tbuckley/cabot-search huggingface dataset:
Effectiveness of a Multimedia Educational Intervention to Improve Understanding of the Risks and Benefits of Palliative Chemotherapy in Patients With Advanced Cancer
Authors: Andrea C. Enzinger, Hajime Uno, Nadine McCleary, Elizabeth Frank, Hanna Sanoff, Katherine Van Loon, Khalid Matin, Andrea Bullock, Christine Cronin, Heather Cibotti, Janet Bagley, Deborah Schrag
Journal: JAMA Oncology (2020)

Despite requirements of informed consent, patients with advanced cancer often receive palliative chemotherapy (PC) without understanding that the likelihood of cure is remote.To determine whether a PC educational video and booklet at treatment initiation could improve patients' understanding of its benefits and risks.Regimen-specific PC videos and booklets presenting information about logistics, potential benefits, life expectancy (optional), adverse effects, and alternatives. Videos featured authentic patients sharing diverse experiences. After receiving treatment recommendations, research assistants distributed materials to patients for independent review.Multicenter randomized clinical trial of patients with advanced colorectal or pancreatic cancer starting first-line or second-line PC in 5 US cancer centers with enrollment from June 2015 to September 2017 and follow-up to December 2019.The primary outcome was accurate expectations of chemotherapy benefits at 3 months, defined as responding "not at all likely" to "What is your understanding of how likely the chemotherapy is to cure your cancer?" (from the Cancer Care Outcomes Research and Surveillance study). Secondary outcomes included understanding of adverse effects, decisional conflict (SURE test), regret (Decisional Regret Scale), and distress (Functional Assessment of Cancer Therapy-General emotional well-being subscale).Among 186 patients with advanced colorectal or pancreatic cancer who were starting first-line or second-line PC (94 randomized to usual care, 92 to intervention; mean [SD] age, 59.3 [12.6] [range, 28-86] years; 107 [58%] male; 118 [63.4%] colorectal and 68 [36.6%] pancreatic cancer), most patients wanted "a lot" of information or "as much information as possible" about adverse effects (149, 80.1%), likelihood of cure (148, 79.6%), and prognosis (148, 79.6%). Among the intervention arm, 59 (78%) reviewed the booklet and 30 (40%) reviewed the video within 2 weeks. The primary outcome did not differ between intervention and control arms (52.6%; 95% CI, 40.3%-65.0%; vs 55.5%; 95% CI, 45.1%-66.0%). Accurate adverse effect understanding was more common among intervention than control patients (56.0%; 95% CI, 44.3%-67.7%; vs 40.2%; 95% CI, 29.5%-50.9%; P = .05), although this did not meet the threshold for statistical significance. The intervention did not increase distress, despite frank prognostic information. Other secondary outcomes were similar.Provision of an educational video and booklet did not alter patients' expectation of cure from PC. Alternative delivery strategies, such as integration with nurse teaching, could be explored in future studies.ClinicalTrials.gov Identifier: NCT02282722.
Abstract 12706: Carotid Plaque Lipid Content is Reduced After 6 Months of Proprotein Convertase Subtilisin Kexin Type 9 Inhibition With Alirocumab: an Interim Analysis of a Serial Magnetic Resonance Imaging Study
Authors: Jie Sun, Norman E Lepor, Gador Canton, Laurn Contreras, Daniel S Hippe, Daniel Isquith, Niranjan Balu, Ilan Kedan, Americo Simonini, Chun Yuan, Xue-Qiao Zhao, Thomas S Hatsukami
Journal: Circulation (2019)

Introduction: In the ODYSSEY OUTCOMES trial, proprotein convertase subtilisin kexin type 9 inhibition (PCSK9i) with alirocumab reduced recurrent major cardiovascular events by 15%, including 27% in...
Spatiotemporal Genetic Diversity of Lions Reveals the Influence of Habitat Fragmentation across Africa
Authors: Caitlin J Curry, Brian W Davis, Laura D Bertola, Paula A White, William J Murphy, James N Derr
Journal: Molecular Biology and Evolution (2020)

