bluuebunny/crossref_metadata_2025_split huggingface dataset:
The use of Bayesian methodology in the development and validation of a tiered assessment approach towards prediction of rat acute oral toxicity
Authors: Firman James W. , Cronin Mark T. D. , Rowe Philip H. , Semenova Elizaveta , Doe John E. 
Published: January 2022

AbstractThere exists consensus that the traditional means by which safety of chemicals is assessed—namely through reliance upon apical outcomes obtained following in vivo testing—is increasingly unfit for purpose. Whilst efforts in development of suitable alternatives continue, few have achieved levels of robustness required for regulatory acceptance. An array of “new approach methodologies” (NAM) for determining toxic effect, spanning in vitro and in silico spheres, have by now emerged. It has been suggested, intuitively, that combining data obtained from across these sources might serve to enhance overall confidence in derived judgment. This concept may be formalised in the “tiered assessment” approach, whereby evidence gathered through a sequential NAM testing strategy is exploited so to infer the properties of a compound of interest. Our intention has been to provide an illustration of how such a scheme might be developed and applied within a practical setting—adopting for this purpose the endpoint of rat acute oral lethality. Bayesian statistical inference is drawn upon to enable quantification of degree of confidence that a substance might ultimately belong to one of five LD50-associated toxicity categories. Informing this is evidence acquired both from existing in silico and in vitro resources, alongside a purposely-constructed random forest model and structural alert set. Results indicate that the combination of in silico methodologies provides moderately conservative estimations of hazard, conducive for application in safety assessment, and for which levels of certainty are defined. Accordingly, scope for potential extension of approach to further toxicological endpoints is demonstrated.
Analysis of recreational psychedelic substance use experiences classified by substance
Authors: Hase Adrian , Erdmann Max , Limbach Verena , Hasler Gregor 
Published: January 2022

AbstractRationale and objectivesDifferences among psychedelic substances regarding their subjective experiences are clinically and scientifically interesting. Quantitative linguistic analysis is a powerful tool to examine such differences. This study compared five psychedelic substance report groups and a non-psychedelic report group on quantitative linguistic markers of psychological states and processes derived from recreational use-based online experience reports.MethodsUsing 2947 publicly available online reports, we compared Ayahuasca and N,N-dimethyltryptamine (DMT, analyzed together), ketamine, lysergic acid diethylamide (LSD), 3,4-methylenedioxymethamphetamine (MDMA), psilocybin (mushroom), and antidepressant drug use experiences. We examined word frequencies related to various psychological states and processes and semantic proximity to psychedelic and mystical experience scales.ResultsLinguistic markers of psychological function indicated distinct effect profiles. For example, MDMA experience reports featured an emotionally intensifying profile accompanied by many cognitive process words and dynamic-personal language. In contrast, Ayahuasca and DMT experience reports involved relatively little emotional language, few cognitive process words, increased analytical thinking-associated language, and the most semantic similarity with psychedelic and mystical experience descriptions. LSD, psilocybin mushroom, and ketamine reports showed only small differences on the emotion-, analytical thinking-, psychedelic, and mystical experience-related language outcomes. Antidepressant reports featured more negative emotional and cognitive process-related words, fewer positive emotional and analytical thinking-related words, and were generally not similar to mystical and psychedelic language.ConclusionThis article addresses an existing research gap regarding the comparison of different psychedelic drugs on linguistic profiles of psychological states, processes, and experiences. The large sample of experience reports involving multiple psychedelic drugs provides valuable information that would otherwise be difficult to obtain. The results could inform experimental research into psychedelic drug effects in healthy populations and clinical trials for psychedelic treatments of psychiatric problems.
Global surface features contribute to human haptic roughness estimations
Authors: Li Huazhi , Yang Jiajia , Yu Yinghua , Wang Wu , Liu Yulong , Zhou Mengni , Li Qingqing , Yang Jingjing , Shao Shiping , Takahashi Satoshi , Ejima Yoshimichi , Wu Jinglong 
Published: January 2022

