tbuckley/cabot-search huggingface dataset:
Switch‐associated protein 70 protects against nonalcoholic fatty liver disease through suppression of TAK1
Authors: Qiaofeng Qian, Yang Li, Jiajun Fu, Dewen Leng, Zhe Dong, Jiajun Shi, Hongjie Shi, Dengwei Cao, Xu Cheng, Yufeng Hu, Qiujie Luo, Manli Hu, Yong Ran, Hao Tang, Hui Liu, Jinping Liu
Journal: Hepatology (2021)

Abstract Background and Aims NAFLD is a progressive disease without known effective drug treatments. Switch‐associated protein 70 (SWAP70) is a guanine nucleotide exchange factor that participates in the regulation of many cellular processes. However, the role of SWAP70 in NAFLD remains unclear. This study aimed to identify the function and mechanism of SWAP70 in NAFLD. Approach and Results The results showed that the expression of SWAP70 was significantly increased in mice and hepatocytes after metabolic stimulation. Overexpression of SWAP70 in hepatocytes suppressed lipid deposition and inflammation, and SWAP70 knockdown created the inverse effect. Using hepatocyte‐specific Swap70 knockout and overexpression mice fed a high‐fat, high‐cholesterol diet, we demonstrated that SWAP70 suppressed the progression of nonalcoholic steatohepatitis by inhibiting lipid accumulation, inflammatory response, and fibrosis. Mechanically, RNA sequencing analysis and immunoprecipitation assays revealed that SWAP70 inhibited the interaction between transforming growth factor β‐activated kinase 1 (TAK1) binding protein 1 and TAK1 and sequentially suppressed the phosphorylation of TAK1 and subsequent c‐Jun N‐terminal kinase/P38 signaling. Inhibition of TAK1 activation blocked hepatocyte lipid deposition and inflammation caused by SWAP70 knockdown. Conclusions SWAP70 is a protective molecule that can suppress the progression of NAFLD by inhibiting hepatic steatosis and inflammation. SWAP70 may be important for mitigating the progression of NAFLD.
Rejuvenation of tumour-specific T cells through bispecific antibodies targeting PD-L1 on dendritic cells
Authors: Longchao Liu, Jiahui Chen, Joonbeom Bae, Huiyu Li, Zhichen Sun, Casey Moore, Eric Hsu, Chuanhui Han, Jian Qiao, Yang-Xin Fu
Journal: Nature Biomedical Engineering (2021)
Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study
Authors: Supriya G Mohile, Mostafa R Mohamed, Huiwen Xu, Eva Culakova, Kah Poh Loh, Allison Magnuson, Marie A Flannery, Spencer Obrecht, Nikesha Gilmore, Erika Ramsdale, Richard F Dunne, Tanya Wildes, Sandy Plumb, Amita Patil, Megan Wells, Lisa Lowenstein, Michelle Janelsins, Karen Mustian, Judith O Hopkins, Jeffrey Berenberg, Navin Anthony, William Dale
Journal: The Lancet (2021)
The effects of the national HPV vaccination programme in England, UK, on cervical cancer and grade 3 cervical intraepithelial neoplasia incidence: a register-based observational study
Authors: Milena Falcaro, Alejandra Castañon, Busani Ndlela, Marta Checchi, Kate Soldan, Jamie Lopez-Bernal, Lucy Elliss-Brookes, Peter Sasieni
Journal: The Lancet (2021)
The spike protein of SARS-CoV-2 variant A.30 is heavily mutated and evades vaccine-induced antibodies with high efficiency
Authors: Prerna Arora, Cheila Rocha, Amy Kempf, Inga Nehlmeier, Luise Graichen, Martin S. Winkler, Martin Lier, Sebastian Schulz, Hans-Martin Jäck, Anne Cossmann, Metodi V. Stankov, Georg M. N. Behrens, Stefan Pöhlmann, Markus Hoffmann
Journal: Cellular and Molecular Immunology (2021)
TCT-415 Predictors of New-Onset Atrial Fibrillation Following Transcatheter Mitral Valve Repair: Insights From the Nationwide Readmissions Database
Authors: Julia Berkowitz, Fabio Lima, Kevin Kennedy, Dhaval Kolte, Marwan Saad, Eyal Ben-Assa, Igor Palacios, Paul Gordon, Antony Chu
Journal: Journal of the American College of Cardiology (2021)
SOX10 Regulates Melanoma Immunogenicity through an IRF4–IRF1 Axis
Authors: Satoru Yokoyama, Atsushi Takahashi, Ryota Kikuchi, Soshi Nishibu, Jennifer A. Lo, Miroslav Hejna, Wooyoung M. Moon, Shinichiro Kato, Yue Zhou, F. Stephen Hodi, Jun S. Song, Hiroaki Sakurai, David E. Fisher, Yoshihiro Hayakawa
Journal: Cancer Research (2021)

