tbuckley/cabot-search huggingface dataset:
Sex Differences in the Progression of Aortic Valve Calcification and Clinical Outcomes
Authors: Lionel Tastet, Mylène Shen, Romain Capoulade, Marie Arsenault, Élisabeth Bédard, Julien Ternacle, Erwan Salaun, Nancy Côté, Philippe Pibarot, Marie-Annick Clavel
Journal: JACC. Cardiovascular imaging (2022)
Four-week omega-3 polyunsaturated fatty acids supplementation for liver left lateral section volume reduction in individuals with morbid obesity undergoing bariatric surgery: A double blind, multicenter, randomized placebo-controlled trial
Authors: Antonio Iannelli, Eric Fontas, Laurence Grec, David Nocca, Maud Robert, Luigi Schiavo, Anne-Sophie Schneck
Journal: International Journal of Surgery (2022)
TCTAP C-053 A Challenging Right Coronary Artery Chronic Total Occlusion Required Hybrid Approach and Multiple Troubleshooting to Achieve Success
Authors: Hou Tee Lu, Heng Shee Kim, Adelyn Nisha Henry, Chu Zhen Quek, Yu Ying Ong, Azrina Abdul Kadir
Journal: Journal of the American College of Cardiology (2022)
Reprogramming the tumor microenvironment by genome editing for precision cancer therapy
Authors: Ke Liu, Jia-Jia Cui, Yan Zhan, Qian-Ying Ouyang, Qi-Si Lu, Dong-Hua Yang, Xiang-Ping Li, Ji-Ye Yin
Journal: Molecular Cancer (2022)

The tumor microenvironment (TME) is essential for immune escape by tumor cells. It plays essential roles in tumor development and metastasis. The clinical outcomes of tumors are often closely related to individual differences in the patient TME. Therefore, reprogramming TME cells and their intercellular communication is an attractive and promising strategy for cancer therapy. TME cells consist of immune and nonimmune cells. These cells need to be manipulated precisely and safely to improve cancer therapy. Furthermore, it is encouraging that this field has rapidly developed in recent years with the advent and development of gene editing technologies. In this review, we briefly introduce gene editing technologies and systematically summarize their applications in the TME for precision cancer therapy, including the reprogramming of TME cells and their intercellular communication. TME cell reprogramming can regulate cell differentiation, proliferation, and function. Moreover, reprogramming the intercellular communication of TME cells can optimize immune infiltration and the specific recognition of tumor cells by immune cells. Thus, gene editing will pave the way for further breakthroughs in precision cancer therapy.
Two sides of the same coin: Protective versus pathogenic CD4 <sup>+</sup> resident memory T cells
Authors: Anna E. Oja, René A. W. van Lier, Pleun Hombrink
Journal: Science Immunology (2022)

The ability of the adaptive immune system to form memory is key to providing protection against secondary infections. Resident memory T cells (TRM) are specialized T cell populations that reside within tissue sites where they await reencounter with their cognate antigen. TRM are distinct from circulating memory cells, including central and effector memory T cells, both functionally and transcriptionally. Since the discovery of TRM, most research has focused on CD8+ TRM, despite that CD4+ TRM are also abundant in most tissues. In the past few years, more evidence has emerged that CD4+ TRM can contribute both protective and pathogenic roles in disease. A complexity inherent to the CD4+ TRM field is the ability of CD4+ T cells to polarize into a multitude of distinct subsets and recognize not only viruses and intracellular bacteria but also extracellular bacteria, fungi, and parasites. In this review, we outline the key features of CD4+ TRM in health and disease, including their contributions to protection against SARS-CoV-2 and potential contributions to immunopathology associated with COVID-19.
