tbuckley/cabot-search huggingface dataset:
Role of surfactant protein d (sp-d) in COVID-19
Authors: S. Sandeep, J. Yang, M. J. Teuber, A. Linderholm, S. Aramyan, C. McReynolds, R. Ravindran, I. Khan, N. Tran, A. Haczku
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Surfactant protein D (SP-D) is a major immune protective molecule produced in the respiratory epithelium. SP-D binds to specific pathogen surfaces through its carbohydrate recognition (lectin) domain, that helps in their neutralization and clearance by phagocytes. SP-D also acts as an anti-inflammatory molecule. We hypothesized that SP-D plays a protective role in COVID-19. Methods: Polar+, a novel quantum computing algorithm for molecular pruning, and classical in silico modeling were used to investigate potential binding sites between SP-D and SARS CoV2. Electronegativity and topologically oriented molecular pruning, calculation of electronic force-fields and electrostatic binding combined with protein-protein docking, geometric fitting and assessment of protein glycosylation sites were employed. SP-D-/- mouse lung was used to study expression of the SARS-CoV-2 viral entry molecules TMPRSS2 and ACE2. Plasma from COVID-19 patients was studied for SP-D leakage, cytokine levels and lipid mediators. Results: We found that SP-D potentially binds to the same SARS CoV-2 glycoprotein (S protein) that it utilizes to bind the cellular receptor, ACE2, with high affinity. However, SP-D binds to subunit 2, instead of subunit 1 (that ACE2 utilizes). Additional studies will need to determine if SP-D binding affects S protein and ACE2 interactions. We also found that SP-D-/- mice had increased expression of the TMRSS2 gene in the lung and that both TMPRSS2 and ACE2 mRNA levels were increased during lung injury, amplified by the lack of SP-D. SP-D leakage from the lung to the circulation was significantly increased in COVID- 19 patients and correlated with expression of pro-neutrophilic inflammatory markers. Conclusions: We speculate that SP-D aids in the protection from SARS CoV2 infection by both acting as a potential natural decoy to prevent coronavirus entry into airway epithelial cells and by attenuating the expression of the viral entry receptor TMPRSS2. Oxidative lung injury results in SP-D leak into the circulation denoting disease severity in COVID-19 patients. (AH) .
Correspondence on ‘Immunogenicity and safety of anti-SARS-CoV-2 mRNA vaccines in patients with chronic inflammatory conditions and immunosuppressive therapy in a monocentric cohort’
Authors: Larissa Valor-Méndez, Koray Tascilar, David Simon, Joerg Distler, Arnd Kleyer, Georg Schett, Juergen Rech
Journal: Annals of the Rheumatic Diseases (2021)

We read with interest the work by Geisen and colleagues1 on the efficacy and safety of anti-SARS-CoV-2 mRNA vaccine in patients with rheumatic diseases. While substantial data on the efficacy and safety of SARS-CoV-2 vaccination have been created during the last months, it is currently unclear whether the vaccination is efficacious and safe in patients with autoinflammatory diseases (AIDs). These patients present with exacerbated innate immune responses associated with enhanced production of interleukin (IL)-1.2

Testing the immune response to SARS-CoV-2 vaccination in patients with AIDs is of interest, as IL-1 has been involved in the pathogenesis of COVID-19; thus, IL-1 expression is massively increased in patients with severe COVID-19.3–5 Furthermore, COVID-19 has shown to trigger an increased inflammatory disease activity in patients with AIDs.6 7 In addition, IL-1 inhibition has been applied in the treatment of COVID-19 and while initial uncontrolled studies revealed promising results,8 a randomised controlled trial showed no improvement of COVID-19 on IL-1 blockade.9 While current data suggest the immune response to SARS-CoV-2 vaccination may be reduced in certain diseases, such as rheumatoid arthritis,10 and certain treatments such as methotrexate,11 such data cannot be applied to AID or to IL-1 inhibitors as the underlying pathophysiology is fundamentally different. Hence, we aimed to investigate SARS-CoV-2 vaccination …
Rebuilding trust after misdiagnosis: where is the liaison between mental and medical?
Authors: Sebastian Kraemer
Journal: BMJ (2021)

