bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action
Authors: Chapman Katherine E. , Wilde Eleanor C. , Chapman Fiona M. , Verma Jatin R. , Shah Ume-Kulsoom , Stannard Leanne M. , Seager Anna L. , Tonkin James A. , Brown M. Rowan , Doherty Ann T. , Johnson George E. , Doak Shareen H. , Jenkins Gareth J. S. 
Published: September 2020

AbstractCurrent in vitro genotoxicity tests can produce misleading positive results, indicating an inability to effectively predict a compound’s subsequent carcinogenic potential in vivo. Such oversensitivity can incur unnecessary in vivo tests to further investigate positive in vitro results, supporting the need to improve in vitro tests to better inform risk assessment. It is increasingly acknowledged that more informative in vitro tests using multiple endpoints may support the correct identification of carcinogenic potential. The present study, therefore, employed a holistic, multiple-endpoint approach using low doses of selected carcinogens and non-carcinogens (0.001–770 µM) to assess whether these chemicals caused perturbations in molecular and cellular endpoints relating to the Hallmarks of Cancer. Endpoints included micronucleus induction, alterations in gene expression, cell cycle dynamics, cell morphology and bioenergetics in the human lymphoblastoid cell line TK6. Carcinogens ochratoxin A and oestradiol produced greater Integrated Signature of Carcinogenicity scores for the combined endpoints than the “misleading” in vitro positive compounds, quercetin, 2,4-dichlorophenol and quinacrine dihydrochloride and toxic non-carcinogens, caffeine, cycloheximide and phenformin HCl. This study provides compelling evidence that carcinogens can successfully be distinguished from non-carcinogens using a holistic in vitro test system. Avoidance of misleading in vitro outcomes could lead to the reduction and replacement of animals in carcinogenicity testing.
Serotonin syndrome by drug interactions with linezolid: clues from pharmacovigilance-pharmacokinetic/pharmacodynamic analysis
Authors: Gatti Milo , Raschi Emanuel , De Ponti Fabrizio 
Published: September 2020

Abstract
Purpose
To characterize the post-marketing reporting of serotonin syndrome (SS) due to drug-drug interactions (DDIs) with linezolid and investigate the relationship with pharmacokinetic/pharmacodynamic (PK/PD) properties of serotonergic agents.

Methods
We queried the worldwide FDA Adverse Event Reporting System to extract SS records due to DDIs where linezolid was reported as suspect. For each serotonergic agent concomitantly reported, proportion of SS reports and mean number of DDIs were calculated and three different “SS reporting zones” were created. Relevant PK (peak concentration, area under plasma concentration curve, volume of distribution (VD), and lipophilicity) and PD (values of binding affinity (Ki) and IC50 for serotonin reuptake transporter (SERT) and 5-HT2A) parameters were extracted for each serotonergic agent, and relevant PK/PD indexes were calculated to assess correlation with mean number of DDIs (PV index).

Results
Six hundred sixty-nine reports of SS mentioning linezolid were found, being linezolid-citalopram (N = 69; 10.3%) the most frequently DDI reported. Citalopram and methadone showed respectively the highest proportion of SS reports (0.28%) and the lowest mean number of DDIs (1.41). Citalopram, escitalopram, and methadone emerged as red (i.e., alert)-zone medications: they exhibited high lipophilicity and large VD (proxies of excellent central nervous system penetration) coupled with high potency. Among PK/PD indexes, a significant correlation with PV index was found for VD/Ki SERT ratio (p = 0.05).

Discussion
Our integrated approach suggests that linezolid is more likely to cause SS when co-administered with citalopram, escitalopram, and methadone, as inferred from their pharmacological properties. Proper management of SS should be tailored on a case-by-case basis.
Surface analysis of ureteral stent before and after implantation in the bodies of child patients
Authors: Arkusz Katarzyna , Pasik Kamila , Halinski Andrzej , Halinski Adam 
Published: September 2020

