tbuckley/cabot-search huggingface dataset:
Mechanisms of Resistance to Noncovalent Bruton’s Tyrosine Kinase Inhibitors
Authors: Eric Wang, Xiaoli Mi, Meghan C. Thompson, Skye Montoya, Ryan Q. Notti, Jumana Afaghani, Benjamin H. Durham, Alex Penson, Matthew T. Witkowski, Sydney X. Lu, Jessie Bourcier, Simon J. Hogg, Caroline Erickson, Dan Cui, Hana Cho, Michael Singer, Tulasigeri M. Totiger, Sana Chaudhry, Mark Geyer, Alvaro Alencar, Adam J. Linley, M. Lia Palomba, Catherine C. Coombs, Jae H. Park, Andrew Zelenetz, Lindsey Roeker, Mary Rosendahl, Donald E. Tsai, Kevin Ebata, Barbara Brandhuber, David M. Hyman, Iannis Aifantis, Anthony Mato, Justin Taylor, Omar Abdel-Wahab
Journal: New England Journal of Medicine (2022)

Covalent (irreversible) Bruton's tyrosine kinase (BTK) inhibitors have transformed the treatment of multiple B-cell cancers, especially chronic lymphocytic leukemia (CLL). However, resistance can arise through multiple mechanisms, including acquired mutations in BTK at residue C481, the binding site of covalent BTK inhibitors. Noncovalent (reversible) BTK inhibitors overcome this mechanism and other sources of resistance, but the mechanisms of resistance to these therapies are currently not well understood.
Non-AUG translation initiation in mammals
Authors: Dmitry E. Andreev, Gary Loughran, Alla D. Fedorova, Maria S. Mikhaylova, Ivan N. Shatsky, Pavel V. Baranov
Journal: Genome biology (2022)

Abstract Recent proteogenomic studies revealed extensive translation outside of annotated protein coding regions, such as non-coding RNAs and untranslated regions of mRNAs. This non-canonical translation is largely due to start codon plurality within the same RNA. This plurality is often due to the failure of some scanning ribosomes to recognize potential start codons leading to initiation downstream—a process termed leaky scanning. Codons other than AUG (non-AUG) are particularly leaky due to their inefficiency. Here we discuss our current understanding of non-AUG initiation. We argue for a near-ubiquitous role of non-AUG initiation in shaping the dynamic composition of mammalian proteomes.
Multiple colony antifungal susceptibility testing detects polyresistance in clinical Candida cultures: a European Confederation of Medical Mycology excellence centers study
Authors: Miriam A. Knoll, Nina Lackner, Hanno Ulmer, Eldina Samardzic, Joerg Steinmann, Robert Krause, Hedda L. Verhasselt, Peter-Michael Rath, Frieder Fuchs, Philipp Koehler, Blandine Denis, Samia Hamane, Alexandre Alanio, Cornelia Lass-Flörl
Journal: Clinical Microbiology and Infection (2022)
Location of Aortic Enlargement and Risk of Type A Dissection at Smaller Diameters
Authors: Asvin M. Ganapathi, David N. Ranney, Mark D. Peterson, Mark E. Lindsay, Himanshu J. Patel, Reed E. Pyeritz, Santi Trimarchi, Stuart Hutchison, Kevin M. Harris, Kevin L. Greason, Takeyoshi Ota, Daniel G. Montgomery, Christoph A. Nienaber, Kim A. Eagle, Eric M. Isselbacher, G. Chad Hughes
Journal: Journal of the American College of Cardiology (2022)
Reaching a consensus on the definition of “difficult” cholecystectomy among Spanish experts. A Delphi project. A qualitative study
Authors: Alba Manuel-Vázquez, Raquel Latorre-Fragua, Cándido Alcázar, Paola Melgar Requena, Roberto de la Plaza, Gerardo Blanco Fernández, Mario Serradilla-Martín, J.M. Ramia, Martín Bailón Cudrado, Juan Luis Blas Laina, Federico Castillo Suescún, Ángel Cuadrado García, Estaban Cugat Andorrá, Daniel Díaz Gómez, David Fernández Luengas, Amador García Ruiz de Gordejuela, Miguel Ángel Gómez Bravo, Santiago López Ben, Alfonso Mansilla Roselló, Pablo Martí Cruchaga, David Martínez Cecilia, Alberto Martínez Isla, Aleix Martínez Pérez, Isabel Mora Oliver, Mikel Prieto, Salvador Morales Conde, Carlos Moreno, Irene Ortega, Paola Fabiano, Antonio Picardo, Manuel Planells Roig, César Ramírez Plaza, Fernando Rotellar Sastre, Santiago Azagra, Ramón Villalonga Puy, Jesús María del Villar Moral, Yolanda Quijano
Journal: International Journal of Surgery (2022)
Melatonin ameliorates tau-related pathology via the miR-504-3p and CDK5 axis in Alzheimer’s disease
Authors: Dongmei Chen, Guihua Lan, Ruomeng Li, Yingxue Mei, Xindong Shui, Xi Gu, Long Wang, Tao Zhang, Chen-Ling Gan, Yongfang Xia, Li Hu, Yuan Tian, Mi Zhang, Tae Ho Lee
Journal: Translational Neurodegeneration (2022)