TCTAP C-096 Coronary Artery Perforation or Normal Friday Night
Authors: Alexey Sozykin, Ludmila Ulyanova, Alexandr Shlykov, Pavel Grigor'evich Emelyanov, Natalya Novikova, Aleksey Nikitin, Evgeniy Averin
Journal: Journal of the American College of Cardiology (2022)
TCTAP C-001 "The Squid Game'- IVUS Guided Angioplasty in a Case of Spontaneous Coronary Artery Dissection Presenting With Ventricular Tachycardia Post-COVID-19 Infection
Authors: Mugilan Sundarajoo, Khin Maung Zan Mohd Saad Jalaluddin, Shaiful Azmi Yahaya
Journal: Journal of the American College of Cardiology (2022)
Multivalent designed proteins neutralize SARS-CoV-2 variants of concern and confer protection against infection in mice
Authors: Andrew C. Hunt, James Brett Case, Young-Jun Park, Longxing Cao, Kejia Wu, Alexandra C. Walls, Zhuoming Liu, John E. Bowen, Hsien-Wei Yeh, Shally Saini, Louisa Helms, Yan Ting Zhao, Tien-Ying Hsiang, Tyler N. Starr, Inna Goreshnik, Lisa Kozodoy, Lauren Carter, Rashmi Ravichandran, Lydia B. Green, Wadim L. Matochko, Christy A. Thomson, Bastian Vögeli, Antje Krüger, Laura A. VanBlargan, Rita E. Chen, Baoling Ying, Adam L. Bailey, Natasha M. Kafai, Scott E. Boyken, Ajasja Ljubetič, Natasha Edman, George Ueda, Cameron M. Chow, Max Johnson, Amin Addetia, Mary-Jane Navarro, Nuttada Panpradist, Michael Gale, Benjamin S. Freedman, Jesse D. Bloom, Hannele Ruohola-Baker, Sean P. J. Whelan, Lance Stewart, Michael S. Diamond, David Veesler, Michael C. Jewett, David Baker
Journal: Science Translational Medicine (2022)

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise and prolong the coronavirus disease 2019 (COVID-19) pandemic. Here, we used a cell-free expression workflow to rapidly screen and optimize constructs containing multiple computationally designed miniprotein inhibitors of SARS-CoV-2. We found the broadest efficacy was achieved with a homotrimeric version of the 75-residue angiotensin-converting enzyme 2 (ACE2) mimic AHB2 (TRI2-2) designed to geometrically match the trimeric spike architecture. Consistent with the design model, in the cryo-electron microscopy structure TRI2-2 forms a tripod at the apex of the spike protein that engaged all three receptor binding domains simultaneously. TRI2-2 neutralized Omicron (B.1.1.529), Delta (B.1.617.2), and all other variants tested with greater potency than the monoclonal antibodies used clinically for the treatment of COVID-19. TRI2-2 also conferred prophylactic and therapeutic protection against SARS-CoV-2 challenge when administered intranasally in mice. Designed miniprotein receptor mimics geometrically arrayed to match pathogen receptor binding sites could be a widely applicable antiviral therapeutic strategy with advantages over antibodies in greater resistance to viral escape and antigenic drift, and advantages over native receptor traps in lower chances of autoimmune responses.
