tbuckley/cabot-search huggingface dataset:
Butterfly Mimicry Polymorphisms Highlight Phylogenetic Limits of Gene Reuse in the Evolution of Diverse Adaptations
Authors: Nicholas W VanKuren, Darli Massardo, Sumitha Nallu, Marcus R Kronforst
Journal: Molecular Biology and Evolution (2019)

Some genes have repeatedly been found to control diverse adaptations in a wide variety of organisms. Such gene reuse reveals not only the diversity of phenotypes these unique genes control but also the composition of developmental gene networks and the genetic routes available to and taken by organisms during adaptation. However, the causes of gene reuse remain unclear. A small number of large-effect Mendelian loci control a huge diversity of mimetic butterfly wing color patterns, but reasons for their reuse are difficult to identify because the genetic basis of mimicry has primarily been studied in two systems with correlated factors: female-limited Batesian mimicry in Papilio swallowtails (Papilionidae) and non-sex-limited Müllerian mimicry in Heliconius longwings (Nymphalidae). Here, we break the correlation between phylogenetic relationship and sex-limited mimicry by identifying loci controlling female-limited mimicry polymorphism Hypolimnas misippus (Nymphalidae) and non-sex-limited mimicry polymorphism in Papilio clytia (Papilionidae). The Papilio clytia polymorphism is controlled by the genome region containing the gene cortex, the classic P supergene in Heliconius numata, and loci controlling color pattern variation across Lepidoptera. In contrast, female-limited mimicry polymorphism in Hypolimnas misippus is associated with a locus not previously implicated in color patterning. Thus, although many species repeatedly converged on cortex and its neighboring genes over 120 My of evolution of diverse color patterns, female-limited mimicry polymorphisms each evolved using a different gene. Our results support conclusions that gene reuse occurs mainly within ∼10 My and highlight the puzzling diversity of genes controlling seemingly complex female-limited mimicry polymorphisms.
Biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents in patients with ST-segment elevation myocardial infarction (BIOSTEMI): a single-blind, prospective, randomised superiority trial
Authors: Juan F Iglesias, Olivier Muller, Dik Heg, Marco Roffi, David J Kurz, Igal Moarof, Daniel Weilenmann, Christoph Kaiser, Maxime Tapponnier, Stefan Stortecky, Sylvain Losdat, Eric Eeckhout, Marco Valgimigli, Ayodele Odutayo, Marcel Zwahlen, Peter Jüni, Stephan Windecker, Thomas Pilgrim
Journal: The Lancet (2019)
Electrocardiographic Progression of Cardiac Conduction Disease
Authors: Ahmed S. Sadek, Anuj Basil, Isaac R. Whitman
Journal: JAMA Internal Medicine (2019)

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SORAVE: Sorafenib and everolimus for treatment of patients with relapsed solid tumors and with KRAS mutated NSCLC—A phase I study.
Authors: Lucia Nogova, Christian Mattonet, Masyar Gardizi, Matthias Scheffler, Marc Christiaan Allardt Bos, Karin Toepelt, Lukas Carl Heukamp, Ahmed Abbas Suleiman, Sebastian Frechen, Fritz Soergel, Uwe Fuhr, Roland Schnell, Ildiko Katay, Dirk M. Behringer, Thomas Geist, Britta Kaminsky, Martina Eichstaedt, Dirk Tummes, Reinhard Buettner, Jurgen Wolf
Journal: Journal of Clinical Oncology (2013)