Direct comparisons between historical and contemporary populations allow for detecting changes in genetic diversity through time and assessment of the impact of habitat fragmentation. Here, we determined the genetic architecture of both historical and modern lions to document changes in genetic diversity over the last century. We surveyed microsatellite and mitochondrial genome variation from 143 high-quality museum specimens of known provenance, allowing us to directly compare this information with data from several recently published nuclear and mitochondrial studies. Our results provide evidence for male-mediated gene flow and recent isolation of local subpopulations, likely due to habitat fragmentation. Nuclear markers showed a significant decrease in genetic diversity from the historical (HE = 0.833) to the modern (HE = 0.796) populations, whereas mitochondrial genetic diversity was maintained (Hd = 0.98 for both). Although the historical population appears to have been panmictic based on nDNA data, hierarchical structure analysis identified four tiers of genetic structure in modern populations and was able to detect most sampling locations. Mitogenome analyses identified four clusters: Southern, Mixed, Eastern, and Western and were consistent between modern and historically sampled haplotypes. Within the last century, habitat fragmentation caused lion subpopulations to become more geographically isolated as human expansion changed the African landscape. This resulted in an increase in fine-scale nuclear genetic structure and loss of genetic diversity as lion subpopulations became more differentiated, whereas mitochondrial structure and diversity were maintained over time.
Value of dynamic contrast perfusion MRI to predict early response to bevacizumab in newly diagnosed glioblastoma: results from ACRIN 6686 multicenter trial
Authors: Kathleen M Schmainda, Melissa A Prah, Helga Marques, Eunhee Kim, Daniel P Barboriak, Jerrold L Boxerman
Journal: Neuro-Oncology (2020)

Abstract Background In Radiation Therapy Oncology Group (RTOG) 0825, a phase III trial of standard therapy with bevacizumab or without (placebo) in newly diagnosed glioblastoma, 44 patients underwent dynamic contrast enhanced (DCE) and/or dynamic susceptibility contrast (DSC) MRI in the American College of Radiology Imaging Network (ACRIN) trial 6686. The association between early changes in relative cerebral blood volume (rCBV) and volume transfer constant (Ktrans) with overall survival (OS) was evaluated. Methods MRI was performed at postop baseline (S0), immediately before (S1), 1 day after (S2), and 7 weeks after (S3) bevacizumab or placebo initiation. Mean normalized and standardized rCBV (nRCBV, sRCBV) and Ktrans were measured within contrast-enhancing lesion. Wilcoxon rank sum tests compared parameter changes from S1–S2 and S1–S3. Association with OS and progression-free survival (PFS) were determined using Kaplan–Meier and log-rank tests. Treatment response for groups stratified by pretreatment nRCBV (S0, S1) was explored. The intraclass correlation coefficient and repeatability coefficient for the placebo arm (S1–S2) were used to assess repeatability. Results Evaluable were 27–36 datasets per time point. Significant differences between treatment arms were found for changes in nRCBV and sRCBV from S1–S2 and S1–S3, and in Ktrans for S1–S3. Improved PFS (P = 0.05) but not OS (P = 0.46) was observed. High pretreatment rCBV predicted improved OS for bevacizumab-treated patients. Based on the intraclass correlation coefficient, sRCBV (0.92) was more repeatable than nRCBV (0.71) and Ktrans (0.75), consistent with repeatability coefficient values. Conclusions Bevacizumab significantly changes rCBV but not Ktrans as early as 1 day posttreatment in newly diagnosed glioblastoma unrelated to outcomes. Improvements in clinical trial design to maximize rCBV benefit are indicated.
Battle of the Sex Chromosomes: Competition between X and Y Chromosome-Encoded Proteins for Partner Interaction and Chromatin Occupancy Drives Multicopy Gene Expression and Evolution in Muroid Rodents
Authors: Charlotte Moretti, Mélina Blanco, Côme Ialy-Radio, Maria-Elisabetta Serrentino, Clara Gobé, Robin Friedman, Christophe Battail, Marjorie Leduc, Monika A Ward, Daniel Vaiman, Frederic Tores, Julie Cocquet
Journal: Molecular Biology and Evolution (2020)