Abstract Background Intracellular accumulation of the microtubule-associated protein tau and its hyperphosphorylated forms is a key neuropathological feature of Alzheimer’s disease (AD). Melatonin has been shown to prevent tau hyperphosphorylation in cellular and animal models. However, the molecular mechanisms by which melatonin attenuates tau hyperphosphorylation and tau-related pathologies are not fully understood. Methods Immunofluorescence, immunoblotting analysis and thioflavin-S staining were employed to examine the effects of early and late treatment of melatonin on tau-related pathology in hTau mice, in which nonmutated human tau is overexpressed on a mouse tau knockout background. High-throughput microRNA (miRNA) sequencing, quantitative RT-PCR, luciferase reporter assay and immunoblotting analysis were performed to determine the molecular mechanism. Results We found that both early and late treatment of melatonin efficiently decreased the phosphorylation of soluble and insoluble tau at sites related to AD. Moreover, melatonin significantly reduced the number of neurofibrillary tangles (NFTs) and attenuated neuronal loss in the cortex and hippocampus. Furthermore, using miRNA microarray analysis, we found that miR-504-3p expression was upregulated by melatonin in the hTau mice. The administration of miR-504-3p mimics dramatically decreased tau phosphorylation by targeting p39, an activator of the well-known tau kinase cyclin-dependent kinase 5 (CDK5). Compared with miR-504-3p mimics alone, co-treatment with miR-504-3p mimics and p39 failed to reduce tau hyperphosphorylation. Conclusions Our results suggest for the first time that melatonin alleviates tau-related pathologies through upregulation of miR-504-3p expression by targeting the p39/CDK5 axis and provide novel insights into AD treatment strategies.
Anticoagulation for Percutaneous Ventricular Assist Device-Supported Cardiogenic Shock
Authors: Christophe Vandenbriele, Deepa J. Arachchillage, Pascal Frederiks, Gennaro Giustino, Diana A. Gorog, Mario Gramegna, Stefan Janssens, Bart Meyns, Amin Polzin, Mara Scandroglio, Benedikt Schrage, Gregg W. Stone, Guido Tavazzi, Thomas Vanassche, Pascal Vranckx, Dirk Westermann, Susanna Price, Alaide Chieffo
Journal: Journal of the American College of Cardiology (2022)