Loss-of-function mutations of JAK1/2 impair cancer cell responsiveness to IFNγ and immunogenicity. Therefore, an understanding of compensatory pathways to activate IFNγ signaling in cancer cells is clinically important for the success of immunotherapy. Here we demonstrate that the transcription factor SOX10 hinders immunogenicity of melanoma cells through the IRF4-IRF1 axis. Genetic and pharmacologic approaches revealed that SOX10 repressed IRF1 transcription via direct induction of a negative regulator, IRF4. The SOX10-IRF4-IRF1 axis regulated PD-L1 expression independently of JAK-STAT pathway activity, and suppression of SOX10 increased the efficacy of combination therapy with an anti-PD-1 antibody and histone deacetylase inhibitor against a clinically relevant melanoma model. Thus, the SOX10-IRF4-IRF1 axis serves as a potential target that can bypass JAK-STAT signaling to immunologically warm up melanoma with a "cold" tumor immune microenvironment. SIGNIFICANCE: This study identifies a novel SOX10/IRF4 pathway that regulates noncanonical induction of IRF1 independent of the JAK-STAT pathway and can be targeted to improve the efficacy of anti-PD-1 therapy in melanoma.
TCT-36 Double Versus Triple Antithrombotic Therapy After Percutaneous Coronary Intervention: Contemporary Real-World Results From the WOEST2 Registry
Authors: Wilbert Bor, Anne de Veer, Sem Rikken, Dean Chan Pin Yin, Tom Adriaenssens, Willem Dewilde, Jurrien Ten Berg
Journal: Journal of the American College of Cardiology (2021)
TCT-20 Five-Year Follow-Up From the CoreValve Expanded Use Transcatheter Aortic Valve-in-Surgical Aortic Valve Study
Authors: Tanvir Bajwa, Roger Laham, Kamal Khabbaz, Harold Dauerman, Ron Waksman, Shuzhen Li, Neal Kleiman, Michael Reardon, Stanley Chetcuti, G. Deeb
Journal: Journal of the American College of Cardiology (2021)
Influence of Hyaluronan Density on the Behavior of Breast Cancer Cells with Different CD44 Expression
Authors: Ana M. Carvalho, Diana Soares da Costa, Rui L. Reis, Iva Pashkuleva
Journal: Advanced Healthcare Materials (2021)

