bluuebunny/crossref_metadata_2025_split huggingface dataset:
Testing the reinforcement learning hypothesis of social conformity
Authors: Levorsen Marie , Ito Ayahito , Suzuki Shinsuke , Izuma Keise 
Published: November 2020

AbstractOur preferences are influenced by the opinions of others. The past human neuroimaging studies on social conformity have identified a network of brain regions related to social conformity that includes the posterior medial frontal cortex (pMFC), anterior insula, and striatum. Since these brain regions are also known to play important roles in reinforcement learning (i.e., processing prediction error), it was previously hypothesized that social conformity and reinforcement learning have a common neural mechanism. However, although this view is currently widely accepted, these two processes have never been directly compared; therefore, the extent to which they shared a common neural mechanism had remained unclear. This study aimed to formally test the hypothesis. The same group of participants (n = 25) performed social conformity and reinforcement learning tasks inside a functional magnetic resonance imaging (fMRI) scanner. Univariate fMRI data analyses revealed activation overlaps in the pMFC and bilateral insula between social conflict and unsigned prediction error and in the striatum between social conflict and signed prediction error. We further conducted multivoxel pattern analysis (MVPA) for more direct evidence of a shared neural mechanism. MVPA did not reveal any evidence to support the hypothesis in any of these regions but found that activation patterns between social conflict and prediction error in these regions were largely distinct. Taken together, the present study provides no clear evidence of a common neural mechanism between social conformity and reinforcement learning.
Parotid gland stem cells: Mini yet mighty
Authors: Sari Sezin Yuce , Yilmaz Melek Tugce , Elmali Aysenur , Yedekci Fazli Yagiz , Yuce Deniz , Ozyigit Gokhan , Cengiz Mustafa , Yazici Gozde 
Published: November 2020

AbstractBackgroundOur aim was to evaluate the correlation between the radiation doses to parotid gland (PG) stem cells and xerostomia.MethodsPatients diagnosed with head and neck cancer (HNC) were retrospectively evaluated, and xerostomia inventory (XI) was applied to these patients. PG stem cells were delineated on the treatment planning CT, and the mean doses to the PG stem cells calculated.ResultsThe total test score and mean doses to bilateral PGs were significantly correlated (r = .34, P = .001), and the mean doses to bilateral PG stem cell niches were significantly correlated with the total test score (r = .32, P = .002).ConclusionsIn this study, we found that the mean dose to PG stem cells can predict dry mouth as much as the mean dose to the PG.
Could the UK Foundation Programme training post allocation process result in regional variations in the knowledge and skills of Foundation doctors? A cross‐sectional study
Authors: Beck Christopher , Brown Celia 
Published: November 2020

AbstractBackground and AimsThe allocation of medical school graduates to Foundation Schools (post‐qualification training, organized at regional level) in the United Kingdom uses a ranking process that takes into account educational performance at medical school and performance on a situational judgment test (SJT). We aimed to compare the performance of United Kingdom graduates allocated to different United Kingdom Foundation School according to three metrics: educational performance measure (EPM), SJT, and prescribing safety assessment (PSA).MethodsWe used a cross‐sectional study design using data from the UK Medical Education Database, studying 19 United Kingdom Foundation School groups. A total of 33 730 graduates from United Kingdom medical schools in the period 2014 to 2018 (inclusive) who started Foundation Training in August 2018 or earlier were included in the study, excluding those allocated to the Academic Foundation Programme or the Armed Forces Deanery. The outcomes were within‐year standardized mean scores (by Foundation School) on the EPM, SJT, and PSA.ResultsThere was a significant difference between Foundation Schools in the Educational Performance Measure (F = 401, P < .001), SJT (F = 213, P < .001), and PSA (F = 95, P < .001). Tukey‐Kramer pairwise comparisons between Foundation Schools showed a very high percentage of statistical significance (78%, 402/513 comparisons). The Cohen's d effect size for the difference in means and Tukey‐Kramer 95% confidence intervals between the Foundation Schools with the highest (North West Thames) and lowest (West Midlands North) means were 1.92 (1.77‐2.07) for the EPM, 1.59 (1.44‐1.73) for the SJT, and 0.94 (0.79‐1.09) for the PSA.ConclusionThere is a statistically significant difference between the knowledge and skills of doctors (as measured by the three metrics used in this study) entering the Foundation Programme in different Foundation Schools. It is less clear whether this has an impact on patient care and thus is unfair from the perspective of the patient.
Safety of hydroxychloroquine for treatment or prevention of SARS‐CoV‐2 infection: A rapid systematic review and meta‐analysis of randomized clinical trials
Authors: Maraolo Alberto Enrico , Grossi Adriano 
Published: November 2020

