tbuckley/cabot-search huggingface dataset:
E-cigarette Unit Sales, by Product and Flavor Type — United States, 2014–2020
Authors: Fatma Romeh M. Ali, Megan C. Diaz, Donna Vallone, Michael A. Tynan, Jamie Cordova, Elizabeth L. Seaman, Katrina F. Trivers, Barbara A. Schillo, Brandon Talley, Brian A. King
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Since electronic cigarettes (e-cigarettes) entered the U.S. marketplace in 2007, the landscape has evolved to include different product types (e.g., prefilled cartridge-based and disposable products) and flavored e-liquids (e.g., fruit, candy, mint, menthol, and tobacco flavors), which have contributed to increases in youth use (1,2). E-cigarettes have been the most commonly used tobacco product among U.S. youths since 2014; in 2019, 27.5% of high school students reported current e-cigarette use (3). To assess trends in unit sales of e-cigarettes in the United States by product and flavor type, CDC, CDC Foundation, and Truth Initiative analyzed retail scanner data during September 14, 2014-May 17, 2020, from Information Resources, Inc. (IRI). During this period, total e-cigarette sales increased by 122.2%, from 7.7 million to 17.1 million units per 4-week interval. By product type, the proportion of total sales that was prefilled cartridge products increased during September 2014-August 2019 (47.5% to 89.4%). During August 2019-May 2020, the proportion of total sales that was disposable products increased from 10.3% to 19.8%, while the proportion that was prefilled cartridge products decreased (89.4% to 80.2%). Among prefilled cartridge sales, the proportion of mint sales increased during September 2014-August 2019 (<0.1% to 47.6%); during August 2019-May 2020, mint sales decreased (47.6% to 0.3%), as menthol sales increased (10.7% to 61.8%). Among disposable e-cigarette sales during September 2014-May 2020, the proportion of mint sales increased (<0.1% to 10.5%), although tobacco-flavored (52.2% to 17.2%) and menthol-flavored (30.3% to 10.2%) sales decreased; during the same period, sales of all other flavors combined increased (17.2% to 62.1%). E-cigarette sales increased during 2014-2020, but fluctuations occurred overall and by product and flavor type, which could be attributed to consumer preferences and accessibility. Continued monitoring of e-cigarette sales and use is critical to inform strategies at the national, state, and community levels to minimize the risks of e-cigarettes on individual- and population-level health. As part of a comprehensive approach to prevent and reduce youth e-cigarettes use, such strategies could include those that address youth-appealing product innovations and flavors.
The emerging role of super enhancer-derived noncoding RNAs in human cancer
Authors: Yutong Wang, Hui Nie, Xiaoyun He, Zhiming Liao, Yangying Zhou, Jianhua Zhou, Chunlin Ou
Journal: Theranostics (2020)

Super enhancers (SEs) are large clusters of adjacent enhancers that drive the expression of genes which regulate cellular identity; SE regions can be enriched with a high density of transcription factors, co-factors, and enhancer-associated epigenetic modifications. Through enhanced activation of their target genes, SEs play an important role in various diseases and conditions, including cancer. Recent studies have shown that SEs not only activate the transcriptional expression of coding genes to directly regulate biological functions, but also drive the transcriptional expression of non-coding RNAs (ncRNAs) to indirectly regulate biological functions. SE-derived ncRNAs play critical roles in tumorigenesis, including malignant proliferation, metastasis, drug resistance, and inflammatory response. Moreover, the abnormal expression of SE-derived ncRNAs is closely related to the clinical and pathological characterization of tumors. In this review, we summarize the functions and roles of SE-derived ncRNAs in tumorigenesis and discuss their prospective applications in tumor therapy. A deeper understanding of the potential mechanism underlying the action of SE-derived ncRNAs in tumorigenesis may provide new strategies for the early diagnosis of tumors and targeted therapy.
Two C-terminal sequence variations determine differential neurotoxicity between human and mouse α-synuclein
Authors: Natalie Landeck, Katherine E. Strathearn, Daniel Ysselstein, Kerstin Buck, Sayan Dutta, Siddhartha Banerjee, Zhengjian Lv, John D. Hulleman, Jagadish Hindupur, Li-Kai Lin, Sonal Padalkar, Lia A. Stanciu, Yuri L. Lyubchenko, Deniz Kirik, Jean-Christophe Rochet
Journal: Molecular Neurodegeneration (2020)