Molecular gradients are common in biosystems and play an essential role in physiological and pathological processes. During carcinogenesis, for example, hyaluronan (HA) homeostasis is dysregulated by cancer cells and the altered synthesis and degradation processes result in the formation of HA gradients within the tumor microenvironment. Herein, a platform is developed to study the biological role of HA gradient in breast cancer cells. Cells with different aggressiveness and expression of CD44-the main HA receptor usually overexpressed in breast cancers, are selected for this study. The developed platform is compatible with several imaging modalities and allows assessment of cell density, morphology, CD44 expression, and cell motility in a function of HA density. Using high-throughput analysis, it is shown that cells that do not express CD44 do not change along the gradient, while CD44 positive cells respond differently to the HA gradient depending on the level of CD44 expression and HA density. This different response is associated with the activation of different signaling pathways by the CD44-HA interactions.
TCT-75 Comparison of Large-Bore Mechanical Thrombectomy and Catheter-Directed Thrombolysis in Patients With Acute Pulmonary Embolism: A Single-Center Experience
Authors: Errol Inci, Matthew Brown, Giancarlo Licitra, John Wight, Arielle Schwartz, Pratik Sandesara, Chandan Devireddy, Gautam Kumar, Michael McDaniel, Wissam Jaber
Journal: Journal of the American College of Cardiology (2021)
The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses
Authors: Ibrahim M Sayed, Stella-Rita Ibeawuchi, Dominique Lie, Mahitha Shree Anandachar, Rama Pranadinata, Manuela Raffatellu, Soumita Das
Journal: Gut Microbes (2021)

Host engulfment protein ELMO1 generates intestinal inflammation following internalization of enteric bacteria. In Shigella, bacterial effector IpgB1 interacts with ELMO1 and promotes bacterial invasion. IpgB1 belongs to the WxxxE effector family, a motif found in several effectors of enteric pathogens. Here, we have studied the role of WxxxE effectors, with emphasis on Salmonella SifA and whether it interacts with ELMO1 to regulate inflammation. In-silico-analysis of WxxxE effectors was performed using BLAST search and Clustal W program. The interaction of ELMO1 with SifA was assessed by GST pulldown assay and co-immunoprecipitation. ELMO1 knockout mice, and ELMO1-depleted murine macrophage J774 cell lines were challenged with WT and SifA mutant Salmonella. Bacterial effectors containing the WxxxE motif were transfected in WT and ELMO1-depleted J774 cells to assess the inflammatory cytokines. ELMO1 generates differential pro-inflammatory cytokines between pathogenic and nonpathogenic bacteria. WxxxE motif is present in pathogens and in the TIR domain of host proteins. The C-terminal part of ELMO1 interacts with SifA where WxxxE motif is important for interaction. ELMO1–SifA interaction affects bacterial colonization, dissemination, and inflammatory cytokines in vivo. Moreover, ELMO1–SifA interaction increases TNF-α and IL-6 production from the macrophage cell line and is associated with enhanced Rac1 activity. ELMO1 also interacts with WxxxE effectors IpgB1, IpgB2, and Map and induces inflammation after challenge with microbes or microbial ligands. ELMO1 generates a differential response through interaction with the WxxxE motif, which is absent in commensals. ELMO1-WxxxE interaction plays a role in bacterial pathogenesis and induction of inflammatory response.
カプセル化膵島細胞移植の機械的安定性のin vivoモニタリングを可能にするフルオロカプセル【JST・京大機械翻訳】
Authors: R Arifin Dian, Kulkarni Mangesh, Kadayakkara Deepak, W M Bulte Jeff
Journal: Biomaterials (2019)
Heightened Innate Immune Response to COVID-19 Infection in CKD: Implications to Poorer Outcome During CKD
Authors: Xiaojia Guo, Leyuan Xu, Tian-Min Chen, Fred Gorelick, Gary V. Desir, Robert L. Safirstein
Journal: Journal of the American Society of Nephrology (2021)

