tbuckley/cabot-search huggingface dataset:
Sexual Orientation Identity Disparities in Awareness and Initiation of the Human Papillomavirus Vaccine Among U.S. Women and Girls
Authors: Madina Agénor, Sarah Peitzmeier, Allegra R. Gordon, Sebastien Haneuse, Jennifer E. Potter, S. Bryn Austin
Journal: Annals of Internal Medicine (2020)

This survey examined the association between sexual orientation identity and human papillomavirus (HPV) vaccination among U.S. women and girls. The authors found that adolescent and young adult les...
53P Role of immune biomarkers in evaluating predictive and prognostic value in advanced stage HER2 positive breast cancer
Authors: S. Pasricha, D. Bansal, A. Jajodia, K.D. Choudhary, G. Gupta, A. Sharma, A. Sharma, G. Durga, M. Kamboj, A. Kumar, S.J. Bothra, M.K. Chllamma, V.P.B. Koyyala, A. Russo, D.C. Doval, A. Mehta
Journal: Annals of Oncology (2020)
tappAS: a comprehensive computational framework for the analysis of the functional impact of differential splicing
Authors: Lorena de la Fuente, Ángeles Arzalluz-Luque, Manuel Tardáguila, Héctor del Risco, Cristina Martí, Sonia Tarazona, Pedro Salguero, Raymond Scott, Alberto Lerma, Ana Alastrue-Agudo, Pablo Bonilla, Jeremy R. B. Newman, Shunichi Kosugi, Lauren M. McIntyre, Victoria Moreno-Manzano, Ana Conesa
Journal: Genome biology (2020)

Recent advances in long-read sequencing solve inaccuracies in alternative transcript identification of full-length transcripts in short-read RNA-Seq data, which encourages the development of methods for isoform-centered functional analysis. Here, we present tappAS, the first framework to enable a comprehensive Functional Iso-Transcriptomics (FIT) analysis, which is effective at revealing the functional impact of context-specific post-transcriptional regulation. tappAS uses isoform-resolved annotation of coding and non-coding functional domains, motifs, and sites, in combination with novel analysis methods to interrogate different aspects of the functional readout of transcript variants and isoform regulation. tappAS software and documentation are available at https://app.tappas.org.
Scrap NHS fees for overseas healthcare staff, says Labour
Authors: Abi Rimmer
Journal: BMJ (2020)

The Labour party has called on the government to scrap the NHS surcharge for overseas health professionals and care workers by seeking an amendment to the Immigration Bill.

Introduced in 2015, the surcharge means that people from outside the EU must pay £400 (€445; $488) per person per year to use the NHS. This charge will increase to £624 per year in October and will apply to EU nationals moving to the UK after the Brexit transition period.

Speaking at Questions to the Prime Minister on 20 …
A piece of my mind. Out of service
Authors: R. P. Keating
Journal: JAMA (1988)

<h3>A Letter to My Patients—and Friends</h3> I shall retire from the practice of medicine at the end of June—39 years after becoming a doctor and 33 years after beginning practice in Ridgewood. After a pause for relaxation and reflection, Barbara and I will move to our home in Truro on Cape Cod. Although I am looking forward to a new way of life, I regret leaving so many patients whose experiences I have, to an extent, shared over the years. Of this leavetaking I wish to say two things: First, I will be most happy to see in the office all who want to make appointments for a final visit or appraisal. Indeed, I am making an unconventionally early announcement to provide ample time for these visits. And I will be pleased to talk by phone to whoever wants to ask for advice or just to say good-bye. Of course,
Association of Blood Pressure Lowering With Incident Dementia or Cognitive Impairment
Authors: Diarmaid Hughes, Conor Judge, Robert Murphy, Elaine Loughlin, Maria Costello, William Whiteley, Jackie Bosch, Martin J. O’Donnell, Michelle Canavan
Journal: JAMA (2020)