Interest in the use of mechanical circulatory support for patients presenting with cardiogenic shock is growing rapidly. The Impella (Abiomed Inc), a microaxial, continuous-flow, short-term, ventricular assist device (VAD), requires meticulous postimplantation management. Because systemic anticoagulation is needed to prevent pump thrombosis, patients are exposed to increased bleeding risk, further aggravated by sepsis, thrombocytopenia, and high shear stress–induced acquired von Willebrand syndrome. The precarious balance between bleeding and thrombosis in percutaneous VAD–supported cardiogenic shock patients is often the main reason that patient outcomes are jeopardized, and there is a lack of data addressing optimal anticoagulation management strategies during percutaneous VAD support. Here, we present a parallel anti-Factor Xa/activated partial thromboplastin time-guided anticoagulation algorithm and discuss pitfalls of heparin monitoring in critically ill patients. This review will guide physicians toward a more standardized (anti)coagulation approach to tackle device-related morbidity and mortality in this critically ill patient group.
Poultry exposure and environmental protection against asthma in rural children
Authors: Yuhan Xing, Maggie H. Wang, Ting‐Fan Leung, Chun‐Kwok Wong, Marjut Roponen, Bianca Schaub, Jing Li, Gary W. K. Wong
Journal: Allergy (2022)

Abstract Background Asthma is one of the most common chronic diseases in childhood, and the prevalence has been increasing over the past few decades. One of the most consistent epidemiological findings is that children living in a farming or rural environment are protected from development of asthma and allergies, but the protective factors in rural China are not clear. Methods A community‐based, cross‐sectional epidemiological study was performed in a total of 17,587 children aged 5–8 years, 3435 from Hong Kong (urban) and 14,152 from Conghua (rural county in southern China). Asthma and allergic symptoms as well as environmental exposures were ascertained by using a standardized and validated questionnaire. Results The prevalence of current wheeze was significantly lower in rural Conghua than that of urban Hong Kong (1.7% vs. 7.7%, p &lt; 0.001). A lower rate of asthma ever was also reported in rural children compared with their urban counterparts (2.5% vs. 5.3%, p &lt; 0.001). After adjusting for confounding factors, exposure to agricultural farming (adjusted odds ratio 0.74, 95% confidence interval: 0.56–0.97) and poultry (0.75, 0.59–0.96) were the most important factors associated with the asthma‐protective effect in the rural area. Further propensity score‐adjusted analysis indicated that such protection conferred by living in the rural environment was mainly attributable to poultry exposure. Conclusions We confirmed that the prevalence of asthma and atopic disorders was significantly lower in rural children when compared with their urban peers. Exposure to poultry and agricultural farming are the most important factors associated with asthma protection in the rural area.
Clonal Hematopoiesis Is Associated with Increased Risk of Severe Neurotoxicity in Axicabtagene Ciloleucel Therapy of Large B-Cell Lymphoma
Authors: Neeraj Y. Saini, David M. Swoboda, Uri Greenbaum, Junsheng Ma, Romil D. Patel, Kartik Devashish, Kaberi Das, Mark R. Tanner, Paolo Strati, Ranjit Nair, Luis Fayad, Sairah Ahmed, Hun Ju Lee, Swaminathan P. Iyer, Raphael Steiner, Nitin Jain, Loretta Nastoupil, Sanam Loghavi, Guilin Tang, Roland L. Bassett, Preetesh Jain, Michael Wang, Jason R. Westin, Michael R. Green, David A. Sallman, Eric Padron, Marco L. Davila, Frederick L. Locke, Richard E. Champlin, Guillermo Garcia-Manero, Elizabeth J. Shpall, Partow Kebriaei, Christopher R. Flowers, Michael D. Jain, Feng Wang, Andrew P. Futreal, Nancy Gillis, Sattva S. Neelapu, Koichi Takahashi
Journal: Blood Cancer Discovery (2022)