AbstractIntroductionHydroxycloroquine (HCQ) has been extensively studied for treatment and prevention of coronavirus diseases 2019 (COVID‐19) from the start of the pandemic. Conflicting evidence about its usefulness has begun to accrue.MethodsIn the face of controversial results about clinical efficacy of HCQ, we performed a rapid systematic review to assess its safety in the framework of COVID‐19 randomized clinical trials.ResultsFive studies investigating 2291 subjects were included. The use of HCQ was associated with higher risk of adverse event compared with placebo or standard of care: odds ratio 4.57, 95% confidence interval 2.14–9.45.ConclusionSafety profile of HCQ appears to be unsatisfactory when used to treat or prevent COVID‐19, especially in the light of unproved clinical benefit.
Local Investigators Significantly Overestimate Overall Response Rates Compared to Blinded Independent Central Reviews in Phase 2 Oncology Trials
Authors: Dello Russo Cinzia , Cappoli Natalia , Pilunni Daniela , Navarra Pierluigi 
Published: November 2020

AbstractThe overall response rate (ORR) is a largely adopted outcome measure in early‐phase oncology trials. ORR is highly relevant in cancer drug development at the time of deciding whether to move to confirmatory phase 3 trials; moreover, ORR is gaining increasing relevance in fast‐track registration procedures. No systematic analysis has been conducted so far to investigate whether a discrepancy exists between ORR assessed by local investigators and those assessed by blinded reviewers in phase 2 oncology trials. In this study, we carried out a search in the clinicaltrials.gov and EudraCT databases, looking at the trials reporting the results of both investigator‐assessed and independently‐assessed ORR. A discrepancy index was obtained by calculating the ratio of each investigator‐assessed ORR on the corresponding independently assessed ORR, so that a discrepancy index >1 indicates that the investigator was “more optimistic,” whereas a discrepancy index <1 indicates the opposite. We also analyzed different subgroups (by tumor type, by drug type, by year). Twenty trials met the search criteria; in some cases, >1 comparison was conducted in the trial, so that the total number of comparisons analyzed was 33. The estimated mean discrepancy index was 1.175 (95% confidence interval, 1.083‐1.264; n = 33). In conclusion, local investigators significantly overestimate ORR compared to paired blinded reviewers in phase 2 oncology trials. This may represent a risk in drug development, when deciding whether to move to confirmatory, more expensive phase 3 trials. Blinded independent central review should be used in ORR assessment if a more conservative estimate of treatment efficacy is required, as in the case of fast‐track drug developments leading to accelerated approvals of cancer therapies.
The hypothalamic–pituitary–gonadal axis controls muscle stem cell senescence through autophagosome clearance
Authors: Kim Ji‐Hoon , Park Inkuk , Shin Hijai R. , Rhee Joonwoo , Seo Ji‐Yun , Jo Young‐Woo , Yoo Kyusang , Hann Sang‐Hyeon , Kang Jong‐Seol , Park Jieon , Kim Ye Lynne , Moon Ju‐Yeon , Choi Man Ho , Kong Young‐Yun 
Published: November 2020