<h3>Importance</h3> The benefit of blood pressure lowering for the prevention of dementia or cognitive impairment is unclear. <h3>Objective</h3> To determine the association of blood pressure lowering with dementia or cognitive impairment. <h3>Data Sources and Study Selection</h3> Search of PubMed, EMBASE, and CENTRAL for randomized clinical trials published from database inception through December 31, 2019, that evaluated the association of blood pressure lowering on cognitive outcomes. The control groups consisted of either placebo, alternative antihypertensive agents, or higher blood pressure targets. <h3>Data Extraction and Synthesis</h3> Data were screened and extracted independently by 2 authors. Random-effects meta-analysis models were used to report pooled treatment effects and CIs. <h3>Main Outcomes and Measures</h3> The primary outcome was dementia or cognitive impairment. The secondary outcomes were cognitive decline and changes in cognitive test scores. <h3>Results</h3> Fourteen randomized clinical trials were eligible for inclusion (96 158 participants), of which 12 reported the incidence of dementia (or composite of dementia and cognitive impairment [3 trials]) on follow-up and were included in the primary meta-analysis, 8 reported cognitive decline, and 8 reported changes in cognitive test scores. The mean (SD) age of trial participants was 69 (5.4) years and 40 617 (42.2%) were women. The mean systolic baseline blood pressure was 154 (14.9) mm Hg and the mean diastolic blood pressure was 83.3 (9.9) mm Hg. The mean duration of follow-up was 49.2 months. Blood pressure lowering with antihypertensive agents compared with control was significantly associated with a reduced risk of dementia or cognitive impairment (12 trials; 92 135 participants) (7.0% vs 7.5% of patients over a mean trial follow-up of 4.1 years; odds ratio [OR], 0.93 [95% CI, 0.88-0.98]; absolute risk reduction, 0.39% [95% CI, 0.09%-0.68%];<i>I2</i> = 0.0%) and cognitive decline (8 trials) (20.2% vs 21.1% of participants over a mean trial follow-up of 4.1 years; OR, 0.93 [95% CI, 0.88-0.99]; absolute risk reduction, 0.71% [95% CI, 0.19%-1.2%];<i>I2</i> = 36.1%). Blood pressure lowering was not significantly associated with a change in cognitive test scores. <h3>Conclusions and Relevance</h3> In this meta-analysis of randomized clinical trials, blood pressure lowering with antihypertensive agents compared with control was significantly associated with a lower risk of incident dementia or cognitive impairment.
Towards immunotherapy for pancreatic cancer Reply
Authors: B T BRETT
Journal: Gut (2000)

Editor,—McKenzie and Apostolopoulos' recent article on immunotherapy for pancreatic carcinoma ( Gut 1999; 44 :767–769) gave an excellent overview. We agree that the poor prognosis of this disease makes it imperative that new agents and novel therapeutic strategies are investigated. However, although this paper discusses classical immunotherapy (where immune competent cells are stimulated to attack pancreatic cancer cells directly), the induction of antibodies directed against growth factors by immunisation (where the immunogen stimulates the immune system to inhibit the growth of tumour cells indirectly) is not mentioned. We are currently undertaking a phase II clinical trial for inoperable pancreatic cancer using one such immunogen, Gastrimmune, which induces neutralising antibodies against amidated gastrin-17 and its precursor glycine extended gastrin-17 (this immunogen is also undergoing a phase II trial for gastric cancer at the University Department of Surgery, Nottingham, UK). Gastrin has been shown to be a growth factor in a variety of malignancies including colorectal, gastric, and pancreatic cancers in both in vitro and in vivo studies1; precursor forms such as progastrin and glycine extended gastrin also have a trophic effect.2 More recently the autocrine/paracrine pathway, in which tumour cells produce and respond to gastrin, has been shown to be increasingly important.3 In vitro and in vivo studies have also shown the trophic effect of gastrin and the inhibitory effect of both gastrin receptor antagonists and anti-gastrin antibodies,1 4 5 and further studies … Professor McKenzie
Localized synchrotron radiation in mice induces persistent systemic genotoxic events mediated by the functional immune system
Authors: Jessica Ventura, Pavel Lobachevsky, Jason Palazzolo, Helen Forrester, Nicole Haynes, Alesia Ivashkevich, Andrew Stevenson, Christopher Hall, Vassilis Gorgoulis, John Hamilton, Alexandros Georgakilas, Calr Sprung, Olga A Martin
Journal: Cancer Research (2018)
68P Deciphering the interplay between nuclear RNA export factors and long non-coding RNAs in breast cancer metabolism
Authors: C. Klec, D. Schwarzenbacher, B. Gottschalk, R. Margit, F. Prinz, T. Bauernhofer, H. Stoeger, W.F. Graier, M. Pichler
Journal: Annals of Oncology (2020)
Oral fluconazole use in the first trimester and risk of congenital malformations: population based cohort study
Authors: Yanmin Zhu, Brian T Bateman, Kathryn J Gray, Sonia Hernandez-Diaz, Helen Mogun, Loreen Straub, Krista F Huybrechts
Journal: BMJ (2020)