Abstract Transmission distorters (TDs) are genetic elements that favor their own transmission to the detriments of others. Slx/Slxl1 (Sycp3-like-X-linked and Slx-like1) and Sly (Sycp3-like-Y-linked) are TDs, which have been coamplified on the X and Y chromosomes of Mus species. They are involved in an intragenomic conflict in which each favors its own transmission, resulting in sex ratio distortion of the progeny when Slx/Slxl1 versus Sly copy number is unbalanced. They are specifically expressed in male postmeiotic gametes (spermatids) and have opposite effects on gene expression: Sly knockdown leads to the upregulation of hundreds of spermatid-expressed genes, whereas Slx/Slxl1-deficiency downregulates them. When both Slx/Slxl1 and Sly are knocked down, sex ratio distortion and gene deregulation are corrected. Slx/Slxl1 and Sly are, therefore, in competition but the molecular mechanism remains unknown. By comparing their chromatin-binding profiles and protein partners, we show that SLX/SLXL1 and SLY proteins compete for interaction with H3K4me3-reader SSTY1 (Spermiogenesis-specific-transcript-on-the-Y1) at the promoter of thousands of genes to drive their expression, and that the opposite effect they have on gene expression is mediated by different abilities to recruit SMRT/N-Cor transcriptional complex. Their target genes are predominantly spermatid-specific multicopy genes encoded by the sex chromosomes and the autosomal Speer/Takusan. Many of them have coamplified with not only Slx/Slxl1/Sly but also Ssty during muroid rodent evolution. Overall, we identify Ssty as a key element of the X versus Y intragenomic conflict, which may have influenced gene content and hybrid sterility beyond Mus lineage since Ssty amplification on the Y predated that of Slx/Slxl1/Sly.
Diagnostic meta-analysis of the Pediatric Sleep Questionnaire, OSA-18, and pulse oximetry in detecting pediatric obstructive sleep apnea syndrome
Authors: Chia-Rung Wu, Yu-Kang Tu, Li-Pang Chuang, Christopher Gordon, Ning-Hung Chen, Pin-Yuan Chen, Faizul Hasan, Maria D. Kurniasari, Sri Susanty, Hsiao-Yean Chiu
Journal: Sleep Medicine Reviews (2020)
Extremely preterm neonates have more <i>Lactobacillus</i> in meconium than very preterm neonates – the <i>in utero</i> microbial colonization hypothesis
Authors: Juliana Morais, Cláudia Marques, Diana Teixeira, Catarina Durão, Ana Faria, Sara Brito, Manuela Cardoso, Israel Macedo, Esmeralda Pereira, Teresa Tomé, Conceição Calhau
Journal: Gut Microbes (2020)

Growing evidence suggests that maternal microbiota can influence the neonates' gut colonization. However, the mechanisms of vertical bacterial transmission remain poorly defined. We believed that the first colonizers of the newborn come from the mother's gut and vagina during pregnancy and that this is independent of the mode of delivery. We conducted an observational longitudinal study to evaluate the link between the maternal gut microbiota and the meconium's microbiota in extremely and very preterm neonates. Bacterial DNA was extracted from samples and specific bacterial groups were quantified by RT-PCR. In this cohort of 117 preterm neonates, we detected bacterial DNA in 88% of meconium samples. Meconium microbiota of neonates born after 28 gestational weeks (very preterm neonates) showed stronger correlations with their mothers' fecal microbiota. However, neonates born before 28 gestational weeks (extremely preterm neonates) had more Lactobacillus – genus that dominated the vaginal microbiota – than very preterm neonates, regardless of the mode of delivery. Collectively, these data support the hypothesis that maternal bacteria from the gut and vagina can play a role in shaping neonates' gut microbiota and that mother-to-infant bacterial transmission is a controlled and time-specific process. ClinicalTrials.gov Identifier: NCT03663556
Risk of Covert Submucosal Cancer in Patients With Granular Mixed Laterally Spreading Tumors
Authors: Ferdinando D’Amico, Arnaldo Amato, Andrea Iannone, Cristina Trovato, Chiara Romana, Stefano Angeletti, Roberta Maselli, Franco Radaelli, Giancarla Fiori, Edi Viale, Emilio Di Giulio, Paola Soriani, Mauro Manno, Emanuele Rondonotti, Piera Alessia Galtieri, Andrea Anderloni, Alessandro Fugazza, Elisa Chiara Ferrara, Silvia Carrara, Milena Di Leo, Gaia Pellegatta, Marco Spadaccini, Laura Lamonaca, Vincenzo Craviotto, Paul J. Belletrutti, Cesare Hassan, Alessandro Repici
Journal: Clinical Gastroenterology and Hepatology (2020)
Government must “stop dithering” and tackle childhood obesity crisis, says Labour
Authors: Jacqui Wise
Journal: BMJ (2020)

The Labour party has urged the government to “stop dithering” over introducing measures to tackle childhood obesity as the crisis shows no signs of slowing.

An analysis by Labour of NHS England’s latest figures show that almost 700 children under 16 were admitted to hospital because of obesity in 2018-19—the second highest number on record.1

The data show that less than half of children (47%) are currently meeting physical activity guidelines, and Labour warned that covid-19 lockdowns are likely to worsen childhood obesity levels, with a lack of exercise potentially leading to weight gain for many children.