8112 Background: Dual inhibition of signaling pathways interfering with cell proliferation and angiogenesis may increase anti-tumor efficacy. Sorafenib and mTOR inhibitors showed preliminary activity in KRAS mutated NSCLC. Methods: In the dose escalation part patients with relapsed solid tumors were treated with escalating doses of everolimus from 2.5-10.0 mg daily p.o. in a 14 days run-in phase followed by the combination with a fixed dose of sorafenib 400 mg bid p.o. Extension phase is currently recruiting patients with KRAS mutated NSCLC. The KRAS mutation status was determined by PCR based high resolution melting curve analysis (HRM) on DNA extracted from FFPE material and validated using Sanger sequencing. The HRM has now been replaced by a multiplex PCR. Pharmacokinetic (PK) analyses are performed during run-in and during the combination. Treatment outcome is validated with CT scans on day 57. Results: (I) In the dose escalation part, 19 patients were recruited. The dose limiting toxicity (DLT) was not reached. At everolimus dose level of 10 mg/day, increased rates of grade 3 thrombocytopenia (3 patients), leukocytopenia (2 patients) and anaemia (2 patients) occurred after the DLT interval of 29 days. Based on these observations, the dose level of 7.5 mg/day everolimus in combination with 400 mg sorafenib bid was defined as a maximal tolerated dose. The AUC and C max values of everolimus at all dose levels were comparable on days 5 and 14. On day 29, AUC and C max of everolimus showed a 20 - 40% reduction when co-administered with sorafenib. The best treatment outcome was stable disease in 11 patients. Median PFS and OS were 3.7 and 5.5 months, respectively. (II) The extension phase in KRAS mutated NSCLC is currently ongoing. Nine patients have been recruited so far. The CT response at day 57 compared to the baseline of 4 evaluable patients is ranging from -22% to +5% in the sum of the longest diameter of all targeted lesions. Conclusions: Treatment with the combination of 7.5 mg everolimus p.o. daily and 400 mg sorafenib p.o. bid is safe and feasible. Current results of an extension phase in KRAS mutated NSCLC patients show preliminary clinical activity in this patient group with an unfavorable prognosis. Clinical trial information: NCT00933777.
Tell women about long term breast cancer risk with HRT, drug agency tells doctors
Authors: Elisabeth Mahase
Journal: BMJ (2019)

The UK drug regulator has asked trusts, GPs, and hospital doctors to ensure women are told about the increased risk of breast cancer associated with menopausal hormone therapy (MHT)—commonly referred to as hormone replacement therapy (HRT).1

The advice from the Medicines and Healthcare Products Regulatory Agency (MHRA) followed research recently published in the Lancet , which found that the longer women take MHT, the higher their risk …
Myelopreservation with the CDK4/6 inhibitor trilaciclib in patients with small-cell lung cancer receiving first-line chemotherapy: a phase Ib/randomized phase II trial
Authors: J.M. Weiss, T. Csoszi, M. Maglakelidze, R.J. Hoyer, J.T. Beck, M. Domine Gomez, A. Lowczak, R. Aljumaily, C.M. Rocha Lima, R.V. Boccia, W. Hanna, P. Nikolinakos, V.K. Chiu, T.K. Owonikoko, S.R. Schuster, M.A. Hussein, D.A. Richards, P. Sawrycki, I. Bulat, J.T. Hamm, L.L. Hart, S. Adler, J.M. Antal, A.Y. Lai, J.A. Sorrentino, Z. Yang, R.K. Malik, S.R. Morris, P.J. Roberts, K.H. Dragnev
Journal: Annals of Oncology (2019)

Chemotherapy-induced damage of hematopoietic stem and progenitor cells (HSPC) causes multi-lineage myelosuppression. Trilaciclib is an intravenous CDK4/6 inhibitor in development to proactively preserve HSPC and immune system function during chemotherapy (myelopreservation). Preclinically, trilaciclib transiently maintains HSPC in G1 arrest and protects them from chemotherapy damage, leading to faster hematopoietic recovery and enhanced antitumor immunity.
Hepcidin and its therapeutic potential in neurodegenerative disorders
Authors: Zhong‐Ming Qian, Ya Ke
Journal: Medicinal Research Reviews (2019)