AbstractBackgroundWith organismal aging, the hypothalamic–pituitary–gonadal (HPG) activity gradually decreases, resulting in the systemic functional declines of the target tissues including skeletal muscles. Although the HPG axis plays an important role in health span, how the HPG axis systemically prevents functional aging is largely unknown.MethodsWe generated muscle stem cell (MuSC)‐specific androgen receptor (Ar) and oestrogen receptor 2 (Esr2) double knockout (dKO) mice and pharmacologically inhibited (Antide) the HPG axis to mimic decreased serum levels of sex steroid hormones in aged mice. After short‐term and long‐term sex hormone signalling ablation, the MuSCs were functionally analysed, and their aging phenotypes were compared with those of geriatric mice (30‐month‐old). To investigate pathways associated with sex hormone signalling disruption, RNA sequencing and bioinformatic analyses were performed.ResultsDisrupting the HPG axis results in impaired muscle regeneration [wild‐type (WT) vs. dKO, P < 0.0001; Veh vs. Antide, P = 0.004]. The expression of DNA damage marker (in WT = 7.0 ± 1.6%, dKO = 32.5 ± 2.6%, P < 0.01; in Veh = 13.4 ± 4.5%, Antide = 29.7 ± 5.5%, P = 0.028) and senescence‐associated β‐galactosidase activity (in WT = 3.8 ± 1.2%, dKO = 10.3 ± 1.6%, P < 0.01; in Veh = 2.1 ± 0.4%, Antide = 9.6 ± 0.8%, P = 0.005), as well as the expression levels of senescence‐associated genes, p16Ink4a and p21Cip1, was significantly increased in the MuSCs, indicating that genetic and pharmacological inhibition of the HPG axis recapitulates the progressive aging process of MuSCs. Mechanistically, the ablation of sex hormone signalling reduced the expression of transcription factor EB (Tfeb) and Tfeb target gene in MuSCs, suggesting that sex hormones directly induce the expression of Tfeb, a master regulator of the autophagy–lysosome pathway, and consequently autophagosome clearance. Transduction of the Tfeb in naturally aged MuSCs increased muscle mass [control geriatric MuSC transplanted tibialis anterior (TA) muscle = 34.3 ± 2.9 mg, Tfeb‐transducing geriatric MuSC transplanted TA muscle = 44.7 ± 6.7 mg, P = 0.015] and regenerating myofibre size [eMyHC+tdTomato+ myofibre cross‐section area (CSA) in control vs. Tfeb, P = 0.002] after muscle injury.ConclusionsOur data show that the HPG axis systemically controls autophagosome clearance in MuSCs through Tfeb and prevents MuSCs from senescence, suggesting that sustained HPG activity throughout life regulates autophagosome clearance to maintain the quiescence of MuSCs by preventing senescence until advanced age.
Deep eutectic solvent‐assisted synthesis of polyaniline by laccase enzyme
Authors: Altundağ Aybike , Ünlü Ayşe Ezgi , Takaç Serpil 
Published: November 2020

AbstractBACKGROUNDDeep eutectic solvents (DESs) have attracted considerable attention for many chemical applications due to their environmentally friendly characteristics, low cost and limited or no health issues. Polyaniline (PANI) has been of a great interest for many years due to its distinctive electrical and optical properties and accordingly its diverse application fields. Enzymatic synthesis of PANI offers mild and environmentally benign conditions. However, the main difficulty of the enzymatic method is the formation of undesired units in the polymer, which can be overcome by the use of templates. Thus, the reaction is guided towards the desired products. This study reports – for the first time – that DESs can be used as templates in the synthesis of polymers.RESULTSSeveral DESs were tested in the oxidation of aniline to form PANI by the catalytic effect of laccase and it was found that d,l‐menthol–decanoic acid (Ment‐DA; 1:1) assisted the polymer formation. The effects of synthesis conditions such as volume concentration of Ment‐DA, laccase activity, initial concentration of aniline, pH of the medium, temperature and agitation rate on the formation of PANI were investigated. In situ doping of PANI with acids during DES‐assisted synthesis of the polymer was also carried out to provide electrically conducting PANI. The resulting polymers were characterized using their UV–visible and Fourier transform infrared spectra, electrical conductivities and morphologies.CONCLUSIONSThis work introduces a new type of template for use in polymerization reactions. © 2020 Society of Chemical Industry
Investigating the neural activity of various 3D visual fatigue degrees using depth‐related visual evoked potentials
Authors: Yue Kang , Wang Danli 
Published: November 2020

