbach, Jürgen Hescheler, Jochen Müller-Ehmsen
Journal: Circulation (2011)

Purpose: For the effectiveness of cardiac cell replacement therapy, the number of persisting new contractile cells within the injured heart is crucial. In previous studies we found that persistence...
Tenofovir reduces the severity of COVID-19 infection in chronic hepatitis B patients
Authors: B. M. Munoz, M. Buti, I. F. Vazquez, M. H. Conde, V. B. Monterde, F. Diaz, R. Morillas, L. Garcia-Buey, E. Badia-Aranda, M. Miquel, A. Amador, S. Rodriguez-Tajes, L. R. Merino, A. Madejon, M. Garcia-Retortillo, J. Arenas, J. Cabezas, J. G. Santiago, C. Fernandez-Rodriguez, P. Cordero, M. Diago, A. Mancebo, A. Pardo, M. Rodriguez, E. Hoyas, J. J. Moreno, J. Turnes, M. A. Simon, C. Marcos-Fosch, J. L. C. Panero, R. Banares, S. Lens, J. Crespo, M. R. Gomez, E. Rodriguez-Santiago, S. M. Guillen, A. Albillos
Journal: Journal of Hepatology (2021)