AbstractThe aim of this work was to determine which part of a double-J ureteral stent (DJ stents) showed the highest tendency to crystal, calculi, and biofilm deposition after ureterorenoscopic-lithotripsy procedure (URS-L) to treat calcium oxalate stones. Additionally, the mechanical strength and the stiffness of DJ stents were evaluated before and after exposure to urine. Obtained results indicated that the proximal (renal pelvis) and distal (urinary bladder) part is the most susceptible for post-URS-L fragments and urea salt deposition. Both, the outer and inner surfaces of the DJ ureteral stents were completely covered even after 7 days of implantation. Encrustation of DJ stents during a 31-day period results in reducing the Young’s modulus by 27–30%, which confirms the loss of DJ stent elasticity and increased probability of cracks or interruption. Performed analysis pointed to the need to use an antibacterial coating in the above-mentioned part of the ureteral stent to prolong its usage time and to prevent urinary tract infection.
Self‐Efficacy, Happiness and Psychological Well‐Being After Sleeve Gastrectomy
Authors: Sobhani Zahra , Amini Masood , Hosseini Seyed Vahid , Khazraei Samaneh , Khazraei Hajar 
Published: September 2020

AbstractPurposeSleeve gastrectomy (SG) is an effective treatment for patients with severe obesity and it leads to significant weight loss and promotes the quality of life. The aim of this study was evaluating the relationship between self‐efficacy, happiness and psychological well‐being after sleeve gastrectomy.MethodsOne hundred patients that underwent SG were participated in this study. They were asked to fill questionnaires 12 months after surgery. To assess self‐efficacy, Sherer and et al. scale, for happiness, oxford happiness scale and for psychological well‐being, Ryff scale were used. Regression analysis was used on psychological well‐being and happiness for evaluating the prediction of self‐efficacy.ResultsThe results showed that 44% of happiness and 4% of psychological well‐being were determined by self‐efficacy after surgery.ConclusionBased on these findings, self‐efficacy is a significant predictor of psychological well‐being and happiness.
Clinical pre-test probability for obstructive coronary artery disease: insights from the European DISCHARGE pilot study
Authors: Feger Sarah , Ibes Paolo , Napp Adriane E. , Lembcke Alexander , Laule Michael , Dreger Henryk , Bokelmann Björn , Davis Gershan K. , Roditi Giles , Diez Ignacio , Schröder Stephen , Plank Fabian , Maurovich-Horvat Pal , Vidakovic Radosav , Veselka Josef , Ilnicka-Suckiel Malgorzata , Erglis Andrejs , Benedek Teodora , Rodriguez-Palomares José , Saba Luca , Kofoed Klaus F. , Gutberlet Matthias , Ađić Filip , Pietilä Mikko , Faria Rita , Vaitiekiene Audrone , Dodd Jonathan D. , Donnelly Patrick , Francone Marco , Kepka Cezary , Ruzsics Balazs , Müller-Nordhorn Jacqueline , Schlattmann Peter , Dewey Marc 
Published: September 2020

Abstract
Objectives
To test the accuracy of clinical pre-test probability (PTP) for prediction of obstructive coronary artery disease (CAD) in a pan-European setting.

Methods
Patients with suspected CAD and stable chest pain who were clinically referred for invasive coronary angiography (ICA) or computed tomography (CT) were included by clinical sites participating in the pilot study of the European multi-centre DISCHARGE trial. PTP of CAD was determined using the Diamond-Forrester (D+F) prediction model initially introduced in 1979 and the updated D+F model from 2011. Obstructive coronary artery disease (CAD) was defined by one at least 50% diameter coronary stenosis by both CT and ICA.

Results
In total, 1440 patients (654 female, 786 male) were included at 25 clinical sites from May 2014 until July 2017. Of these patients, 725 underwent CT, while 715 underwent ICA. Both prediction models overestimated the prevalence of obstructive CAD (31.7%, 456 of 1440 patients, PTP: initial D+F 58.9% (28.1–90.6%), updated D+F 47.3% (34.2–59.9%), both p < 0.001), but overestimation of disease prevalence was higher for the initial D+F (p < 0.001). The discriminative ability was higher for the updated D+F 2011 (AUC of 0.73 95% confidence interval [CI] 0.70–0.76 versus AUC of 0.70 CI 0.67–0.73 for the initial D+F; p < 0.001; odds ratio (or) 1.55 CI 1.29–1.86, net reclassification index 0.11 CI 0.05–0.16, p < 0.001).

Conclusions
Clinical PTP calculation using the initial and updated D+F prediction models relevantly overestimates the actual prevalence of obstructive CAD in patients with stable chest pain clinically referred for ICA and CT suggesting that further refinements to improve clinical decision-making are needed.

