tbuckley/cabot-search huggingface dataset:
Seasonal coronavirus–specific B cells with limited SARS-CoV-2 cross-reactivity dominate the IgG response in severe COVID-19
Authors: Muriel Aguilar-Bretones, Brenda M. Westerhuis, Matthijs P. Raadsen, Erwin de Bruin, Felicity D. Chandler, Nisreen M.A. Okba, Bart L. Haagmans, Thomas Langerak, Henrik Endeman, Johannes P.C. van den Akker, Diederik A.M.P.J. Gommers, Eric C.M. van Gorp, Corine H. GeurtsvanKessel, Rory D. de Vries, Ron A.M. Fouchier, Barry H.G. Rockx, Marion P.G. Koopmans, Gijsbert P. van Nierop
Journal: Journal of Clinical Investigation (2021)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019 (COVID-19). Little is known about the interplay between preexisting immunity to endemic seasonal coronaviruses and the development of a SARS-CoV-2-specific IgG response. We investigated the kinetics, breadth, magnitude, and level of cross-reactivity of IgG antibodies against SARS-CoV-2 and heterologous seasonal and epidemic coronaviruses at the clonal level in patients with mild or severe COVID-19 as well as in disease control patients. We assessed antibody reactivity to nucleocapsid and spike antigens and correlated this IgG response to SARS-CoV-2 neutralization. Patients with COVID-19 mounted a mostly type-specific SARS-CoV-2 response. Additionally, IgG clones directed against a seasonal coronavirus were boosted in patients with severe COVID-19. These boosted clones showed limited cross-reactivity and did not neutralize SARS-CoV-2. These findings indicate a boost of poorly protective CoV-specific antibodies in patients with COVID-19 that correlated with disease severity, revealing "original antigenic sin."
The Additive Diagnostic Value of Prostate-specific Membrane Antigen Positron Emission Tomography Computed Tomography to Multiparametric Magnetic Resonance Imaging Triage in the Diagnosis of Prostate Cancer (PRIMARY): A Prospective Multicentre Study
Authors: Louise Emmett, James Buteau, Nathan Papa, Daniel Moon, James Thompson, Matthew J. Roberts, Kris Rasiah, David A. Pattison, John Yaxley, Paul Thomas, Anthony C. Hutton, Shikha Agrawal, Amer Amin, Alexandar Blazevski, Venu Chalasani, Bao Ho, Andrew Nguyen, Victor Liu, Jonathan Lee, Gemma Sheehan-Dare, Raji Kooner, Geoff Coughlin, Lyn Chan, Thomas Cusick, Benjamin Namdarian, Jada Kapoor, Omar Alghazo, Henry H. Woo, Nathan Lawrentschuk, Declan Murphy, Michael S. Hofman, Phillip Stricker
Journal: European Urology (2021)
Cypher stent留置3年後に発症したVery late stent thrombosisによるAMIの1例
Authors: 真栄平直也, 嘉数敦, 知念敏也, 野村悠, 大庭影介, 嘉数朗, 嘉数真教, 玉城正弘, 新崎修, 新城哲治
Journal: Circulation (2008)
A transcriptome-wide association study of Alzheimer’s disease using prediction models of relevant tissues identifies novel candidate susceptibility genes
Authors: Yanfa Sun, Jingjing Zhu, Dan Zhou, Saranya Canchi, Chong Wu, Nancy J. Cox, Robert A. Rissman, Eric R. Gamazon, Lang Wu
Journal: Genome Medicine (2021)

Abstract Background Genome-wide association studies (GWAS) have identified over 56 susceptibility loci associated with Alzheimer’s disease (AD), but the genes responsible for these associations remain largely unknown. Methods We performed a large transcriptome-wide association study (TWAS) leveraging modified UTMOST (Unified Test for MOlecular SignaTures) prediction models of ten brain tissues that are potentially related to AD to discover novel AD genetic loci and putative target genes in 71,880 (proxy) cases and 383,378 (proxy) controls of European ancestry. Results We identified 53 genes with predicted expression associations with AD risk at Bonferroni correction threshold ( P value &lt; 3.38 × 10 −6 ). Based on fine-mapping analyses, 21 genes at nine loci showed strong support for being causal. Conclusions Our study provides new insights into the etiology and underlying genetic architecture of AD.
Oligonucleotide aptamers for pathogen detection and infectious disease control
Authors: Quanyuan Wan, Xiaohui Liu, Youli Zu
Journal: Theranostics (2021)

