bluuebunny/crossref_metadata_2025_split huggingface dataset:
The risk of misdiagnosis in acute thoracic aortic dissection: a review of current guidelines
Authors: Salmasi M Yousuf , Al-Saadi Nina , Hartley Philip , Jarral Omar A , Raja Shahzad , Hussein Muthana , Redhead Julian , Rosendahl Ulrich , Nienaber Christoph A , Pepper John R , Oo Aung Y , Athanasiou Thanos 
Published: March 2020

Acute aortic syndrome and in particular aortic dissection (AAD) persists as a cause of significant morbidity and mortality despite improvements in surgical management. This clinical review aims to explore the risks of misdiagnosis, outcomes associated with misdiagnosis and evaluate current diagnostic methods for reducing its incidence.Due to the nature of the pathology, misdiagnosing the condition and delaying management can dramatically worsen patient outcomes. Several diagnostic challenges exist, including low prevalence, rapidly propagating pathology, non-discrete symptomatology, non-specific signs, analogy with other acute conditions and lack of management infrastructure. A similarity to acute coronary syndromes is a specific concern and risks patient maltreatment. AAD with malperfusion syndromes are both a cause of misdiagnosis and marker of disease complication, requiring specifically tailored management plans from the emergency setting.Despite improvements in diagnostic measures, including imaging modalities and biomarkers, misdiagnosis of AAD remains commonplace and current guidelines are relatively limited in preventing its occurrence. This paper recommends the early use of AAD risk scoring, focused echocardiography and most importantly, fast-tracking patients to cross-sectional imaging where the suspicion of AAD is high. This has the potential to improve the diagnostic process for AAD and limit the risk of misdiagnosis. However, our understanding remains limited by the lack of large patient datasets and an adequately audited processes of emergency department practice.
Pre-existing inflammatory immune microenvironment predicts the clinical response of vulvar high-grade squamous intraepithelial lesions to therapeutic HPV16 vaccination
Authors: Abdulrahman Ziena , de Miranda Noel , van Esch Edith M G , de Vos van Steenwijk Peggy J , Nijman Hans W , J. P. Welters Marij , van Poelgeest Mariette I E , van der Burg Sjoerd H 
Published: March 2020

BackgroundVulvar high-grade squamous intraepithelial lesion (vHSIL) is predominantly induced by high-risk human papilloma virus type 16 (HPV16). In two independent trials, therapeutic vaccination against the HPV16 E6 and E7 oncoproteins resulted in objective partial and complete responses (PRs/CRs) in half of the patients with HPV16+vHSIL at 12-month follow-up. Here, the prevaccination and postvaccination vHSIL immune microenvironment in relation to the vaccine-induced clinical response was investigated.MethodsTwo novel seven-color multiplex immunofluorescence panels to identify T cells (CD3, CD8, Foxp3, Tim3, Tbet, PD-1, DAPI) and myeloid cells (CD14, CD33, CD68, CD163, CD11c, PD-L1, DAPI) were designed and fully optimized for formalin-fixed paraffin-embedded tissue. 29 prevaccination and 24 postvaccination biopsies of patients with vHSIL, and 27 healthy vulva excisions, were stained, scanned with the Vectra multispectral imaging system, and automatically phenotyped and counted using inForm advanced image analysis software.ResultsHealthy vulvar tissue is strongly infiltrated by CD4 and CD8 T cells expressing Tbet and/or PD-1 and CD14+HLA-DR+inflammatory myeloid cells. The presence of such a coordinated pre-existing proinflammatory microenvironment in HPV16+vHSIL is associated with CR after vaccination. In partial responders, a disconnection between T cell and CD14+myeloid cell infiltration was observed, whereas clinical non-responders displayed overall lower immune cell infiltration. Vaccination improved the coordination of local immunity, reflected by increased numbers of CD4+Tbet+T cells and HLA-DR+CD14+expressing myeloid cells in patients with a PR or CR, but not in patients with no response. CD8+T cell infiltration was not increased after vaccination.ConclusionA prevaccination inflamed type 1 immune contexture is required for stronger vaccine-induced immune infiltration and is associated with better clinical response. Therapeutic vaccination did not overtly increase immune infiltration of cold lesions.
Pneumoconiosis progression patterns in US coal miner participants of a job transfer programme designed to prevent progression of disease
Authors: Hall Noemi B , Blackley David J , Halldin Cara N , Laney A Scott 
Published: March 2020