Trial registration
https://www.clinicaltrials.gov/ct2/show/NCT02400229

Key Points
• Clinical pre-test probability calculation using the initial and updated D+F model overestimates the prevalence of obstructive CAD identified by ICA and CT.
• Overestimation of disease prevalence is higher for the initial D+F compared with the updated D+F.
• Diagnostic accuracy of PTP assessment varies strongly between different clinical sites throughout Europe.
Prognostic implications of pericardial and pleural effusion in patients with cardiac amyloidosis
Authors: Binder Christina , Duca Franz , Binder Thomas , Rettl René , Dachs Theresa Marie , Seirer Benjamin , Camuz Ligios Luciana , Dusik Fabian , Capelle Christophe , Qin Hong , Agis Hermine , Kain Renate , Hengstenberg Christian , Badr Eslam Roza , Bonderman Diana 
Published: September 2020

Abstract
Background
Pericardial and pleural effusion are common findings in patients with cardiac amyloidosis (CA). It is not known, whether effusions correlate with right ventricular (RV) function in these patients. Furthermore, data on the prognostic significance of pleural and pericardial effusion in CA is scarce.

Methods
Patients with transthyretin (ATTR) and light chain (AL) CA were included in a clinical registry. All patients underwent transthoracic echocardiography at baseline. The presence of pericardial and pleural effusion was determined in every patient. The clinical endpoint was defined as cardiac death or heart failure hospitalization.

Results
In total, 143 patients were analysed. Of these, 85 patients were diagnosed with ATTR and 58 patients with AL. Twenty-four patients presented with isolated pericardial effusion and 35 with isolated pleural effusion. In 19 patients, both pericardial and pleural effusion were found and in 65 patients no effusion was present at baseline. The presence of pleural effusion correlated well with poor RV function, measured by global RV free-wall strain (p = 0.007) in patients with AL, but not in ATTR. No such correlation could be found for pericardial effusion in either amyloidosis subtype. Patients with AL presenting with pleural effusion had worse outcomes compared to patients with pericardial effusion alone or no effusion at baseline. In the ATTR group, there was no difference in outcomes according to presence and type of effusion.

Conclusion
More than 50% of patients with CA presented with pleural and/or pericardial effusions. While pleural effusion was clearly associated with poor RV function in AL, we were not able to detect this association with pericardial effusion.
Enlarged vestibular aqueduct and Mondini Malformation: audiological, clinical, radiologic and genetic features
Authors: Forli F. , Lazzerini F. , Auletta G. , Bruschini L. , Berrettini S. 
Published: September 2020

Abstract
Purpose
When referring to enlarged vestibular aqueduct (EVA) we should differentiate between nonsyndromic enlarged vestibular aqueduct (NSEVA) and Pendred Syndrome (PDS), a disease continuum associated with pathogenic sequence variants of Pendrin’s Gene (SLC26A4) in about half of the cases. The study was aimed to analyse the clinical and audiological features of a monocentric cohort of Caucasian patients with NSEVA/PDS, their genetic assessment and morphological inner ear features.

Methods
We retrospectively reviewed the audiologic, genetic and anamnestic data of 66 patients with NSEVA/PDS followed by our audiology service.

Results
SLC26A4 mutations was significantly correlated with the presence of PDS rather than NSEVA (p < 0.019), with the expression of inner ear malformations (p < 0.001) and with different severity of hearing loss (p = 0.001). Furthermore, patients with PDS showed significantly worse pure tone audiometry (PTA) than patients with NSEVA (p = 0.001). Anatomically normal ears presented significantly better PTA than ears associated with Mondini Malformation or isolated EVA (p < 0.001), but no statistically significative differences have been observed in PTA between patients with Mondini Malformation and isolated EVA.

Conclusion
NSEVA/PDS must be investigated in all the congenital hearing loss, but also in progressive, late onset, stepwise forms. Even mixed or fluctuating hearing loss may constitute a sign of a NSEVA/PDS pathology. Our findings can confirm the important role of SLC26A4 mutations in determining the phenotype of isolated EVA/PDS, both for the type/degree of the malformation, the hearing impairment and the association with thyroid dysfunction.
Spleen contraction elevates hemoglobin concentration at high altitude during rest and exercise
Authors: Schagatay Erika , Lunde Alexander , Nilsson Simon , Palm Oscar , Lodin-Sundström Angelica 
Published: September 2020

Abstract
Purpose
Hypoxia and exercise are known to separately trigger spleen contraction, leading to release of stored erythrocytes. We studied spleen volume and hemoglobin concentration (Hb) during rest and exercise at three altitudes.

