tbuckley/cabot-search huggingface dataset:
Addressing the carbon footprint, healthfulness, and costs of self-selected diets in the USA: a population-based cross-sectional study
Authors: Amelia Willits-Smith, Rodrigo Aranda, Martin C Heller, Donald Rose
Journal: The Lancet Planetary Health (2020)

BackgroundThe role of diet in health is well established and, in the past decade, more attention has been given to the role of food choices in the environment. The agricultural sector produces about a quarter of the world's greenhouse gas emissions (GHGE), and meat production, especially beef, is an important contributor to global GHGE. Our study aimed to address a fundamental gap in the diet-climate literature: identifying consumers who are receptive to making dietary changes, and the effect of their potential changes on GHGE, diet healthfulness, and diet costs.MethodsDietary data on US individuals from a nationally representative survey were linked to food-related GHGE. We identified individuals receptive to changing their diets (potential changers) as those who reported trying US dietary guidance and were likely to agree that humans contribute to climate change. We assessed GHGE, diet healthfulness measured by the Healthy Eating Index (HEI), and diet costs before and after hypothetical changes replacing either beef or meats with poultry or plant-protein foods.FindingsOur sample comprised 7188 individuals, of whom 16% were potential changers. These were disproportionately women, highly educated, or had higher income compared with individuals deemed not likely to change. Replacing 100% of beef intake in potential changers with poultry reduced mean dietary GHGE by 1·38 kg CO2-equivalents per person per day (95% CI 1·19–1·58), a 35·7% decrease. This replacement also increased mean HEI by 1·7% and reduced mean diet costs by 1·7%. We observed the largest changes when replacing all beef, pork, or poultry intake with plant-protein foods (GHGE decreased by 49·6%, mean HEI increased by 8·7%, and dietary costs decreased by 10·5%). Hypothetical replacements in the potential changers alone resulted in whole population reductions in 1-day dietary GHGE of 1·2% to 6·7%, equivalent to 22–126 million fewer passenger vehicle km.InterpretationIndividual-level diet studies that include a variation in response by consumers can improve our understanding of the effects of climate policies such as those that include sustainability information in national dietary guidance. In our study, we found that changes by a small percentage of motivated individuals can modestly reduce the national dietary GHGE. Moreover, these substitutions can modestly improve diet healthfulness and reduce diet costs for individuals who make these changes.FundingWellcome Trust.
Experimental Parasite Infection Causes Genome-Wide Changes in DNA Methylation
Authors: Kostas Sagonas, Britta S Meyer, Joshka Kaufmann, Tobias L Lenz, Robert Häsler, Christophe Eizaguirre
Journal: Molecular Biology and Evolution (2020)

Parasites are arguably among the strongest drivers of natural selection, constraining hosts to evolve resistance and tolerance mechanisms. Although, the genetic basis of adaptation to parasite infection has been widely studied, little is known about how epigenetic changes contribute to parasite resistance and eventually, adaptation. Here, we investigated the role of host DNA methylation modifications to respond to parasite infections. In a controlled infection experiment, we used the three-spined stickleback fish, a model species for host-parasite studies, and their nematode parasite Camallanus lacustris. We showed that the levels of DNA methylation are higher in infected fish. Results furthermore suggest correlations between DNA methylation and shifts in key fitness and immune traits between infected and control fish, including respiratory burst and functional trans-generational traits such as the concentration of motile sperm. We revealed that genes associated with metabolic, developmental, and regulatory processes (cell death and apoptosis) were differentially methylated between infected and control fish. Interestingly, genes such as the neuropeptide FF receptor 2 and the integrin alpha 1 as well as molecular pathways including the Th1 and Th2 cell differentiation were hypermethylated in infected fish, suggesting parasite-mediated repression mechanisms of immune responses. Altogether, we demonstrate that parasite infection contributes to genome-wide DNA methylation modifications. Our study brings novel insights into the evolution of vertebrate immunity and suggests that epigenetic mechanisms are complementary to genetic responses against parasite-mediated selection.
10 Minute consultation: Acute cough in children
Authors: Alastair D Hay, Knut Schroeder, Tom Fahey
Journal: BMJ (2004)

A previously well boy of 24 months is brought in by his mother in February. For 10 days he has had worsening cough, fever, and coryza. Both parents have asthma, and his mother is worried that he too might have asthma.
Irish Supreme Court upholds win for woman whose cervical cancer was missed
Authors: Clare Dyer
Journal: BMJ (2020)

A mother who developed cervical cancer after twice being told her smear tests were clear has won her case in the Irish Supreme Court, in a ruling that will set a benchmark for resolving dozens of similar cases in Ireland’s cervical screening scandal.1

Ruth Morrissey, now aged 38 and terminally ill with cancer, and her husband Paul sued the Irish Health Service Executive, which operated the CervicalCheck national screening programme, and two multinationals to whom the executive contracted out screening tests.

