tbuckley/cabot-search huggingface dataset:
Targeting ferroptosis-based cancer therapy using nanomaterials: strategies and applications
Authors: Lianxiang Luo, Han Wang, Wen Tian, Xiaoling Li, Zheng Zhu, Riming Huang, Hui Luo
Journal: Theranostics (2021)

As an iron-dependent mode of programmed cell death induced by lipid peroxidation, ferroptosis plays an important role in cancer therapy. The metabolic reprogramming in tumor microenvironment allows the possibility of targeting ferroptosis in cancer treatment. Recent studies reveal that nanomaterials targeting ferroptosis have prospects for the development of new cancer treatments. However, the design ideas of nanomaterials targeting ferroptosis sometimes vary. Therefore, in addition to the need for a systematic summary of these ideas, new ideas and insights are needed to make possible the construction of nanomaterials for effectively targeting this cell death pathway. At the same time, further optimization of nanomaterials design is required to make them appropriate for clinical treatment. In this context, we summarize this cross-cutting research area covering from the known mechanism of ferroptosis to providing feasible ideas for nanomaterials design as well as their clinical application. We aim to provide new insights and enlightenment for the next step in developing new nanomaterials for cancer treatment.
Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: experience of a large-volume European FMT center
Authors: Gianluca Ianiro, Stefano Bibbò, Serena Porcari, Carlo Romano Settanni, Federica Giambò, Andreea Roxana Curta, Gianluca Quaranta, Franco Scaldaferri, Luca Masucci, Maurizio Sanguinetti, Antonio Gasbarrini, Giovanni Cammarota
Journal: Gut Microbes (2021)

Inflammatory bowel disease (IBD) is a risk factor for C. difficile infection (CDI), which, in turn, complicates the clinical course of IBD. Fecal microbiota transplantation (FMT) is safe and effective in patients with IBD and recurrent CDI (rCDI). In our study, patients with IBD and rCDI received FMT by colonoscopy and were followed-up for 8 weeks. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Eighteen patients with IBD were enrolled. Eight patients received sequential FMT either for pseudomembranous colitis or failure of single fecal infusion. At 8-week follow-up the C. difficile toxin was negative in 17 patients, and most (83%) experienced also improvement of IBD disease activity. Overall, we did not observe any serious adverse event.FMT appears to be highly effective and safe in patients with IBD and rCDI and is likely not only to eradicate CDI but also to improve disease activity of IBD.
Abstract 14692: Lifetime History of Smoking, Cessation and the Risk of Cardiovascular Disease: Prospective Results From the Framingham Heart Study
Authors: Meredith S Duncan, Matthew S Freiberg, Robert Greevy, Suman Kundu, Ramachandran S Vasan, Hilary A Tindle
Journal: Circulation (2018)

Among adults without CVD, the decline in CVD risk attributable to cigarette smoking after quitting is unclear. Much evidence supports rapid elimination of excess risk within a few years since quitt...
National and international kidney failure registries: characteristics, commonalities, and contrasts
Authors: Monica S.Y. Ng, Vivek Charu, David W. Johnson, Michelle M. O’Shaughnessy, Andrew J. Mallett
Journal: Kidney International (2021)

Registries are essential for health infrastructure planning, benchmarking, continuous quality improvement, hypothesis generation, and real-world trials. To date, data from these registries have predominantly been analyzed in isolated "silos," hampering efforts to analyze "big data" at the international level, an approach that provides wide-ranging benefits, including enhanced statistical power, an ability to conduct international comparisons, and greater capacity to study rare diseases. This review serves as a valuable resource to clinicians, researchers, and policymakers, by comprehensively describing kidney failure registries active in 2021, before proposing approaches for inter-registry research under current conditions, as well as solutions to enhance global capacity for data collaboration. We identified 79 kidney-failure registries spanning 77 countries worldwide. International Society of Nephrology exemplar initiatives, including the Global Kidney Health Atlas and Sharing Expertise to support the set-up of Renal Registries (SharE-RR), continue to raise awareness regarding international healthcare disparities and support the development of universal kidney-disease registries. Current barriers to inter-registry collaboration include underrepresentation of lower-income countries, poor syntactic and semantic interoperability, absence of clear consensus guidelines for healthcare data sharing, and limited researcher incentives. This review represents a call to action for international stakeholders to enact systemic change that will harmonize the current fragmented approaches to kidney-failure registry data collection and research.
Single-Dose Ad26.COV2.S Vaccine—Room for Improvement
Authors: Zahra Rikhtegaran Tehrani, Mohammad M. Sajadi
Journal: JAMA Network Open (2021)

