tbuckley/cabot-search huggingface dataset:
Engagement with health in national climate change commitments under the Paris Agreement: a global mixed-methods analysis of the nationally determined contributions
Authors: Niheer Dasandi, Hilary Graham, Pete Lampard, Slava Jankin Mikhaylov
Journal: The Lancet Planetary Health (2021)

BackgroundInstituted under the Paris Agreement, nationally determined contributions (NDCs) outline countries' plans for mitigating and adapting to climate change. They are the primary policy instrument for protecting people's health in the face of rising global temperatures. However, evidence on engagement with health in the NDCs is scarce. In this study, we aimed to examine how public health is incorporated in the NDCs, and how different patterns of engagement might be related to broader inequalities and tensions in global climate politics.MethodsWe analysed the NDCs in the UN Framework Convention on Climate Change registry submitted by 185 countries. Using content analysis and natural language processing (NLP) methods, we developed measures of health engagement. Multivariate regression analyses examined whether country-level factors (eg, population size, gross domestic product [GDP], and climate-related exposures) were associated with greater health engagement. Using NLP methods, we compared health engagement with other climate-related challenges (ie, economy, energy, and agriculture) and examined broader differences in the keyword terms used in countries with high and low health engagement in their NDCs.FindingsCountries that did not mention health in their NDCs were clustered in high-income countries, whereas greater health engagement was concentrated in low-income and middle-income countries. Having a low GDP per capita and being a small island developing state were associated with higher levels of health engagement. In addition, higher levels of population exposure to temperature change and ambient air pollution were associated with more health coverage included in a country's NDC. Variation in health engagement was greater than for other climate-related issues and reflected wider differences in countries' approaches to the NDCs.InterpretationA focus on health in the NDCs follows broader patterns of global inequalities. Poorer and climate-vulnerable countries that contribute least to climate change are more likely to engage with health in their NDCs, while richer countries focus on non-health sectors in their NDCs, such as energy and the economy.FundingThis work was in part funded through an unrestricted grant from the Wellcome Trust and supported by The Economic and Social Research Council.
Advances in retina imaging as potential biomarkers for early diagnosis of Alzheimer’s disease
Authors: Ying Zhang, Yanjiang Wang, Ce Shi, Meixiao Shen, Fan Lu
Journal: Translational Neurodegeneration (2021)