Abstract Background α-Synuclein (aSyn) aggregation is thought to play a central role in neurodegenerative disorders termed synucleinopathies, including Parkinson’s disease (PD). Mouse aSyn contains a threonine residue at position 53 that mimics the human familial PD substitution A53T, yet in contrast to A53T patients, mice show no evidence of aSyn neuropathology even after aging. Here, we studied the neurotoxicity of human A53T, mouse aSyn, and various human-mouse chimeras in cellular and in vivo models, as well as their biochemical properties relevant to aSyn pathobiology. Methods Primary midbrain cultures transduced with aSyn-encoding adenoviruses were analyzed immunocytochemically to determine relative dopaminergic neuron viability. Brain sections prepared from rats injected intranigrally with aSyn-encoding adeno-associated viruses were analyzed immunohistochemically to determine nigral dopaminergic neuron viability and striatal dopaminergic terminal density. Recombinant aSyn variants were characterized in terms of fibrillization rates by measuring thioflavin T fluorescence, fibril morphologies via electron microscopy and atomic force microscopy, and protein-lipid interactions by monitoring membrane-induced aSyn aggregation and aSyn-mediated vesicle disruption. Statistical tests consisted of ANOVA followed by Tukey’s multiple comparisons post hoc test and the Kruskal-Wallis test followed by a Dunn’s multiple comparisons test or a two-tailed Mann-Whitney test. Results Mouse aSyn was less neurotoxic than human aSyn A53T in cell culture and in rat midbrain, and data obtained for the chimeric variants indicated that the human-to-mouse substitutions D121G and N122S were at least partially responsible for this decrease in neurotoxicity. Human aSyn A53T and a chimeric variant with the human residues D and N at positions 121 and 122 (respectively) showed a greater propensity to undergo membrane-induced aggregation and to elicit vesicle disruption. Differences in neurotoxicity among the human, mouse, and chimeric aSyn variants correlated weakly with differences in fibrillization rate or fibril morphology. Conclusions Mouse aSyn is less neurotoxic than the human A53T variant as a result of inhibitory effects of two C-terminal amino acid substitutions on membrane-induced aSyn aggregation and aSyn-mediated vesicle permeabilization. Our findings highlight the importance of membrane-induced self-assembly in aSyn neurotoxicity and suggest that inhibiting this process by targeting the C-terminal domain could slow neurodegeneration in PD and other synucleinopathy disorders.
Family Meetings on Behalf of Patients with Serious Illness
Authors: Eric Widera, Wendy G. Anderson, Lekshmi Santhosh, Kanako Y. McKee, Alexander K. Smith, James Frank
Journal: New England Journal of Medicine (2020)

Family Meetings on Behalf of Patients with Serious Illness Effective family meetings build rapport and offer support, provide updates about a patient’s medical status and prognosis, and ensure trea...
Author Correction: A dynamic COVID-19 immune signature includes associations with poor prognosis
Authors: Adam G. Laing, Anna Lorenc, Irene del Molino del Barrio, Abhishek Das, Matthew Fish, Leticia Monin, Miguel Muñoz-Ruiz, Duncan R. McKenzie, Thomas S. Hayday, Isaac Francos-Quijorna, Shraddha Kamdar, Magdalene Joseph, Daniel Davies, Richard Davis, Aislinn Jennings, Iva Zlatareva, Pierre Vantourout, Yin Wu, Vasiliki Sofra, Florencia Cano, Maria Greco, Efstathios Theodoridis, Joshua D. Freedman, Sarah Gee, Julie Nuo En Chan, Sarah Ryan, Eva Bugallo-Blanco, Pärt Peterson, Kai Kisand, Liis Haljasmägi, Loubna Chadli, Philippe Moingeon, Lauren Martinez, Blair Merrick, Karen Bisnauthsing, Kate Brooks, Mohammad A. A. Ibrahim, Jeremy Mason, Federico Lopez Gomez, Kola Babalola, Sultan Abdul-Jawad, John Cason, Christine Mant, Jeffrey Seow, Carl Graham, Katie J. Doores, Francesca Di Rosa, Jonathan Edgeworth, Manu Shankar-Hari, Adrian C. Hayday
Journal: Nature Medicine (2020)