Juan Corchado-Garcia, PhD; David Zemmour, MD, PhD; Travis Hughes, MD, PhD; Hari Bandi, PhD; Tudor Cristea-Platon, PhD; Patrick Lenehan, BS; Colin Pawlowski, PhD; Sairam Bade, BS; John C. O’Horo, MD; Gregory J. Gores, MD; Amy W. Williams, MD; Andrew D. Badley, MD; John Halamka, MD; Abinash Virk, MD; Melanie D. Swift, MD, MPH; Tyler Wagner, PhD; Venky Soundararajan, PhD
Microneedle arrays integrated with living organisms for smart biomedical applications
Authors: Bo Cai, Yusheng Gong, Zheng Wang, Lin Wang, Wei Chen
Journal: Theranostics (2021)

Various living organisms have proven to influence human health significantly, either in a commensal or pathogenic manner. Harnessing the creatures may remarkably improve human healthcare and cure the intractable illness that is challenged using traditional drugs or surgical approaches. However, issues including limited biocompatibility, poor biosafety, inconvenience for personal handling, and low patient compliance greatly hinder the biomedical and clinical applications of living organisms when adopting them for disease treatment. Microneedle arrays (MNAs), emerging as a promising candidate of biomedical devices with the functional diversity and minimal invasion, have exhibited great potential in the treatment of a broad spectrum of diseases, which is expected to improve organism-based therapies. In this review, we systemically summarize the technologies employed for the integration of MNAs with specific living organisms including diverse viruses, bacteria, mammal cells and so on. Moreover, their applications such as vaccination, anti-infection, tumor therapy and tissue repairing are well illustrated. Challenges faced by current strategies, and the perspectives of integrating more living organisms, adopting smarter materials, and developing more advanced technologies in MNAs for future personalized and point-of-care medicine, are also discussed. It is believed that the combination of living organisms with functional MNAs would hold great promise in the near future due to the advantages of both biological and artificial species.
Predictive Enrichment in Kidney RCTs: Is Albuminuria the Answer?
Authors: Ayodele Odutayo, David Z.I. Cherney
Journal: Journal of the American Society of Nephrology (2021)

<h3>Introduction</h3> To evaluate the impact of non-technical skills (NTS) on team performance, workload and clinical outcomes. <h3>Methods</h3> The operating room (OR) environment of 20 robot-assisted radical prostatectomies performed by three different surgeons was recorded. Trained observers assessed NTS utilising the Non-Technical Skills for Surgeons (NOTSS) questionnaire. Associations between NOTSS scores, teamwork attributes (anticipation and inconveniences), workload (measured by National Aeronautics and Space Administration-Task Load Index (NASA-TLX)) and clinical outcomes (operative time, blood loss and surgical complexity) were determined using logistic regression and Pearson correlation. <h3>Results</h3> 1780 requests were observed, 703 (39%) were non-verbal. Utilisation of non-verbal requests differed significantly among surgeons (26%, 36% and 44%, p&lt;0.001). Anticipation was significantly associated with 'Situational Awareness' (OR 2.59, 95% CI 1.52 to 4.38, p&lt;0.001), 'Decision Making' (OR 0.42, 95% CI 0.33 to 0.55, p&lt;0.001) and 'Communication and Teamwork' (OR 0.43, 95% CI 0.25 to 0.74, p=0.002) domains. Inconveniences were significantly associated with 'Situational Awareness' (OR 0.21, 95% CI 0.08 to 0.59, p=0.003), 'Decision Making' (OR 2.73, 95% CI 1.53 to 4.86, p&lt;0.001), and 'Leadership' (OR 0.62, 95% CI 0.41 to 0.94, p=0.03). There was a significant positive correlation between NOTSS scores and perceived physical and mental workload measures of NASA-TLX, as well as self-perceived performance. There was no significant association between NOTSS scores and any of the investigated clinical outcomes. <h3>Conclusion</h3> NTS in the OR were associated with team efficiency, fewer surgical flow disruptions and an improved self-perceived performance.
Abstract 16260: Glutaredoxin1 Preserves Endoplasmic Reticulum Stress Response in Aortic Endothelium in Aging
Authors: Tomoko Mori, Yuxiang Zhou, Jingyan Han
Journal: Circulation (2019)