Abstract Abnormally high brain iron, resulting from the disrupted expression or function of proteins involved in iron metabolism in the brain, is an initial cause of neuronal death in neuroferritinopathy and aceruloplasminemia, and also plays a causative role in at least some of the other neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Friedreich's ataxia. As such, iron is believed to be a novel target for pharmacological intervention in these disorders. Reducing iron toward normal levels or hampering the increases in iron associated with age in the brain is a promising therapeutic strategy for all iron‐related neurodegenerative disorders. Hepcidin is a crucial regulator of iron homeostasis in the brain. Recent studies have suggested that upregulating brain hepcidin levels can significantly reduce brain iron content through the regulation of iron transport protein expression in the blood‐brain barrier and in neurons and astrocytes. In this review, we focus on the discussion of the therapeutic potential of hepcidin in iron‐associated neurodegenerative diseases and also provide a systematic overview of recent research progress on how misregulated brain iron metabolism is involved in the development of multiple neurodegenerative disorders.
Prospective Investigation of Serum Metabolites, Coffee Drinking, Liver Cancer Incidence, and Liver Disease Mortality
Authors: Erikka Loftfield, Joseph A Rothwell, Rashmi Sinha, Pekka Keski-Rahkonen, Nivonirina Robinot, Demetrius Albanes, Stephanie J Weinstein, Andriy Derkach, Joshua Sampson, Augustin Scalbert, Neal D Freedman
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Coffee has been consistently associated with lower risk of liver cancer and chronic liver disease, suggesting that coffee affects mechanisms underlying disease development. Methods We measured serum metabolites using untargeted metabolomics in 1:1 matched nested case-control studies of liver cancer (n = 221 cases) and fatal liver disease (n = 242 cases) in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention cohort (n = 29 133). Associations between baseline coffee drinking and metabolites were identified using linear regression; conditional logistic regression models were used to identify associations with subsequent outcomes. Results Overall, 21 metabolites were associated with coffee drinking and also each subsequent endpoint; nine metabolites and trigonelline, a known coffee biomarker, were identified. Tyrosine and two bile acids, glycochenodeoxycholic acid (GCDCA) and glycocholic acid (GCA), were inversely associated with coffee but positively associated with both outcomes; odds ratios (ORs) comparing the 90th to 10th percentile (modeled on a continuous basis) ranged from 3.93 (95% confidence interval [CI] = 2.00 to 7.74) for tyrosine to 4.95 (95% CI = 2.64 to 9.29) for GCA and from 4.00 (95% CI = 2.42 to 6.62) for GCA to 6.77 (95% CI = 3.62 to 12.65) for GCDCA for liver cancer and fatal liver disease, respectively. The remaining six metabolites and trigonelline were positively associated with coffee drinking but inversely associated with both outcomes; odds ratio ranged from 0.16 to 0.37. Associations persisted following diet adjustment and for outcomes occurring greater than 10 years after blood collection. Conclusions A broad range of compounds were associated with coffee drinking, incident liver cancer, and liver disease death over 27 years of follow-up. These associations provide novel insight into chronic liver disease and liver cancer etiology and support a possible hepatoprotective effect of coffee.
Potential Effect of Immunotherapy Agents on Cognitive Function in Cancer Patients
Authors: Florence Joly, Hélène Castel, Laure Tron, Marie Lange, Janette Vardy
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract A paradigm shift is occurring in cancer therapy, where instead of targeting tumor cells, immunotherapy agents (IA) target the immune system to overcome cancer tolerance and to stimulate an antitumor immune response. IA using immune checkpoint inhibitors (CPI) or chimeric antigen receptor T-cells have emerged as the most encouraging approaches to treat cancer patients. CPI are reported to induce moderate-to-severe neurologic immune-related adverse events in less than 1% of patients, whereas chimeric antigen receptor T-cell therapy is associated with frequent neurological toxicities that can be severe or even fatal. Cognitive difficulties have been described following chemotherapy and targeted therapy, but not specifically explored in patients receiving IA. The aim of this review is to establish a picture of the first published studies suggesting some biological and physiopathological effects of IA on cognitive functions among cancer patients. The first results originate from a preclinical study evaluating the role of CPI associated with peripheral radiation on cognitive dysfunction and the recent discovery of the central nervous lymphatic system allowing leukocytes to penetrate the central nervous system. Evaluating possible side effects of IA on cognitive function will be an important challenge for future clinical trials and for better understanding the underlying mechanisms through preclinical animal models.
Trends in Hospitalization vs Observation Stay for Ambulatory Care–Sensitive Conditions
Authors: Jose F. Figueroa, Laura G. Burke, Jie Zheng, E. John Orav, Ashish K. Jha
Journal: JAMA Internal Medicine (2019)

This study of Medicare-defined avoidable hospital stays for conditions such as urinary tract infection and complications of diabetes uses Medicare Fee-for-Service Inpatient and Outpatient Claim Files to investigate whether a decrease in inpatient admissions from 2011 to 2015 represented real gains in ambulatory care.
Effect of patient education on palliative care knowledge and acceptability of outpatient palliative care service among gynecologic oncology patients.
Authors: Ashley Graul, Ashley Ford Haggerty, Carolyn Stickley, Pallavi Kumar, Knashawn Morales, Hillary Bogner, Robert Burger, Morgan Mark, Emily Ko
Journal: Journal of Clinical Oncology (2019)