Dual checkpoint targeting of B7-H3 and PD-1 with enoblituzumab and pembrolizumab in advanced solid tumors: interim results from a multicenter phase I/II trial
Authors: Charu Aggarwal, Amy Prawira, Scott Antonia, Osama Rahma, Anthony Tolcher, Roger B Cohen, Yanyan Lou, Ralph Hauke, Nicholas Vogelzang, Dan P Zandberg, Arash Rezazadeh Kalebasty, Victoria Atkinson, Alex A Adjei, Mahesh Seetharam, Ariel Birnbaum, Andrew Weickhardt, Vinod Ganju, Anthony M Joshua, Rosetta Cavallo, Linda Peng, Xiaoyu Zhang, Sanjeev Kaul, Jan Baughman, Ezio Bonvini, Paul A Moore, Stacie M Goldberg, Fernanda I Arnaldez, Robert L Ferris, Nehal J Lakhani
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Availability of checkpoint inhibitors has created a paradigm shift in the management of patients with solid tumors. Despite this, most patients do not respond to immunotherapy, and there is considerable interest in developing combination therapies to improve response rates and outcomes. B7-H3 (CD276) is a member of the B7 family of cell surface molecules and provides an alternative immune checkpoint molecule to therapeutically target alone or in combination with programmed cell death-1 (PD-1)–targeted therapies. Enoblituzumab, an investigational anti-B7-H3 humanized monoclonal antibody, incorporates an immunoglobulin G1 fragment crystallizable (Fc) domain that enhances Fcγ receptor-mediated antibody-dependent cellular cytotoxicity. Coordinated engagement of innate and adaptive immunity by targeting distinct members of the B7 family (B7-H3 and PD-1) is hypothesized to provide greater antitumor activity than either agent alone. Methods In this phase I/II study, patients received intravenous enoblituzumab (3–15 mg/kg) weekly plus intravenous pembrolizumab (2 mg/kg) every 3 weeks during dose-escalation and cohort expansion. Expansion cohorts included non–small cell lung cancer (NSCLC; checkpoint inhibitor [CPI]–naïve and post-CPI, programmed death-ligand 1 [PD-L1] &lt;1%), head and neck squamous cell carcinoma (HNSCC; CPI-naïve), urothelial cancer (post-CPI), and melanoma (post-CPI). Disease was assessed using Response Evaluation Criteria in Solid Tumors version 1.1 after 6 weeks and every 9 weeks thereafter. Safety and pharmacokinetic data were provided for all enrolled patients; efficacy data focused on HNSCC and NSCLC cohorts. Results Overall, 133 patients were enrolled and received ≥1 dose of study treatment. The maximum tolerated dose of enoblituzumab with pembrolizumab at 2 mg/kg was not reached. Intravenous enoblituzumab (15 mg/kg) every 3 weeks plus pembrolizumab (2 mg/kg) every 3 weeks was recommended for phase II evaluation. Treatment-related adverse events occurred in 116 patients (87.2%) and were grade ≥3 in 28.6%. One treatment-related death occurred (pneumonitis). Objective responses occurred in 6 of 18 (33.3% [95% CI 13.3 to 59.0]) patients with CPI-naïve HNSCC and in 5 of 14 (35.7% [95% CI 12.8 to 64.9]) patients with CPI-naïve NSCLC. Conclusions Checkpoint targeting with enoblituzumab and pembrolizumab demonstrated acceptable safety and antitumor activity in patients with CPI-naïve HNSCC and NSCLC. Trial registration number NCT02475213 .
Diagnosis and Treatment of Pulmonary Arterial Hypertension
Authors: Nicole F. Ruopp, Barbara A. Cockrill
Journal: JAMA (2022)

<h3>Importance</h3> Pulmonary arterial hypertension (PAH) is a subtype of pulmonary hypertension (PH), characterized by pulmonary arterial remodeling. The prevalence of PAH is approximately 10.6 cases per 1 million adults in the US. Untreated, PAH progresses to right heart failure and death. <h3>Observations</h3> Pulmonary hypertension is defined by a mean pulmonary artery pressure greater than 20 mm Hg and is classified into 5 clinical groups based on etiology, pathophysiology, and treatment. Pulmonary arterial hypertension is 1 of the 5 groups of PH and is hemodynamically defined by right heart catheterization demonstrating a mean pulmonary artery pressure greater than 20 mm Hg, a pulmonary artery wedge pressure of 15 mm Hg or lower, and a pulmonary vascular resistance of 3 Wood units or greater. Pulmonary arterial hypertension is further divided into subgroups based on underlying etiology, consisting of idiopathic PAH, heritable PAH, drug- and toxin-associated PAH, pulmonary veno-occlusive disease, PAH in long-term responders to calcium channel blockers, and persistent PH of the newborn, as well as PAH associated with other medical conditions including connective tissue disease, HIV, and congenital heart disease. Early presenting symptoms are nonspecific and typically consist of dyspnea on exertion and fatigue. Currently approved therapy for PAH consists of drugs that enhance the nitric oxide–cyclic guanosine monophosphate biological pathway (sildenafil, tadalafil, or riociguat), prostacyclin pathway agonists (epoprostenol or treprostinil), and endothelin pathway antagonists (bosentan and ambrisentan). With these PAH-specific therapies, 5-year survival has improved from 34% in 1991 to more than 60% in 2015. Current treatment consists of combination drug therapy that targets more than 1 biological pathway, such as the nitric oxide–cyclic guanosine monophosphate and endothelin pathways (eg, ambrisentan and tadalafil), and has shown demonstrable improvement in morbidity and mortality compared with the previous conventional single-pathway targeted monotherapy. <h3>Conclusions and Relevance</h3> Pulmonary arterial hypertension affects an estimated 10.6 per 1 million adults in the US and, without treatment, typically progresses to right heart failure and death. First-line therapy with drug combinations that target multiple biological pathways are associated with improved survival.