Methods
Eleven healthy lowlanders did a 5-min modified Harvard step test at 1370, 3700 and 4200 m altitude. Spleen volume was measured via ultrasonic imaging and capillary Hb with Hemocue during rest and after the step test, and arterial oxygen saturation (SaO2), heart rate (HR), expiratory CO2 (ETCO2) and respiratory rate (RR) across the test.

Results
Resting spleen volume was reduced with increasing altitude and further reduced with exercise at all altitudes. Mean (SE) baseline spleen volume at 1370 m was 252 (20) mL and after exercise, it was 199 (15) mL (P < 0.01). At 3700 m, baseline spleen volume was 231 (22) mL and after exercise 166 (12) mL (P < 0.05). At 4200 m baseline volume was 210 (23) mL and after exercise 172 (20) mL (P < 0.05). After 10 min, spleen volume increased to baseline at all altitudes (NS). Baseline Hb increased with altitude from 138.9 (6.1) g/L at 1370 m, to 141.2 (4.1) at 3700 m and 152.4 (4.0) at 4200 m (P < 0.01). At all altitudes Hb increased from baseline during exercise to 146.8 (5.7) g/L at 1370 m, 150.4 (3.8) g/L at 3700 m and 157.3 (3.8) g/L at 4200 m (all P < 0.05 from baseline). Hb had returned to baseline after 10 min rest at all altitudes (NS). The spleen-derived Hb elevation during exercise was smaller at 4200 m compared to 3700 m (P < 0.05). Cardiorespiratory variables were also affected by altitude during both rest and exercise.

Conclusions
The spleen contracts and mobilizes stored red blood cells during rest at high altitude and contracts further during exercise, to increase oxygen delivery to tissues during acute hypoxia. The attenuated Hb response to exercise at the highest altitude is likely due to the greater recruitment of the spleen reserve during rest, and that maximal spleen contraction is reached with exercise.
Arthroscopic isolated long head of biceps tenotomy in patients with degenerative rotator cuff tears: mid-term clinical results and prognostic factors
Authors: Veen Egbert J. D. , Boeddha Ashvin V. , Diercks Ronald L. , Kleinlugtenbelt Ydo V. , Landman Ellie B. M. , Koorevaar Cornelis T. 
Published: September 2020

Abstract
Introduction
The long head of biceps tendon is frequently involved in degenerative rotator cuff tears. Therefore, this study explored the clinical results of an isolated biceps tenotomy and identified prognostic factors for improvement in pain and function.

Materials and methods
Between 2008 and 2017, an arthroscopic isolated biceps tenotomy was performed on 64 patients with a degenerative rotator cuff tear (> 65 years). Primary outcome was patient-perceived improvement in pain and function. Potential prognostic factors for improvement in pain and function were identified.

Results
A perceived improvement in pain was reported in 78% of the patients at three months after surgery and in 75% at a mean follow-up of 4.2 years (1–7 years; n = 55). A perceived improvement in function was observed in 49% of patients at three months and in 76% of patients at follow-up. Patients with a preoperatively normal acromiohumeral distance (> 10 mm) reported an improvement in pain and function significantly more often. Retraction of the supraspinatus tendon Patte 3 was significantly associated with worse functional outcome.

Conclusions
A biceps tenotomy can be a reliable treatment option for patients with symptomatic degenerative cuff tears who fail conservative treatment and have a normal acromiohumeral distance (> 10 mm).
Hirntumoren auf den Punkt gebracht
Authors: Woehrer Adelheid 
Published: September 2020

ZusammenfassungHirntumoren sind insgesamt sehr seltene Krebserkrankungen, die jedoch aufgrund ihrer Lage in Gehirn und Rückenmark schwer zu diagnostizieren und therapieren sind. Die anatomische Lage führt nicht nur zu Unterschieden in der Präsentation und neurologischen Symptomatik, sie limitiert häufig die Möglichkeiten einer kompletten Resektion. Trotz adjuvanter Radio- und Chemotherapie ist die Prognose für Betroffene meist ungünstig. Basierend auf histologischen und molekularen Merkmalen unterscheidet man mehr als 120 Tumortypen, die in 4 Malignitätsgrade eingeteilt werden. Aus bislang unzureichend verstandenen Gründen treten bösartige Hirntumoren häufiger bei Männern und gutartige Hirntumoren häufiger bei Frauen auf.
Online remote-controlled and cost-effective fouling and clogging surveillance of a groundwater heat pump system
Authors: Gjengedal Sondre , Stenvik Lars A. , Ramstad Randi K. , Ulfsnes Jan I. , Hilmo Bernt O. , Frengstad Bjørn S. 
Published: September 2020