11583 Background: This was a randomized control trial to estimate the effect of an interventional video on improving palliative care knowledge and acceptability of outpatient services in gynecologic oncology patients. Methods: Women receiving active treatment for gynecologic malignancy (persistent or progressive disease despite primary treatment) were recruited at an academic tertiary care center from 2/2018 to 1/2019 and randomized to: palliative care educational video or non-directive cancer center informational video (control). The primary outcome was desire for referral to palliative care. Function and knowledge were assessed using the Functional Assessment of Cancer Therapy (FACT-G) and the Palliative Care Knowledge Scales. Data analyses were performed using t-tests, Wilcoxon rank sum or Fisher’s exact tests with significance level of α=0.05. Results: 111 women were enrolled. Demographic characteristics were equally distributed between groups (mean age 63.4 vs 65.4 years; 78% vs 82% Caucasian, 58% vs 68% stage III, 71% vs 64% ovarian cancer, 65% vs 72% platinum-sensitive). There was no statistical difference in knowledge scores or in desire for referral to palliative care (29% vs 27%; p=0.79). Secondary analysis showed a statistically significant increase in utilization of palliative care services compared to historic institutional data (8.8% to 29.7%; p=&lt;0.001). Further, those that desired referral had significantly worse FACT-G scores at time of referral choice (table). Conclusions: Use of a palliative care educational video did not increase knowledge or acceptability of palliative care services within this RCT. However, the rate of patients seeking palliative care referral tripled compared to historic rates. Further studies should investigate whether discussion regarding palliative care services alone may increase desire for referral, and if use of Fact-G scores may identify patients in greatest need of services. [Table: see text]
European Respiratory Society guidelines on long-term home non-invasive ventilation for management of COPD
Authors: Begum Ergan, Simon Oczkowski, Bram Rochwerg, Annalisa Carlucci, Michelle Chatwin, Enrico Clini, Mark Elliott, Jesus Gonzalez-Bermejo, Nicholas Hart, Manel Lujan, Jacek Nasilowski, Stefano Nava, Jean Louis Pepin, Lara Pisani, Jan Hendrik Storre, Peter Wijkstra, Thomy Tonia, Jeanette Boyd, Raffaele Scala, Wolfram Windisch
Journal: European Respiratory Journal (2019)

While the role of acute non-invasive ventilation (NIV) has been shown to improve outcome in acute life-threatening hypercapnic respiratory failure in COPD, the evidence of clinical efficacy of long-term home NIV (LTH-NIV) for management of COPD is less. This document provides evidence-based recommendations for the clinical application of LTH-NIV in chronic hypercapnic COPD patients.The European Respiratory Society task force committee was composed of clinicians, methodologists and experts in the field of LTH-NIV. The committee developed recommendations based on the GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology. The GRADE Evidence to Decision framework was used to formulate recommendations. A number of topics were addressed under a narrative format which provides a useful context for clinicians and patients.The task force committee delivered conditional recommendations for four actionable PICO (target population-intervention-comparator-outcome) questions, 1) suggesting for the use of LTH-NIV in stable hypercapnic COPD; 2) suggesting for the use of LTH-NIV in COPD patients following a COPD exacerbation requiring acute NIV 3) suggesting for the use of NIV settings targeting a reduction in carbon dioxide and 4) suggesting for using fixed pressure support as first choice ventilator mode.Managing hypercapnia may be an important intervention for improving the health outcome of COPD patients with chronic respiratory failure. The task force conditionally supports the application of LTH-NIV to improve health outcome by targeting a reduction in carbon dioxide in COPD patients with persistent hypercapnic respiratory failure. These recommendations should be applied in clinical practice by practitioners that routinely care for chronic hypercapnic COPD patients.
Disparities in Acceptance of Deceased Donor Kidneys Between the United States and France and Estimated Effects of Increased US Acceptance
Authors: Olivier Aubert, Peter P. Reese, Benoit Audry, Yassine Bouatou, Marc Raynaud, Denis Viglietti, Christophe Legendre, Denis Glotz, Jean-Phillipe Empana, Xavier Jouven, Carmen Lefaucheur, Christian Jacquelinet, Alexandre Loupy
Journal: JAMA Internal Medicine (2019)