ObjectivesPneumoconiosis prevalence and severity among US coal miners has been increasing for the past 20 years. An examination of the current approaches to primary and secondary prevention efforts is warranted. One method of secondary prevention is the Mine Safety and Health Administration-administered part 90 option programme where US coal miners with radiographic evidence of pneumoconiosis can exercise their right to be placed in a less dusty area of the mine. This study focuses on characterising the progression of disease among US coal miners who participated in the National Institute for Occupational Safety and Health-administered Coal Workers’ Health Surveillance Programme (CWHSP) and exercised their part 90 job transfer option.MethodsChest radiograph classifications of working underground coal miners who exercised their part 90 job transfer option during 1 January 1986 to 21 November 2016 and participated in the CWHSP during 1 January 1981 to 19 March 2019 were analysed.Results513 miners exercised their part 90 option and participated in the CWHSP at least once during this time period. Of the 149 miners with ≥2 radiographs available, 48 (32%) showed progression after exercising part 90 and had more severe disease prior to exercising, compared with miners who did not progress (severity score of 2.8 vs 1.7, p=0.0002).ConclusionThe part 90 job transfer option programme is not routinely used as intended to prevent progression of pneumoconiosis among US coal miners. The one-third of miners who participated in part 90 and continued to progress, exercised their part 90 option at a later stage of disease compared with non-progressors.
HYR-PB21-LA, a potential extended-release bupivacaine formulation, produces long-lasting local anesthesia in rats and guinea pigs
Authors: Peng Jiashi , Liu Chang , Liu Jingjing , Wang Yihua , Lu Xiaorong , Sun Hongzhang , Yu Yunxian , Gao Shu , Zhang Shanchun 
Published: March 2020

BackgroundEffective postoperative pain management plays a key role in enhancing recovery of patients after surgery. Bupivacaine hydrochloride is one of the most commonly local anesthetics used for the postoperative pain control. However, the relatively short anesthesia duration of bupivacaine preparations limited their clinical application.MethodsBoth guinea pig pin-prick study and rat tail-flick test were performed to evaluate the local anesthesia efficacy of HYR-PB21-LA, a new microparticle suspension injection of bupivacaine pamoate.ResultsIn the pin-prick test, the complete cutaneous trunci muscle reflex inhibitions were observed at 30 min in all treatment groups containing bupivacaine. In comparison with 6.7 mg/mL HYR-PB21-LA, both 10 and 20 mg/mL HYR-PB21-LA groups had significantly higher area under effect time curve (AUEC) values (p<0.001 and p<0.0001) and slower offset time (p<0.0001). Significantly higher AUEC (p<0.0001) and slower offset time (p<0.0001) were also found in 10 mg/mL HYR-PB21-LA treatment group compared with bupivacaine liposome injectable suspension (liposomal bupivacaine). In the rat tail-flick test, significantly increased local anesthesia effect was lasted for 5 hours after 2.5 mg/mL HYR-PB21-LA administration, which was fivefold longer than bupivacaine hydrochloride. The longer lasted efficacy of significantly increased local anesthesia was also observed in 5 mg/mLHYR-PB21-LA than those in liposomal bupivacaine (8 hour vs 1 hour).ConclusionsThe results demonstrated that the HYR-PB21-LA produced longer local anesthesia effect than current clinical preparations of bupivacaine in two animal models. These findings raise the potential clinical value of HYR-PB21-LA as a long-lasting local anesthesia for controlling postsurgical pain in humans.
Use of smartphones to aid the teaching of equine ocular fundus examination
Authors: Shipman Emma , Burford John H , Bowen Mark , Duz Marco 
Published: March 2020

BackgroundTeaching and learning how to perform examination of the ocular fundus is challenging. Smartphones can support to enhance students’ confidence and experience.MethodsFollowing an optional year‐4 ophthalmoscopy practical using hand‐held ophthalmoscopes, students completed a questionnaire using a visual analogue scale (VAS) investigating if students felt smartphone use aided learning and if student's self‐assessed confidence in visualising the ocular fundus had improved. VAS scores were compared using the Wilcoxon signed rank test (significance: P<0.05).ResultsAll 30 year‐4 students attending the practical participated to the study. Confidence in performing direct ophthalmoscopy significantly increased after the practical. Confidence after the practical was 65.3 (±19.8) per cent compared with before the practical when confidence was 20.1 (±15.6) per cent (P<0.001). The perceived usefulness of traditional teaching was 62.3 (±23.8) per cent. The perceived usefulness of the teaching with the smartphone was 91.1 (±8.6) per cent. While students found both methods useful, they perceived the use of the smartphone to be significantly more useful (P<0.001). Free‐text comments on the use of the smartphone were all positive and included ‘useful’, ‘fun’ and ‘good teaching tool’.ConclusionsThis study shows that students positively received the use of the smartphone, which can be a useful tool to teach the equine ocular examination to undergraduate veterinary students.
FIFTY YEARS OF LITERATURE ON EXPORT ASSISTANCE PROGRAMMES: A BIBLIOMETRIC ANALYSIS
Authors: RIBEIRO JOANA , FORTE ROSA 
Published: March 2020