AbstractFouling and clogging of groundwater wells and heat exchangers are among the major operational challenges for groundwater heat pump (GWHP) and aquifer thermal energy storage (ATES) systems. This article presents the application of a step-test surveillance procedure developed for early detection of clogging in distinct parts of the GWHP system, tested at Lena Terrace in Melhus Norway. Three versions of the test procedure are presented and demonstrate that the test can be performed with a minimum of four steps, each of 15-min duration, while the GWHP system is actively producing heat. The results prove that the surveillance test can detect changes in the hydraulic resistance of the groundwater circuit and locate clogging problems within all of the relevant system components in the groundwater circuit simultaneously. At the Lena Terrace GWHP system, these tests indicate a gradual increase of hydraulic resistance with time, which verify that clogging issues are continuously developing in the injection well, in the production well, and in the groundwater heat exchanger. Cleaning of the heat exchanger was then performed. This increased the pumping capacity by 8.3% points, but continuous clogging of the injection well and the production well necessitates further maintenance to ensure a reliable operation. It is demonstrated that multidisciplinary competence and experience with GWHP-systems, aquifers, and groundwater wells are needed for the evaluation of the results. These results can therefore serve as a reference for other GWHP systems with similar design configurations.
Partial rewarding during clicker training does not improve naïve dogs’ learning speed and induces a pessimistic-like affective state
Authors: Cimarelli Giulia , Schoesswender Julia , Vitiello Roberta , Huber Ludwig , Virányi Zsófia 
Published: September 2020

AbstractClicker training is considered a welfare-friendly way of teaching novel behaviors to animals because it is mostly based on the positive reinforcement. However, trainers largely vary in their way of applying this training technique. According to the most, a reward (e.g., food) should follow every click, while others claim that dogs learn faster when the reward is sometimes omitted. One argument against the use of partial rewarding is that it induces frustration in the animal, raising concerns over its welfare consequences. Here, we investigated the effect of partial rewarding not only on training efficacy (learning speed), but also on dogs’ affective state. We clicker-trained two groups of dogs: one group received food after every click while the other group received food only 60% of the time. Considering previous evidence of the influencing role of personality on reactions to frustrated expectations, we included measurements of dogs’ emotional reactivity. We compared the number of trials needed to reach a learning criterion and their pessimistic bias in a cognitive bias test. No difference between the two groups emerged in terms of learning speed; however, dogs that were partially rewarded during clicker training showed a more pessimistic bias than dogs that were continuously rewarded. Generally, emotional reactivity was positively associated with a more pessimistic bias. Partial rewarding does not improve training efficacy, but it is associated with a negatively valenced affective state, bringing support to the hypothesis that partial rewarding might negatively affect dogs’ welfare.
Survival during the pre-fledging period rather than during post-fledging drives variation in local recruitment of an endangered migratory shorebird, the Southern Dunlin Calidris alpina schinzii
Authors: Pakanen Veli-Matti , Hagstedt Robin , Pauliny Angela , Blomqvist Donald 
Published: September 2020

AbstractThe declines in wet-grassland breeding shorebird populations are considered to mainly result from changes in reproduction. While there is plenty of information on nest survival, little reliable information exists on local recruitment due to confounding effects of permanent emigration. Furthermore, few studies have been able to study the roles of pre- and post-fledging survival on local recruitment. Therefore, it is unclear whether local recruitment of young reflects conditions at the breeding sites or at non-breeding sites. We studied an isolated population of the endangered Southern Dunlin (Calidris alpina schinzii) breeding on the west coast of Sweden to examine (1) brood survival (probability of at least one chick fledging) by following broods fates and (2) local recruitment (survival from hatching to 1 year old) using capture-recapture data. We then examined how much of the annual variation in juvenile survival was explained by variation in brood survival. Brood survival was on average 0.58 (annual range 0.08–1.00) and explained 64% of variation in annual local recruitment. Still local recruitment was rather high for a shorebird (0.17, SE = 0.023), which reflects the isolated nature of the study population. Our results suggest that local recruitment seems to be mainly constrained by chick survival during the pre-fledging period. Therefore, management of breeding sites leading to increased brood survival, e.g., reducing predation on chicks, should have strong impacts on local recruitment and local population growth.