Mechanotransduction-induced glycolysis epigenetically regulates a CXCL1-dominant angiocrine signaling program in liver sinusoidal endothelial cells in vitro and in vivo
Authors: Thomas Greuter, Usman Yaqoob, Can Gan, Nidhi Jalan-Sakrikar, Enis Kostallari, Jianwen Lu, Jinhang Gao, Liankang Sun, Mengfei Liu, Tejasav S. Sehrawat, Samar H. Ibrahim, Kunimaro Furuta, Katerina Nozickova, Bing Q. Huang, Bin Gao, Michael Simons, Sheng Cao, Vijay H. Shah
Journal: Journal of Hepatology (2022)
Cutaneous manifestations of monoclonal gammopathy
Authors: Jean-Sebastien Claveau, David A. Wetter, Shaji Kumar
Journal: Blood Cancer Journal (2022)

Monoclonal gammopathy associated with dermatological manifestations are a well-recognized complication. These skin disorders can be associated with infiltration and proliferation of a malignant plasma cells or by a deposition of the monoclonal immunoglobulin in a nonmalignant monoclonal gammopathy. These disorders include POEMS syndrome, light chain amyloidosis, Schnitzler syndrome, scleromyxedema and TEMPI syndrome. This article provides a review of clinical manifestations, diagnostics criteria, natural evolution, pathogenesis, and treatment of these cutaneous manifestations.
Resolving the Mutually Exclusive Immune Responses of Chitosan with Nanomechanics and Immunological Assays
Authors: Suyoung Lee, Seohyun Byun, Changhon Lee, Sun Hee Park, Dipayan Rudra, Yoichiro Iwakura, You Jeong Lee, Sin‐Hyeog Im, Dong Soo Hwang
Journal: Advanced Healthcare Materials (2022)

Multifaceted functions displayed by both pro- and anti-inflammatory properties of chitosan hinder its effective development as an immunomodulatory agent. Herein, the contributions of the bending stiffness of chitosan with regard to its immune regulatory properties toward inflammation are investigated. The anti-inflammatory properties of chitosan molecular weight (MW) with a shorter (≈1 kDa) or longer (≈15 kDa) than the persistent length (LP ) are compared using immunological assays and nanomechanics-based experiments on the surface forces apparatus (SFA). Interestingly, 1 kDa chitosan significantly enhances the generation of anti-inflammatory regulatory T cells (Tregs) through the Dectin-1-dependent pattern recognition receptor (PRR) on antigen-presenting cells. SFA analyses also show a similar trend of interaction forces between chitosan and diverse PRRs depending on their MW. The results obtained in the immunological and nanomechanical experiments are consistent and imply that the binding features of PRRs vary depending on the MW of chitosan, which may alter immune activity. In accordance, in vivo administration of only 1 kDa represses inflammatory responses and suppresses the progression of experimental colitis. This study elucidates a previously unexplored bending stiffness-dependent immune regulatory property of chitosan and suggests the applicability of low MW (rod-like) chitosan as a pharmaceutical ingredient to treat diverse inflammatory disorders.
