tbuckley/cabot-search huggingface dataset:
Association of Sulfur, Transition Metals, and the Oxidative Potential of Outdoor PM2.5 with Acute Cardiovascular Events: A Case-Crossover Study of Canadian Adults
Authors: Scott Weichenthal, Eric Lavigne, Alison Traub, Dana Umbrio, Hongyu You, Krystal Pollitt, Tim Shin, Ryan Kulka, Dave M. Stieb, Jill Korsiak, Barry Jessiman, Jeff R. Brook, Marianne Hatzopoulou, Greg Evans, Richard T. Burnett
Journal: Environmental Health Perspectives (2021)

Background: We do not currently understand how spatiotemporal variations in the composition of fine particulate air pollution [fine particulate matter with aerodynamic diameter ≤2.5μm (PM2.5)] affects population health risks. However, recent evidence suggests that joint concentrations of transition metals and sulfate may influence the oxidative potential (OP) of PM2.5 and associated health impacts. Objectives: The purpose of the study was to evaluate how combinations of transition metals/OP and sulfur content in outdoor PM2.5 influence associations with acute cardiovascular events. Methods: We conducted a national case-crossover study of outdoor PM2.5 and acute cardiovascular events in Canada between 2016 and 2017 (93,344 adult cases). Monthly mean transition metal and sulfur (S) concentrations in PM2.5 were determined prospectively along with estimates of OP using acellular assays for glutathione (OPGSH), ascorbate (OPAA), and dithiothreitol depletion (OPDTT). Conditional logistic regression models were used to estimate odds ratios (OR) [95% confidence intervals (CI)] for PM2.5 across strata of transition metals/OP and sulfur. Results: Among men, the magnitudes of observed associations were strongest when both transition metal and sulfur content were elevated. For example, an OR of 1.078 (95% CI: 1.049, 1.108) (per 10μg/m3) was observed for cardiovascular events in men when both copper and S were above the median, whereas a weaker association was observed when both elements were below median values (OR=1.019, 95% CI: 1.007, 1.031). A similar pattern was observed for OP metrics. PM2.5 was not associated with acute cardiovascular events in women. Discussion: The combined transition metal and sulfur content of outdoor PM2.5 influences the strength of association with acute cardiovascular events in men. Regions with elevated concentrations of both sulfur and transition metals in PM2.5 should be examined as priority areas for regulatory interventions. https://doi.org/10.1289/EHP9449
FP01.04 Prospective Observational Study of Activities of Daily Livings in Elderly Patients After Lung Cancer Surgery (JCOG1710A)
Authors: H. Takei, H. Kunitoh, M. Wakabayashi, T. Kataoka, T. Mizutani, M. Tsuboi, N. Ikeda, H. Asamura, M. Okada, M. Takahama, Y. Ohde, J. Okami, S. Shiono, K. Aokage, S. Watanabe
Journal: Journal of Thoracic Oncology (2021)
Changes in COVID-19 Vaccine Intent From April/May to June/July 2021
Authors: Peter G. Szilagyi, Kyla Thomas, Megha D. Shah, Nathalie Vizueta, Yan Cui, Sitaram Vangala, Arie Kapteyn
Journal: JAMA (2021)

Aaron J. Siegler, MHS, PhD; Nicole Luisi, MS; Eric W. Hall, MPH, PhD; Heather Bradley, PhD; Travis Sanchez, PhD, DVM; Benjamin A. Lopman, PhD; Patrick S. Sullivan, PhD, DVM
Factors Affecting Genetic Consultation in Adolescent and Young Adult Patients With Sarcoma
Authors: Grace E. McKay, Anna L. Zakas, Fauzia Osman, Amanda Parkes
Journal: Journal of the National Comprehensive Cancer Network (2021)

Given a link between sarcomas and hereditary cancer predisposition syndromes, including Li-Fraumeni syndrome, the consideration for genetic counseling is recommended for all adolescent and young adult (AYA) patients diagnosed with sarcoma. The aim of this study was to evaluate factors influencing genetic consultations in AYA patients with sarcoma at the University of Wisconsin (UW).
Evaluation of health outcomes in patients aged 70 years and above with glioblastoma multiforme in NHS Tayside between 2017-2020
Authors: Caitlin Finnan, Hannah Lord
Journal: Neuro-Oncology (2021)