AbstractSevere visual fatigue symptoms occur while users view three‐dimensional (3D) content. These symptoms adversely affect the user experience and hinder the widespread application of 3D media. Existing studies mainly used electroencephalography (EEG) power (based on frequency domain analysis) to evaluate 3D visual fatigue (3DVF), but their results were often contradictory and confusing. To address this problem, we investigated the relationship between EEG features and visual fatigue from the perspective of both time and time‐frequency domain. Random‐dot stereograms (RDS) with various disparities were employed to elicit depth‐related visual evoked potentials (VEPs). The experiment lasted about 27 min for each subject to induce fatigue, and the EEG was recorded synchronously. VEPs of different fatigue levels were processed to extract both time (such as P120 and N170 components in VEPs) and time‐frequency (like event‐related spectral perturbation [ERSP]) domain characteristics. A significant increase in P120 amplitude was observed in the parietal region, and time‐frequency analysis also revealed a significant ERSP decrease of theta bands in the central‐frontal region with a latency of 200 to 300 ms when subjects suffered fatigue. Our results confirm the hypothesis that activity of theta decreased with 3DVF level, or rather, we found ERSPs of theta bands on FC4 and Cz in the 200‐ to 300‐ms window decreased significantly across four fatigue levels. Furthermore, we first reported the relationship between P120 amplitude and 3DVF, which implied this feature could be considered as a feature of 3DVF evaluation. In summary, our studies could provide a new insight for 3DVF evaluation using EEG.
Isopropanol dehydration reaction rate kinetics measurement using H2O time histories
Authors: Cooper Sean P. , Mulvihill Clayton R. , Mathieu Olivier , Petersen Eric L. 
Published: November 2020

AbstractH2O formation during thermal decomposition of isopropanol was measured behind reflected shock waves at temperatures ranging from 1127 to 1621 K at an average pressure of 1.42 atm using a laser absorption technique. Of the five modern chemical kinetics models used to compare the H2O time histories, the model from Li et al (Combust. Flame 2019;207:171‐185) showed the best overall agreement. Sensitivity and rate of production analyses using the Li et al model (as well as those from AramcoMech 3.0, CRECK, and Togbe et al (Energy Fuel. 2011;25:676‐683)) showed unimolecular dehydration of isopropanol, iC3H7OH ⇌ H2O + C3H6 (R1), is nearly the sole reaction controlling H2O production at early times, allowing for an a priori measurement of the forward rate constant k1. The Arrhenius expression k1 (s–1) = 2.60 × 1013 exp(−31 120 K/T) was determined to represent best the data from this study. According to the models and previous experimental investigations, the pressure investigated is well within the high‐pressure limit (HPL) for this reaction. Additional, higher‐pressure experiments also confirmed the HPL assumption. An uncertainty analysis was performed by varying secondary reactions within their uncertainties and examining their effect on the overall prediction, establishing an uncertainty within ±20% for all but the highest temperature cases, which have a maximum uncertainty of ±40%. Experiments conducted with a radical trapper, toluene, showed little influence from radical chemistry, suggesting this estimated uncertainty is fairly conservative. Experimental data from Heyne et al (Z Phys Chem. 2015;229:881‐907) were found to be in good agreement with the rate measurements from this study and, therefore, a second Arrhenius expression, k1 (s–1) = 2.11 × 1013 exp(−30 820 K/T), was found to represent both datasets well. This second expression has a larger temperature range of 976‐1621 K. The present study provides the first high‐temperature data collected for this reaction, adding to the limited data available for isopropanol in the literature.
Early Postoperative Magnetic Resonance in the Diagnosis of Persistent Juvenile Angiofibroma
Authors: Schreiber Alberto , Ravanelli Marco , Ferrari Marco , Mattavelli Davide , Rampinelli Vittorio , Bolzoni Villaret Andrea , Bertazzoni Giacomo , Tomasoni Michele , Gualtieri Tommaso , Zorza Ivan , Farina Davide , Maroldi Roberto , Nicolai Piero 
Published: November 2020

Objectives/HypothesisDespite improvements in the treatment of juvenile angiofibroma (JA), the rate of persistence (pJA) is still not negligible. In the present study, we assessed the value of early postoperative magnetic resonance imaging (MRI) in depicting unintentional pJAs and designed a MRI‐driven decisional flow‐chart for pJA management and follow‐up.Study DesignObservational study.MethodsPatients undergoing early postoperative MRI after endoscopic resection of JA in the Unit of Otorhinolaryngology – ASST Spedali Civili, University of Brescia from 2007 to 2017 were enrolled. MRI was defined as negative or positive based on defined radiological criteria. The diagnostic performance of MRI was evaluated.ResultsThe analysis included 26 patients, with a mean age of 16.5 years (range, 11–25). Early MRI was negative for pJA in 21 (80.8%) patients and positive in five (19.2%). No patient with a negative finding was found positive at subsequent follow‐up MRIs. The accuracy of a positive finding was confirmed by pathologic examination (three cases) or follow‐up MRIs (two cases). The diagnostic performance of MRI was excellent with sensitivity and specificity of 100%. An MRI‐driven flow‐chart for pJA management and follow‐up was designed.ConclusionsEarly postoperative MRI demonstrated a high diagnostic accuracy in the detection of unintentional pJA. Our MRI‐driven strategy and decisional flow‐chart could aid in the decision‐making process in the management of pJA and definition of postoperative surveillance.Level of evidence4 Laryngoscope, 131:E2436–E2441, 2021
Self‐Healing Epoxy and Reversible Diels‐Alder Based Interpenetrating Networks
Authors: Strachota Beata , Hodan Jiří , Dybal Jiří , Matějka Libor 
Published: November 2020

