bluuebunny/crossref_metadata_2025_split huggingface dataset:
Media coverage of calls to rename low-risk cancers: a content analysis
Authors: Nickel Brooke , Moynihan Ray , Barratt Alexandra , Brito Juan P , McCaffery Kirsten 
Published: July 2020

ObjectivesThe use of more medicalised labels can increase both concern about illness and the desire for more invasive treatment. This study analyses the media’s coverage of an Analysis article in The BMJ which generated a large amount of high-profile international media coverage. It aims to understand how to better communicate messages about low-risk cancers and overdiagnosis to the public.DesignContent analysis of media coverage.SettingMedia was identified by Isentia Media Portal, searched in Google News and cross-checked in Factiva and Proquest databases from August 2018.MethodsMedia headlines, full text and open access public comments responding to the coverage on the article proposing to ‘rename low-risk conditions currently labelled as cancer’ were analysed to determine the main themes.Results45 original media articles and their associated public comments (n=167) were identified and included in the analysis. Overall, headlines focused on cancer generally and there was little mention of ‘low-risk’, ‘overdiagnosis’ or ‘overtreatment’. The full text generally presented a more balanced view of the evidence and were supportive of the proposal, however, public responses tended to be more negative towards the idea of renaming low-risk cancers and indicated confusion. Comments seemed to focus on the headlines rather than the full article.ConclusionsThis study offers a novel insight into media coverage of the complex and counterintuitive problem of overdiagnosis. Continued deliberation on how to communicate similar topics to the public through the mainstream media is needed. Future work in the area of low-risk cancer communication should consider the powerful impact of people’s previous experience with a cancer diagnosis and the criticism about being paternalistic and concealing the truth from patients.
Does probe-tube verification of real-ear hearing aid amplification characteristics improve outcomes in adult hearing aid users? A protocol for a systematic review
Authors: Almufarrij Ibrahim , Munro Kevin J , Dillon Harvey 
Published: July 2020

IntroductionUsing a probe-tube microphone to measure and adjust the real-ear performance of the hearing aid to match the prescription target is recommended and widely used in clinical practice. Hearing aid fitting software can approximately match the amplification characteristics of the hearing aid to the prescription without real-ear measurements (REMs), but using REM improves the match to the prescribed target. What is unclear is if the improved match results in a better patient-reported outcome. The primary objective of this review is to determine whether the use of REM improves patient-reported outcomes in adult hearing aid users.Methods and analysisThe review’s methods are in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. MEDLINE, EMBASE, PsycINFO, CINAHL, Web of Science and CENTRAL via Cochrane Library will be searched to identify relevant studies. The review’s population of interest will include adults with any degree of sensorineural or mixed hearing loss who have been prescribed with acoustic hearing aids. The included studies should compare REM fitting to the initial fit provided by the manufacturer’s fitting software. Hearing-specific health-related quality of life is the primary outcome but secondary outcomes include self-reported listening ability, speech recognition scores, generic health-related quality of life, hours of use, number of required follow-up sessions and adverse events. Randomised and non-randomised controlled trials will be included. The risk of bias in the included studies will be evaluated using Down and Black’s checklist. The quality of the overall evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations tool.Ethics and disseminationEthical approval will not be sought because this systematic review will only retrieve and analyse data from published studies. Review results will be published in a peer-reviewed journal and presented at relevant scientific conferences.PROSPERO registration numberCRD42020166074.
Quality of cancer end-of-life care: discordance between bereaved relatives and professional proxies
Authors: Bertocchi Elisabetta , Artioli Giovanna , Rabitti Elisa , Bedini Gabriele , Di Leo Silvia , Asensio Sierra Nuria Maria , Braglia Luca , Costantini Massimo 
Published: July 2020