Abstract Aims The aim of this study is to evaluate health-related outcomes in patients aged 70 years and above diagnosed with glioblastoma multiforme (GBM) in NHS Tayside between 2017-2020. Objectives include identification of factors which influence the oncological treatment modalities pursued; disease progression/recurrence and outcomes within each treatment modality category. Method Medical databases were reviewed retrospectively to identify patients aged 70 years and above diagnosed with GBM in NHS Tayside, between 2017-2020. Analysed data identified patients' past medical history, symptoms and investigations preceding diagnosis; date of first brain imaging which demonstrated abnormality in-keeping with a likely diagnosis of GBM; factors influencing treatment modalities undertaken, molecular and genetic analysis of tumour samples; disease recurrence/progression, and date of death if applicable. Results 54 patients diagnosed with GBM. 13 patients were aged over 70 years. 8 males, 5 females. Commonest co-morbid conditions were hypertension and gout. 2/13 received best supportive care only, based on poor performance status and extensive disease burden. 9/13 underwent neurosurgery; 7 debulked; 2 biopsy only. 7 isocitrate dehydrogenase (IDH1) wild-type; 2 IDH classification not known. 3 MGMT methylated; 4 unmethylated; 2 MGMT classification not known.3/13 received temozolomide (TMZ) alone. 2 later received palliative radiotherapy (30Gy in 6 #) to control symptoms. 4/13 received 40Gy in 15 # with concurrent TMZ 4/13 received 60Gy in 30 # with concurrent TMZ. 5 received adjuvant TMZ following initial chemo-radiation: 3 after 40Gy and 2 after 60Gy. As of March 2021, 6/13 were alive, including all 4 who had received hypofractionated radiotherapy. 4 of these continue to demonstrate stable disease on most recent imaging. Conclusion Baseline fitness levels of patients were generally high, with few having significant co-morbidity pre-diagnosis. Prognosis and morbidity was significantly poorer in patients who did not undergo any form of radiotherapy. Patients who received hypofractionated radiotherapy demonstrated most favourable health-related outcomes, demonstrating longest survival and least evidence of disease recurrence/progression.Although the sample size for this study is small, it highlights the potential benefits of radiotherapy on survival, particularly hypofractionated courses such as 40Gy in 15 fractions in a real-world population, even during a global pandemic. It would be useful to prospectively follow-up elderly patients with GBM to assess outcomes and quality of life.
Distinct Features of Probands With Early Repolarization and Brugada Syndromes Carrying SCN5A Pathogenic Variants
Authors: Zhong-He Zhang, Hector Barajas-Martínez, Hao Xia, Bian Li, John A. Capra, Jerome Clatot, Gan-Xiao Chen, Xiu Chen, Bo Yang, Hong Jiang, Gary Tse, Yoshiyasu Aizawa, Michael H. Gollob, Melvin Scheinman, Charles Antzelevitch, Dan Hu
Journal: Journal of the American College of Cardiology (2021)
Self‐Cycling Free Radical Generator from LDH‐Based Nanohybrids for Ferroptosis‐Enhanced Chemodynamic Therapy
Authors: Xueting Yang, Li Wang, Shuaitian Guo, Ran Li, Fangzhen Tian, Shanyue Guan, Shuyun Zhou, Jun Lu
Journal: Advanced Healthcare Materials (2021)