During an epidemic or pandemic, the primary task is to rapidly develop precise diagnostic approaches and effective therapeutics. Oligonucleotide aptamer-based pathogen detection assays and control therapeutics are promising, as aptamers that specifically recognize and block pathogens can be quickly developed and produced through simple chemical synthesis. This work reviews common aptamer-based diagnostic techniques for communicable diseases and summarizes currently available aptamers that target various pathogens, including the SARS-CoV-2 virus. Moreover, this review discusses how oligonucleotide aptamers might be leveraged to control pathogen propagation and improve host immune system responses. This review offers a comprehensive data source to the further develop aptamer-based diagnostics and therapeutics specific for infectious diseases.
The methods and advances of adaptive immune receptors repertoire sequencing
Authors: Hongmei Liu, Wenjing Pan, Congli Tang, Yujie Tang, Haijing Wu, Akihiko Yoshimura, Yan Deng, Nongyue He, Song Li
Journal: Theranostics (2021)

The adaptive immune response is a powerful tool, capable of recognizing, binding to, and neutralizing a vast number of internal and external threats via T or B lymphatic receptors with widespread sets of antigen specificities. The emergence of high-throughput sequencing technology and bioinformatics provides opportunities for research in the fields of life sciences and medicine. The analysis and annotation for immune repertoire data can reveal biologically meaningful information, including immune prediction, target antigens, and effective evaluation. Continuous improvements of the immunological repertoire sequencing methods and analysis tools will help to minimize the experimental and calculation errors and realize the immunological information to meet the clinical requirements. That said, the clinical application of adaptive immune repertoire sequencing requires appropriate experimental methods and standard analytical tools. At the population cell level, we can acquire the overview of cell groups, but the information about a single cell is not obtained accurately. The information that is ignored may be crucial for understanding the heterogeneity of each cell, gene expression and drug response. The combination of high-throughput sequencing and single-cell technology allows us to obtain single-cell information with low-cost and high-throughput. In this review, we summarized the current methods and progress in this area.
A Cost-Effectiveness Analysis for Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis Prophylaxis in the United States
Authors: Nikhil R. Thiruvengadam, Monica Saumoy, Yecheskel Schneider, Sara Attala, Joseph Triggs, Peter Lee, Michael L. Kochman
Journal: Clinical Gastroenterology and Hepatology (2021)
Sacubitril/Valsartan Adherence and Postdischarge Outcomes Among Patients Hospitalized for Heart Failure With Reduced Ejection Fraction
Authors: Anthony P Carnicelli, Zhen Li, Melissa A Greiner, Steven J Lippmann, Stephen J Greene, Robert J Mentz, N Chantelle Hardy, Vanessa Blumer, Xian Shen, Clyde W Yancy, Pamela N Peterson, Larry A Allen, Gregg C Fonarow, Emily C O'Brien
Journal: JACC Heart Failure (2021)
Clinical characteristics and outcomes of COVID-19 breakthrough infections among vaccinated patients with systemic autoimmune rheumatic diseases
Authors: Claire Cook, Naomi J Patel, Kristin M. D’Silva, Tiffany Y -T Hsu, Michael DiIorio, Lauren Prisco, Lily W Martin, Kathleen Vanni, Alessandra Zaccardelli, Derrick Todd, Jeffrey A Sparks, Zachary Scott Wallace
Journal: Annals of the Rheumatic Diseases (2021)

SARS-CoV-2 vaccines reduce the risk of COVID-19.1–3 However, some disease-modifying anti-rheumatic drugs (DMARDs), particularly glucocorticoids, methotrexate, mycophenolate mofetil and rituximab, may blunt the immunological response to COVID-19 vaccination.4 Little is known about the clinical efficacy of these vaccines at preventing COVID-19 infection in patients with systemic autoimmune rheumatic diseases (SARDs).