As the most common form of dementia, Alzheimer's disease (AD) is characterized by progressive cognitive impairments and constitutes a major social burden. Currently, the invasiveness and high costs of tests have limited the early detection and intervention of the disease. As a unique window of the brain, retinal changes can reflect the pathology of the brain. In this review, we summarize current understanding of retinal structures in AD, mild cognitive impairment (MCI) and preclinical AD, focusing on neurodegeneration and microvascular changes measured using optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) technologies. The literature suggests that the impairment of retinal microvascular network and neural microstructure exists in AD, MCI and even preclinical AD. These findings provide valuable insights into a better understanding of disease pathogenesis and demonstrate that retinal changes are potential biomarkers for early diagnosis of AD and monitoring of disease progression.
Multimodal Strategy for Myocardial Protection During Cardiac Surgery
Authors: Pascal Chiari, Nathan Mewton, Delphine Maucort-Boulch, Olivier Desebbe, Michel Durand, Marc-Olivier Fischer, Diane Lena-Quintard, Jean-Charles Palao, Michel Ovize, Jean-Luc Fellahi
Journal: Journal of the American College of Cardiology (2021)
Mitochondrial Inhibitor Atovaquone Increases Tumor Oxygenation and Inhibits Hypoxic Gene Expression in Patients with Non–Small Cell Lung Cancer
Authors: Michael Skwarski, Daniel R. McGowan, Elizabeth Belcher, Francesco Di Chiara, Dionisios Stavroulias, Mark McCole, Jennifer L. Derham, Kwun-Ye Chu, Eugene Teoh, Jagat Chauhan, Dawn O’Reilly, Benjamin H.L. Harris, Philip S. Macklin, Joshua A. Bull, Marcus Green, Gonzalo Rodriguez-Berriguete, Remko Prevo, Lisa K. Folkes, Leticia Campo, Petra Ferencz, Paula L. Croal, Helen Flight, Cathy Qi, Jane Holmes, James P.B. O’Connor, Fergus V. Gleeson, W. Gillies McKenna, Adrian L. Harris, Daniel Bulte, Francesca M. Buffa, Ruth E. Macpherson, Geoff S. Higgins
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Tumor hypoxia fuels an aggressive tumor phenotype and confers resistance to anticancer treatments. We conducted a clinical trial to determine whether the antimalarial drug atovaquone, a known mitochondrial inhibitor, reduces hypoxia in non–small cell lung cancer (NSCLC). Patients and Methods: Patients with NSCLC scheduled for surgery were recruited sequentially into two cohorts: cohort 1 received oral atovaquone at the standard clinical dose of 750 mg twice daily, while cohort 2 did not. Primary imaging endpoint was change in tumor hypoxic volume (HV) measured by hypoxia PET-CT. Intercohort comparison of hypoxia gene expression signatures using RNA sequencing from resected tumors was performed. Results: Thirty patients were evaluable for hypoxia PET-CT analysis, 15 per cohort. Median treatment duration was 12 days. Eleven (73.3%) atovaquone-treated patients had meaningful HV reduction, with median change −28% [95% confidence interval (CI), −58.2 to −4.4]. In contrast, median change in untreated patients was +15.5% (95% CI, −6.5 to 35.5). Linear regression estimated the expected mean HV was 55% (95% CI, 24%–74%) lower in cohort 1 compared with cohort 2 (P = 0.004), adjusting for cohort, tumor volume, and baseline HV. A key pharmacodynamics endpoint was reduction in hypoxia-regulated genes, which were significantly downregulated in atovaquone-treated tumors. Data from multiple additional measures of tumor hypoxia and perfusion are presented. No atovaquone-related adverse events were reported. Conclusions: This is the first clinical evidence that targeting tumor mitochondrial metabolism can reduce hypoxia and produce relevant antitumor effects at the mRNA level. Repurposing atovaquone for this purpose may improve treatment outcomes for NSCLC.
Outcomes of a Mobile App to Monitor Patient‐Reported Outcomes in Rheumatoid Arthritis: A Randomized Controlled Trial
Authors: Yvonne C. Lee, Fengxin Lu, Joshua Colls, Dee Luo, Penny Wang, Dorothy D. Dunlop, Lutfiyya N. Muhammad, Jing Song, Kaleb Michaud, Daniel H. Solomon
Journal: Arthritis & Rheumatology (2021)

Objective To examine the effects of a smartphone application (app) to monitor longitudinal electronic patient‐reported outcomes (ePROs) on patient satisfaction and disease activity in patients with rheumatoid arthritis (RA). Methods We conducted a 6‐month randomized controlled trial of care coordination along with an app (intervention) versus care coordination alone (control) in 191 RA patients. Participants in the intervention group were prompted to provide information daily using ePROs. In both the intervention and control groups, a care coordinator contacted participants at 6 and 18 weeks to assess for flares. The main outcome measures were the global satisfaction score from the Treatment Satisfaction Questionnaire for Medication (TSQM), the score from the Perceived Efficacy in Patient‐Physician Interactions (PEPPI) Questionnaire, and the Clinical Disease Activity Index (CDAI) score. Results Groups were similar at baseline. The median TSQM score at 6 months was 83.3 in both groups, and the median PEPPI score at 6 months was 50 in both groups. The median CDAI score at 6 months was 8 in the intervention group versus 10 in the control group. No statistically significant group differences in the medians of TSQM, PEPPI, or CDAI scores at 6 months were detected. Of the 67 intervention participants who completed the exit survey, 90% rated their likelihood of recommending the app as ≥7 of 10. Of the 11 physicians who completed the exit survey, 73% agreed/strongly agreed that they wanted to continue offering the app to patients. Conclusion A mobile app designed to collect ePRO data on RA symptoms did not significantly improve patient satisfaction or disease activity compared to care coordination alone. However, both patients and physicians reported positive experiences with the app.
Antibacterial fatty acids: An update of possible mechanisms of action and implications in the development of the next-generation of antibacterial agents
Authors: Giancarlo Casillas-Vargas, Carlimar Ocasio-Malavé, Solymar Medina, Christian Morales-Guzmán, René García Del Valle, Néstor M. Carballeira, David J. Sanabria-Ríos
Journal: Progress in Lipid Research (2021)