The Morrisseys, who have an 8 year old daughter, won a High Court …
Abstract P4-09-11: PIK3CA somatic alterations in 412 chinese invasive breast cancers: Higher frequency of mutant H1047R detected by next generation sequencing compared to breast cancer in caucasians
Authors: Minghan Jia, Ning Liao, Bo Chen, Guochun Zhang, Yulei Wang, Xiaoqing Chen, Liping Guo, Li Cao, Hsiaopei Mok, Chongyang Ren, Kai Li, Cheukfai Li, Lingzhu Wen, Jiali Lin, Guangnan Wei, Zhou Zhang, Charles M Balch
Journal: Cancer Research (2020)

Abstract Purpose: Somatic alterations of PIK3CA gene is an important therapeutic target in breast cancer (BC). The PI3Kα-specific inhibitor alpelisib was remarkably active against PIK3CA-mutated, HR-positive/HER2-negative BC in the SOLAR-1 trial. We hypothesized that PIK3CA alterations in Chinese BC patients across different molecular subtypes might differ from other ethnic groups and this information would be useful for selecting anti-PI3K therapy. Methods: The molecular profile of the PIK3CA gene was analyzed in 412 Chinese untreated invasive BC patients with ER/HER2 molecular subtypes, using a 540 gene next-generation sequencing panel. The results were compared to the molecular profile of Caucasian breast cancer patients in The Cancer Genome Atlas(TCGA-white). Results: Compared to wild type, PIK3CA alterations were more frequent in the ER+ subtype (49.3%, p=0.024), and tumors with low ki67 proliferation (58.3%, p=0.007) and low histological grade (grade I/II/III 80%, 53.4%, 35.9%, p&amp;lt;0.001). Compared to TCGA Caucasian race (TCGA-white), Chinese BC patients had a higher alteration frequency (45.6% vs. 34.7%, p&amp;lt;0.001). The p.H1047R mutation predominantly occurred among three hot spots (p.E545K, p.E542K and p.H1047R) for Chinese BC compared to that of the TCGA-white cohort (66.1% vs 43.7%, p=0.01). Nine novel mutation sites of PIK3CA were observed in the Chinese cohort that was absent among Caucasian BC patients. Among the four ER/HER2 molecular subtypes, ER+/HER2+ tumors harbored the most PIK3CA alterations (51.6%), while ER-/HER2- harbored the least (30.0%). However the latter presented the highest frequency of copy number amplification (19.05%). Conclusion: PIK3CA alterations prevail in nearly half of Chinese BC patients and has some different molecular features compared to that of Caucasian BC patients. The PIK3CA distribution patterns differed among four ER/HER2 subtypes. The results provide more insights for evaluating the results of PIK3CA inhibitors. Citation Format: Minghan Jia, Ning Liao, Bo Chen, Guochun Zhang, Yulei Wang, Xiaoqing Chen, Liping Guo, Li Cao, Hsiaopei Mok, Chongyang Ren, Kai Li, Cheukfai Li, Lingzhu Wen, Jiali Lin, Guangnan Wei, Zhou Zhang, Charles M Balch. PIK3CA somatic alterations in 412 chinese invasive breast cancers: Higher frequency of mutant H1047R detected by next generation sequencing compared to breast cancer in caucasians [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-09-11.
Predictors of contrast-induced acute kidney injury in patients with coronary artery disease receiving contrast agents twice within 30 days
Authors: Chong-Huai Gu, Xiao-Zeng Wang, Ya-Ling Han, Quan-Min Jing, Li-Li Ren, Yan Zhang, Jun-Yin Peng, Xin Zhao
Journal: Military Medical Research (2020)