To examine the risk of congenital malformations associated with exposure to oral fluconazole at commonly used doses in the first trimester of pregnancy for the treatment of vulvovaginal candidiasis.Population based cohort study.A cohort of pregnancies publicly insured in the United States, with data from the nationwide Medicaid Analytic eXtract 2000-14.Pregnancies of women enrolled in Medicaid from three or more months before the last menstrual period to one month after delivery, and infants enrolled for three or more months after birth.Use of fluconazole and topical azoles was established by requiring one or more prescriptions during the first trimester of pregnancy.Risk of musculoskeletal malformations, conotruncal malformations, and oral clefts (primary outcomes), associated with exposure to oral fluconazole, diagnosed during the first 90 days after delivery, were examined.The study cohort of 1 969 954 pregnancies included 37 650 (1.9%) pregnancies exposed to oral fluconazole and 82 090 (4.2%) pregnancies exposed to topical azoles during the first trimester. The risk of musculoskeletal malformations was 52.1 (95% confidence interval 44.8 to 59.3) per 10 000 pregnancies exposed to fluconazole versus 37.3 (33.1 to 41.4) per 10 000 pregnancies exposed to topical azoles. The risks of conotruncal malformations were 9.6 (6.4 to 12.7) versus 8.3 (6.3 to 10.3) per 10 000 pregnancies exposed to fluconazole and topical azoles, respectively; risks of oral clefts were 9.3 (6.2 to 12.4) versus 10.6 (8.4 to 12.8) per 10 000 pregnancies, respectively. The adjusted relative risk after fine stratification of the propensity score was 1.30 (1.09 to 1.56) for musculoskeletal malformations, 1.04 (0.70 to 1.55) for conotruncal malformations, and 0.91 (0.61 to 1.35) for oral clefts overall. Based on cumulative doses of fluconazole, the adjusted relative risks for musculoskeletal malformations, conotruncal malformations, and oral clefts overall were 1.29 (1.05 to 1.58), 1.12 (0.71 to 1.77), and 0.88 (0.55 to 1.40) for 150 mg of fluconazole; 1.24 (0.93 to 1.66), 0.61 (0.26 to 1.39), and 1.08 (0.58 to 2.04) for more than 150 mg up to 450 mg of fluconazole; and 1.98 (1.23 to 3.17), 2.30 (0.93 to 5.65), and 0.94 (0.23 to 3.82) for more than 450 mg of fluconazole, respectively.Oral fluconazole use in the first trimester was not associated with oral clefts or conotruncal malformations, but an association with musculoskeletal malformations was found, corresponding to a small adjusted risk difference of about 12 incidents per 10 000 exposed pregnancies overall.
Abstract 16750: Discordant Stress Echocardiography Test Results with Normal Stress Echocardiogram Imaging Does Not Predict a Low Probability for Significant Coronary Artery Disease
Authors: Bhavananda T Reddy, Cory M Nitzel, Hamilton S Gillespie, Boaz Rosen, Chris McGann
Journal: Circulation (2011)

Introduction: Prior studies have indicated that when compared to stress electrocardiography (ECG) alone, the addition of echocardiography conveys a higher sensitivity and specificity for the diagnosis of coronary artery disease (CAD). Limited data is available focusing on discordant stress testing results, defined as abnormal electrocardiography and normal echocardiography. Our hypothesis is that discordant results should not be equated with a low probability for significant obstructive CAD. Methods: A retrospective analysis of 147 discordant stress echocardiography test results in patients who underwent subsequent coronary imaging either with invasive or CT angiography was performed. Discordant stress tests were defined as ECG results with ST segment depressions &gt;1.0 mm at peak exercise or at target heart rate on Dobutamine stress and normal rest and stress echocardiogram wall motion. Coronary stenoses were determined quantitatively with ≥70% stenosis or ≥50% for left main coronary artery stenosis defined as significant obstructive CAD. Results: Out of 147 cases (mean age 61±10 years, 56% male) with discordant stress echocardiography tests, 51 (35%) were found to have significant obstructive CAD on angiography. Though a larger number of patients underwent exercise (111) vs. Dobutamine (36) stress, correlation with significant obstructive CAD was similar (34% vs. 36%, respectively, p value=0.98). Conclusion: Greater than one third of patients with discordant stress echocardiography test results have significant obstructive CAD.
Reply: Fatalism Is Not Justified when Evaluating the Critically Ill Elderly
Authors: Theodore J. Iwashyna, Kenneth M. Langa, Giora Netzer, Christine Cigolle
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