Abstract To explore the role of clonal hematopoiesis (CH) in chimeric antigen receptor (CAR) T-cell therapy outcomes, we performed targeted deep sequencing on buffy coats collected during the 21 days before lymphodepleting chemotherapy from 114 large B-cell lymphoma patients treated with anti-CD19 CAR T cells. We detected CH in 42 (36.8%) pretreatment samples, most frequently in PPM1D (19/114) and TP53 (13/114) genes. Grade ≥3 immune effector cell-associated neurotoxicity syndrome (ICANS) incidence was higher in CH-positive patients than CH-negative patients (45.2% vs. 25.0%, P = 0.038). Higher toxicities with CH were primarily associated with DNMT3A, TET2, and ASXL1 genes (DTA mutations). Grade ≥3 ICANS (58.9% vs. 25%, P = 0.02) and ≥3 cytokine release syndrome (17.7% vs. 4.2%, P = 0.08) incidences were higher in DTA-positive than in CH-negative patients. The estimated 24-month cumulative incidence of therapy-related myeloid neoplasms after CAR T-cell therapy was higher in CH-positive than CH-negative patients [19% (95% CI, 5.5–38.7) vs. 4.2% (95% CI, 0.3–18.4), P = 0.028]. Significance: Our study reveals that CH mutations, especially those associated with inflammation (DNMT3A, TET2, and ASXL1), are associated with severe-grade neurotoxicities in lymphoma patients receiving anti-CD19 CAR T-cell therapy. Further studies to investigate the mechanisms and interventions to improve toxicities in the context of CH are warranted. See related content by Uslu and June, p. 382. This article is highlighted in the In This Issue feature, p. 369
Corrigendum to ‘Population-level estimates of hepatitis C reinfection post scale-up of direct-acting antivirals among people who inject drugs’ [J Hepatol 76 (2022) 549–557]
Authors: Alan Yeung, Norah E. Palmateer, John F. Dillon, Scott A. McDonald, Shanley Smith, Stephen Barclay, Peter C. Hayes, Rory N. Gunson, Kate Templeton, David J. Goldberg, Matthew Hickman, Sharon J. Hutchinson
Journal: Journal of Hepatology (2022)
International consensus definition of disease flare in hidradenitis suppurativa
Authors: Tessa M. LeWitt, Athena Mammis-Gierbolini, Michaela Parnell, Akua Sarfo, So Yeon Paek, Farida Benhadou, Véronique del Marmol, Jennifer L. Hsiao, Joslyn Kirby, Steven Daveluy
Journal: British Journal of Dermatology (2022)

Retrofit and design of thermal cladding systems provide an opportunity to improve the acoustic properties of a building.However, the complexity of the calculation process to predict sound insulation improvement may inhibit rather than encourage novelty and innovation.This paper investigates whether it is realistic to calculate the frequency dependant sound insulation improvement due to modern thermal insulation wall lining systems with just a few input parameters.The calculation procedure is tested using measured results for one external thermal insulation composite system (ETICS) and three curtain wall systems.The accuracy of the procedure is examined using three factors: (1) precision of the measurement, (2) variation of some of the basic parameters of the calculation procedure, and (3) an estimation of the standard error of the calculation.For the ETICS, agreement within <6.0 dB is achieved across much of the frequency range and the trend of the extended dip due to the spring-mass action of the panel is corroborated.The case for using this methodology on curtain wall systems is adequate, however, the trend of calculated results is mostly outside of the 95% confidence limits of the measured results.Possible reasons for this include lack of airtightness of all curtain wall systems and additional transmission due to radiation into and out of the cavity, neither of which are included in the model.The assumption of radiating points or lines, rather than a radiating surface involving the whole panel, gave better agreement at high frequencies for three of the four measured systems (f ≥ 2500 Hz).
An activation to memory differentiation trajectory of tumor-infiltrating lymphocytes informs metastatic melanoma outcomes
Authors: Abhinav Jaiswal, Akanksha Verma, Ruth Dannenfelser, Marit Melssen, Itay Tirosh, Benjamin Izar, Tae-Gyun Kim, Christopher J Nirschl, K Sanjana P Devi, Walter C Olson, Craig L Slingluff, Victor H Engelhard, Levi Garraway, Aviv Regev, Kira Minkis, Charles H Yoon, Olga Troyanskaya, Olivier Elemento, Mayte Suárez-Fariñas, Niroshana Anandasabapathy
Journal: Cancer Cell (2022)
Reappraisal of sepsis-3 and CLIF-SOFA as predictors of mortality in patients with cirrhosis and infection presenting to the emergency department: A multicenter study
Authors: Ji Hyun Kim, Baek Gyu Jun, Minjong Lee, Hye Ah Lee, Tae Suk Kim, Jeong Won Heo, Da Hye Moon, Seong Hee Kang, Ki Tae Suk, Moon Young Kim, Young Don Kim, Gab Jin Cheon, Soon Koo Baik, Dong Joon Kim, Dae Hee Choi
Journal: Clinical and Molecular Hepatology (2022)