The antibacterial activity of fatty acids (FA) is well known in the literature and represents a promising option for developing the next-generation of antibacterial agents to treat a broad spectrum of bacterial infections. FA are highly involved in living organisms' defense system against numerous pathogens, including multidrug-resistant bacteria. When combined with other antibacterial agents, the remarkable ability of FA to enhance their bactericidal properties is a critical feature that is not commonly observed in other naturally-occurring compounds. More reviews focusing on FA antibacterial activity, traditional and non-traditional mechanisms and biomedical applications are needed. This review is intended to update the reader on the antibacterial properties of recent FA and how their chemical structures influence their antibacterial activity. This review also aims to better understand both traditional and non-traditional mechanisms involved in these recently explored FA antibacterial activities.
Involvement of the microbiota-gut-brain axis in chronic restraint stress: disturbances of the kynurenine metabolic pathway in both the gut and brain
Authors: Yuanyuan Deng, Manfei Zhou, Junfeng Wang, Jiaxi Yao, Jing Yu, Wenwei Liu, Linlin Wu, Jun Wang, Rong Gao
Journal: Gut Microbes (2021)

Emerging evidence suggests that the gut microbiota may interact with the host brain and play pivotal roles in the pathogenesis of neuropsychiatric disorders. However, the mechanism underlying reciprocal interactions along the microbiota-gut-brain axis in depression remains unclear. In this study, a murine model of chronic restraint stress (CRS) was established to investigate the metabolic signaling of tryptophan (Trp) neurotransmission at the intestinal and central levels in depression. The results showed that CRS mice displayed depression- and anxiety-like behaviors. Additionally, kynurenine (Kyn) and its metabolites, an important Trp metabolic pathway, were strongly activated in the brain. Intriguingly, the Kyn toxic signaling was exacerbated in the gut, especially in the colon. Indoleamine 2,3-dioxygenase (IDO), a rate-limiting enzyme responsible for Kyn metabolic pathway initiation, was significantly upregulated in the brain and gut in CRS mice compared with control mice, promoting transfer of Trp metabolic pathway to Kyn signaling. Additionally, administration of IDO inhibitor, 1-methyl-tryptophan (1-MT), partially rescued CRS-induced depression- and anxiety-like changes. Moreover, the enhanced intestinal permeability mediated by CRS allowed toxic metabolites to "leak" into the bloodstream. The microbiome profiles of CRS mice displayed obviously altered taxonomic composition and negative correlations were observed between Enterorhabdus, Parabacteroides and Kyn levels in the brain. Reciprocal crosstalk between the brain and gut was further validated by citalopram treatment, IDO inhibitor and microbiota intervention, which counteracted depression-like behavior, Kyn metabolic signaling and microbiota composition in CRS mice. Meanwhile, Parabacteroides treatment affected Trp metabolism in mouse hippocampus, manifesting as elevated concentration of 5-HT as well as ratio of 5-HT to Trp. These results suggest that long-term stress disrupts Kyn metabolism and endocrine function along the gut-brain axis, accompanied by the disrupted homeostasis of certain microbiota, which collectively contribute to the development of depression-like behavior.
Abstract 19441: Novel Telecommunications Software for Two-Way Interaction during ST-Segment Elevation Myocardial Infarction Management Improves Door-to-Balloon Times
Authors: Gabriel Sardi, Lowell Satler, Joshua Loh, Rebecca Torguson, Kenneth Kent, William Suddath, Augusto Pichard, Ron Waksman
Journal: Circulation (2012)

Background: A pre-hospital electrocardiogram (ECG) improves the management of patients with ST-segment elevation myocardial infarction (STEMI). Current telecommunication systems do not permit real-time interaction with first responders in the field or with care providers at referring hospitals. Our institution has developed a novel telecommunications system based on a software application that is downloadable to multiple platforms to permit real-time, two-way video and voice interaction over a secured, Health Insurance Portability and Accountability Act (HIPPA) compliant network. Hypothesis: Use of the CodeHeart application (CHap) for patients with possible acute coronary syndrome (ACS) will reduce door-to-balloon (DTB) times of STEMI patients. Methods: All STEMI system activations after implementation of the CHap were prospectively entered into a database. Consecutive CHap activations were compared to routine activations as controls, during the same time period (03/14/2011 to 12/31/2011). System quality measures were calculated and compared using Student’s t test or the Mann-Whitney U test as appropriate. Results: A total of 360 STEMI system activations occurred. 62 (17%) employed CHap and 298 (83%) routine channels. DTB times were reduced by the use of CHap when compared to controls (95.3±35’ vs. 154.6±102.4’, p=0.0009) as were first call-to-balloon times (68.9±29.3’ vs. 91.7±40’, p=0.004), which highlights the efficiency of the system for transferred patients. The percentage of catheterization laboratory activations for a true STEMI was higher with the use of CHap, although this trend did not reach statistical significance. [CHap 38/62 (61.3%) vs. routine 148/298 (49.7%), p=0.12]. Conclusion: The implementation of a two-way telecommunications system that allows for real-time interactions between interventional cardiologists and referring practitioners improves overall DTB time and transfer time. In addition, it has the potential to decrease the frequency of false activations, therefore improving cost-efficiency of a network’s STEMI system.
Predicting COVID-19 mortality with electronic medical records
Authors: Hossein Estiri, Zachary H. Strasser, Jeffy G. Klann, Pourandokht Naseri, Kavishwar B. Wagholikar, Shawn N. Murphy
Journal: npj Digital Medicine (2021)