Abstract Background None of study mentioned about contrast-induced acute kidney injury (CI-AKI) in people who have received contrast agents twice within in a short period of time. This study is trying to identify the predictors. Methods We enrolled 607 patients between Oct. 2010 and Jul. 2015 who received contrast agents twice within 30 days in the Department of Cardiology of the General Hospital of Shenyang Military Region. The primary outcome was CI-AKI within 72 h after contrast agent exposure. Patients were divided into groups A ( n = 559) and group B ( n = 48) according to whether CI-AKI occurred after the second agent. Results Patients in group B (CI-AKI occurred after the second agent) had a more rapid heart rate and more usage of diuretics and digitalis. In group B, CI-AKI occurred more frequently after the first agent. Multivariate logistic regression showed that diuretic ( P = 0.006) and intra-aortic balloon pump (IABP) usage ( P = 0.012) were independent predictors of CI-AKI after the first agent. Angiotensin-converting enzyme inhibitor/Angiotensin II receptor antagonist (ACEI/ARB) usage ( P = 0.039), IABP usage ( P = 0.040) and CI-AKI occurring after administration of the first agent ( P = 0.015) were independent predictors of CI-AKI after the second. Furthermore, dividing the patients into tertiles of the time interval between the two agents showed that CI-AKI occurred more frequently when the second agent was administered within 1–3 days after the first exposure than within 4–6 days (12.4% vs. 5.0%, P = 0.008) or ≥ 7 days (12.4% vs. 6.4%, P = 0.039). Conclusions Diuretic and IABP usage are independent predictors of CI-AKI following exposure to a first contrast agent. The major predictors of CI-AKI after exposure to a second agent are time since the first contrast exposure, ACEI/ARB usage, and IABP usage. More importantly, a three-day interval between the two agents is associated with a higher incidence of CI-AKI following the second administration.
Assessment of Effectiveness and Safety of Osimertinib for Patients With Intracranial Metastatic Disease
Authors: Anders W. Erickson, Priscilla K. Brastianos, Sunit Das
Journal: JAMA Network Open (2020)

Intracranial metastatic disease (IMD) is a serious and life-altering complication for many patients with cancer. Targeted therapy may address the limitations of current treatments as an additional agent to achieve intracranial disease control in some patients with IMD. Given the paucity of evidence regarding effectiveness, current guidelines have not made recommendations on the use of targeted therapy. Osimertinib mesylate is a mutant epidermal growth factor receptor (EGFR) inhibitor that can penetrate the blood-brain barrier and inhibit tumor cell survival and proliferation in patients with non-small cell lung cancer (NSCLC) with specific EGFR alterations.
Perioperative Presentation of COVID‐19 Disease in a Liver Transplant Recipient
Authors: Juanjuan Qin, Haitao Wang, Xian Qin, Peng Zhang, Lihua Zhu, Jingjing Cai, Yufeng Yuan, Hongliang Li
Journal: Hepatology (2020)

Qin, Juanjuan; Wang, Haitao; Qin, Xian; Zhang, Peng; Zhu, Lihua; Cai, Jingjing; Yuan, Yufeng; Li, Hongliang Author Information
Abstract 103: Rewarming Speed Affects Cardiopulmonary and Neurological Functions After Deep Hypothermic Cardiac Arrest
Authors: Daniele Linardi, Beat H Walpoth, Romel Mani, Maddalena M Tessari, Ilaria Decimo, Sissi Dolci, Annalisa Cavada, Giovanni Luciani, Giuseppe Faggian, Alessio Rungatscher
Journal: Circulation (2019)