Nonapoptotic ferroptosis has been a novel form of programmed cell death, which provides a new solution to enrich the anticancer treatment efficacy of traditional apoptotic therapeutic modality. Herein, a novel nanohybrid is designed by loading the PEG-encapsulated Artemisinin (denoted as A@P) on the ultrathin MgFe-LDH nanosheets (denoted as uLDHs) for improved chemodynamic therapy (CDT). The A@P/uLDHs cannot only realize the self-assembly between the Art and carrier but also be regarded as free radical generator. A comprehensive mechanistic study suggests that this unique A@P/uLDHs is able to in situ activate Art and self-cycling generate toxic C-centered free radical inside the cancer cells, without depending on abundant H2 O2 , accompanied with diminished cancerous antioxidation by depleting glutathione (GSH). The accumulation of ROS and depletion of GSH can further oxidize unsaturated fatty acid to generate lipid peroxide, whose overexpression can induce cell ferroptosis accompanied by cellular iron homeostasis turbulence. Both in vitro and in vivo results exhibit that A@P/uLDHs are an efficient nanoagent for highly efficient ferroptosis-enhanced CDT treatment. This work imparts the promising new visions about the ferroptosis-enhanced CDT via fine regulation of material design for improved cancer treatments.
P39.01 Long-Term Outcomes and Characteristics of Unresectable Locally Advanced Thymic Malignancies
Authors: A. Sideris, X. Li, H. Oufkir, M. Curry, K.S. Tan, J. Araujo-Filho, E. Robinson, D. Jones, M. Ginsberg, A. Rimner, G. Riely, J. Huang
Journal: Journal of Thoracic Oncology (2021)
Nails with bloodstained discoloration
Authors: Stamatios Gregoriou, Eftychia Platsidaki,, Polytimi Sidiropoulou, Dimitrios Rigopoulos
Journal: BMJ (2021)

A woman in her 60s presented with a four month history of nail discoloration (chromonychia). On examination, diffuse erythema with a purpuric hue was noted on the nail bed of all fingernails (nail bed haemorrhage), as well as loss of adhesion of the nail to the nail bed (onycholysis) (fig 1). There were no clinical signs on the toenails. The palms and soles presented a fine desquamation that extended all the way to the dorsal surface and the tips. Diffuse alopecia was evident on the scalp. The patient had no other symptoms or signs involving the skin or any other system.



Fig 1 
Diffuse purpuric erythema on all fingernails of a 60 year old woman



Six months earlier she had undergone surgery for advanced breast cancer and was started on docetaxel at a dose of 75 mg/m …
Predicted impact of intravenous thrombolysis
Authors: J. Berwaerts
Journal: BMJ (2000)