Literature on export assistance programmes (EAPs) was first published over half a century ago and has focused on many topics, such as the impact of EAPs on firms’ performance, their usefulness and use, among others. The numerous papers published in this area justify the present bibliometric analysis aimed at examining the trends in EAP literature from 1966 until 2017. An analysis of 367 studies published in this period allowed us to conclude that most of the works are empirical, adopt the perspective of the provider (the content of the specific programmes offered by public entities), and focus on macroeconomic evaluations (the impact of EAPs on countries’ exports). The bulk of studies have analysed advanced economies, such as the USA or UK. The publications are scattered among a large number of journals, and the influence of this literature is relatively small (few publications have a significant number of citations).
Long-term Trends in Prostate Cancer Incidence by Stage at Diagnosis in Japan Using the Multiple Imputation Approach, 1993–2014
Authors: Saito Eiko , Hori Megumi , Matsuda Tomohiro , Yoneoka Daisuke , Ito Yuri , Katanoda Kota 
Published: March 2020

AbstractBackground:This study aimed to assess long-term trends in the incidence of prostate cancer by stage at diagnosis before and after the introduction of population-based PSA screening.Methods:We used data from three population-based cancer registries in Japan. A total of 29,458 malignant prostate cancer cases diagnosed between 1993 and 2014 were used for the analysis. Multiple imputation with chained equations was used to impute a specific stage at diagnosis for cases with “unknown” and missing status. We estimated the age-standardized incidence rates by stage at diagnosis from 1993 to 2014, and used joinpoint linear regression models to assess changes in trend.Results:Joinpoint analyses after imputation showed that localized cancer was stable from 1993 to 2000, followed by a pronounced but insignificant increase through 2003 (from 12.1 per 100,000 in 2001 to 34.1 per 100,000 in 2003), and a significant increase thereafter [annual percentage change (APC), 4.1%]. For regional cancer, the imputed data showed that the increasing trend lasted from 1993 to 2006 (APC, 12.5%), then leveled off through 2014. For distant prostate cancer, the imputed data showed the increasing trend continued from 1993 to 2004 (APC, 2.4%), and started to marginally decline thereafter (APC, −2.2%).Conclusions:Our study confirmed a significantly rapid increase in localized prostate cancer after the spread of PSA screening in Japan, with a marginal decrease in distant prostate cancer after 2004.Impact:Evaluation of the effectiveness of PSA screening would require a comprehensive analysis of changes in mortality, survival, and treatment practices over time.
Dietary Intake of Acrylamide and Risk of Breast, Endometrial, and Ovarian Cancers: A Systematic Review and Dose–Response Meta-analysis
Authors: Adani Giorgia , Filippini Tommaso , Wise Lauren A. , Halldorsson Thorhallur I. , Blaha Ludek , Vinceti Marco 
Published: March 2020

Abstract
Acrylamide is a probable human carcinogen. Aside from occupational exposures and smoking, diet is the main source of exposure in humans. We performed a systematic review of the association between estimated dietary intake of acrylamide and risk of female breast, endometrial, and ovarian cancers in nonexperimental studies published through February 25, 2020, and conducted a dose–response meta-analysis. We identified 18 papers covering 10 different study populations: 16 cohort and two case–control studies. Acrylamide intake was associated with a slightly increased risk of ovarian cancer, particularly among never smokers. For endometrial cancer, risk was highest at intermediate levels of exposure, whereas the association was more linear and positive among never smokers. For breast cancer, we found evidence of a null or inverse relation between exposure and risk, particularly among never smokers and postmenopausal women. In a subgroup analysis limited to premenopausal women, breast cancer risk increased linearly with acrylamide intake starting at 20 μg/day of intake. High acrylamide intake was associated with increased risks of ovarian and endometrial cancers in a relatively linear manner, especially among never smokers. Conversely, little association was observed between acrylamide intake and breast cancer risk, with the exception of premenopausal women.
Stromal-MDM2 Promotes Lung Cancer Cell Invasion through Tumor–Host Feedback Signaling
Authors: Kamer Iris , Daniel-Meshulam Inbal , Zadok Oranit , Bab-Dinitz Elizabeta , Perry Gili , Feniger-Barish Rotem , Perelman Marina , Barshack Iris , Ben-Nun Alon , Onn Amir , Bar Jair 
Published: March 2020