Abstract This study aims to predict death after COVID-19 using only the past medical information routinely collected in electronic health records (EHRs) and to understand the differences in risk factors across age groups. Combining computational methods and clinical expertise, we curated clusters that represent 46 clinical conditions as potential risk factors for death after a COVID-19 infection. We trained age-stratified generalized linear models (GLMs) with component-wise gradient boosting to predict the probability of death based on what we know from the patients before they contracted the virus. Despite only relying on previously documented demographics and comorbidities, our models demonstrated similar performance to other prognostic models that require an assortment of symptoms, laboratory values, and images at the time of diagnosis or during the course of the illness. In general, we found age as the most important predictor of mortality in COVID-19 patients. A history of pneumonia, which is rarely asked in typical epidemiology studies, was one of the most important risk factors for predicting COVID-19 mortality. A history of diabetes with complications and cancer (breast and prostate) were notable risk factors for patients between the ages of 45 and 65 years. In patients aged 65–85 years, diseases that affect the pulmonary system, including interstitial lung disease, chronic obstructive pulmonary disease, lung cancer, and a smoking history, were important for predicting mortality. The ability to compute precise individual-level risk scores exclusively based on the EHR is crucial for effectively allocating and distributing resources, such as prioritizing vaccination among the general population.
An Open-label, Multicenter, Single-arm, Phase II Study of Fluzoparib in Patients with Germline <i>BRCA1/2</i> Mutation and Platinum-sensitive Recurrent Ovarian Cancer
Authors: Ning Li, Hualei Bu, Jihong Liu, Jianqing Zhu, Qi Zhou, Li Wang, Rutie Yin, Xiaohua Wu, Shuzhong Yao, Kangsheng Gu, Hui Zhang, Guiling Li, Hongming Pan, Qiang Wu, Ruifang An, Xinfeng Yang, Yaping Zhu, Xiaoping Wan, Wei Duan, Jianping Xiong, Hongyan Guo, Ge Lou, Jing Wang, Wenjing Hu, Xin Zhang, Yuanguang Meng, Ben Zhang, Yuting Wang, Quanren Wang, Lingying Wu
Journal: Clinical Cancer Research (2021)

Fluzoparib (PARP inhibitor) showed promising antitumor activity for advanced ovarian cancer in a phase I study. This study aimed to assess the efficacy and safety of fluzoparib in patients with germline BRCA1/2-mutated recurrent ovarian cancer.This open-label, multicenter, single-arm, phase II study enrolled patients with platinum-sensitive recurrent ovarian cancer and germline BRCA1/2 mutation who had previously received two to four lines of platinum-based chemotherapy. Fluzoparib 150 mg was administered orally twice daily. The primary endpoint was independent review committee (IRC)-assessed objective response rate per RECIST v1.1.A total of 113 patients were enrolled and received at least one dose of fluzoparib. As of data cutoff on March 21, 2020, the median follow-up period was 15.9 months (interquartile range, 13.5-18.5). The IRC- and investigator-assessed objective response rates were 69.9% [95% confidence interval (CI), 60.6-78.2] and 70.8% (95% CI, 61.5-79.0), respectively. The objective response rates were similar across all prespecified subgroups. The median IRC- and investigator-assessed progression-free survival was 12.0 months (95% CI, 9.3-13.9) and 10.3 months (95% CI, 9.2-12.0), respectively. The 12-month survival rate was 93.7% (95% CI, 87.2-96.9). Grade ≥3 adverse events occurred in 63.7% (72/113) of the patients, with the most common one being anemia/decreased hemoglobin. Adverse events that led to treatment interruption, dose reduction, and discontinuation occurred in 39.8%, 34.5%, and 0.9% of patients, respectively. One treatment-related death occurred.Fluzoparib demonstrated promising antitumor activity and acceptable safety profile in germline BRCA1/2-mutated, platinum-sensitive relapsed ovarian cancer. Thus, fluzoparib might be a novel treatment option for this population.
Diffuse Glioma Heterogeneity and Its Therapeutic Implications
Authors: James G. Nicholson, Howard A. Fine
Journal: Cancer Discovery (2021)