# Patients who died or recovered fully should have been included in analysis {#article-title-2} EDITOR—Jørgensen et al report a simulation of the impact of intravenous thrombolysis on prognosis for a general population of stroke patients.1 Although we do not argue with their conclusion that comparatively few patients with acute ischaemic stroke will benefit from thrombolytic treatment, we believe that their analysis of the data is flawed. During their retrospective analysis Jørgensen et al identified patients who fulfilled the criteria for thrombolysis and then excluded patients who died or had a full recovery. They subsequently excluded the same groups of patients from the ideal scenario in which all patients were admitted within the time window for thrombolysis. Had thrombolysis actually been given, the outcomes for these patients would have been unknown at the time of administration. These patients should therefore have been included in the analysis. 1. 1.↵1. Jørgensen HS, 2. Nakayama H, 3. Kammersgaard LP, 4. Raaschou HO, 5. Olsen TS . Predicted impact of intravenous thrombolysis on prognosis of general population of stroke patients: simulation model. BMJ 1999; 319: 288–289. (31 July.) [OpenUrl][1][FREE Full Text][2] # Another trial is needed {#article-title-4} EDITOR—The paper by Jørgensen et al provides a small counterbalance to the enormous propaganda behind an expensive, minimally tested, and potentially harmful intervention.1 The real ratio of benefit to risk of thrombolytics for stroke may even be far worse than Jørgensen et al calculate, for the following reasons. Firstly, even fewer … [1]: {openurl}?query=rft.jtitle%253DBMJ%26rft.stitle%253DBMJ%26rft.issn%253D0007-1447%26rft.aulast%253DJorgensen%26rft.auinit1%253DH.%2BS.%26rft.volume%253D319%26rft.issue%253D7205%26rft.spage%253D288%26rft.epage%253D289%26rft.atitle%253DPredicted%2Bimpact%2Bof%2Bintravenous%2Bthrombolysis%2Bon%2Bprognosis%2Bof%2Bgeneral%2Bpopulation%2Bof%2Bstroke%2Bpatients%253A%2Bsimulation%2Bmodel%26rft_id%253Dinfo%253Apmid%252F10426737%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/ijlink?linkType=FULL&journalCode=bmj&resid=319/7205/288&atom=%2Fbmj%2F320%2F7240%2F1006.atom
FP05.05 A Prospective Observational Study of Osimertinib Using Plasma Concentrations in NSCLC With Acquired EGFR T790M Mutation
Authors: T. Nakagawa, T. Fukuhara, K. Imai, R. Igusa, H. Yokota, K. Watanabe, A. Suzuki, M. Morita, A. Inoue, M. Miura, Y. Minamiya, M. Maemondo
Journal: Journal of Thoracic Oncology (2021)
OA15.02 Phase 1 Studies of DZD9008, an Oral Selective EGFR/HER2 Inhibitor in Advanced NSCLC with EGFR Exon20 Insertion Mutations
Authors: P. Janne, M. Wang, P. Mitchell, J. Fang, W. Nian, C. Chiu, J. Zhou, Y. Zhao, W. Su, D.R. Camidge, T. Yang, V. Zhu, M. Millward, Y. Fan, W. Huang, Y. Cheng, L. Jiang, D. Brungs, L. Bazhenova, C.K. Lee, B. Gao, S. Qi, X. Yu, C. Deng, K. Chen, X. Ye, L. Zheng, Z. Yang, J.C. Yang
Journal: Journal of Thoracic Oncology (2021)
P51.03 Oritinib (SH-1028), a Third-generation EGFR-TKI in Advanced NSCLC Patients with Positive EGFR T790M: Results of a Single-arm Phase Ib Trial
Authors: C. Zhou, A. Xiong, L. Miao, J. Chen, K. Li, H. Liu, Z. Ma, H. Wang, Z. Lu, J. Shen, J. Zhao, W. Li, M. Bi, J. Zhang, L. Xing
Journal: Journal of Thoracic Oncology (2021)
Cystic fibrosis-related liver disease: Clinical presentations, diagnostic and monitoring approaches in the era of CFTR modulator therapies
Authors: Jérémy Dana, Dominique Debray, Aurélie Beaufrère, Sophie Hillaire, Monique Fabre, Caroline Reinhold, Thomas F. Baumert, Laureline Berteloot, Valérie Vilgrain
Journal: Journal of Hepatology (2021)
Molecular Characterization of Peritoneal Mesotheliomas
Authors: Michael Offin, Soo-Ryum Yang, Jacklynn Egger, Gowtham Jayakumaran, Rowanne S Spencer, Jessica Lopardo, Garrett M Nash, Andrea Cercek, William D Travis, Mark G Kris, Marc Ladanyi, Jennifer L Sauter, Marjorie G Zauderer
Journal: Journal of Thoracic Oncology (2021)
I didn’t train as a GP to legally kill my patients
Authors: John E Etherton
Journal: BMJ (2021)

On 14 September 2021, I analysed the rapid responses to Hurley and colleagues’ article on assisted dying of 9 September 2021,1 finding that all 11 responses expressed opposition. This reflects a response to the partisan stance of The BMJ , which is not proportionately representative of BMA members’ views.

Breen’s response, “Mercy killing—malice of …
Analgesic Potential of Terpenes Derived from<i>Cannabis sativa</i>
Authors: Erika Liktor-Busa, Attila Keresztes, Justin LaVigne, John M. Streicher, Tally M. Largent-Milnes
Journal: Pharmacological Reviews (2021)