Mass General Brigham (MGB) is a large multicentre healthcare system in the Boston, Massachusetts, USA area. Patients with SARDs with a positive SARS-CoV-2 PCR or antigen test between 30 January 2020 and 30 July 2021 at MGB were identified using diagnostic billing codes or were referred by physicians, as previously described.5 From this cohort, we identified breakthrough infections in fully vaccinated patients, defined as a positive test ≥14 days after the final vaccine dose.6

Of 786 SARD patients with COVID-19, 340 occurred after the initial emergency use authorisation for COVID-19 vaccination in the USA. Of these, 16 (4.7%) were breakthrough infections (online supplemental figure 1). Among the breakthrough infections, 12 (75%) were female, 11 (69%) were white, the median age was 50 years and 12 (75%) had ≥1 comorbidity (table 1). The most common SARDs included rheumatoid arthritis (6, 38%), inflammatory myositis (3, 19%) and systemic lupus erythematosus (3, 19%). Rituximab (5, …
Commensal Clostridiales strains mediate effective anti-cancer immune response against solid tumors
Authors: Ana Montalban-Arques, Egle Katkeviciute, Philipp Busenhart, Anna Bircher, Jakob Wirbel, Georg Zeller, Yasser Morsy, Lubor Borsig, Jesus F. Glaus Garzon, Anne Müller, Isabelle C. Arnold, Mariela Artola-Boran, Michael Krauthammer, Anna Sintsova, Nicola Zamboni, Gabriel E. Leventhal, Laura Berchtold, Tomas de Wouters, Gerhard Rogler, Katharina Baebler, Marlene Schwarzfischer, Larissa Hering, Ivan Olivares-Rivas, Kirstin Atrott, Claudia Gottier, Silvia Lang, Onur Boyman, Ralph Fritsch, Markus G. Manz, Marianne R. Spalinger, Michael Scharl
Journal: Cell Host & Microbe (2021)
Risk for Post-Colonoscopy Irritable Bowel Syndrome in Patients With and Without Antibiotic Exposure: A Retrospective Cohort Study
Authors: Ravy K. Vajravelu, Jordan M. Shapiro, Josephine Ni, Shivani U. Thanawala, James D. Lewis, Hashem B. El-Serag
Journal: Clinical Gastroenterology and Hepatology (2021)
A novel and efficient tandem CD19- and CD22-directed CAR for B cell ALL
Authors: Samanta Romina Zanetti, Talia Velasco-Hernandez, Francisco Gutierrez-Agüera, Víctor M. Díaz, Paola Alejandra Romecín, Heleia Roca-Ho, Diego Sánchez-Martínez, Néstor Tirado, Matteo Libero Baroni, Paolo Petazzi, Raúl Torres-Ruiz, Oscar Molina, Alex Bataller, José Luis Fuster, Paola Ballerini, Manel Juan, Irmela Jeremias, Clara Bueno, Pablo Menéndez
Journal: Molecular Therapy (2021)

CD19-directed chimeric antigen receptor (CAR) T cells have yielded impressive response rates in refractory/relapse B cell acute lymphoblastic leukemia (B-ALL); however, most patients ultimately relapse due to poor CAR T cell persistence or resistance of either CD19+ or CD19- B-ALL clones. CD22 is a pan-B marker whose expression is maintained in both CD19+ and CD19- relapses. CD22-CAR T cells have been clinically used in B-ALL patients, although relapse also occurs. T cells engineered with a tandem CAR (Tan-CAR) containing in a single construct both CD19 and CD22 scFvs may be advantageous in achieving higher remission rates and/or preventing antigen loss. We have generated and functionally validated using cutting-edge assays a 4-1BB-based CD22/CD19 Tan-CAR using in-house-developed novel CD19 and CD22 scFvs. Tan-CAR-expressing T cells showed similar in vitro expansion to CD19-CAR T cells with no increase in tonic signaling. CRISPR-Cas9-edited B-ALL cells confirmed the bispecificity of the Tan-CAR. Tan-CAR was as efficient as CD19-CAR in vitro and in vivo using B-ALL cell lines, patient samples, and patient-derived xenografts (PDXs). Strikingly, the robust antileukemic activity of the Tan-CAR was slightly more effective in controlling the disease in long-term follow-up PDX models. This Tan-CAR construct warrants a clinical appraisal to test whether simultaneous targeting of CD19 and CD22 enhances leukemia eradication and reduces/delays relapse rates and antigen loss.
Immunogenicity and Safety of the BNT162b2 mRNA COVID-19 Vaccine Among Actively Treated Cancer Patients
Authors: Hagai Ligumsky, Esraa Safadi, Tal Etan, Noam Vaknin, Manuel Waller, Assaf Croll, Alla Nikolaevski-Berlin, Inbal Greenberg, Tami Halperin, Asaf Wasserman, Lior Galazan, Nadir Arber, Ido Wolf
Journal: JNCI Journal of the National Cancer Institute (2021)