Background: Meta-analyses reveal show a significant association of chronic kidney disease (CKD) with severe COVID-19. The double stranded RNA virus SARS-CoV-2 can evoke a damaging inflammatory response. To understand the mechanism for the greater severity of the disease in patients with CKD, we studied an animal model of CKD exposed to polyinosinic-polycytidylic acid [poly(I:C), a synthetic analog of double-stranded RNA that recapitulates the innate immune response provoked by SARS-CoV-2]. Methods: C57Bl6j mice were injected with 2 doses of cisplatin at 15 mg / kg or vehicle control subcutaneously, 2 weeks apart. After CKD established, control and CKD mice were subsequently injected with poly(I:C) at 30 mg/kg intravenously and monitored for body weight loss and mortality. Bone marrow cells were isolated 2 weeks post poly(I:C) treatment and grown in serum-free medium supplemented with macrophage colony stimulation factor for 7 days to obtain bone marrow derived macrophages (BMDM). These cells were stimulated with 10 ug / ml poly (I:C), followed by measurement of proinflammatory cytokines. Single cell RNA sequencing was used to compare transcriptome between normal and CKD kidneys. Results: CKD animals had elevated plasma creatinine (0.14 ± 0.02 mg / dL, n=8, control mice 0.09 ± 0.01 mg / dL, n=5, p<0.05) and elevated plasma levels kidney injury marker 1 (KIM-1;133.6 ± 29.9 pg /ml, vs undetectable, n=5, p<0.05). Poly (I:C) treatment induced a greater body weight loss in CKD animals (9.9± 2.9 %, n=8 vs control mice 6.8 ± 2.0 %, n=5, p<0.0005) and greater mortality of CKD mice (46% mortality within 24h in CDK mice vs no mortality in control mice). BMDMs from CKD mice produced greater levels of IL-6 than control BMDM upon poly (I:C) stimulation at both the mRNA and protein levels. In addition, Single cell RNA sequencing revealed that there is 3-fold higher relative number of macrophages in CKD kidneys. Conclusions: Our results show that CKD mice are more sensitive to foreign double strand RNA insult. BMDM isolated from cisplatin-induced CKD demonstrated a greater innate immune response during CKD. We propose that the inherent hyperinflammatory nature of CKD drives a greater innate immune response in this model of viral injury and may be responsible, at least partially, for the poor outcomes in CKD patients with Covid-19 infection.
Nonfatal Myocardial Infarction—Poor Surrogate for Mortality
Authors: Mithi del Rosario, Vinay Guduguntla, Tracy Y. Wang
Journal: JAMA Internal Medicine (2021)

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Excess Vitamin C Leading to Hyperoxaluria and AKI
Authors: Katherine Julian, Catherine Abendroth, Ali M. Zebi, Amanda A. Karasinski, Rohit Jain
Journal: Journal of the American Society of Nephrology (2021)

Julian, Katherine; Abendroth, Catherine; Zebi, Ali M.; Karasinski, Amanda A.; Jain, Rohit Author Information
Recovery from AKI Requiring Kidney Replacement Therapy in Critically Ill Patients with COVID-19
Authors: Caroline M. Hsu, Shruti Gupta, Hocine Tighiouart, Nitender Goyal, Anthony J. Faugno, Asma Tariq, David E. Leaf, Daniel E. Weiner
Journal: Journal of the American Society of Nephrology (2021)