Clark writes, “As I had received several psychiatric diagnoses, the pain team wouldn’t help with my physical pain.”1 As long as medical and mental services work in separate silos, many patients with unexplained symptoms will be neglected, or worse. A good mental health liaison team, on the other hand, will work with medical specialists so the patient feels looked after …
肺静脈伝導部位に対する追加アブレーションによる「一括PVI」は発作性心房細動の再発を阻止できる
Authors: Yamane Teiichi, Matsuo Seiichiro, Tokutake Kenichi, Yokoyama Kenichi, Hioki Mika, Narui Ryohsuke, Tanigawa Shinichi, Inada Keiichi, Tokuda Michifumi, Yoshimura Michihiro
Journal: Circulation (2015)
Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease
Authors: Steven N. Austad, Scott Ballinger, Thomas W. Buford, Christy S. Carter, Daniel L. Smith, Victor Darley-Usmar, Jianhua Zhang
Journal: Acta Pharmaceutica Sinica B (2021)

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.
Serum BCMA levels predict outcomes in MGUS and smoldering myeloma patients
Authors: A. Visram, C. Soof, S. V. Rajkumar, S. K. Kumar, S. Bujarski, T. M. Spektor, R. A. Kyle, J. R. Berenson, A. Dispenzieri
Journal: Blood Cancer Journal (2021)

Abstract Soluble BCMA (sBCMA) levels are elevated in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). However, the association between sBCMA levels and prognosis in MGUS and SMM has not been studied. We retrospectively analyzed sBCMA levels in stored samples from 99 MGUS and 184 SMM patients. Baseline sBCMA levels were significantly higher in MGUS and SMM patients progressing to MM during clinical follow up. When stratified according to the median baseline sBCMA level for each cohort, higher levels were associated with a shorter PFS for MGUS (HR 3.44 comparing sBCMA ≥77 vs &lt;77 ng/mL [95% CI 2.07–5.73, p &lt; 0.001] and SMM (HR 2.0 comparing sBCMA ≥128 vs &lt;128 ng/mL, 95% 1.45–2.76, p &lt; 0.001) patients. The effect of sBCMA on PFS was similar even after adjusting for the baseline MGUS or SMM risk stratification. We evaluated paired serum samples and found that sBCMA increased significantly in MGUS and SMM patients who eventually progressed to MM, whereas among MGUS non-progressors the sBCMA level remained stable. While our results require independent validation, they suggest that sBCMA may be a useful biomarker to identify MGUS and SMM patients at increased risk of progression to MM independent of the established risk models.
The Clinical Significance of Fragmented-Onset QRS in Daily Medical Practice
Authors: Muta Yumiko, Watanabe Shigeyuki, Toyama Masahiro, Ojima Eiji, Oishi Yuta, Suzuki Hidetaka, Kuroda Yasuhisa, Kimura Sachiko, Uchida Seichi, Ishimitsu Toshiyuki, Aonuma Kazutaka
Journal: Circulation (2016)
Evaluation of Health Equity in COVID-19 Vaccine Distribution Plans in the United States
Authors: Amber Hardeman, Taylor Wong, Joshua L. Denson, Radu Postelnicu, Juan C. Rojas
Journal: JAMA Network Open (2021)

Sickle cell Chronic immunosuppression CKD CAD CHF HTN Chronic lung condition requiring O 2 Age >75 y Liver diseaseOf 51 vaccination plans, 50 identified high-risk conditions.One state did not specify what conditions they considered to be high risk.CAD indicates coronary artery disease; CHF, congestive heart failure; CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; HTN, hypertension.
Abstract 353: P2Y <sub>2</sub> Nucleotide Receptor Overexpression: Letting Blind Cardiac Progenitor Cells ‘See’ Again
Authors: Farid Khalafalla, Steven Greene, Jonathan Nguyen, Kelli Ilves, Benjamin Norman, Roberto J Alvarez, Mark Sussman
Journal: Circulation Research (2016)