Pain prevalence among adults in the United States has increased 25% over the past two decades, resulting in high health-care costs and impacts to patient quality of life. In the last 30 years, our understanding of pain circuits and (intra)cellular mechanisms has grown exponentially, but this understanding has not yet resulted in improved therapies. Options for pain management are limited. Many analgesics have poor efficacy and are accompanied by severe side effects such as addiction, resulting in a devastating opioid abuse and overdose epidemic. These problems have encouraged scientists to identify novel molecular targets and develop alternative pain therapeutics. Increasing preclinical and clinical evidence suggests that cannabis has several beneficial pharmacological activities, including pain relief. <i>Cannabis sativa</i> contains more than 500 chemical compounds, with two principle phytocannabinoids, Δ<sup>9</sup>-tetrahydrocannabinol (Δ<sup>9</sup>-THC) and cannabidiol (CBD). Beyond phytocannabinoids, more than 150 terpenes have been identified in different cannabis chemovars. Although the predominant cannabinoids, Δ<sup>9</sup>-THC and CBD, are thought to be the primary medicinal compounds, terpenes including the monoterpenes <i>β</i>-myrcene, <i>α</i>-pinene, limonene, and linalool, as well as the sesquiterpenes <i>β</i>-caryophyllene and <i>α</i>-humulene may contribute to many pharmacological properties of cannabis, including anti-inflammatory and antinociceptive effects. The aim of this review is to summarize our current knowledge about terpene compounds in cannabis and to analyze the available scientific evidence for a role of cannabis-derived terpenes in modern pain management. <h3>Significance Statement</h3> Decades of research have improved our knowledge of cannabis polypharmacy and contributing phytochemicals, including terpenes. Reform of the legal status for cannabis possession and increased availability (medicinal and recreational) have resulted in cannabis use to combat the increasing prevalence of pain and may help to address the opioid crisis. Better understanding of the pharmacological effects of cannabis and its active components, including terpenes, may assist in identifying new therapeutic approaches and optimizing the use of cannabis and/or terpenes as analgesic agents.
P59.30 Genomic Landscape of Lung Cancer in the Young
Authors: R. Ruiz, M. Galvez-Nino, K. Roque, J. Montes, M. Nuñez, L. Raez, S. Sánchez-Gambetta, S. Jauregui, S. Viale, E. Smith, L. Mas, J. Pinto
Journal: Journal of Thoracic Oncology (2021)
Positive Selection and Horizontal Gene Transfer in the Genome of a Male-Killing <i>Wolbachia</i>
Authors: Tom Hill, Robert L Unckless, Jessamyn I Perlmutter
Journal: Molecular Biology and Evolution (2021)

Wolbachia are a genus of widespread bacterial endosymbionts in which some strains can hijack or manipulate arthropod host reproduction. Male killing is one such manipulation in which these maternally transmitted bacteria benefit surviving daughters in part by removing competition with the sons for scarce resources. Despite previous findings of interesting genome features of microbial sex ratio distorters, the population genomics of male-killers remain largely uncharacterized. Here, we uncover several unique features of the genome and population genomics of four Arizonan populations of a male-killing Wolbachia strain, wInn, that infects mushroom-feeding Drosophila innubila. We first compared the wInn genome with other closely related Wolbachia genomes of Drosophila hosts in terms of genome content and confirm that the wInn genome is largely similar in overall gene content to the wMel strain infecting D. melanogaster. However, it also contains many unique genes and repetitive genetic elements that indicate lateral gene transfers between wInn and non-Drosophila eukaryotes. We also find that, in line with literature precedent, genes in the Wolbachia prophage and Octomom regions are under positive selection. Of all the genes under positive selection, many also show evidence of recent horizontal transfer among Wolbachia symbiont genomes. These dynamics of selection and horizontal gene transfer across the genomes of several Wolbachia strains and diverse host species may be important underlying factors in Wolbachia's success as a male-killer of divergent host species.
Nonalcoholic fatty liver disease and early prediction of gestational diabetes mellitus using machine learning methods
Authors: Seung Mi Lee, Suhyun Hwangbo, Errol R. Norwitz, Ja Nam Koo, Ig Hwan Oh, Eun Saem Choi, Young Mi Jung, Sun Min Kim, Byoung Jae Kim, Sang Youn Kim, Gyoung Min Kim, Won Kim, Sae Kyung Joo, Sue Shin, Chan-Wook Park, Taesung Park, Joong Shin Park
Journal: Clinical and Molecular Hepatology (2021)