BackgroundQuality of care for patients dying in hospital remains suboptimal. A major problem is the identification of valid sources of information about the views and experiences of dying patients and their relatives.AimThis study aimed to estimate the agreement on quality of end-of-life care from the perspectives of bereaved relatives, physicians and nurses interviewed after the patients’ death.DesignIn this prospective study, we interviewed, after the patient death, the bereaved relatives, the attending physicians and the reference nurses, using the Toolkit After-death Family Interview and the View Of Informal Carers-Evaluation of Services (VOICES). Agreement was assessed using Lin’s concordance correlation coefficient, Cohen’s kappa, overall concordance correlation coefficient and Fleiss’ kappa.Setting/participantsWe enrolled a consecutive series of 40 adult patients who died of cancer between January and December 2016 who had spent at least 48 hours in the medical oncology ward of the Santa Maria Hospital of Reggio Emilia, Italy.ResultsWe interviewed all physicians and nurses, and 26 (65.0%) out of 40 relatives. We found a poor agreement on overall quality of care among the three proxies (+0.21; −0.04 to 0.44), between relatives and nurses (+0.05; −0.39 to +0.47), and between relatives and physicians (+0.25; −0.13 to +0.57). A similar poor agreement was observed for all the other Toolkit and VOICES scales.ConclusionsThe agreement was rather poor, confirming previous results in different settings. Information from professional proxies should not be used for assessing the quality of care or for estimating missing information from bereaved relatives.
Small thrombus size, thrombus composition, and poor collaterals predict pre-interventional thrombus migration
Authors: Sporns Peter B , Krähling Hermann , Psychogios Marios N , Jeibmann Astrid , Minnerup Jens , Broocks Gabriel , Meyer Lukas , Brehm Alex , Wildgruber Moritz , Fiehler Jens , Kniep Helge , Hanning Uta 
Published: July 2020

BackgroundDifferent imaging characteristics such as clot burden score, collaterals, and pre-interventional thrombus migration are associated with functional outcome in patients with acute ischemic stroke. Moreover, histological thrombus composition is associated with pre-interventional thrombus migration. We hypothesized that smaller clots may more likely migrate and that collateral status in ischemic stroke patients may mediate this tendency of the clot to migrate.MethodsIn this prospective cohort of consecutive ischemic stroke patients, clot burden scores and collateral scores were rated and the retrieved thrombi were histologically analyzed. We then investigated the relationship between clot burden score, probability for thrombus migration, and collateral scores using mediation analysis.Results163 patients are included of which 36 (22.1%) had a clot migration. Probability of thrombus migration was significantly associated with lower collateral scores (P<0.01), higher clot burden scores (P<0.01), shorter thrombi (P<0.01), and higher RBC count (P<0.01). In the mediator pathway, higher collateral scores were significantly associated with higher clot burden scores (P<0.01) and younger age (P=0.029). The total effect of an increase in clot burden score by one grade on thrombus migration is composed of the direct effect (+18%, P<0.01) and the collateral score-mediated indirect effect (−5%, P<0.01).ConclusionsSmaller, erythrocyte-rich thrombi tend to migrate more often. Good collaterals seem to have a considerable effect on limiting migration. This supports the hypothesis that larger clots have stronger adherence with the vessel wall and that good collaterals increase the counter pressure distal of the clot.
A Genetic Vaccine Encoding Shared Cancer Neoantigens to Treat Tumors with Microsatellite Instability
Authors: Leoni Guido , D'Alise Anna Morena , Cotugno Gabriella , Langone Francesca , Garzia Irene , De Lucia Maria , Fichera Imma , Vitale Rosa , Bignone Veronica , Tucci Fabio Giovanni , Mori Federica , Leuzzi Adriano , Di Matteo Elena , Troise Fulvia , Abbate Adele , Merone Rossella , Ruzza Valentino , Diodoro Maria Grazia , Yadav Mahesh , Gordon-Alonso Monica , Vanhaver Cristophe , Panigada Maddalena , Soprana Elisa , Siccardi Antonio , Folgori Antonella , Colloca Stefano , van der Bruggen Pierre , Nicosia Alfredo , Lahm Armin , Catanese Maria Teresa , Scarselli Elisa 
Published: July 2020