Introduction/Hypothesis: Vascular aging is associated with endoplasmic reticulum (ER) stress and oxidative stress, which are closely linked mechanisms that predispose the elderly to cardiovascular ...
Synergy between<i>Toxoplasma gondii</i>type I Δ<i>GRA17</i>immunotherapy and PD-L1 checkpoint inhibition triggers the regression of targeted and distal tumors
Authors: Yu-Chao Zhu, Hany M Elsheikha, Jian-Hua Wang, Shuai Fang, Jun-Jun He, Xing-Quan Zhu, Jia Chen
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background In this study, we hypothesize that the ability of the protozoan Toxoplasma gondii to modulate immune response within the tumor might improve the therapeutic effect of immune checkpoint blockade. We examined the synergetic therapeutic activity of attenuated T. gondii RH Δ GRA17 strain and programmed death ligand-1 (PD-L1) treatment on both targeted and distal tumors in mice. Methods The effects of administration of T. gondii RH Δ GRA17 strain on the tumor volume and survival rate of mice bearing flank B16-F10, MC38, or LLC tumors were studied. We characterized the effects of Δ GRA17 on tumor biomarkers’ expression, PD-L1 expression, immune cells infiltrating the tumors, and expression of immune-related genes by using immunohistochemistry, immunofluorescence, flow cytometry, NanoString platform, and real-time quantitative PCR, respectively. The role of immune cells in the efficacy of Δ GRA17 plus PD-L1 blockade therapy was determined via depletion of immune cell subtypes. Results Treatment with T. gondii Δ GRA17 tachyzoites and anti-PD-L1 therapy significantly extended the survival of mice and suppressed tumor growth in preclinical mouse models of melanoma, Lewis lung carcinoma, and colon adenocarcinoma. Attenuation of the tumor growth was detected in the injected and distant tumors, which was associated with upregulation of innate and adaptive immune pathways. Complete regression of tumors was underpinned by late interferon-gamma-producing CD8 + cytotoxic T cells. Conclusion The results from these models indicate that intratumoral injection of Δ GRA17 induced a systemic effect, improved mouse immune response, and sensitized immunologically ‘cold’ tumors and rendered them sensitive to immune checkpoint blockade therapy.
TCT-390 Clinical and Echocardiographic Outcomes of SAPIEN 3 Ultra TAVR in Extremely Undersized Versus Nominally Sized Annuli
Authors: Amit Hooda, Anthony Chuang, Syed Zaid, Parasuram Krishnamoorthy, Sahil Khera, Stamatios Lerakis, Hasan Ahmad, Joshua Goldberg, David Wood, Jonathon Leipsic, Philipp Blanke, George Dangas, Samin Sharma, Annapoorna Kini, John Webb, Janarthanan Sathananthan, Gilbert Tang
Journal: Journal of the American College of Cardiology (2021)
Diversity of Intratumoral Regulatory T Cells in Non-Hodgkin Lymphoma
Authors: Ivana Spasevska, Ankush Sharma, Chloe B. Steen, Sarah Josefsson, Yngvild Nuvin Blaker, Even H Rustad, Saskia Meyer, Stalin Chellappa, Kushi Kushekhar, Arne Kolstad, Klaus Beiske, Harald Holte, Bjørn Østenstad, Eva Kimby, Johanna Olweus, Kjetil Tasken, Suzanne Lorenz, Erlend B. Smeland, Ash A. Alizadeh, Kanutte Huse, June Helen Myklebust
Journal: Blood (2021)
Understanding Associations Between Attention-Deficit/Hyperactivity Disorder and Traumatic Brain Injury
Authors: Aparna Das, Kalpana P. Padala, Prasad R. Padala
Journal: JAMA Pediatrics (2021)

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Gas exchange: the neglected piece in the PAH puzzle
Authors: Paul M. Hassoun, Rogerio Souza, Marius M. Hoeper
Journal: European Respiratory Journal (2021)