A Correction to this paper has been published: https://doi.org/10.1038/s41591-020-01186-5
Breast Cancer Screening Trials: Endpoints and Overdiagnosis
Authors: Ismail Jatoi, Paul F Pinsky
Journal: JNCI Journal of the National Cancer Institute (2020)

Screening mammography was assessed in 9 randomized trials initiated between 1963 and 1990, with breast cancer-specific mortality as the primary endpoint. In contrast, breast cancer detection has been the primary endpoint in most screening trials initiated during the past decade. These trials have evaluated digital breast tomosynthesis, magnetic resonance imaging, and ultrasound, and novel screening strategies have been recommended solely on the basis of improvements in breast cancer detection rates. Yet, the assumption that increases in tumor detection produce reductions in cancer mortality has not been validated, and tumor-detection endpoints may exacerbate the problem of overdiagnosis. Indeed, the detection of greater numbers of early stage breast cancers in the absence of a subsequent decline in rates of metastatic cancers and cancer-related mortality is the hallmark of overdiagnosis. There is now evidence to suggest that both ductal carcinoma in situ and invasive cancers are overdiagnosed as a consequence of screening. For each patient who is overdiagnosed with breast cancer, the adverse consequences include unnecessary anxiety, financial hardships, and a small risk of morbidity and mortality from unnecessary treatments. Moreover, the overtreatment of breast cancer, as a consequence of overdiagnosis, is costly and contributes to waste in health-care spending. In this article, we argue that there is a need to establish better endpoints in breast cancer screening trials, including quality of life and composite endpoints. Tumor-detection endpoints should be abandoned, because they may lead to the implementation of screening strategies that increase the risk of overdiagnosis.
Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial
Authors: Keren Shahar-Nissan, Joseph Pardo, Orit Peled, Irit Krause, Efraim Bilavsky, Arnon Wiznitzer, Eran Hadar, Jacob Amir
Journal: The Lancet (2020)
The US politicisation of the pandemic: Raul Grijalva on masks, BAME, and covid-19
Authors: Paul D Thacker
Journal: BMJ (2020)

Democratic congressman Raul Grijalva infamously caught covid-19 after attending a Black Lives Matter hearing with a Republican who downplayed wearing a mask. He speaks to <b>Paul D Thacker</b> about the politicisation of the pandemic and disproportionate health burdens affecting minority groups
Exploring the structural distribution of genetic variation in SARS-CoV-2 with the COVID-3D online resource
Authors: Stephanie Portelli, Moshe Olshansky, Carlos H. M. Rodrigues, Elston N. D’Souza, Yoochan Myung, Michael Silk, Azadeh Alavi, Douglas E. V. Pires, David B. Ascher
Journal: Nature Genetics (2020)
I sympathise with both the supporters and naysayers of hierarchical communication rules
Authors: Eugene Y H Yeung
Journal: BMJ (2020)

I sympathise with both the supporters and naysayers of hierarchical communication “rules.”1 When your job is to advise over the telephone, you want the caller to have seen the patient and have the investigation results handy. It is frustrating if the caller provides inadequate or inaccurate information, especially when all you receive is “this patient needs to be reviewed.” It appears the …
Altered Hemodynamics and End-Organ Damage in Heart Failure
Authors: Frederik H. Verbrugge, Marco Guazzi, Jeffrey M. Testani, Barry A. Borlaug
Journal: Circulation (2020)