Activity and safety of the SARS-CoV-2 BNT162b2 vaccine in actively treated patients with solid tumors is currently unknown.We conducted a retrospective study of 326 patients with solid tumors treated with anticancer medications to determine the proportion of cancer patients with immunogenicity against SARS-CoV-2 following 2 doses of the BNT162b2 vaccine. The control group comprised 164 vaccinated healthy adults. Anti-SARS-CoV-2 S immunoglobulin G antibodies were measured using a level greater than 50 AU/mL as a cutoff for seropositivity. Information on adverse effects was collected using a questionnaire. All statistical tests were 2-sided.Most patients (205, 62.9%) were treated with chemotherapy either alone or with additional therapy; 55 (16.9%) were treated with immune checkpoint inhibitors and 38 (11.7%) with targeted therapy alone; 28 (8.6%) received other combinations. The vaccine was well tolerated, and no severe side effects were reported. Among patients with cancer, 39 (11.9%) were seronegative compared with 5 (3.0%) of the control group (P = .001). Median immunoglobulin G titers were statistically significantly lower among patients with cancer compared with control (931 AU/mL vs 2817 AU/mL, P = .003). Seronegativity proportions were higher in the chemotherapy-treated group (n = 19; 18.8%) compared with the immune checkpoint inhibitor-treated patients (n = 5; 9.1%) and with those treated with targeted therapy (n = 1; 2.6%) (P = .02). Titers were also statistically significantly different among treatment types (P = .002).The BNT162b2 vaccine is safe and effective in actively treated patients with cancer. The relatively lower antibody titers and lower proportion of seropositive patients, especially among chemotherapy-treated patients, call for continuing the use of personal protective measures in these patients, even following vaccination.
Development of preclinical and clinical models for immune-related adverse events following checkpoint immunotherapy: a perspective from SITC and AACR
Authors: Nicholas L Bayless, Jeffrey A Bluestone, Samantha Bucktrout, Lisa H Butterfield, Elizabeth M Jaffee, Christian A Koch, Bart O Roep, Arlene H Sharpe, William J Murphy, Alexandra-Chloé Villani, Theresa L Walunas
Journal: Journal for ImmunoTherapy of Cancer (2021)

Recent advances in cancer immunotherapy have completely revolutionized cancer treatment strategies. Nonetheless, the increasing incidence of immune-related adverse events (irAEs) is now limiting the overall benefits of these treatments. irAEs are well-recognized side effects of some of the most effective cancer immunotherapy agents, including antibody blockade of the cytotoxic T-lymphocyte-associated protein 4 and programmed death protein 1/programmed-death ligand 1 pathways. To develop an action plan on the key elements needed to unravel and understand the key mechanisms driving irAEs, the Society for Immunotherapy for Cancer and the American Association for Cancer Research partnered to bring together research and clinical experts in cancer immunotherapy, autoimmunity, immune regulation, genetics and informatics who are investigating irAEs using animal models, clinical data and patient specimens to discuss current strategies and identify the critical next steps needed to create breakthroughs in our understanding of these toxicities. The genetic and environmental risk factors, immune cell subsets and other key immunological mediators and the unique clinical presentations of irAEs across the different organ systems were the foundation for identifying key opportunities and future directions described in this report. These include the pressing need for significantly improved preclinical model systems, broader collection of biospecimens with standardized collection and clinical annotation made available for research and integration of electronic health record and multiomic data with harmonized and standardized methods, definitions and terminologies to further our understanding of irAE pathogenesis. Based on these needs, this report makes a set of recommendations to advance our understanding of irAE mechanisms, which will be crucial to prevent their occurrence and improve their treatment.
包括的心臓リハビリテーション期間中のB型ナトリウム利尿ペプチド(BNP)の減少に関連する因子
Authors: Nikaido Akira, Oikawa Keiko, Okamoto Nami, Takikawa Michio, Kasai Takeaki, Kiyooka Takahiko, Hata Yoshiki
Journal: Circulation (2009)
Diagnostic yield of staging brain magnetic resonance imaging is low in Merkel cell carcinoma: A single-institution cohort study
Authors: Farees Saqlain, Sophia Z. Shalhout, Kevin S. Emerick, Howard L. Kaufman, Yen-Lin E. Chen, James C. Cusack, Kayla Wright, David Michael Miller
Journal: Journal of the American Academy of Dermatology (2021)
The role of fats in the transition to sustainable diets
Authors: Bojana Bajželj, Federica Laguzzi, Elin Röös
Journal: The Lancet Planetary Health (2021)