Introduction: The optimal rewarming rate from accidental or induced deep hypothermia is still unknown. Fast extracorporeal rewarming by extracorporeal circulation has been associated with cardiac dysfunction, pulmonary edema and poor neurologic outcome. Hypothesis: This study investigates whether the speed of rewarming after deep hypothermic cardiac arrest has neurological and cardiopulmonary effects. Methods: Thirty male Sprague-Dawley adult rats (450-550g) were rapidly cooled (ice packs) until 15°C core body temperature. Deep hypothermic cardiac arrest was maintained for 60 min. Thereafter rats were randomised to receive slow (90 minutes) or fast (30 minutes) rewarming by cardiopulmonary bypass to a target temperature of 35°C. After 90 minutes of reperfusion all animals underwent hemodynamic assessment by biventricular pressure-volume analysis, brain MRI and heart, lungs and brain were collected. Results: Slow rewarming preserved cardiac systolic and diastolic functions, ventricular arterial coupling and endothelium dependent relaxation. Lung edema was attenuated after slow rewarming. Cardimyocytes pro-survival kinases ERK and Akt activation were significantly higher in the slow rewarming group. MRI demonstrated enhancement of cerebral blood flow and reduction of cerebral edema after slow rewarming. Neurologic inflammatory response measured by IL-6, ICAM-1, CCL5 and TNF-α expression was significantly decreased in the slow rewarming group. Oxidative stress assessed by malondialdehyde was significantly reduced after slow rewarming. Conclusion: Slow rewarming by extracorporeal circulation after deep hypothermic cardiac arrest might improve systolic and diastolic function, preserve ventricular-arterial coupling, attenuate cerebral perfusion impairment and reduce neuronal damage.
A Framework for Advancing Precision Medicine in Clinical Trials for Mental Disorders
Authors: Eric J. Lenze, Thomas L. Rodebaugh, Ginger E. Nicol
Journal: JAMA Psychiatry (2020)

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Abstract P5-08-19: The risk of breast, ovarian and endometrial cancer in obese women submitted to bariatric surgery: A meta-analysis
Authors: Beatriz Pércia Ishihara, Daniela Farah, Marcelo Cunio Machado Fonseca, Afonso Celso Pinto Nazário
Journal: Cancer Research (2020)

Abstract Background: Obesity is related to major risk factors for a number of noncommunicable diseases including cancer. There is a high incidence of breast and endometrial cancer in obese women. Thus, we performed a systematic review followed by meta-analysis to evaluate the relationship between bariatric surgery, a method widely used to treat obesity, and the risk of developing breast, ovarian and endometrial cancer in obese women. Methods: MEDLINE, EMBASE, LILACS and Cochrane databases were searched from inception until January 2019 which retrieve studies to assessed the risk of breast, ovarian and endometrial cancer in obese women submitted to bariatric surgery. There was no language restriction. We extracted and combined data from studies in order to assess the risk ratio (RR) of developing these cancers. A random-effects, meta-analytic model was applied in all calculations. The New Castle Ottawa and GRADE were used to assess quality and bias of the included studies. Trial registered in PROSPERO (CRD42019112927). Results: We found 188 articles and only seven of those were included in our meta-analysis, which incorporated a total of 150,528 patients in the bariatric surgery arm and 1,461,938 women in the control arm. The total risk of developing breast, ovarian and endometrial cancer was 0.37 (95%CI [0.28 to 0.48]; I2=87%; 7 studies). The risk of breast cancer was reduced by 61% [RR: 0.39 (95%CI [0.24 to 0.64]; I2= 90%; 6 studies). The risk of ovarian cancer was reduced by 53% [RR: 0.47 (95%CI [0.27 to 0.81]; I2= 0%; 3 studies). The risk of endometrial cancer was reduced by 67% [RR: 0.33 (95%CI [0.21 to 0.51]; I2= 88%; 7 studies). Conclusion: Bariatric surgery may have a protective effect by reducing the risk of developing breast, ovarian and endometrial cancer in obese women. However, high heterogeneity was found and not explained by our subgroup analysis. Although we couldn’t separate the types of surgeries performed, we hypothesized that the high heterogeneity might be due to the types of surgery. Therefore, we suggest more research with appropriate report of the type of the surgery by group. Citation Format: Beatriz Pércia Ishihara, Daniela Farah, Marcelo Cunio Machado Fonseca, Afonso Celso Pinto Nazário. The risk of breast, ovarian and endometrial cancer in obese women submitted to bariatric surgery: A meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-08-19.
Abstract P2-12-04: Efficacy of intravenous (IV) NEPA and oral NEPA, fixed NK1/5-HT3 receptor antagonist (RA) combination agents, for prevention of chemotherapy-induced nausea and vomiting (CINV) following anthracycline-cyclophosphamide (AC)-based chemotherapy
Authors: Matti Aapro, Lee Schwartzberg
Journal: Cancer Research (2020)