To develop an early prediction model for gestational diabetes mellitus (GDM) using machine learning and to evaluate whether the inclusion of nonalcoholic fatty liver disease (NAFLD)-associated variables increases the performance of model.This prospective cohort study evaluated pregnant women for NAFLD using ultrasound at 10-14 weeks and screened them for GDM at 24-28 weeks of gestation. The clinical variables before 14 weeks were used to develop prediction models for GDM (setting 1, conventional risk factors; setting 2, addition of new risk factors in recent guidelines; setting 3, addition of routine clinical variables; setting 4, addition of NALFD-associated variables, including the presence of NAFLD and laboratory results; and setting 5, top 11 variables identified from a stepwise variable selection method). The predictive models were constructed using machine learning methods, including logistic regression, random forest, support vector machine, and deep neural networks.Among 1,443 women, 86 (6.0%) were diagnosed with GDM. The highest performing prediction model among settings 1-4 was setting 4, which included both clinical and NAFLD-associated variables (area under the receiver operating characteristic curve [AUC] 0.563-0.697 in settings 1-3 vs. 0.740-0.781 in setting 4). Setting 5, with top 11 variables (which included NAFLD and hepatic steatosis index), showed similar predictive power to setting 4 (AUC 0.719-0.819 in setting 5, P=not significant between settings 4 and 5).We developed an early prediction model for GDM using machine learning. The inclusion of NAFLDassociated variables significantly improved the performance of GDM prediction. (ClinicalTrials.gov Identifier: NCT02276144).
Genetic inhibition of nuclear factor of activated T-cell c2 prevents atrial fibrillation in CREM transgenic mice
Authors: Li Ni, Satadru K Lahiri, Jiali Nie, Xiaolu Pan, Issam Abu-Taha, Julia O Reynolds, Hannah M Campbell, Haihao Wang, Markus Kamler, Wilhelm Schmitz, Frank Ulrich Müller, Na Li, Xiang Wei, Dao Wen Wang, Dobromir Dobrev, Xander H T Wehrens
Journal: Cardiovascular Research (2021)

Abstract Aims Abnormal intracellular calcium (Ca2+) handling contributes to the progressive nature of atrial fibrillation (AF), the most common sustained cardiac arrhythmia. Evidence in mouse models suggests that activation of the nuclear factor of activated T-cell (NFAT) signalling pathway contributes to atrial remodelling. Our aim was to determine the role of NFATc2 in AF in humans and mouse models. Methods and results Expression levels of NFATc1–c4 isoforms were assessed by quantitative reverse transcription–polymerase chain reaction in right atrial appendages from patients with chronic AF (cAF). NFATc1 and NFATc2 mRNA levels were elevated in cAF patients compared with those in normal sinus rhythm (NSR). Western blotting revealed increased cytosolic and nuclear levels of NFATc2 in AF patients. Similar findings were obtained in CREM-IbΔC-X transgenic (CREM) mice, a model of progressive AF. Telemetry ECG recordings revealed age-dependent spontaneous AF in CREM mice, which was prevented by NFATc2 knockout in CREM:NFATc2–/– mice. Programmed electrical stimulation revealed that CREM:NFATc2–/– mice lacked an AF substrate. Morphometric analysis and histology revealed increased atrial weight and atrial fibrosis in CREM mice compared with wild-type controls, which was reversed in CREM:NFATc2–/– mice. Confocal microscopy showed an increased Ca2+ spark frequency despite a reduced sarcoplasmic reticulum (SR) Ca2+ load in CREM mice compared with controls, whereas these abnormalities were normalized in CREM:NFATc2–/– mice. Western blotting revealed that genetic inhibition of Ca2+/calmodulin-dependent protein kinase II-mediated phosphorylation of S2814 on ryanodine receptor type 2 (RyR2) in CREM:RyR2-S2814A mice suppressed NFATc2 activation observed in CREM mice, suggesting that NFATc2 is activated by excessive SR Ca2+ leak via RyR2. Finally, chromatin immunoprecipitation sequencing from AF patients identified Ras and EF-hand domain-containing protein (Rasef) as a direct target of NFATc2-mediated transcription. Conclusion Our findings reveal activation of the NFAT signalling pathway in patients of Chinese and European descent. NFATc2 knockout prevents the progression of AF in the CREM mouse model.
Assisted dying doesn’t require doctors but due legal process to protect patients, doctors, and society
Authors: Susan Bewley
Journal: BMJ (2021)

Caring doctors are divided when the noble ends of prolonging life and relieving suffering conflict.12 Most agree with supporting dignified death and respecting patients’ wishes. As others have already noted,3 it’s incorrect that assisted dying requires doctors.4 Doctors need not be given the power of enabler decision makers, even for …