Abstract

Tumor–host interactions play a major role in malignancies' initiation and progression. We have reported in the past that tumor cells attenuate genotoxic stress–induced p53 activation in neighboring stromal cells. Herein, we aim to further elucidate cancer cells' impact on signaling within lung cancer stroma. Primary cancer-associated fibroblasts were grown from resected human lung tumors. Lung cancer lines as well as fresh cultures of resected human lung cancers were used to produce conditioned medium (CM) or cocultured with stromal cells. Invasiveness of cancer cells was evaluated by transwell assays, and in vivo tumor growth was tested in Athymic nude mice. We found CM of a large variety of cancer cell lines as well as ex vivo–cultured lung cancers to rapidly induce protein levels of stromal-MDM2. CM of nontransformed cells had no such effect. Mdm2 induction occurred through enhanced translation, was mTORC1-dependent, and correlated with activation of AKT and p70 S6 Kinase. AKT or MDM2 knockdown in fibroblasts reduced the invasion of neighboring cancer cells, independently of stromal-p53. MDM2 overexpression in fibroblasts enhanced cancer cells' invasion and growth of inoculated tumors in mice. Our results indicate that stromal-MDM2 participates in a p53-independent cancer–host feedback mechanism. Soluble cancer-originated signals induce enhanced translation of stromal-MDM2 through AKT/mTORC1 signaling, which in turn enhances the neighboring cancer cells' invasion ability. The role of these tumor–host interactions needs to be further explored.

Implications:
We uncovered a novel tumor–stroma signaling loop, which is a potentially new therapeutic target in lung cancer and possibly in additional types of cancer.
Problematic Alcohol and Drug Use Is Associated with Low Self-Directedness and Cooperativeness
Authors: Steingrimsson Steinn , Carlsen Hanne Krage , Lundström Emil , Lundström Sebastian , Nilsson Thomas 
Published: March 2020

<b><i>Background:</i></b> Personality traits, such as self-directedness (SD) and cooperativeness (CO), may be indicative of problematic alcohol and/or drug use. <b><i>Objectives:</i></b> The aim of this study was to quantify the association of substance use with SD and CO in a large cohort of adolescents. <b><i>Method:</i></b> A total of 6,917 individuals (58% women) at the age of 18 who had filled in the Alcohol Use Disorder Identification Test (AUDIT) and Drug Use Disorder Identification Test (DUDIT), and the SD and CO scales from the Temperament and Character ­Inventory, as part of the Child and Adolescent Twin study in Sweden were included in the analyses. <b><i>Results:</i></b> High AUDIT scores (&#x3e;15) were found in 2.4% of the population and high DUDIT scores (&#x3e;7) in 1.2% of the population. Total score on the AUDIT was negatively correlated (<i>p</i> &#x3c; 0.001) with SD (<i>r</i> = –0.18) and CO (<i>r</i> = –0.15), as well as total DUDIT with SD (<i>r</i> = –0.11) and CO (<i>r</i> = –0.08). The risk of high AUDIT (&#x3e;15) and DUDIT (&#x3e;7) was highest for those with a low (1 standard deviation below mean) SD score (ORs 4.1 and 4.5, <i>p</i> &#x3c; 0.001) and a low CO score (ORs 3.5 and 4.5, <i>p</i> &#x3c; 0.001). However, at 1 standard deviation above mean, no association between alcohol or drug use and SD or CO was seen. Using SD and CO scores to predict AUDIT &#x3e;15 or DUDIT &#x3e;7 yielded a sensitivity between 62.4 and 71.3% and a specificity between 64.9 and 70.4%. <b><i>Conclusions:</i></b> Personality traits of low SD and CO are associated with increased alcohol and drug use. These findings support the notion that personality traits can be used to identify individuals at high risk of substance abuse.
Early Escalation of Mechanical Circulatory Support Stabilizes and Potentially Rescues Patients in Refractory Cardiogenic Shock
Authors: Tongers Jörn , Sieweke Jan-Thorben , Kühn Christian , Napp L. Christian , Flierl Ulrike , Röntgen Philipp , Schmitto Jan D. , Sedding Daniel G. , Haverich Axel , Bauersachs Johann , Schäfer Andreas 
Published: March 2020