Background: Acute kidney injury (AKI) requiring kidney replacement therapy (KRT) occurs in as many as one in five critically ill patients with COVID-19. Expanding on previous work by this group, we examined the association of clinical factors at the time of KRT initiation with the outcome of kidney recovery at hospital discharge, accounting for the competing outcome of death. Methods: We used data from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID), a multicenter cohort study that enrolled adults with COVID-19 admitted to ICUs at 68 hospitals across the US from March 4 to June 22, 2020. Among those who acutely required KRT, the outcome of kidney non-recovery (continued dialysis dependence at hospital discharge) was explored with multinomial logistic regression, with kidney recovery (independence from dialysis at discharge) as the reference outcome and death as an alternate outcome. Exposures of interest included demographics, baseline medical status, and markers of illness acuity at the time of KRT initiation. Results: Of 876 patients with AKI-KRT, 588 (67%) died, 95 (11%) survived to discharge and remained dependent on KRT, and 193 (22%) survived to discharge without KRT dependence. Patients with lower baseline eGFR had greater odds of kidney non-recovery, with OR 8.58 (95% CI: 3.03-24.28) among patients with eGFR ≤15 vs >60. Reduced urine output on the day of KRT initiation was also associated with kidney non-recovery, with OR 4.23 (95% CI: 1.61-11.15) for urine output  500 mL/day (Figure). Conclusions: Among critically ill patients with COVID-19 with AKI requiring KRT, lower baseline kidney function and reduced urine output at the time of KRT initiation are associated with kidney non-recovery.
Limitations of Heartburn and Other Societies’ Criteria in Barrett’s Screening for Detecting De Novo Esophageal Adenocarcinoma
Authors: Tarek Sawas, Shawn A. Zamani, Sarah Killcoyne, Andrew Dullea, Kenneth K. Wang, Prasad G. Iyer, Rebecca C. Fitzgerald, David A. Katzka
Journal: Clinical Gastroenterology and Hepatology (2021)
Establishment of tumor inflammasome clusters with distinct immunogenomic landscape aids immunotherapy
Authors: Qingyu Liang, Jianqi Wu, Xin Zhao, Shuai Shen, Chen Zhu, Tianqi Liu, Xiao Cui, Ling Chen, Chunmi Wei, Peng Cheng, Wen Cheng, Anhua Wu
Journal: Theranostics (2021)

Inflammasome signaling is a reaction cascade that influences immune response and cell death. Although the inflammasomes participate in tumorigenesis, their role as an oncogenic booster or a tumor suppresser is still controversial. Therefore, it is important to comprehensively investigate the inflammasome signaling status across various cancers to clarify its clinical and therapeutic significance. Methods: A total of 9881 patients across 33 tumor types from The Cancer Genome Atlas database were included in this study. Five gene sets were identified to step-wisely profile inflammasome signaling. Unsupervised clustering was used for sample classification based on gene set enrichment. Machine learning and in vitro and in vivo experiments were used to confirm the implications of inflammasome classification. Results: A hundred and forty-one inflammasome-signaling-related genes were identified to construct five gene sets representing the sensing, activation, and termination steps of the inflammasome signaling. Six inflammasome clusters were robustly established with distinct molecular, biological, clinical, and therapeutic features. Importantly, clusters with inflammasome signaling activation were found to be immunosuppressive and resistant to ICB treatment. Inflammasome inhibition reverted the therapeutic failure of ICB in inflammasome-activated tumors. Moreover, based on the proposed classification and therapeutic implications, an open website was established to provide tumor patients with comprehensive information on inflammasome signaling. Conclusions: Our study conducted a systematical investigation on inflammasome signaling in various tumor types. These findings highlight the importance of inflammasome evaluation in tumor classification and provide a foundation for improving relevant therapeutic regimens.
ケトン生成は内臓脂肪組織における代謝防御γδT細胞を活性化する【JST・京大機械翻訳】
Authors: L Goldberg Emily, Shchukina Irina, L Asher Jennifer, Sidorov Sviatoslav, N Artyomov Maxim, Dixit Vishwa Deep
Journal: Nature Metabolism (2020)
Scaling Up Public Health Interventions: Engaging Partners Across Multiple Levels
Authors: Jennifer Leeman, Alix Boisson, Vivian Go
Journal: Annual Review of Public Health (2021)

Advancing the science of intervention scale-up is essential to increasing the impact of effective interventions at the regional and national levels. In contrast with work in high-income countries (HICs), where scale-up research has been limited, researchers in low- and middle-income countries (LMICs) have conducted numerous studies on the regional and national scale-up of interventions. In this article, we review the state of the science on intervention scale-up in both HICs and LMICs. We provide an introduction to the elements of scale-up followed by a description of the scale-up process, with an illustrative case study from our own research. We then present findings from a scoping review comparing scale-up studies in LMIC and HIC settings. We conclude with lessons learned and recommendations for improving scale-up research.
Hidradenitis Suppurativa in Patients With Inflammatory Bowel Disease: A Population-Based Cohort Study in Olmsted County, Minnesota
Authors: Siddhant Yadav, Siddharth Singh, Jithinraj Edakkanambeth Varayil, W. Scott Harmsen, Alan R. Zinsmeister, William J. Tremaine, Mark Denis P. Davis, David A. Wetter, Jean-Frederic Colombel, Edward V. Loftus
Journal: Clinical Gastroenterology and Hepatology (2015)
Demonstrations erupt in Poland after new abortion law is blamed in woman’s death
Authors: Owen Dyer
Journal: BMJ (2021)