AbstractDual networks, containing Diels‐Alder (DA) based reversible and epoxy networks, are studied as self‐healing thermoset materials. The thermoreversible DA network acts as a healing agent at healing procedure and the epoxy network (E) keeps the material integrity. Two types of the dual networks are investigated, the interpenetrating networks (IPN) and the DA‐epoxy copolymers. The rate of bonds breaking and reformation is monitored by Fourier transform infrared spectroscopy and dynamic mechanical analysis. Two healing steps are followed: the sealing of the notch by microscopy and recovery of the structure by tensile tests. The factors governing the healing efficiency are determined and analyzed. The fraction of the sol generated at healing is found to be the crucial parameter. The novel architecture of the IPN with a high content of the DA network is designed. This IPN generates a high amount of the sol at healing and shows the healing efficiency approaching to 100%.
In Vivo Assessment of Neuroinflammation in 4‐Repeat Tauopathies
Authors: Palleis Carla , Sauerbeck Julia , Beyer Leonie , Harris Stefanie , Schmitt Julia , Morenas‐Rodriguez Estrella , Finze Anika , Nitschmann Alexander , Ruch‐Rubinstein Francois , Eckenweber Florian , Biechele Gloria , Blume Tanja , Shi Yuan , Weidinger Endy , Prix Catharina , Bötzel Kai , Danek Adrian , Rauchmann Boris‐Stephan , Stöcklein Sophia , Lindner Simon , Unterrainer Marcus , Albert Nathalie L. , Wetzel Christian , Rupprecht Rainer , Rominger Axel , Bartenstein Peter , Herms Jochen , Perneczky Robert , Haass Christian , Levin Johannes , Höglinger Günter U. , Brendel Matthias 
Published: November 2020

ABSTRACTBackgroundNeuroinflammation has received growing interest as a therapeutic target in neurodegenerative disorders, including 4‐repeat tauopathies.ObjectivesThe aim of this cross‐sectional study was to investigate 18 kDa translocator protein positron emission tomography (PET) as a biomarker for microglial activation in the 4‐repeat tauopathies corticobasal degeneration and progressive supranuclear palsy.MethodsSpecific binding of the 18 kDa translocator protein tracer 18F‐GE‐180 was determined by serial PET during pharmacological depletion of microglia in a 4‐repeat tau mouse model. The 18 kDa translocator protein PET was performed in 30 patients with corticobasal syndrome (68 ± 9 years, 16 women) and 14 patients with progressive supranuclear palsy (69 ± 9 years, 8 women), and 13 control subjects (70 ± 7 years, 7 women). Group comparisons and associations with parameters of disease progression were assessed by region‐based and voxel‐wise analyses.ResultsTracer binding was significantly reduced after pharmacological depletion of microglia in 4‐repeat tau mice. Elevated 18 kDa translocator protein labeling was observed in the subcortical brain areas of patients with corticobasal syndrome and progressive supranuclear palsy when compared with controls and was most pronounced in the globus pallidus internus, whereas only patients with corticobasal syndrome showed additionally elevated tracer binding in motor and supplemental motor areas. The 18 kDa translocator protein labeling was not correlated with parameters of disease progression in corticobasal syndrome and progressive supranuclear palsy but allowed sensitive detection in patients with 4‐repeat tauopathies by a multiregion classifier.ConclusionsOur data indicate that 18F‐GE‐180 PET detects microglial activation in the brain of patients with 4‐repeat tauopathy, fitting to predilection sites of the phenotype. The 18 kDa translocator protein PET has a potential for monitoring neuroinflammation in 4‐repeat tauopathies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society