Background:
Limited progress has been made in the management of cardiogenic shock (CS). Morbidity and mortality of refractory CS remain high. The effects of mechanical circulatory support (MCS) are promising, although many aspects are elusive. We evaluated efficacy and safety of early combined MCS (Impella microaxial pump + venoarterial extracorporeal membrane oxygenation [VA-ECMO]) in refractory CS and aimed to determine factors for decision-making in combined MCS.

Methods and Results:

We analyzed 69 consecutive patients with refractory CS from our registry requiring combined MCS. In 12 cases, therapy was actively withdrawn according to patient’s will. Patients were severely sick (Survival After Venoarterial ECMO score mean±SD, –8.9±4.4) predicting 30% in-hospital survival; ventilation 94%, dialysis 56%. Impella pumps and VA-ECMO were combined early (duration of combined MCS: median 94 hours; interquartile range, 49–150 hours). Early MCS escalation stabilized patients rapidly, reducing number and doses of catecholamines (
P
<0.05 versus baseline) while hemodynamics improved. Reflecting an improved microcirculation, lactate levels normalized within 24 hours (
P
<0.05 versus baseline). Despite refractory CS and disease severity, survival was favorable (on MCS 61%, 30 days 49%, 6 months 40%). In multivariate Cox-regression, duration of shock-to-first device (hours, hazard ratio, 1.05 [95% CI, 1.01–1.08];
P
=0.007) and lactate levels after 12 hours of MCS (hazard ratio, 1.28 [95% CI, 1.09–1.51];
P
=0.002) independently predicted survival. Additional right ventricular failure predisposed to futility (hazard ratio, 8.48 [95% CI, 1.85–38.91];
P
=0.006).

Conclusions:
The early and consequent combination of MCS by Impella microaxial pumps and VA-ECMO enables stabilization and may rescue high-risk patients with refractory CS at low overall risk. Independent predictors of survival may guide prognostication, decision-making, and allocation of medical resources.
Dual-Tracer Positron-Emission Tomography for Identification of Culprit Carotid Plaques and Pathophysiology In Vivo
Authors: Evans Nicholas R. , Tarkin Jason M. , Chowdhury Mohammed M. , Le Elizabeth P.V. , Coughlin Patrick A. , Rudd James H.F. , Warburton Elizabeth A. 
Published: March 2020

Background:

Inflammation and microcalcification are interrelated processes contributing to atherosclerotic plaque vulnerability. Positron-emission tomography can quantify these processes in vivo. This study investigates (1)
18
F-fluorodeoxyglucose (FDG) and
18
F-sodium fluoride (NaF) uptake in culprit versus nonculprit carotid atheroma, (2) spatial distributions of uptake, and (3) how macrocalcification affects this relationship.

Methods:

Individuals with acute ischemic stroke with ipsilateral carotid stenosis of ≥50% underwent FDG-positron-emission tomography and NaF-positron-emission tomography. Tracer uptake was quantified using maximum tissue-to-background ratios (TBR
max
) and macrocalcification quantified using Agatston scoring.

Results:

In 26 individuals, median most diseased segment TBR
max
(interquartile range) was higher in culprit than in nonculprit atheroma for both FDG (2.08 [0.52] versus 1.89 [0.40];
P
<0.001) and NaF (2.68 [0.63] versus 2.39 [1.02];
P
<0.001). However, whole vessel TBR
max
was higher in culprit arteries for FDG (1.92 [0.41] versus 1.71 [0.31];
P
<0.001) but not NaF (1.85 [0.28] versus 1.79 [0.60];
P
=0.10). NaF uptake was concentrated at carotid bifurcations, while FDG was distributed evenly throughout arteries. Correlations between FDG and NaF TBR
max
differed between bifurcations with low macrocalcification (
r
s
=0.38;
P
<0.001) versus high macrocalcification (
r
s
=0.59;
P
<0.001).

Conclusions:
This is the first study to demonstrate increased uptake of both FDG and NaF in culprit carotid plaques, with discrete distributions of pathophysiology influencing vulnerability in vivo. These findings have implications for our understanding of the natural history of the disease and for the clinical assessment and management of carotid atherosclerosis.