Abstract

Tumors with microsatellite instability (MSI) are caused by a defective DNA mismatch repair system that leads to the accumulation of mutations within microsatellite regions. Indels in microsatellites of coding genes can result in the synthesis of frameshift peptides (FSP). FSPs are tumor-specific neoantigens shared across patients with MSI. In this study, we developed a neoantigen-based vaccine for the treatment of MSI tumors. Genetic sequences from 320 MSI tumor biopsies and matched healthy tissues in The Cancer Genome Atlas database were analyzed to select shared FSPs. Two hundred nine FSPs were selected and cloned into nonhuman Great Ape Adenoviral and Modified Vaccinia Ankara vectors to generate a viral-vectored vaccine, referred to as Nous-209. Sequencing tumor biopsies of 20 independent patients with MSI colorectal cancer revealed that a median number of 31 FSPs out of the 209 encoded by the vaccine was detected both in DNA and mRNA extracted from each tumor biopsy. A relevant number of peptides encoded by the vaccine were predicted to bind patient HLA haplotypes. Vaccine immunogenicity was demonstrated in mice with potent and broad induction of FSP-specific CD8 and CD4 T-cell responses. Moreover, a vaccine-encoded FSP was processed in vitro by human antigen-presenting cells and was subsequently able to activate human CD8 T cells. Nous-209 is an “off-the-shelf” cancer vaccine encoding many neoantigens shared across sporadic and hereditary MSI tumors. These results indicate that Nous-209 can induce the optimal breadth of immune responses that might achieve clinical benefit to treat and prevent MSI tumors.

Significance:
These findings demonstrate the feasibility of an “off-the-shelf” vaccine for treatment and prevention of tumors harboring frameshift mutations and neoantigenic peptides as a result of microsatellite instability.
Infarction of the Splenium of the Corpus Callosum in the Age of COVID-19
Authors: Sparr Steven A. , Bieri Phyllis L. 
Published: July 2020

Background and Purpose:
Ischemic infarction of the corpus callosum is rare and infarction isolated to the corpus callosum alone rarer still, accounting for much <1% of ischemic stroke in most stroke registries. About half of callosal infarctions affect the splenium.

Methods:
During a 2-week period, at the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City, 4 patients at Montefiore Medical Center in the Bronx were found to have ischemic lesions of the splenium of the corpus callosum, 2 with infarction isolated to the corpus callosum.

Results:
All patients tested positive for COVID-19 and 3 had prolonged periods of intubation. All had cardiovascular risk factors. Clinically, all presented with encephalopathy and had evidence of coagulopathy and raised inflammatory markers.

Conclusions:
Infarction of the splenium of the corpus callosum is exceedingly rare and a cluster of such cases suggests COVID-19 as an inciting agent, with the mechanisms to be elucidated.
Consistent Unsupervised Estimators for Anchored PCFGs
Authors: Clark Alexander , Fijalkow Nathanaël 
Published: July 2020

AbstractLearning probabilistic context-free grammars (PCFGs) from strings is a classic problem in computational linguistics since Horning (1969). Here we present an algorithm based on distributional learning that is a consistent estimator for a large class of PCFGs that satisfy certain natural conditions including being anchored (Stratos et al., 2016). We proceed via a reparameterization of (top–down) PCFGs that we call a bottom–up weighted context-free grammar. We show that if the grammar is anchored and satisfies additional restrictions on its ambiguity, then the parameters can be directly related to distributional properties of the anchoring strings; we show the asymptotic correctness of a naive estimator and present some simulations using synthetic data that show that algorithms based on this approach have good finite sample behavior.
Transient Overturning Compensation between Atlantic and Indo-Pacific Basins
Authors: Sun Shantong , Thompson Andrew F. , Eisenman Ian 
Published: July 2020

AbstractClimate models consistently project (i) a decline in the formation of North Atlantic Deep Water (NADW) and (ii) a strengthening of the Southern Hemisphere westerly winds in response to anthropogenic greenhouse gas forcing. These two processes suggest potentially conflicting tendencies of the Atlantic meridional overturning circulation (AMOC): a weakening AMOC due to changes in the North Atlantic but a strengthening AMOC due to changes in the Southern Ocean. Here we focus on the transient evolution of the global ocean overturning circulation in response to a perturbation to the NADW formation rate. We propose that the adjustment of the Indo-Pacific overturning circulation is a critical component in mediating AMOC changes. Using a hierarchy of ocean and climate models, we show that the Indo-Pacific overturning circulation provides the first response to AMOC changes through wave processes, whereas the Southern Ocean overturning circulation responds on longer (centennial to millennial) time scales that are determined by eddy diffusion processes. Changes in the Indo-Pacific overturning circulation compensate AMOC changes, which allows the Southern Ocean overturning circulation to evolve independently of the AMOC, at least over time scales up to many decades. In a warming climate, the Indo-Pacific develops an overturning circulation anomaly associated with the weakening AMOC that is characterized by a northward transport close to the surface and a southward transport in the deep ocean, which could effectively redistribute heat between the basins. Our results highlight the importance of interbasin exchange in the response of the global ocean overturning circulation to a changing climate.
Reduced risk for hospitalization due to hyponatraemia in lithium treated patients: A Swedish population-based case–control study
Authors: Falhammar Henrik , Skov Jakob , Calissendorff Jan , Lindh Jonatan D , Mannheimer Buster 
Published: July 2020