Association of Perceived Job Insecurity With Subsequent Memory Function and Decline Among Adults 55 Years or Older in England and the US, 2006 to 2016
Authors: Xuexin Yu, Kenneth M. Langa, Tsai-Chin Cho, Lindsay C. Kobayashi
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Intensified global economic competition and recent financial crises, including those associated with the COVID-19 pandemic, have contributed to uncertainty about job security. However, little is known about the association of perceived job insecurity with memory function and decline among older adults. <h3>Objectives</h3> To investigate the association between perceived job insecurity and subsequent memory function and rate of memory decline among older adults in the US and England. <h3>Design, Setting, and Participants</h3> This 10-year prospective population-based cohort study used data from the US Health and Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA) collected from 2006 to 2016. Participants included 9538 adults 55 years or older. Data were analyzed from August 1 to 31, 2021. <h3>Exposures</h3> Perceived job insecurity (yes vs no) at baseline. <h3>Main Outcomes and Measures</h3> Episodic memory<i>z</i>scores at baseline and rate of decline during the follow-up. <h3>Results</h3> Among the 9538 study participants, the mean (SD) age at baseline was 60.97 (6.06) years, and 4981 (52.22%) were women. A total of 2320 participants (24.32%) reported job insecurity at baseline (1088 of 3949 [27.55%] in England and 1232 of 5589 [22.04%] in the US). Perceived job insecurity after 55 years of age was associated with lower baseline memory<i>z</i>scores in the fully adjusted model (β = −0.04 [95% CI, −0.08 to −0.01]) but not with rate of memory decline (β = 0.01 [95% CI, −0.01 to 0.01]). The association appeared to be stronger in the US than in England (job insecurity × US, β = −0.05 [95% CI, −0.11 to 0.02]), but the estimate was imprecise, potentially owing to low statistical power. <h3>Conclusions and Relevance</h3> The findings of this cohort study suggest that exposure to job insecurity in middle to late life was associated with worse memory function among older adults in the US and England. This association may vary across socioeconomic and social welfare contexts, although future studies with large samples from diverse socioeconomic settings are warranted.
The medical algorithmic audit
Authors: Xiaoxuan Liu, Ben Glocker, Melissa M McCradden, Marzyeh Ghassemi, Alastair K Denniston, Lauren Oakden-Rayner
Journal: The Lancet Digital Health (2022)

Artificial intelligence systems for health care, like any other medical device, have the potential to fail. However, specific qualities of artificial intelligence systems, such as the tendency to learn spurious correlates in training data, poor generalisability to new deployment settings, and a paucity of reliable explainability mechanisms, mean they can yield unpredictable errors that might be entirely missed without proactive investigation. We propose a medical algorithmic audit framework that guides the auditor through a process of considering potential algorithmic errors in the context of a clinical task, mapping the components that might contribute to the occurrence of errors, and anticipating their potential consequences. We suggest several approaches for testing algorithmic errors, including exploratory error analysis, subgroup testing, and adversarial testing, and provide examples from our own work and previous studies. The medical algorithmic audit is a tool that can be used to better understand the weaknesses of an artificial intelligence system and put in place mechanisms to mitigate their impact. We propose that safety monitoring and medical algorithmic auditing should be a joint responsibility between users and developers, and encourage the use of feedback mechanisms between these groups to promote learning and maintain safe deployment of artificial intelligence systems.