Approximately 3500 donated kidneys are discarded in the United States each year, drawing concern from Medicare and advocacy groups.To estimate the effects of more aggressive allograft acceptance practices on the donor pool and allograft survival for the population of US wait-listed kidney transplant candidates.A nationwide study using validated registries from the United States and France comprising comprehensive cohorts of deceased donors with organs offered to kidney transplant centers between January 1, 2004, and December 31, 2014. Data were analyzed between September 1, 2018, and April 5, 2019.The primary outcome was kidney allograft discard. The secondary outcome was allograft failure after transplantation. We used logistic regression to model organ acceptance and discard practices in both countries. We then quantified using computer simulation models the number of kidneys discarded in the United States that a more aggressive system would have instead used for transplantation. Finally, based on actual survival data, we quantified the additional years of allograft life that a redesigned US system would have saved.In the United States, 156 089 kidneys were recovered from deceased donors between 2004 and 2014, of which 128 102 were transplanted, and 27 987 (17.9%) were discarded. In France, among the 29 984 kidneys recovered between 2004 and 2014, 27 252 were transplanted, and 2732 (9.1%, P < .001 vs United States) were discarded. The mean (SD) age of kidneys transplanted in the United States was 36.51 (17.02) years vs 50.91 (17.34) years in France (P < .001). Kidney quality showed little change in the United States over time (mean [SD] kidney donor risk index [KDRI], 1.30 [0.48] in 2004 vs 1.32 [0.46] in 2014), whereas a steadily rising KDRI in France reflected a temporal trend of more aggressive organ use (mean [SD] KDRI, 1.37 [0.47] in 2004 vs 1.74 [0.72] in 2014; P < .001). We applied the French-based allocation model to the population of US deceased donor kidneys and found that 17 435 (62%) of kidneys discarded in the United States would have instead been transplanted under the French system. We further determined that a redesigned system with more aggressive organ acceptance practices would generate an additional 132 445 allograft life-years in the United States over the 10-year observation period.Greater acceptance of kidneys from deceased donors who are older and have more comorbidities could provide major survival benefits to the population of US wait-listed patients.ClinicalTrials.gov identifier: NCT03723668.
Prevalence, 12-Month Prognosis, and Clinical Management Need of Depression in Coronary Heart Disease Patients: A Prospective Cohort Study
Authors: Stella L. Kuhlmann, Volker Arolt, Wilhelm Haverkamp, Peter Martus, Andreas Ströhle, Johannes Waltenberger, Nina Rieckmann, Jacqueline Müller-Nordhorn
Journal: Psychotherapy and Psychosomatics (2019)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Screening for depression in patients with coronary heart disease (CHD) remains controversial. There is limited data on the actual depression management need in routine care. The aim of this study was to examine the prevalence, treatment rates, prognosis, and management need of clinical and subclinical depression in CHD patients according to the American Heart Association recommendations and the National Institute for Health and Care Excellence (NICE) guideline “Depression in Adults with a Chronic Physical Health Problem”. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; Patients were recruited at 2 German university clinics between 2012 and 2014. Depressive disorders were assessed according to the DSM-IV and depressive symptom severity at baseline and during follow-up was evaluated with the Patient Health Questionnaire (PHQ-9). Depression management need was determined by the severity and longitudinal course of depression symptoms. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Of 1,024 patients (19% women), 12% had clinical depression (depressive disorder) and 45% had subclinical depression (PHQ-9 score ≥5) at baseline. Among those with clinical depression, 46% were in treatment at least once during 12 months; 26% were continuously in treatment during follow-up. Depressive disorder and depressive symptoms were significant risk factor-adjusted predictors of the 12-months mortality (adjusted HR = 3.19; 95% CI 1.32–7.69, and adjusted HR = 1.09; 95% CI 1.02–1.16, respectively). Depressive symptoms persisted in 85% of the clinically depressed and in 47% of the subclinically depressed patients. According to current recommendations, 29% of all CHD patients would require depression management within 1 year. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; There is a need for enhanced recognition, referral, and continuous and improved clinical management of depression in CHD patients.