In comparison with protein, dietary fat receives little attention in the food system sustainability literature, although we calculate that the average consumption of fats in many populous regions of the world is below nutritional recommendations. Animal products are the major source of dietary fat, particularly in regions with excess fat consumption. We estimate that an additional 45 Mt of dietary fat per year need to be produced and consumed for the global population to reach recommended levels of fat consumption, and we review different strategies to fill this gap sustainably. These strategies include diverting oils currently used for energy production to human consumption, increasing palm oil and peanut oil yields while avoiding further deforestation, developing sustainable cropping systems for the production of rapeseed and soybean oils, increasing the consumption of whole soybeans and derived products, and expanding the use of animal fats already produced.
What would it take to die well? A systematic review of systematic reviews on the conditions for a good death
Authors: Mehreen Zaman, Sara Espinal-Arango, Ashita Mohapatra, Alejandro R Jadad
Journal: The Lancet Healthy Longevity (2021)

The medicalisation of life under the influence of health-care systems, focused on curing diseases, has made dying well challenging. This systematic review identifies common themes from published systematic reviews about the conditions for a good death as a means to guide decisions around this universal event. MEDLINE, Embase, APA PsycInfo, and AMED were searched for citations with "good death" or "dying well" in their titles on Sept 23, 2020, and complemented with backward reference and forward citation screening with Google Scholar. Articles published in peer-reviewed journals in any language were included. Articles that focused on the identification of conditions for a good death and described how primary studies were sought and selected were also included. Data on general characteristics, quality, and themes were extracted independently. 13 of 275 potentially eligible reviews were included. Common themes were dying at the preferred place, relief from pain and psychological distress, emotional support from loved ones, autonomous treatment decision making, avoidance of futile life-prolonging interventions and of being a burden to others, right to assisted suicide or euthanasia, effective communication with professionals, and performance of rituals. No reviews specified the meaning or timing of death, connected themes, or prioritised them. Vague jargon was often used to describe complex concepts. Most conditions for a good death could be offered to most dying people, without costly medical infrastructure or specialised knowledge. Efforts to describe these conditions clearly, to identify whether there are exceptions or missing items, and whether they apply in non-dominant settings (ie, outstide institutional, affluent, anglophone, and Christian settings) are needed.
Porphyromonas gingivalis infection promotes mitochondrial dysfunction through Drp1-dependent mitochondrial fission in endothelial cells
Authors: Tong Xu, Qin Dong, Yuxiao Luo, Yanqing Liu, Liang Gao, Yaping Pan, Dongmei Zhang
Journal: International Journal of Oral Science (2021)

Abstract Porphyromonas gingivalis ( P. gingivalis ), a key pathogen in periodontitis, has been shown to accelerate the progression of atherosclerosis (AS). However, the definite mechanisms remain elusive. Emerging evidence supports an association between mitochondrial dysfunction and AS. In our study, the impact of P. gingivalis on mitochondrial dysfunction and the potential mechanism were investigated. The mitochondrial morphology of EA.hy926 cells infected with P. gingivalis was assessed by transmission electron microscopy, mitochondrial staining, and quantitative analysis of the mitochondrial network. Fluorescence staining and flow cytometry analysis were performed to determine mitochondrial reactive oxygen species (mtROS) and mitochondrial membrane potential (MMP) levels. Cellular ATP production was examined by a luminescence assay kit. The expression of key fusion and fission proteins was evaluated by western blot and immunofluorescence. Mdivi-1, a specific Drp1 inhibitor, was used to elucidate the role of Drp1 in mitochondrial dysfunction. Our findings showed that P . gingivalis infection induced mitochondrial fragmentation, increased the mtROS levels, and decreased the MMP and ATP concentration in vascular endothelial cells. We observed upregulation of Drp1 (Ser616) phosphorylation and translocation of Drp1 to mitochondria. Mdivi-1 blocked the mitochondrial fragmentation and dysfunction induced by P . gingivalis . Collectively, these results revealed that P . gingivalis infection promoted mitochondrial fragmentation and dysfunction, which was dependent on Drp1. Mitochondrial dysfunction may represent the mechanism by which P . gingivalis exacerbates atherosclerotic lesions.