Background/Aims: Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) have been advocated to be used in defining sepsis in the general population. We aimed to compare the Sepsis-3 criteria and Chronic Liver Failure-SOFA (CLIF-SOFA) scores as predictors of in-hospital mortality in cirrhotic patients admitted to the emergency department (ED) for infections.Methods: A total of 1,622 cirrhosis patients admitted at the ED for infections were assessed retrospectively. We analyzed their demographic, laboratory, and microbiological data upon diagnosis of the infection. The primary endpoint was inhospital mortality rate. The predictive performances of baseline CLIF-SOFA, Sepsis-3, and qSOFA scores for in-hospital mortality were evaluated.Results: The CLIF-SOFA score proved to be significantly better in predicting in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.80; 95% confidence interval [CI], 0.78–0.82) than the Sepsis-3 (AUROC, 0.75; 95% CI, 0.72–0.77, &lt;i&gt;P&lt;/i&gt;&lt;0.001) and qSOFA (AUROC, 0.67; 95% CI, 0.64–0.70; &lt;i&gt;P&lt;/i&gt;&lt;0.001) score. The CLIF-SOFA, CLIF-C-AD scores, Sepsis-3 criteria, septic shock, and qSOFA positivity were significantly associated with in-hospital mortality (adjusted hazard ratio [aHR], 1.24; 95% CI, 1.19–1.28; aHR, 1.13; 95% CI, 1.09–1.17; aHR, 1.19; 95% CI, 1.15–1.24; aHR, 1.88; 95% CI, 1.42–2.48; aHR, 2.06; 95% CI, 1.55–2.72; respectively; all &lt;i&gt;P&lt;/i&gt;&lt;0.001). For CLIF-SOFA scores ≥6, in-hospital mortality was &gt;10%; this is the cutoff point for the definition of sepsis.Conclusions: Among cirrhosis patients presenting with infections at the ED, CLIF-SOFA scores showed a better predictive performance for mortality than both Sepsis-3 criteria and qSOFA scores, and can be a useful tool of risk stratification in cirrhotic patients requiring timely intervention for infection.
A new paradigm for diagnosis of neurodegenerative diseases: peripheral exosomes of brain origin
Authors: Neelam Younas, Leticia Camila Fernandez Flores, Franziska Hopfner, Günter U. Höglinger, Inga Zerr
Journal: Translational Neurodegeneration (2022)

Neurodegenerative diseases are a heterogeneous group of maladies, characterized by progressive loss of neurons. These diseases involve an intricate pattern of cross-talk between different types of cells to maintain specific signaling pathways. A component of such intercellular cross-talk is the exchange of various types of extracellular vesicles (EVs). Exosomes are a subset of EVs, which are increasingly being known for the role they play in the pathogenesis and progression of neurodegenerative diseases, e.g., synucleinopathies and tauopathies. The ability of the central nervous system exosomes to cross the blood-brain barrier into blood has generated enthusiasm in their study as potential biomarkers. However, the lack of standardized, efficient, and ultra-sensitive methods for the isolation and detection of brain-derived exosomes has hampered the development of effective biomarkers. Exosomes mirror heterogeneous biological changes that occur during the progression of these incurable illnesses, potentially offering a more comprehensive outlook of neurodegenerative disease diagnosis, progression and treatment. In this review, we aim to discuss the challenges and opportunities of peripheral biofluid-based brain-exosomes in the diagnosis and biomarker discovery of Alzheimer's and Parkinson's diseases. In the later part, we discuss the traditional and emerging methods used for the isolation of exosomes and compare their advantages and disadvantages in clinical settings.
Abstract 12911: Has Low Attenuation Plaque Volume in Coronary Computed Tomographic Angiography an Incremental Value For Prediction of Cardiac Events?
Authors: Martin Hadamitzky, Christin Jähnichen, Tanja Meyer, Franziska Hein, Bernhard Bischoff, Bettina Gramer, Stefan Martinoff, Albert Schömig, Jörg Hausleiter
Journal: Circulation (2010)