Heart failure (HF) is a leading cause of death in the US due to limited capability of adult mammalian heart to regenerate after myocardial infarction (MI). Autologous stem cell therapy holds promise for promoting regeneration of injured heart but stem cells derived from diseased organs exhibit poor proliferative, migratory and survival capabilities. Empowering cardiac-derived progenitor cells (CPC) with prosurvival genes has been attempted. However, molecular mechanisms by which stem cells detect stress signals to subsequently initiate appropriate regenerative responses are poorly understood. In this regard, purinergic receptors represent a major detector for extracellular nucleotides released during injury/stress and serve as an intracellular platform harboring numerous signaling pathways that regulate proinflammatory and regenerative responses required for the healing process. Despite the established roles of purinergic signaling in cardiovascular diseases, it has not been well-defined in CPCs. This study shows, for the first time, that the majority of P2 purinergic receptors are expressed and exhibit functional responses to ATP and UTP in human CPCs (hCPC) isolated from HF patients. The G protein-coupled P2Y 2 R is a pivotal stress detector that senses ATP and UTP accumulated in extracellular space after injury and mediates regenerative responses in various injury models, including MI model, and in stem cells from diverse origins. Interestingly, hCPCs with relatively slower growth kinetics and enhanced senescence show dramatic decreases in P2Y 2 receptor (P2Y 2 R) expression compared to fast-growing hCPCs, consistent with our hypothesis that overexpressing P2Y 2 R enables diseased hCPCs to better detect stress stimuli and react with the proper regenerative responses. Along this line, P2Y 2 R stimulation with UTP enhances hCPC proliferation and migration. Interestingly, preliminary results demonstrate that UTP treatment induces YAP activation and nuclear shuttling. Moreover, inhibition of YAP/TEAD interaction impairs UTP-induced proliferation and migration revealing a novel link between extracellular nucleotides released during cardiac ischemia and Hippo signaling that has been recently implicated in cardiac regeneration.
KASL clinical practice guidelines: Management of nonalcoholic fatty liver disease
Authors: Seong Hee Kang, Hye Won Lee, Jeong-Ju Yoo, Yuri Cho, Seung Up Kim, Tae Hee Lee, Byoung Kuk Jang, Sang Gyune Kim, Sang Bong Ahn, Haeryoung Kim, Dae Won Jun, Joon-Il Choi, Do Seon Song, Won Kim, Soung Won Jeong, Moon Young Kim, Hong Koh, Sujin Jeong, Jin-Woo Lee, Yong Kyun Cho
Journal: Clinical and Molecular Hepatology (2021)

Evidence collectionThe committee systematically collected and reviewed the international and domestic literature published in PubMed, MEDLINE, KoreaMed, and other databases.The literature was limited to research papers published in the English and Korean languages.The keywords used were 'nonalcoholic fatty liver disease,' 'nonalcoholic fatty liver,' 'nonalcoholic steatohepatitis,' 'fatty liver,' 'hepatic steatosis,' and 'steatohepatitis.'In addition, keywords related to specific clinical questions were included. Levels of evidence and grades of recommendationsThe literature gathered for data collection was analyzed in a systematic review, and the quality of evidence was classified based on the modified Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system (Table 1).According to the types of studies, randomized, controlled studies were approached from a high level of evidence, while observational studies were approached from a low level of evidence.Subsequently, the level of evidence basis sets in corresponding stud-
“Winter in June” as emergency departments see surges in young children with fever
Authors: Shaun Griffin
Journal: BMJ (2021)

Paediatric emergency doctors around the UK are seeing a surge in anxious parents attending with children with mild fever, with one referring to the situation as “winter in June.”

The Royal College of Paediatrics and Child Health (RCPCH) said that many parents who have not seen fever in their children before—particularly those born during lockdown—are taking them directly to emergency departments rather than seeking help from pharmacies, GPs, NHS 111, or online.

Camilla Kingdon, college president, said, “Many emergency departments are currently overwhelmed and there has been a particularly steep rise in the number of young children presenting. Some have seen the highest ever numbers of children in their department and waiting times can …
Abstract 16802: Should We Recommend Triple Therapy in Elderly Patients With Atrial Fibrillation Undergoing Coronary Stenting?
Authors: Maria Mutuberria, Antonia Sambola, Bruno Garcia del Blanco, Albert Alonso, Hector Bueno, Angel Cequier, Jose Antonio Barrabés, David Garcia Dorado
Journal: Circulation (2013)