Heart failure is characterized by pathologic hemodynamic derangements, including elevated cardiac filling pressures (“backward” failure), which may or may not coexist with reduced cardiac output (“forward” failure). Even when normal during unstressed conditions such as rest, hemodynamics classically become abnormal during stressors such as exercise in patients with heart failure. This has important upstream and downstream effects on multiple organ systems, particularly with respect to the lungs and kidneys. Hemodynamic abnormalities in heart failure are affected by processes that extend well beyond the cardiac myocyte, including important roles for pericardial constraint, ventricular interaction, and altered venous capacity. Hemodynamic perturbations have widespread effects across multiple heart failure phenotypes, ranging from reduced to preserved ejection fraction, acute to chronic disease, and cardiogenic shock to preserved perfusion states. In the lung, hemodynamic derangements lead to the development of abnormalities in ventilatory control and efficiency, pulmonary congestion, capillary stress failure, and eventually pulmonary vascular disease. In the kidney, hemodynamic perturbations lead to sodium and water retention and worsening renal function. Improved understanding of the mechanisms by which altered hemodynamics in heart failure affect the lungs and kidneys is needed in order to design novel strategies to improve clinical outcomes.
A new role for circulating T follicular helper cells in humoral response to anti-PD-1 therapy
Authors: Santiago Sánchez-Alonso, Giulia Setti-Jerez, Montserrat Arroyo, Tathiana Hernández, Mª Inmaculada Martos, Jose Miguel Sánchez-Torres, Ramon Colomer, Almudena R Ramiro, Arantzazu Alfranca
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Lung cancer is one of the most frequent malignancies in humans and is a major cause of death. A number of therapies aimed at reinforcing antitumor immune response, including antiprogrammed cell death protein 1 (anti-PD-1) antibodies, are successfully used to treat several neoplasias as non-small cell lung cancer (NSCLC). However, host immune mechanisms that participate in response to anti-PD-1 therapy are not completely understood. Methods We used a syngeneic immunocompetent mouse model of NSCLC to analyze host immune response to anti-PD-1 treatment in secondary lymphoid organs, peripheral blood and tumors, by flow cytometry, immunohistochemistry and quantitative real-time PCR (qRT-PCR). In addition, we also studied specific characteristics of selected immune subpopulations in ex vivo functional assays. Results We show that anti-PD-1 therapy induces a population of circulating T follicular helper cells (cTfh) with enhanced B activation capacity, which participates in tumor response to treatment. Anti-PD-1 increases the number of tertiary lymphoid structures (TLS), which correlates with impaired tumor growth. Of note, TLS support cTfh-associated local antibody production, which participates in host immune response against tumor. Conclusion These findings unveil a novel mechanism of action for anti-PD-1 therapy and provide new targets for optimization of current therapies against lung cancer.
Abstract 15367: The Association of Coronary Artery Calcium With Cause-Specific Mortality in Adults Aged 30-49 Years: The CAC Consortium
Authors: Michael D Miedema, Zeina A Dardari, Khurram Nasir, Thomas Knickelbine, Sandra Oberembt, Leslee Shaw, John Rumberger, Alan Rozanski, Daniel S Berman, Matthew Budoff, Michael J Blaha
Journal: Circulation (2017)

Introduction: Coronary artery calcium (CAC) is a strong predictor of CHD, ASCVD, and total mortality in middle-aged and older adults, but the impact of CAC on mortality in young adults is less clea...
LncRNA DSCAM-AS1 interacts with YBX1 to promote cancer progression by forming a positive feedback loop that activates FOXA1 transcription network
Authors: Yin Zhang, Yong-Xin Huang, Dan-Lan Wang, Bing Yang, Hai-Yan Yan, Le-Hang Lin, Yun Li, Jie Chen, Li-Min Xie, Yong-Sheng Huang, Jian-You Liao, Kai-Shun Hu, Jie-Hua He, Phei Er Saw, Xiaoding Xu, Dong Yin
Journal: Theranostics (2020)