Diffuse gliomas represent a heterogeneous group of universally lethal brain tumors characterized by minimally effective genotype-targeted therapies. Recent advances have revealed that a remarkable level of genetic, epigenetic, and environmental heterogeneity exists within each individual glioma. Together, these interconnected layers of intratumoral heterogeneity result in extreme phenotypic heterogeneity at the cellular level, providing for multiple mechanisms of therapeutic resistance and forming a highly adaptable and resilient disease. In this review, we discuss how glioma intratumoral heterogeneity and malignant cellular state plasticity drive resistance to existing therapies and look to a future in which these challenges may be overcome. SIGNIFICANCE: Glioma intratumoral heterogeneity and malignant cell state plasticity represent formidable hurdles to the development of novel targeted therapies. However, the convergence of genotypically diverse glioma cells into a limited set of epigenetically encoded transcriptional cell states may present an opportunity for a novel therapeutic strategy we call "State Selective Lethality." In this approach, cellular states (as opposed to genetic perturbations/mutations) are the subject of therapeutic targeting, and plasticity-mediated resistance is minimized through the design of cell state "trapping agents."
COVID-19 and Common Variable Immunodeficiency
Authors: Marina Kaminski, Gabriela Yoshimoto, Luiza Silva, Ana Garcia, Natasha Ferraroni
Journal: Journal of Allergy and Clinical Immunology (2021)

Common Variable Immunodeficiency (CVI) is rare primary immunodeficiency. The COVID-19 pandemics rised the risc os infection in these patients. We describe a 27 year old male patient with CVI, in regular replacement of human immunoglobulin (600mg/kg), with parotiditis and night sweating. The diagnosis os COVID was suspected. Two days later, he presented diarrhea. The diagnosis of COVID-19 was made by blood test -serology and a RT-qPCR for SARS-CoV-2. He received azithromycin, zinc, ivermectin and vitamin D, and he received human gammaglobulin 1 week in advance. IgM anti-SARS CoV-2 serology of 4.73 AU / ml (Reference <1) and IgG negative. In addition, a C-reactive protein test was requested, which showed a high result 8.712 mg/dL. Chest CT scan was ordered and showed no changes related to early stages of viral infections. IL-6, fibrinogen and D-dimer were normal. At the time of infecction IgG=1150 (700-1600mg/dL), IgA=28 (70-400mg/dL), IgM=19 (40-230mg/dL). The literature is scarce with regard to the relationship between primary immunodeficiencies and SARS CoV-2 infection, however, there is a consensus that patients with primary immunodeficiencies mostly present more severe conditions when infected with this virus. Fortunately, this patient recovered well, and progressed to cure of the viral syndrome. CT chest scan was unremakable. To our knowledge, this is the first report of parotidis in a patient with CVI and COVID-19.
Iron homeostasis in host and gut bacteria – a complex interrelationship
Authors: Yohannes Seyoum, Kaleab Baye, Christèle Humblot
Journal: Gut Microbes (2021)

Iron deficiency is the most frequent nutritional deficiency in the world with an estimated 1.4 billion people affected. The usual way to fight iron deficiency is iron fortification, but this approach is not always effective and can have undesirable side effects including an increase in the growth and virulence of gut bacterial pathogens responsible for diarrhea and gut inflammation. Iron is mainly absorbed in the duodenum and is tightly regulated in mammals. Unabsorbed iron enters the colonic lumen where many microorganisms, referred to as gut microbiota, reside. Iron is essential for these bacteria, and its availability consequently affects this microbial ecosystem. The aim of this review is to provide further insights into the complex relationship between iron and gut microbiota. Given that overcoming anemia caused by iron deficiency is still a challenge today, gut microbiota could help identify more efficient ways to tackle this public health problem.