From the Authors:

The evolving research on survivorship complicates the already complex art of patient-centered decision making for the critically ill. Several groups have now presented data showing frequent problems among survivors of critical illness—some new, some preexisting, some likely the acute recognition of chronic processes. Our study (1) and others’ studies have implications for practice, as patients may be less willing to accept treatment with modest risks of cognitive impairment and disability than they would the same risk of death (2). But given the difficulties of conveying prognostic information to families (3), and our lack of nuanced and accurate risk-prediction tools in most cases, it is not yet clear how a humane and evidence-based physician should incorporate these data.

We agree with Drs. Spronk and Hofhuis that a blanket fatalism is not justified in evaluating the older and oldest critically ill. But more so, we would argue that fatalism is not justified when considering the challenges of ICU survivors. Instead, a new challenge has been identified for critical care physicians and our collaborators. In our opinion, a crucial and underappreciated opportunity is collaborating with and organizing survivors of critical illness and their families into full partners (4). Their knowledge of the survivorship experience is necessary in clarifying present care needs and priorities for future research, many of which fall outside the disease-based medical model. We also must rigorously test innovative and diverse interventions. In some cases, these interventions will involve preventing new problems; in others, helping patients and their caregivers better adapt to and accommodate new problems; and in others, treating long-standing but previously underrecognized problems. We need a portfolio of new therapies to match the diverse challenges our older adult survivors face.
Abstract 208: Can Transesophageal Echocardiography During CPR Change Resuscitation Outcomes in Prolonged Cardiac Arrest?
Authors: Woo Jin Jung
Journal: Circulation (2018)

Background and Purpose: Early diagnosis of a potential cause of cardiac arrest is crucial for resuscitating the cardiac arrest victim. Transesophageal echocardiography (TEE) provides an excellent window to visualize the heart and aorta without any interruption of resuscitation effort during cardiopulmonary resuscitation (CPR). This study was to investigate whether TEE during CPR influences resuscitation outcome in patients with non-traumatic adult cardiac arrest who receive prolonged resuscitation attempt. Subjects and Methods: This prospective observational study was conducted by analyzing the patients with non-traumatic adult cardiac arrest (age over 20 year-old) who underwent TEE during CPR in the emergency department of a university hospital. According to the availability of TEE and experienced emergency physicians, TEE was performed during CPR when resuscitation attempt was prolonged longer than 10 minutes. Patients were divided into two groups. TEE (+) group was composed of those who have any structural abnormality observed by TEE. TEE (-) group was those who have no structural abnormality. Primary outcome measure was restoration of spontaneous circulation (ROSC). Results: 108 patients (mean age: 69 year-old, 66 males) were enrolled. 31 patients (29%) were included in TEE(+) group and 77 patients (61%) were included in TEE(-) group. Abnormalities observed in TEE(+) group included aortic dissection in 18 patients, pulmonary thromboembolism (PTE) in 9 patients, cardiac tamponade in 3 patients and intra-cardiac thrombus in 1 patient. There was no significant difference in age, rate of bystander CPR, time from collapse to CPR, CPR duration, first monitoring ECG rhythm, and etiology of cardiac arrest between two groups. The rate of ROSC and survival discharge was not different between TEE(-) group and TEE (+) group (ROSC: 38 vs 29%, P = 0.268, survival discharge: 6.5 vs. 6.5%). Two patients with pulmonary PTE who received fibrinolysis survived. Conclusion: TEE during CPR does not change resuscitation outcomes in patients with prolonged cardiac arrest. However, resuscitation outcome might be changed with TEE in patients with specific etiology such as PTE or cardiac tamponade.
AMELIE speeds Mendelian diagnosis by matching patient phenotype and genotype to primary literature
Authors: Johannes Birgmeier, Maximilian Haeussler, Cole A. Deisseroth, Ethan H. Steinberg, Karthik A. Jagadeesh, Alexander J. Ratner, Harendra Guturu, Aaron M. Wenger, Mark E. Diekhans, Peter D. Stenson, David N. Cooper, Christopher Ré, Alan H. Beggs, Jonathan A. Bernstein, Gill Bejerano
Journal: Science Translational Medicine (2020)