Background: Many drugs used in psychiatry have been reported to cause hyponatraemia. However, lithium may be an exception due to its potential for causing nephrogenic diabetes insipidus, but clinical data are largely absent. The objective of this investigation was to study the association between lithium therapy and hospitalization due to hyponatraemia. Methods: This study was a register-based case–control investigation of the general Swedish population. Patients hospitalized with a principal diagnosis of hyponatraemia ( n=11,213) were compared with matched controls ( n=44,801). Analyses using multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations and socioeconomic factors were deployed to calculate the association between severe hyponatraemia and the use of lithium. Additionally, newly initiated (⩽90 days) and ongoing lithium therapy was studied separately. Results: Compared with controls, the unadjusted odds ratio (OR) (95% confidence interval (CI)) for hospitalization due to hyponatraemia was 1.07 (0.70–1.59) for lithium. However, after adjustment for confounding factors the risk was reduced (adjusted OR: 0.53 (0.31–0.87)). Newly initiated lithium therapy was not significantly associated with hyponatraemia (adjusted OR 0.73 (0.35–5.38)). In contrast, for ongoing therapy the corresponding adjusted OR was significantly reduced (adjusted OR: 0.52 (0.30–0.87)). Conclusions: A marked inverse association was found between ongoing lithium therapy and hospitalization due to hyponatraemia.
The µ-opioid system in midline thalamic nuclei modulates defence strategies towards a conditioned fear stimulus in male mice
Authors: Bengoetxea Xabier , Goedecke Lena , Blaesse Peter , Pape Hans-Christian , Jüngling Kay 
Published: July 2020

Background: Nuclei located in the dorsal midline thalamus, such as the paraventricular nucleus of the thalamus (PVT), are crucial to modulate fear and aversive behaviour. In addition, the PVT shows a dense expression of µ-opioid receptors (MORs) and could mediate the anxiolytic effects of opioids. Methods: We analysed the contribution of MORs in the dorsal midline thalamus (i.e. the PVT) to the performance of mice in a classical fear conditioning paradigm. We locally injected a specific agonist (DAMGO), an antagonist (CTAP) of MOR or saline as a control into the dorsal midline thalamus of male mice, prior to fear extinction training. We assessed freezing as a typical measure of fear and extended our analysis by evaluation of aversive, non-aversive and neutral behavioural features using compositional data analysis. Results: Pharmacological blockade of MORs through CTAP in the dorsal midline thalamus induced a fear memory extinction deficit, as evidenced by maintained freezing during extinction sessions. Stimulation of MORs by DAMGO resulted in an overall increase in locomotor activity, associated with decreased freezing during recall of extinction. Compositional data analysis confirmed the freezing-related pharmacological effects and revealed specific differences in basic behavioural states. CTAP-treated mice remained in an aversive state, whereas DAMGO-treated mice displayed predominantly neutral behaviour. Conclusions: Fear extinction requires the integrity of the µ-opioid system in the dorsal midline thalamus. Pharmacological stimulation of MOR and associated facilitation of fear extinction recall suggest a potential therapeutic avenue for stress-related or anxiety disorders.
Ovarian metastasis from malignant pleural mesothelioma
Authors: Naldi Giuseppe , Bergomi Serenella , Visca Paolo , Cecere Fabiana Letizia 
Published: July 2020

Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive disease of the pleura with a dismal prognosis. Distant metastases most commonly occur in the liver, spleen, and thyroid gland. To our knowledge, ovarian metastases have never been described. Case description: We describe a case of a woman with recurrent malignant pleural mesothelioma presenting a single ovarian metastasis, surgically resected. Conclusions: This case report highlights the importance of using a complete staging protocol in patients with MPM to improve patient management. A whole-body computed tomography (CT) scan with contrast enhancement and possibly positron emission tomography–CT should be performed to identify any distant metastases before deciding on treatment strategy.
The Effect of β-Blockers for Burn Patients on Clinical Outcomes: Systematic Review and Meta-Analysis
Authors: Hassoun-Kheir Nasreen , Henig Oryan , Avni Tomer , Leibovici Leonard , Paul Mical 
Published: July 2020

Objectives: To assess the effects and safety of β-blockers in hospitalized patients with burns. Methods: A systematic review and meta-analysis of the literature. A broad search was conducted to identify all randomized controlled trials (RCTs) comparing β-blockers to control in hospitalized patients with burns. The primary outcome was 3-month all-cause mortality. Secondary outcomes were clinical patient-relevant end points. We subgrouped results by children/adults and burn severity. Risk of bias was assessed using the individual domain approach. Results: Four RCTs reported in 11 publications were included. Primary outcome of mortality was assessed in children (2 trials, n = 424) and adults (2 trials, n = 148) with severe burns. No significant difference was found between propranolol and control for mortality (risk ratio [RR] = 0.82, 95% CI = 0.48-1.39, 4 trials with broad confidence intervals in adults and children), sepsis (RR = 0.81, 95% CI = 0.46-1.43, 2 trials), and survivors’ length of stay (absolute mean difference = 2.53, 95% CI = −2.58–7.63, 3 trials). There was no significant difference in bradycardia (RR = 1.33, 95% CI = 0.77-2.3, 2 trials), hypotension (RR = 1.26, 95% CI = 0.73-2.17, 3 trials), or cardiac arrhythmia (RR: 2.97, 95% CI: 0.12-71.87, 1 trial). The evidence was graded as very low certainty, due to trial’s internal risk of bias, imprecision, and possible selective reporting. Conclusions: No sufficient evidence was found to support or refute an advantage for β-blocker use in children or adults after burns. Additional studies are needed to create a consensus and formulate practice guidelines on the optimal β-blocker to use, indications for initiation, and duration of treatment.
Safety of Intravenous Push Lacosamide Compared With Intravenous Piggyback at a Tertiary Academic Medical Center
Authors: McLaughlin Kevin , Carabetta Shannon , Hunt Nicholas , Schuler Brian R. , Ting Clara , Tran Lena K. , Szumita Paul M. , Anger Kevin E. 
Published: July 2020

Background: There are limited data regarding the incidence of adverse events associated with administering lacosamide by intravenous push (IVP) compared with IV piggyback (IVPB). Objective: The objective of this analysis was to compare the safety profile, including cardiovascular effects, sedative effects, and IV site reactions of IVP and IVPB lacosamide administration. Methods: A retrospective pre/post cohort analysis comparing patients who received lacosamide via IVP and IVPB was conducted. Safety end points included hypotension, bradycardia, medication-related sedation, and IV site reactions. The relationship between patient characteristics and the incidence of safety end points was analyzed using the Student t-test and χ2 test as appropriate. Results: Bradycardia occurred after 0.19% of IVP administrations and 1.09% of IVPB administrations assessed ( P = 0.07). Hypotension was observed in 3.16% of IVP administrations compared to 1.59% in the IVPB cohort ( P = 0.12). Post lacosamide-related sedation was noted in 11.32% and 11.68% of the IVP and IVPB cohorts, respectively ( P = 0.87). Infusion site reaction rates of 1.80% and 0.84% were documented in the IVP and IVPB cohorts, respectively ( P = 0.33). Of note, only 1 adverse event required clinical intervention. One 200-mg dose in the IVP cohort required a fluid bolus postadministration. Conclusion and Relevance: IVP lacosamide was associated with a similar incidence of cardiovascular, neurological, and infusion site–related adverse events compared with IVPB, in which nearly every adverse event was deemed clinically insignificant. Lacosamide administered via IVP may be considered a safe alternative method of administration in the acute care setting.