ACC/AHA/ESC recommends triple therapy (TT: anticoagulation and DAPT with ASA and Clopidogrel) for patients in atrial fibrillation (AF) submitted to coronary stenting (CS). However, a high percentag...
Memory-like Differentiation Enhances NK Cell Responses to Melanoma
Authors: Nancy D. Marin, Bradley A. Krasnick, Michelle Becker-Hapak, Leah Conant, Simon P. Goedegebuure, Melissa M. Berrien-Elliott, Keenan J. Robbins, Jennifer A. Foltz, Mark Foster, Pamela Wong, Celia C. Cubitt, Jennifer Tran, Christopher B. Wetzel, Miriam Jacobs, Alice Y. Zhou, David Russler-Germain, Lynne Marsala, Timothy Schappe, Ryan C. Fields, Todd A. Fehniger
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Treatment of advanced melanoma is a clinical challenge. Natural killer (NK) cells are a promising cellular therapy for T cell–refractory cancers, but are frequently deficient or dysfunctional in patients with melanoma. Thus, new strategies are needed to enhance NK-cell antitumor responses. Cytokine-induced memory-like (ML) differentiation overcomes many barriers in the NK-cell therapeutics field, resulting in potent cytotoxicity and enhanced cytokine production against blood cancer targets. However, the preclinical activity of ML NK against solid tumors remains largely undefined. Experimental Design: Phenotypic and functional alterations of blood and advanced melanoma infiltrating NK cells were evaluated using mass cytometry. ML NK cells from healthy donors (HD) and patients with advanced melanoma were evaluated for their ability to produce IFNγ and kill melanoma targets in vitro and in vivo using a xenograft model. Results: NK cells in advanced melanoma exhibited a decreased cytotoxic potential compared with blood NK cells. ML NK cells differentiated from HD and patients with advanced melanoma displayed enhanced IFNγ production and cytotoxicity against melanoma targets. This included ML differentiation enhancing melanoma patients' NK-cell responses against autologous targets. The ML NK-cell response against melanoma was partially dependent on the NKG2D- and NKp46-activating receptors. Furthermore, in xenograft NSG mouse models, human ML NK cells demonstrated superior control of melanoma, compared with conventional NK cells. Conclusions: Blood NK cells from allogeneic HD or patients with advanced melanoma can be differentiated into ML NK cells for use as a novel immunotherapeutic treatment for advanced melanoma, which warrants testing in early-phase clinical trials.
Identification of a Novel Class of Photolyases as Possible Ancestors of Their Family
Authors: Lei Xu, Simeng Chen, Bin Wen, Hao Shi, Changbiao Chi, Chenxi Liu, Kangyu Wang, Xianglin Tao, Ming Wang, Jun Lv, Liang Yan, Liefeng Ling, Guoping Zhu
Journal: Molecular Biology and Evolution (2021)

UV irradiation induces the formation of cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts in DNA. These two types of lesions can be directly photorepaired by CPD photolyases and 6-4 photolyases, respectively. Recently, a new class of 6-4 photolyases named iron-sulfur bacterial cryptochromes and photolyases (FeS-BCPs) were found, which were considered as the ancestors of all photolyases and their homologs-cryptochromes. However, a controversy exists regarding 6-4 photoproducts only constituting ∼10-30% of the total UV-induced lesions that primordial organisms would hardly survive without a CPD repair enzyme. By extensive phylogenetic analyses, we identified a novel class of proteins, all from eubacteria. They have relatively high similarity to class I/III CPD photolyases, especially in the putative substrate-binding and FAD-binding regions. However, these proteins are shorter, and they lack the "N-terminal α/β domain" of normal photolyases. Therefore, we named them short photolyase-like. Nevertheless, similar to FeS-BCPs, some of short photolyase-likes also contain four conserved cysteines, which may also coordinate an iron-sulfur cluster as FeS-BCPs. A member from Rhodococcus fascians was cloned and expressed. It was demonstrated that the protein contains a FAD cofactor and an iron-sulfur cluster, and has CPD repair activity. It was speculated that this novel class of photolyases may be the real ancestors of the cryptochrome/photolyase family.
Entecavir versus tenofovir in patients with chronic hepatitis B: Enemies or partners in the prevention of hepatocellular carcinoma
Authors: Sung Won Lee, Jonggi Choi, Seung Up Kim, Young-Suk Lim
Journal: Clinical and Molecular Hepatology (2021)

Over the past several decades, entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have remained the first-line antiviral agents in several international guidelines. These two antiviral agents have shown similar short to intermediateterm efficacy, including virologic, biochemical, serologic, and histologic responses. However, huge controversies regarding the antiviral efficacy of ETV and TDF in preventing the development of hepatocellular carcinoma (HCC) still exist. In this review, we summarized recent studies that compared the treatment efficacy of ETV and TDF in terms of HCC development.
Abstract 463: Communicating Through Chaos: A Hybrid Educational Initiative for Urgent Care Oncology Nurses
Authors: Julie Moore, Maggie Dilling
Journal: Circulation (2019)