An automated pipeline parses primary literature about Mendelian diseases to rank patient candidate causative genes, thereby accelerating diagnosis.
Neoadjuvant Chemotherapy in High-Risk Soft Tissue Sarcomas: Final Results of a Randomized Trial From Italian (ISG), Spanish (GEIS), French (FSG), and Polish (PSG) Sarcoma Groups
Authors: Alessandro Gronchi, Emanuela Palmerini, Vittorio Quagliuolo, Javier Martin Broto, Antonio Lopez Pousa, Giovanni Grignani, Antonella Brunello, Jean-Yves Blay, Oscar Tendero, Robert Diaz Beveridge, Virginia Ferraresi, Iwona Lugowska, Domenico Franco Merlo, Valeria Fontana, Emanuela Marchesi, Luca Braglia, Davide Maria Donati, Elena Palassini, Giuseppe Bianchi, Andrea Marrari, Carlo Morosi, Silvia Stacchiotti, Silvia Bagué, Jean Michel Coindre, Angelo Paolo Dei Tos, Piero Picci, Paolo Bruzzi, Paolo Giovanni Casali
Journal: Journal of Clinical Oncology (2020)

To determine whether the administration of histology-tailored neoadjuvant chemotherapy (HT) was superior to the administration of standard anthracycline plus ifosfamide neoadjuvant chemotherapy (A+I) in high-risk soft tissue sarcoma (STS) of an extremity or the trunk wall.This was a randomized, open-label, phase III trial. Patients had localized high-risk STS (grade 3; size, ≥ 5 cm) of an extremity or trunk wall, belonging to one of the following five histologic subtypes: high-grade myxoid liposarcoma (HG-MLPS); leiomyosarcoma (LMS), synovial sarcoma (SS), malignant peripheral nerve sheath tumor (MPNST), and undifferentiated pleomorphic sarcoma (UPS). Patients were randomly assigned in a 1:1 ratio to receive three cycles of A+I or HT. The HT regimens were as follows: trabectedin in HG-MLPS; gemcitabine plus dacarbazine in LMS; high-dose prolonged-infusion ifosfamide in SS; etoposide plus ifosfamide in MPNST; and gemcitabine plus docetaxel in UPS. Primary and secondary end points were disease-free survival (DFS) and overall survival (OS), estimated using the Kaplan-Meier method and compared using Cox models adjusted for treatment and stratification factors. The study is registered at ClinicalTrials.gov (identifier NCT01710176).Between May 2011 and May 2016, 287 patients (UPS: n = 97 [33.8%]; HG-MLPS: n = 65 [22.6%]; SS: n = 70 [24.4%]; MPNST: n = 27 [9.4%]; and LMS: n = 28 [9.8%]) were randomly assigned to either A+I or HT. At the final analysis, with a median follow-up of 52 months, the projected DFS and OS probabilities were 0.55 and 0.47 (log-rank P = .323) and 0.76 and 0.66 (log-rank P = .018) at 60 months in the A+I arm and HT arm, respectively. No treatment-related deaths were observed.In a population of patients with localized high-risk STS, HT was not associated with a better DFS or OS, suggesting that A+I should remain the regimen to choose whenever neoadjuvant chemotherapy is used in patients with high-risk STS.
Ambient Air Pollution and Mortality in 652 Cities
Authors: Cong Liu, Antonio Gasparrini, Haidong Kan
Journal: New England Journal of Medicine (2019)

In response to the article by Liu et al. (Aug.22 issue) 1 : the inhalable fraction of particulate matter with an aerodynamic diameter of 10 μm or less (PM 10 ) in the real world is made up of a mixture of substances probably derived from many sources. 2In urban areas, a substan-Mongolia Gobi Desert Tangshan