Rationale: The forkhead box A1 (FOXA1) is a crucial transcription factor in initiation and development of breast, lung and prostate cancer. Previous studies about the FOXA1 transcriptional network were mainly focused on protein-coding genes. Its regulatory network of long non-coding RNAs (lncRNAs) and their role in FOXA1 oncogenic activity remains unknown. Methods: The Cancer Genome Atlas (TCGA) data, RNA-seq and ChIP-seq data were used to analyze FOXA1 regulated lncRNAs. RT-qPCR was used to detect the expression of DSCAM-AS1, RT-qPCR and Western blotting were used to determine the expression of FOXA1, estrogen receptor α (ERα) and Y box binding protein 1 (YBX1). RNA pull-down and RIP-qPCR were employed to investigate the interaction between DSCAM-AS1 and YBX1. The effect of DSCAM-AS1 on malignant phenotypes was examined through in vitro and in vivo assays. Results: In this study, we conducted a global analysis of FOXA1 regulated lncRNAs. For detailed analysis, we chose lncRNA DSCAM-AS1, which is specifically expressed in lung adenocarcinoma, breast and prostate cancer. The expression level of DSCAM-AS1 is regulated by two super-enhancers (SEs) driven by FOXA1. High expression levels of DSCAM-AS1 was associated with poor prognosis. Knockout experiments showed DSCAM-AS1 was essential for the growth of xenograft tumors. Moreover, we demonstrated DSCAM-AS1 can regulate the expression of the master transcriptional factor FOXA1. In breast cancer, DSCAM-AS1 was also found to regulate ERα. Mechanistically, DSCAM-AS1 interacts with YBX1 and influences the recruitment of YBX1 in the promoter regions of FOXA1 and ERα. Conclusion: Our study demonstrated that lncRNA DSCAM-AS1 was transcriptionally activated by super-enhancers driven by FOXA1 and exhibited lineage-specific expression pattern. DSCAM-AS1 can promote cancer progression by interacting with YBX1 and regulating expression of FOXA1 and ERα.
CheXaid: deep learning assistance for physician diagnosis of tuberculosis using chest x-rays in patients with HIV
Authors: Pranav Rajpurkar, Chloe O’Connell, Amit Schechter, Nishit Asnani, Jason Li, Amirhossein Kiani, Robyn L. Ball, Marc Mendelson, Gary Maartens, Daniël J. van Hoving, Rulan Griesel, Andrew Y. Ng, Tom H. Boyles, Matthew P. Lungren
Journal: npj Digital Medicine (2020)

Tuberculosis (TB) is the leading cause of preventable death in HIV-positive patients, and yet often remains undiagnosed and untreated. Chest x-ray is often used to assist in diagnosis, yet this presents additional challenges due to atypical radiographic presentation and radiologist shortages in regions where co-infection is most common. We developed a deep learning algorithm to diagnose TB using clinical information and chest x-ray images from 677 HIV-positive patients with suspected TB from two hospitals in South Africa. We then sought to determine whether the algorithm could assist clinicians in the diagnosis of TB in HIV-positive patients as a web-based diagnostic assistant. Use of the algorithm resulted in a modest but statistically significant improvement in clinician accuracy (p = 0.002), increasing the mean clinician accuracy from 0.60 (95% CI 0.57, 0.63) without assistance to 0.65 (95% CI 0.60, 0.70) with assistance. However, the accuracy of assisted clinicians was significantly lower (p < 0.001) than that of the stand-alone algorithm, which had an accuracy of 0.79 (95% CI 0.77, 0.82) on the same unseen test cases. These results suggest that deep learning assistance may improve clinician accuracy in TB diagnosis using chest x-rays, which would be valuable in settings with a high burden of HIV/TB co-infection. Moreover, the high accuracy of the stand-alone algorithm suggests a potential value particularly in settings with a scarcity of radiological expertise.
Redox‐Responsive Self‐Assembled Nanoparticles for Cancer Therapy
Authors: Dandan Li, Ruhe Zhang, Guiting Liu, Yang Kang, Jun Wu
Journal: Advanced Healthcare Materials (2020)