Background: Coronary plaques with low attenuation in coronary computed tomographic angiography (CCTA) are supposed to be indicative of vulnerable plaques and to be particularly prone to plaque rupt...
Cancer in sub-Saharan Africa: a Lancet Oncology Commission
Authors: Wilfred Ngwa, Beatrice W Addai, Isaac Adewole, Victoria Ainsworth, James Alaro, Olusegun I Alatise, Zipporah Ali, Benjamin O Anderson, Rose Anorlu, Stephen Avery, Prebo Barango, Noella Bih, Christopher M Booth, Otis W Brawley, Jean-Marie Dangou, Lynette Denny, Jennifer Dent, Shekinah N C Elmore, Ahmed Elzawawy, Diane Gashumba, Jennifer Geel, Katy Graef, Sumit Gupta, Serigne-Magueye Gueye, Nazik Hammad, Laila Hessissen, Andre M Ilbawi, Joyce Kambugu, Zisis Kozlakidis, Simon Manga, Lize Maree, Sulma I Mohammed, Susan Msadabwe, Miriam Mutebi, Annet Nakaganda, Ntokozo Ndlovu, Kingsley Ndoh, Jerry Ndumbalo, Mamsau Ngoma, Twalib Ngoma, Christian Ntizimira, Timothy R Rebbeck, Lorna Renner, Anya Romanoff, Fidel Rubagumya, Shahin Sayed, Shivani Sud, Hannah Simonds, Richard Sullivan, William Swanson, Verna Vanderpuye, Boateng Wiafe, David Kerr
Journal: The Lancet Oncology (2022)
Beyond the Cover—Children’s Books as Tools for Positive Social Identity Formation
Authors: Jasmyne Jackson, Anthony Mell
Journal: JAMA Pediatrics (2022)

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Reply to Alan J. Yaghoubian, Jonathan A. Khusid, and Mantu Gupta’s Letter to the Editor re: Øyvind Ulvik, Mathias Sørstrand Æsøy, Patrick Juliebø-Jones, Peder Gjengstø, Christian Beisland. Thulium Fibre Laser Versus Holmium:YAG for Ureteroscopic Lithotripsy: Outcomes from a Prospective Randomised Clinical Trial. Eur Urol. 2022;82:73–9
Authors: Øyvind Ulvik, Mathias Sørstrand Æsøy, Patrick Juliebø-Jones, Peder Gjengstø, Christian Beisland
Journal: European Urology (2022)
Disinfection By-Products in Drinking Water and Bladder Cancer: Evaluation of Risk Modification by Common Genetic Polymorphisms in Two Case–Control Studies
Authors: Laura E. Beane Freeman, Manolis Kogevinas, Kenneth P. Cantor, Cristina M. Villanueva, Ludmila Prokunina-Olsson, Oscar Florez-Vargas, Jonine D. Figueroa, Mary H. Ward, Stella Koutros, Dalsu Baris, Montserrat Garcia-Closas, Molly Schwenn, Allison Johnson, Consol Serra, Adonina Tardon, Reina Garcia-Closas, Alfredo Carrato, Nuria Malats, Margaret R. Karagas, Nathaniel Rothman, Debra T. Silverman
Journal: Environmental Health Perspectives (2022)

By-products are formed when disinfectants react with organic matter in source water. The most common class of disinfection by-products, trihalomethanes (THMs), have been linked to bladder cancer. Several studies have shown exposure-response associations with THMs in drinking water and bladder cancer risk. Few epidemiologic studies have evaluated gene-environment interactions for total THMs (TTHMs) with known bladder cancer susceptibility variants.