Crowds gathered in several Polish cities this week to protest the death of a woman who died of septic shock in a Pszczyna hospital after doctors chose to let her non-viable fetus die in the womb rather than remove it, a medical decision that the woman’s family say was driven by fear of the country’s restrictive new law on abortion.

In Warsaw, a crowd gathered outside the Constitutional Tribunal, which in October 2020 ruled that severe and irreversible fetal impairment could no longer be grounds for abortion. In Krakow, demonstrators marched to the headquarters of the ruling Law and Justice (PiS) party, which has dominated appointments to that court. Łodź, Poznan, Pszczyna, and Wroclaw also saw protestors gather under the slogan “Not one more.”

The 30 year old woman has been named only as Izabela, …
Surface modification to enhance cell migration on biomaterials and its combination with 3D structural design of occluders to improve interventional treatment of heart diseases
Authors: Yang Shen, Wanqian Zhang, Yumei Xie, Anning Li, Xiuli Wang, Xianmiao Chen, Qingsong Liu, Qunsong Wang, Gui Zhang, Qiong Liu, Jianxiong Liu, Deyuan Zhang, Zhiwei Zhang, Jiandong Ding
Journal: Biomaterials (2021)
Potential bioactive coating system for high-performance absorbable magnesium bone implants
Authors: Murni Nazira Sarian, Nida Iqbal, Pedram Sotoudehbagha, Mehdi Razavi, Qamar Uddin Ahmed, Cortino Sukotjo, Hendra Hermawan
Journal: Bioactive Materials (2021)

Magnesium alloys are considered the most suitable absorbable metals for bone fracture fixation implants. The main challenge in absorbable magnesium alloys is their high corrosion/degradation rate that needs to be controlled. Various coatings have been applied to magnesium alloys to slow down their corrosion rates to match their corrosion rate to the regeneration rate of the bone fracture. In this review, a bioactive coating is proposed to slow down the corrosion rate of magnesium alloys and accelerate the bone fracture healing process. The main aim of the bioactive coatings is to enhance the direct attachment of living tissues and thereby facilitate osteoconduction. Hydroxyapatite, collagen type I, recombinant human bone morphogenetic proteins 2, simvastatin, zoledronate, and strontium are six bioactive agents that show high potential for developing a bioactive coating system for high-performance absorbable magnesium bone implants. In addition to coating, the substrate itself can be made bioactive by alloying magnesium with calcium, zinc, copper, and manganese that were found to promote bone regeneration.
Mosunetuzumab Monotherapy Is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Who Have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study
Authors: L. Elizabeth Budde, Laurie H. Sehn, Matthew J. Matasar, Stephen J. Schuster, Sarit Assouline, Pratyush Giri, John Kuruvilla, Miguel Canales, Sascha Dietrich, Keith Fay, Matthew Ku, Loretta Nastoupil, Michael C. Wei, Shen Yin, Michelle Y. Doral, Chi-Chung Li, Huang Huang, Raluca Negricea, Elicia Penuel, Carol O'Hear, Nancy L. Bartlett
Journal: Blood (2021)
左心耳閉鎖-脳卒中予防の代替治療-欧州の多数例手術施設からの報告
Authors: Matsuo Yae, Winkler Sven-Moebius, Sandri Marcus, Mangner Norman, Schuler Gerhard, Funada Ryuichi, Takama Noriaki, Kurabayashi Masahiko
Journal: Circulation (2014)