Pulmonary arterial hypertension (PAH) remains a deadly disease despite the use of modern therapy, which consists essentially of vasodilators targeting three different pathways, the endothelin, nitric oxide and prostacyclin signalling pathways [1]. Factors helping the clinician to predict prognosis have long been sought after to identify patients at risk for poor survival [2], in order to guide therapy. More recently, the European Society of Cardiology (ESC)/European Respiratory Society (ERS) guidelines provided a comprehensive, multidimensional risk assessment table based on parameters most frequently used in pulmonary hypertension (PH) centres [3]. These variables would be obtained on regular visits with the understanding that not all would necessarily be checked at each visit. While most of the chosen variables and their cut-off criteria were based on expert opinion, the risk stratification assessment hence proposed was rapidly validated, mainly retrospectively, by various groups using their own PAH cohorts [4–6]. Boucly et al. [6] further demonstrated, in a subgroup of patients, that achieving adequate thresholds for three non-invasive criteria (World Health Organization/New York Heart Association functional class, 6-min walk distance and brain natriuretic peptide/N-terminal pro-BNP) at first re-evaluation also helped discriminate prognostic groups. Interestingly enough, markers of gas exchange are not part of current risk assessment strategies. Gas exchange parameters should be considered in PAH risk stratification <https://bit.ly/2SNrUEw>
Dissecting the heterogeneity and tumorigenesis of BRCA1 deficient mammary tumors via single cell RNA sequencing
Authors: Heng Sun, Jianming Zeng, Zhengqiang Miao, Kuan Cheok Lei, Chen Huang, Lingling Hu, Sek Man Su, Un In Chan, Kai Miao, Xu Zhang, Aiping Zhang, Sen Guo, Si Chen, Ya Meng, Min Deng, Wenhui Hao, Haipeng Lei, Ying Lin, Zhonglin Yang, Dongjiang Tang, Koon Ho Wong, Xiaohua Douglas Zhang, Xiaoling Xu, Chu-Xia Deng
Journal: Theranostics (2021)

Background: BRCA1 plays critical roles in mammary gland development and mammary tumorigenesis. And loss of BRCA1 induces mammary tumors in a stochastic manner. These tumors present great heterogeneity at both intertumor and intratumor levels. Methods: To comprehensively elucidate the heterogeneity of BRCA1 deficient mammary tumors and the underlying mechanisms for tumor initiation and progression, we conducted bulk and single cell RNA sequencing (scRNA-seq) on both mammary gland cells and mammary tumor cells isolated from Brca1 knockout mice. Results: We found the BRCA1 deficient tumors could be classified into four subtypes with distinct molecular features and different sensitivities to anti-cancer drugs at the intertumor level. Whereas within the tumors, heterogeneous subgroups were classified mainly due to the different activities of cell proliferation, DNA damage response/repair and epithelial-to-mesenchymal transition (EMT). Besides, we reconstructed the BRCA1 related mammary tumorigenesis to uncover the transcriptomes alterations during this process via pseudo-temporal analysis of the scRNA-seq data. Furthermore, from candidate markers for BRCA1 mutant tumors, we discovered and validated one oncogene Mrc2, whose loss could reduce mammary tumor growth in vitro and in vivo. Conclusion: Our study provides a useful resource for better understanding of mammary tumorigenesis induced by BRCA1 deficiency.
Dalpiciclib or placebo plus fulvestrant in hormone receptor-positive and HER2-negative advanced breast cancer: a randomized, phase 3 trial
Authors: Binghe Xu, Qingyuan Zhang, Pin Zhang, Xichun Hu, Wei Li, Zhongsheng Tong, Tao Sun, Yuee Teng, Xinhong Wu, Quchang Ouyang, Xi Yan, Jing Cheng, Qiang Liu, Jifeng Feng, Xiaojia Wang, Yongmei Yin, Yanxia Shi, Yueyin Pan, Yongsheng Wang, Weimin Xie, Min Yan, Yunjiang Liu, Ping Yan, Fei Wu, Xiaoyu Zhu, Jianjun Zou
Journal: Nature Medicine (2021)
Anti-GD2 IgA kills tumors by neutrophils without antibody-associated pain in the preclinical treatment of high-risk neuroblastoma
Authors: Mitchell Evers, Marjolein Stip, Kaylee Keller, Hanneke Willemen, Maaike Nederend, Marco Jansen, Chilam Chan, Kevin Budding, Stefan Nierkens, Thomas Valerius, Friederike Meyer-Wentrup, Niels Eijkelkamp, Jeanette Leusen
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background The addition of monoclonal antibody therapy against GD2 to the treatment of high-risk neuroblastoma led to improved responses in patients. Nevertheless, administration of GD2 antibodies against neuroblastoma is associated with therapy-limiting neuropathic pain. This severe pain is evoked at least partially through complement activation on GD2-expressing sensory neurons. Methods To reduce pain while maintaining antitumor activity, we have reformatted the approved GD2 antibody ch14.18 into the IgA1 isotype. This novel reformatted IgA is unable to activate the complement system but efficiently activates leukocytes through the FcαRI (CD89). Results IgA GD2 did not activate the complement system in vitro nor induced pain in mice. Importantly, neutrophil-mediated killing of neuroblastoma cells is enhanced with IgA in comparison to IgG, resulting in efficient tumoricidal capacity of the antibody in vitro and in vivo. Conclusions Our results indicate that employing IgA GD2 as a novel isotype has two major benefits: it halts antibody-induced excruciating pain and improves neutrophil-mediated lysis of neuroblastoma. Thus, we postulate that patients with high-risk neuroblastoma would strongly benefit from IgA GD2 therapy.
Polycystic Liver Disease: Advances in Understanding and Treatment
Authors: Tatyana V. Masyuk, Anatoliy I. Masyuk, Nicholas F. LaRusso
Journal: Annual Review of Pathology Mechanisms of Disease (2021)