Abstract Background: The antiemetic guideline-based standard of care for prevention of CINV in patients receiving AC-based chemotherapy is the combination of an NK1 RA, a 5-HT3 RA, and dexamethasone (DEX). An IV formulation of NEPA (fixed combination of the NK1 RA, fosnetupitant and 5-HT3 RA, palonosetron) was recently approved in the United States. Two studies were completed in patients receiving cisplatin (Phase 3) or AC (Phase 3b) to assess the safety of IV NEPA, with specific attention paid to injection-site/hypersensitivity reactions as such events have occurred with other NK1 RAs, particularly in the AC setting. No treatment-related injection-site reactions were reported in &amp;gt;1300 infusions of IV NEPA. Oral NEPA was previously shown to be superior to palonosetron in a Phase 3 AC study. This analysis presents the efficacy data of IV NEPA and oral NEPA in the AC setting. Methods: Data is compiled from the IV NEPA Phase 3b study as well as from an oral NEPA registration study in females with breast cancer undergoing AC-based chemotherapy. IV NEPA was administered as a single 30-minute infusion and oral NEPA was given as a single capsule 60 minutes prior to AC. Patients also received DEX prior to AC on Day 1 only. Complete response (CR: no emesis/no rescue medication) rates are summarized for the acute (Day 1), delayed (Days 2-5) and overall (Days 1-5) phases of Cycle 1 for each treatment/study and also pooled for oral NEPA across the 2 studies. No formal statistical comparisons were performed. Results: Patient characteristics were similar in both studies. CR rates were comparable for IV NEPA and oral NEPA in the individual studies as well as with oral NEPA when pooled across the 2 studies (Table). Cycle 1 Complete Response IV NEPA StudyOral NEPA Study Pooled Studies % Patients IV NEPAOral NEPAOral NEPAOral NEPA(N = 200)(N = 202)(N = 708)(N = 910)Acute (0-24 h)86.588.688.388.4Delayed (25-120 h)75.578.776.476.9Overall (0-120 h)73.077.273.974.6 Conclusions: Both IV and oral formulations of NEPA in combination with DEX represent guideline-compliant single-dose antiemetic agents that are highly effective over 5 days in patients receiving AC-based chemotherapy. Citation Format: Matti Aapro, Lee Schwartzberg. Efficacy of intravenous (IV) NEPA and oral NEPA, fixed NK1/5-HT3 receptor antagonist (RA) combination agents, for prevention of chemotherapy-induced nausea and vomiting (CINV) following anthracycline-cyclophosphamide (AC)-based chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-04.
Abstract MS2-1: Mechanisms of resistance to CDK4/6 inhibitors and new therapeutic approaches
Authors: S Chandarlapaty
Journal: Cancer Research (2020)

Abstract Activation of the CDK4/6 kinases is a well-established mechanism whereby estrogens and other mitogens drive breast cancer growth. ATP competitive inhibitors of the CDK4/6 kinases have had a transformational impact on the clinical approach to ER+ breast cancer patients. However, with prolonged CDK4/6i therapy, most tumors ultimately develop resistance. Unlike the case for acquired resistance to many other targeted therapies, CDK4/6i resistance does not appear to be occur through mutations of the drug target. Second site, missense mutations in CDK4 and CDK6 have not been identified in either preclinical resistance screens or clinical biopsies of resistant tumors. This raises several questions including: (1) what are the genetic alterations and pathways that mediate resistance to CDK4/6i therapy in breast cancer, (2) what therapeutic approaches are effective after tumors have developed resistance to CDK4/6i, and (3) what can these understandings about resistance teach us about the underlying basis for sensitivity to CDK4/6i therapy. In this talk, published and unpublished data on mechanisms of resistance to CDK4/6i will be reviewed to elucidate how tumors can either restore CDK4/6 activity or else bypass the requirement for these G1 checkpoint kinases. Data on potential vulnerabilities for each class of drug-resistant tumors will then be discussed. Finally, the findings on resistance will be used to revisit the original understandings on the basis for CDK4/6i sensitivity and how that informs the ongoing use of these drugs in other settings and with more effective combinations that might suppress the emergence of resistance. Citation Format: S Chandarlapaty. Mechanisms of resistance to CDK4/6 inhibitors and new therapeutic approaches [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr MS2-1.