Illness in the Family and Shared Stress, Work, and Struggle
Authors: Douglas L. Hill, Dimitri A. Christakis, Chris Feudtner
Journal: JAMA Pediatrics (2022)

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TCTAP A-086 Application of Emla Cream Prior to Radial Puncture: An Initiative to Improve Patient Experience
Authors: An Shing Ang, Ki Fung Cliff Li, Paul JL. Ong, Nur Fatin Nazira Abdul Malek, Nurul Syahiirah Zulkefli Mat Yusuff, Hee Hwa Ho
Journal: Journal of the American College of Cardiology (2022)
Noninvasive Prenatal Test Results Indicative of Maternal Malignancies: A Nationwide Genetic and Clinical Follow-Up Study
Authors: Catharina J. Heesterbeek, Sietse M. Aukema, Robert-Jan H. Galjaard, Elles M.J. Boon, Malgorzata I. Srebniak, Katelijne Bouman, Brigitte H.W. Faas, Lutgarde C.P. Govaerts, Mariëtte J.V. Hoffer, Nicolette S. den Hollander, Klaske D. Lichtenbelt, Merel C. van Maarle, Lisanne van Prooyen Schuurman, Maartje C. van Rij, G. Heleen Schuring-Blom, Servi J.C. Stevens, Gita Tan-Sindhunata, Masoud Zamani Esteki, Christine E.M. de Die-Smulders, Vivianne C.G. Tjan-Heijnen, Lidewij Henneman, Erik A. Sistermans, Merryn V.E. Macville
Journal: Journal of Clinical Oncology (2022)

Noninvasive prenatal testing (NIPT) for fetal aneuploidy screening using cell-free DNA derived from maternal plasma can incidentally raise suspicion for cancer. Diagnostic routing after malignancy suspicious-NIPT faces many challenges. Here, we detail malignancy suspicious-NIPT cases, and describe the clinical characteristics, chromosomal aberrations, and diagnostic routing of the patients with a confirmed malignancy. Clinical lessons can be learned from our experience.Patients with NIPT results indicative of a malignancy referred for tumor screening between April 2017 and April 2020 were retrospectively included from a Dutch nationwide NIPT implementation study, TRIDENT-2. NIPT profiles from patients with confirmed malignancies were reviewed, and the pattern of chromosomal aberrations related to tumor type was analyzed. We evaluated the diagnostic contribution of clinical and genetic examinations.Malignancy suspicious-NIPT results were reported in 0.03% after genome-wide NIPT, and malignancies confirmed in 16 patients (16/48, 33.3%). Multiple chromosomal aberrations were seen in 23 of 48 patients with genome-wide NIPT, and a malignancy was confirmed in 16 patients (16/23, 69.6%). After targeted NIPT, 0.005% malignancy suspicious-NIPT results were reported, in 2/3 patients a malignancy was confirmed. Different tumor types and stages were diagnosed, predominantly hematologic malignancies (12/18). NIPT data showed recurrent gains and losses in primary mediastinal B-cell lymphomas and classic Hodgkin lymphomas. Magnetic resonance imaging and computed tomography were most informative in diagnosing the malignancy.In 231,896 pregnant women, a low percentage (0.02%) of NIPT results were assessed as indicative of a maternal malignancy. However, when multiple chromosomal aberrations were found, the risk of a confirmed malignancy was considerably high. Referral for extensive oncologic examination is recommended, and may be guided by tumor-specific hallmarks in the NIPT profile.
Response to Hypoxia and the Ensuing Dysregulation of Inflammation Impacts<i>Mycobacterium tuberculosis</i>Pathogenicity
Authors: Allison N. Bucşan, Ashley Veatch, Dhiraj K. Singh, Sadia Akter, Nadia A. Golden, Melanie Kirkpatrick, Breanna Threeton, Chivonne Moodley, Mushtaq Ahmed, Lara A. Doyle, Kasi Russell-Lodrigue, Elizabeth B. Norton, Peter J. Didier, Chad J. Roy, Robert B. Abramovitch, Smriti Mehra, Shabaana A. Khader, Deepak Kaushal
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

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