Obesity and associated conditions such as …
Abstract 2207: Fetal Long QT Syndrome: The QTc Predicts Symptom Severity - A Magnetocardiographic Study
Authors: Bettina F Cuneo, Hitoshi Horigome, Gretchen Eckstein, Janette Strasburger, Ronald Wakai
Journal: Circulation (2009)

Introduction: Fetal long QT syndrome (fLQTS) has been successfully diagnosed with magnetocardiography (MCG), but there is limited data comparing MCG findings to other clinical manifestations of fLQ...
Effect of Flash Glucose Monitoring on Glycemic Control, Hypoglycemia, Diabetes-Related Distress, and Resource Utilization in the Association of British Clinical Diabetologists (ABCD) Nationwide Audit
Authors: Harshal Deshmukh, Emma G. Wilmot, Robert Gregory, Dennis Barnes, Parth Narendran, Simon Saunders, Niall Furlong, Shafie Kamaruddin, Rumaisa Banatwalla, Roselle Herring, Anne Kilvert, Jane Patmore, Chris Walton, Robert E.J. Ryder, Thozhukat Sathyapalan
Journal: Diabetes Care (2020)

OBJECTIVE The FreeStyle Libre (FSL) flash glucose-monitoring device was made available on the U.K. National Health Service (NHS) drug tariff in 2017. This study aims to explore the U.K. real-world experience of FSL and the impact on glycemic control, hypoglycemia, diabetes-related distress, and hospital admissions. RESEARCH DESIGN AND METHODS Clinicians from 102 NHS hospitals in the U.K. submitted FSL user data, collected during routine clinical care, to a secure web-based tool held within the NHS N3 network. The t and Mann-Whitney U tests were used to compare the baseline and follow-up HbA1c and other baseline demographic characteristics. Linear regression analysis was used to identify predictors of change in HbA1c following the use of FSL. Within-person variations of HbA1c were calculated using . RESULTS Data were available for 10,370 FSL users (97% with type 1 diabetes), age 38.0 (±18.8) years, 51% female, diabetes duration 16.0 (±49.9) years, and BMI of 25.2 (±16.5) kg/m2 (mean [±SD]). FSL users demonstrated a −5.2 mmol/mol change in HbA1c, reducing from 67.5 (±20.9) mmol/mol (8.3%) at baseline to 62.3 (±18.5) mmol/mol (7.8%) after 7.5 (interquartile range 3.4–7.8) months of follow-up (n = 3,182) (P &amp;lt; 0.0001). HbA1c reduction was greater in those with initial HbA1c ≥69.5 mmol/mol (&amp;gt;8.5%), reducing from 85.5 (±16.1) mmol/mol (10%) to 73.1 (±15.8) mmol/mol (8.8%) (P &amp;lt; 0.0001). The baseline Gold score (score for hypoglycemic unawareness) was 2.7 (±1.8) and reduced to 2.4 (±1.7) (P &amp;lt; 0.0001) at follow-up. A total of 53% of those with a Gold score of ≥4 at baseline had a score &amp;lt;4 at follow-up. FSL use was also associated with a reduction in diabetes distress (P &amp;lt; 0.0001). FSL use was associated with a significant reduction in paramedic callouts and hospital admissions due to hypoglycemia and hyperglycemia/diabetic ketoacidosis. CONCLUSIONS We show that the use of FSL was associated with significantly improved glycemic control and hypoglycemia awareness and a reduction in hospital admissions.
Extramedullary Myeloma of the Uterus on 18F-FDG PET/CT
Authors: Pamela Ines Causa Andrieu, Jeeban Paul Das, Sungmin Woo, Reddy Ryan, Oguz Akin, Gary A. Ulaner
Journal: Clinical Nuclear Medicine (2020)

Involvement of the uterus by myeloma is an extremely rare manifestation of extramedullary multiple myeloma (MM), denoting a poor prognosis. Extramedullary MM occurs in 7% to 18% of newly diagnosed patients with MM, and 6% to 20% of patients can develop it later. We present a case of extramedullary MM of the uterus suspected on F-FDG PET/CT as a site of disease recurrence in a 47-year-old woman previously in remission. Further evaluation with pelvic MRI identified an infiltrative process involving the uterus, and subsequent tissue sampling confirmed malignant plasma cell infiltration of the uterus. This case highlights a rare site of myeloma recurrence, which can be detected by F-FDG PET/CT.
Shared reality and abstraction: The social nature of predictive models—ERRATUM
Authors: Maya Rossignac-Milon, Federica Pinelli, E. Tory Higgins
Journal: Behavioral and Brain Sciences (2020)