Introduction: Cancer and cardiovascular disease are two leading causes of death in North America and can occur concurrently in oncology patients. Novel cancer treatments can cause direct cardiovascular side effects, increasing patient mortality. We aimed to educate oncology nurses of ST-Elevated Myocardial Infarction (STEMI) recognition and treatment using a hybrid educational model of didactic and simulation methods with contextual learning. Hypothesis: We hypothesize that a hybrid model including didactic and simulation methodology would result in increased knowledge, skills, and attitudes in the management of patients with STEMI. This would lead to decreased STEMI-related morbidity and improve interprofessional care co-ordination. Methods: Education was provided to 71% (5/7) of Registered Nurses in the Urgent Care Centre of Princess Margaret Hospital in Toronto, Canada. From a unit-wide needs assessment, RNs determined that patient management, care co-ordination and communication skills were areas of educational need, and simulation and lectures were preferred education methods. Current evidence, treatment, and policies for STEMI were incorporated into a short lecture, followed immediately by in situ high fidelity simulation scenarios. All education incorporated the AHA principle of contextual learning to support clinically-relevant knowledge acquisition. Educational gain was assessed using pre- and post-education testing. Results: Following the educational intervention, all learners had an increase in post-test scores. Recognition of the need for an ECG improved by 60% (3/5) and nurses felt more confident in caring for STEMI patients (3.6/4 average score). Learners found the education beneficial and relevant to their practice (100% of respondents). Nurses emphasized the value of didactic education followed by skills application in simulated cases as valuable to their learning from qualitative survey feedback. Conclusion: We developed and implemented a highly-relevant hybrid STEMI educational initiative following a needs assessment. Learners exhibited knowledge acquisition through pre and post-test results. Data collection regarding door-to-ECG and door-to-diagnosis times post-education is ongoing.
P48.05 Anlotinib Plus Platinum-Etoposide in 1st-Line Treatment of Extensive-Stage Small-Cell Lung Cancer: A Single-Arm Phase II Trial
Authors: P. Deng, H. Yang, C. Chen, C. Hu, L. Cao, Q. Gu, J. An, B. Li, Y. Tang, J. Meng, L. Qin, J. Feng
Journal: Journal of Thoracic Oncology (2021)
Genetic Variation in the Mitochondrial Glycerol‐3‐Phosphate Acyltransferase Is Associated With Liver Injury
Authors: Aaron Hakim, Matthew Moll, Joseph Brancale, Jiangyuan Liu, Jessica A. Lasky‐Su, Edwin K. Silverman, Silvia Vilarinho, Z. Gordon Jiang, Yered H. Pita‐Juárez, Ioannis S. Vlachos, Xuehong Zhang, Fredrik Åberg, Nezam H. Afdhal, Brian D. Hobbs, Michael H. Cho
Journal: Hepatology (2021)

Background and Aims Most of the genetic basis of chronic liver disease remains undiscovered. Approach and Results To identify genetic loci that modulate the risk of liver injury, we performed genome-wide association studies on circulating levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin across 312,671 White British participants in the UK Biobank. We focused on variants associated with elevations in all four liver biochemistries at genome-wide significance (P < 5 × 10−8) and that replicated using Mass General Brigham Biobank in 19,323 European ancestry individuals. We identified a genetic locus in mitochondrial glycerol-3-phosphate acyltransferase (GPAM rs10787429) associated with increased levels of ALT (P = 1.4 × 10−30), AST (P = 3.6 × 10−10), ALP (P = 9.5 × 10−30), and total bilirubin (P = 2.9 × 10−12). This common genetic variant was also associated with an allele dose-dependent risk of alcohol-associated liver disease (odd ratio [OR] = 1.34, P = 2.6 × 10−5) and fatty liver disease (OR = 1.18, P = 5.8 × 10−4) by International Classification of Diseases, 10th Revision codes. We identified significant interactions between GPAM rs10787429 and elevated body mass index in association with ALT and AST (P = 7.1 × 10−9 and 3.95 × 10−8, respectively), as well as between GPAM rs10787429 and weekly alcohol consumption in association with ALT, AST, and alcohol-associated liver disease (P = 4.0 × 10−2, 1.6 × 10−2, and 1.3 × 10−2, respectively). Unlike previously described genetic variants that are associated with an increased risk of liver injury but confer a protective effect on circulating lipids, GPAM rs10787429 was associated with an increase in total cholesterol (P = 2.0 × 10−17), LDL cholesterol (P = 2.0 × 10−10), and HDL cholesterol (P = 6.6 × 10−37). Single-cell RNA-sequencing data demonstrated hepatocyte-predominant expression of GPAM in cells that co-express genes related to VLDL production (P = 9.4 × 10−103). Conclusions Genetic variation in GPAM is associated with susceptibility to liver injury. GPAM may represent a therapeutic target in chronic liver disease.