Polycystic liver disease (PLD) is a group of genetic disorders characterized by progressive development of cholangiocyte-derived fluid-filled hepatic cysts. PLD is the most common manifestation of autosomal dominant and autosomal recessive polycystic kidney diseases and rarely occurs as autosomal dominant PLD. The mechanisms of PLD are a sequence of the primary (mutations in PLD-causative genes), secondary (initiation of cyst formation), and tertiary (progression of hepatic cystogenesis) interconnected molecular and cellular events in cholangiocytes. Nonsurgical, surgical, and limited pharmacological treatment options are currently available for clinical management of PLD. Substantial evidence suggests that pharmacological targeting of the signaling pathways and intracellular processes involved in the progression of hepatic cystogenesis is beneficial for PLD. Many of these targets have been evaluated in preclinical and clinical trials. In this review, we discuss the genetic, molecular, and cellular mechanisms of PLD and clinical and preclinical treatment strategies.
Exercise capacity impairment after COVID-19 pneumonia is mainly caused by deconditioning
Authors: Kathleen Jahn, Mihaela Sava, Gregor Sommer, Desiree M. Schumann, Stefano Bassetti, Martin Siegemund, Manuel Battegay, Daiana Stolz, Michael Tamm, Nina Khanna, Katrin E. Hostettler
Journal: European Respiratory Journal (2021)

Not pulmonary factors, but physical deconditioning is the main limiting factor of exercise capacity in patients after severe COVID-19 pneumonitis. This underscores the importance of an early rehabilitative intervention in these patients. <https://bit.ly/2XVvr6C>
Transcriptional Reprogramming Differentiates Active from Inactive ESR1 Fusions in Endocrine Therapy-Refractory Metastatic Breast Cancer
Authors: Xuxu Gou, Meenakshi Anurag, Jonathan T. Lei, Beom-Jun Kim, Purba Singh, Sinem Seker, Diana Fandino, Airi Han, Saif Rehman, Jianhong Hu, Viktoriya Korchina, Harshavardhan Doddapaneni, Lacey E. Dobrolecki, Nicholas Mitsiades, Michael T. Lewis, Alana L. Welm, Shunqiang Li, Adrian V. Lee, Dan R. Robinson, Charles E. Foulds, Matthew J. Ellis
Journal: Cancer Research (2021)

Abstract Genomic analysis has recently identified multiple ESR1 gene translocations in estrogen receptor alpha–positive (ERα+) metastatic breast cancer (MBC) that encode chimeric proteins whereby the ESR1 ligand binding domain (LBD) is replaced by C-terminal sequences from many different gene partners. Here we functionally screened 15 ESR1 fusions and identified 10 that promoted estradiol-independent cell growth, motility, invasion, epithelial-to-mesenchymal transition, and resistance to fulvestrant. RNA sequencing identified a gene expression pattern specific to functionally active ESR1 gene fusions that was subsequently reduced to a diagnostic 24-gene signature. This signature was further examined in 20 ERα+ patient-derived xenografts and in 55 ERα+ MBC samples. The 24-gene signature successfully identified cases harboring ESR1 gene fusions and also accurately diagnosed the presence of activating ESR1 LBD point mutations. Therefore, the 24-gene signature represents an efficient approach to screening samples for the presence of diverse somatic ESR1 mutations and translocations that drive endocrine treatment failure in MBC. Significance: This study identifies a gene signature diagnostic for functional ESR1 fusions that drive poor outcome in advanced breast cancer, which could also help guide precision medicine approaches in patients harboring ESR1 mutations.
Cell-to-cell Interaction between Endothelial Cell and Monocyte Enhances MMP-9 Activity: Possible Role of Adhesion Molecule P-selectin
Authors: Yamamoto Yuko, Osanai Tomohiro, Sagara Shigeki, Izumiyama Kei, Hanada Kenji, Shibutani Shuji, Yokoyama Hiroaki, Yokota Takashi, Okumura Ken
Journal: Circulation (2010)