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Noninvasive Ventilation Use in Critically Ill Patients with Acute Asthma Exacerbations
Authors: Meghan D. Althoff, Fernando Holguin, Fan Yang, Gary K. Grunwald, Marc Moss, R. William Vandivier, P. Michael Ho, Tyree H. Kiser, Ellen L. Burnham
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Noninvasive ventilation decreases the need for invasive mechanical ventilation and mortality among patients with chronic obstructive pulmonary disease but has not been well studied in asthma.
Mitochondria and lipid peroxidation in the mechanism of neurodegeneration: Finding ways for prevention
Authors: Plamena R. Angelova, Noemi Esteras, Andrey Y. Abramov
Journal: Medicinal Research Reviews (2020)

Abstract The world's population aging progression renders age‐related neurodegenerative diseases to be one of the biggest unsolved problems of modern society. Despite the progress in studying the development of pathology, finding ways for modifying neurodegenerative disorders remains a high priority. One common feature of neurodegenerative diseases is mitochondrial dysfunction and overproduction of reactive oxygen species, resulting in oxidative stress. Although lipid peroxidation is one of the markers for oxidative stress, it also plays an important role in cell physiology, including activation of phospholipases and stimulation of signaling cascades. Excessive lipid peroxidation is a hallmark for most neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and many other neurological conditions. The products of lipid peroxidation have been shown to be the trigger for necrotic, apoptotic, and more specifically for oxidative stress‐related, that is, ferroptosis and neuronal cell death. Here we discuss the involvement of lipid peroxidation in the mechanism of neuronal loss and some novel therapeutic directions to oppose it.
Dietary anthocyanidin delphinidin modulates β-catenin signaling pathway in human prostate cancer PC-3 cells
Authors: Jung-Mi Yun, Farrukh Afaq, Hasan Mukhtar
Journal: Cancer Research (2008)

469  Prostate cancer (PCa) is the most commonly diagnosed cancer in men within the Western world and the third leading cause of cancer related deaths. Because of unsatisfactory treatment options for PCa there is a need to develop novel preventive approaches for this malignancy. One such strategy is through chemoprevention by the use of non toxic dietary substances and botanical products. Delphinidin, the most abundant and major anthocyanidin present in pigmented fruits and vegetables, possesses strong anti-oxidant and anti-inflammatory properties. Inhibition of Wnt/β-catenin signaling pathway is an attractive target for new chemopreventive and chemotherapeutic approaches. The Wnt signaling pathway and its key component β-catenin play critical roles in embryonic development as well as in human diseases, including various malignancies. Since deregulation of β-catenin signaling pathway contributes to PCa progression, we examined the effect of delphinidin on β-catenin signaling pathway in human prostate cancer PC3 cells. We found that delphinidin (30-180µM; 72 h) treatment resulted in a dose-dependent growth inhibition of cells as assessed by an MTT assay. Delphinidin treatment to cells also resulted in increased phosphorylation of β-catenin at serine and threonine residues and decreased the levels of cytoplasmic β-catenin. Furthermore, treatment of cells to delphinidin inhibited nuclear translocation of β-catenin and suppressed the expression of cyclin D, c-myc, axin-2 and T cell factor-1 (TCF-1) which are downstream target genes of β-catenin. Employing electrophoretic mobility shift assay, we found that treatment of cells with delphinidin decreased the TCF DNA binding activity. We further investigated the effect of delphinidin on β-catenin destruction complex by analyzing the expression of APC, GSK3β and axin. Delphinidin treatment of cells was found to result in the induction of phosphorylation of GSK3β, and protein expression of APC and axin. Moreover, delphinidin treatment resulted in modulation of E-cadherin, Frzb/secreted Frizzled-related protein-3 (FRP3), low density lipoprotein receptor-related protein 6 (LRP6), Dickkopf (Dkk-1) and Dishevelled (Dvl2) proteins. Our results indicate that cell growth inhibition of cells by delphinidin is mediated, at least in part, by modulating β-catenin signaling pathway. We suggest that delphinidin could be a potent inhibitor of Wnt/β-catenin signaling in human prostate cancer cells and suggests its potential use as a cancer therapeutic agent against PCa.