Abstract Chemotherapy, combined with other treatments, is widely applied in the clinical treatment of cancer. However, deficiencies inherited from the traditional route of administration limit its successful application. With the development of nanotechnology, a series of smart nanodelivery systems have been developed to utilize the unique tumor environment (pH changes, different enzymes, and redox potential gradients) and exogenous stimuli (thermal changes, magnetic fields, and light) to improve the curative effect of anticancer drugs. In this review, endogenous and exogenous stimuli are briefly introduced. Among these stimuli, various redox‐sensitive linkages are primarily described in detail, and their application with self‐assembled nanoparticles is recounted. Finally, the application of redox‐responsive self‐assembled nanoparticles in cancer therapy is summarized.
Immune-checkpoint inhibitors plus chemotherapy versus chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer
Authors: Fei Zhou, Wencheng Zhao, Xiaomei Gong, Shengxiang Ren, Chunxia Su, Tao Jiang, Caicun Zhou
Journal: Journal for ImmunoTherapy of Cancer (2020)

We performed a meta-analysis to comprehensively investigate the efficacy and safety of immune-checkpoint inhibitors (ICIs) plus chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC). The primary outcome was overall survival (OS). The secondary outcomes included progression-free survival (PFS), objective response rate (ORR) and ≥grade 3 adverse events (AEs). A total of six studies involving 2905 patients were identified, including 469 patients receiving program death ligand 1 (PD-L1) inhibitor plus chemotherapy, 308 receiving PD-1 inhibitors plus chemotherapy, 563 receiving CTLA-4 inhibitors plus chemotherapy, 268 receiving PD-L1/CTLA-4 inhibitors plus chemotherapy, and 1297 receiving chemotherapy alone. 10.8% (283/2615) patients had baseline brain metastases (BMs). Notably, ICIs plus chemotherapy was associated with significantly improved OS (HR, 0.82; 95% CI, 0.75 to 0.89). Subgroup analyses revealed that PD-1 inhibitors (HR, 0.77; 95% CI, 0.64 to 0.92) and PD-L1 inhibitors (HR, 0.73; 95% CI, 0.63 to 0.85) plus chemotherapy yielded a statistically significant improvement in OS while CTLA-4 inhibitors did not (HR, 0.92; 95% CI, 0.81 to 1.06). In patients with baseline BMs, ICIs plus chemotherapy showed no survival benefits over chemotherapy alone (HR, 1.23; 95% CI, 0.92 to 1.64). ICIs plus chemotherapy also significantly prolonged PFS (HR, 0.81; 95% CI, 0.75 to 0.87) while the pooled ORRs were comparable between ICIs plus chemotherapy and chemotherapy alone (RR, 1.04; 95% CI, 0.99 to 1.10). Patients treated with CTLA-4 inhibitors (relative risk (RR), 1.12; 95% CI, 0.99 to 1.28) experienced more≥grade 3 AEs than those treated with PD-1/PD-L1 inhibitors (RR, 1.03; 95% CI, 0.96 to 1.11). The addition of PD-1/PD-L1 inhibitors to chemotherapy resulted in significant improvements in both PFS and OS for patients with treatment-naïve ES-SCLC, not at the cost of increased AEs.
Building an Evidence Base for Survivors of Critical Illness
Authors: Daniela Lamas
Journal: New England Journal of Medicine (2020)

On rounds in the long-term acute care hospital, I am surprised to see a familiar name on my list — a patient with respiratory failure whom I had initially admitted to our intensive care unit (ICU). In the early days of his critical illness, we had debated ventilator management and choice of antibiotic agents, with every decision dictated by a body of evidence. Now, months later, I am at his bedside once again. And this time he has a question for me. Gesturing impatiently to the tracheostomy tube in his neck, he asks, "When can this come out?" I hesitate. . . .