AbstractPrevious studies have paid special attention to the relationship between local features (e.g., raised dots) and human roughness perception. However, the relationship between global features (e.g., curved surface) and haptic roughness perception is still unclear. In the present study, a series of roughness estimation experiments was performed to investigate how global features affect human roughness perception. In each experiment, participants were asked to estimate the roughness of a series of haptic stimuli that combined local features (raised dots) and global features (sinusoidal-like curves). Experiments were designed to reveal whether global features changed their haptic roughness estimation. Furthermore, the present study tested whether the exploration method (direct, indirect, and static) changed haptic roughness estimations and examined the contribution of global features to roughness estimations. The results showed that sinusoidal-like curved surfaces with small periods were perceived to be rougher than those with large periods, while the direction of finger movement and indirect exploration did not change this phenomenon. Furthermore, the influence of global features on roughness was modulated by local features, regardless of whether raised-dot surfaces or smooth surfaces were used. Taken together, these findings suggested that an object’s global features contribute to haptic roughness perceptions, while local features change the weight of the contribution that global features make to haptic roughness perceptions.
Pancreatic cancer survival prediction via inflammatory serum markers
Authors: Lanki Mira , Seppänen Hanna , Mustonen Harri , Salmiheimo Aino , Stenman Ulf-Håkan , Salmi Marko , Jalkanen Sirpa , Haglund Caj 
Published: January 2022

Abstract
Background
For prognostic evaluation of pancreatic ductal adenocarcinoma (PDAC), the only well-established serum marker is carbohydrate antigen CA19-9. To improve the accuracy of survival prediction, we tested the efficacy of inflammatory serum markers.

Methods
A preoperative serum panel comprising 48 cytokines plus high-sensitivity CRP (hs-CRP) was analyzed in 173 stage I–III PDAC patients. Analysis of the effect of serum markers on survival utilized the Cox regression model, with the most promising cytokines chosen with the aid of the lasso method. We formed a reference model comprising age, gender, tumor stage, adjuvant chemotherapy status, and CA19-9 level. Our prognostic study model incorporated these data plus hs-CRP and the cytokines. We constructed time-dependent ROC curves and calculated an integrated time-averaged area under the curve (iAUC) for both models from 1 to 10 years after surgery.

Results
Hs-CRP and the cytokines CTACK, MIF, IL-1β, IL-3, GRO-α, M-CSF, and SCF, were our choices for the prognostic study model, in which the iAUC was 0.837 (95% CI 0.796–0.902), compared to the reference model’s 0.759 (95% CI 0.691–0.836, NS). These models divided the patients into two groups based on the maximum value of Youden’s index at 7.5 years. In our study model, 60th percentile survival times were 4.5 (95% CI 3.7–NA) years (predicted high-survival group, n = 34) and 1.3 (95% CI 1.0–1.7) years (predicted low-survival group, n = 128), log rank p < 0.001. By the reference model, the 60th percentile survival times were 2.8 (95% CI 2.1–4.4) years (predicted high-survival group, n = 44) and 1.3 (95% CI 1.0–1.7) years (predicted low-survival group, n = 118), log rank p < 0.001.

Conclusion
Hs-CRP and the seven cytokines added to the reference model including CA19-9 are potential prognostic factors for improved survival prediction for PDAC patients.
Global tree-ring response and inferred climate variation following the mid-thirteenth century Samalas eruption
Authors: Büntgen Ulf , Smith Sylvie Hodgson , Wagner Sebastian , Krusic Paul , Esper Jan , Piermattei Alma , Crivellaro Alan , Reinig Frederick , Tegel Willy , Kirdyanov Alexander , Trnka Mirek , Oppenheimer Clive 
Published: January 2022

AbstractThe largest explosive volcanic eruption of the Common Era in terms of estimated sulphur yield to the stratosphere was identified in glaciochemical records 40 years ago, and dates to the mid-thirteenth century. Despite eventual attribution to the Samalas (Rinjani) volcano in Indonesia, the eruption date remains uncertain, and the climate response only partially understood. Seeking a more global perspective on summer surface temperature and hydroclimate change following the eruption, we present an analysis of 249 tree-ring chronologies spanning the thirteenth century and representing all continents except Antarctica. Of the 170 predominantly temperature sensitive high-frequency chronologies, the earliest hints of boreal summer cooling are the growth depressions found at sites in the western US and Canada in 1257 CE. If this response is a result of Samalas, it would be consistent with an eruption window of circa May–July 1257 CE. More widespread summer cooling across the mid-latitudes of North America and Eurasia is pronounced in 1258, while records from Scandinavia and Siberia reveal peak cooling in 1259. In contrast to the marked post-Samalas temperature response at high-elevation sites in the Northern Hemisphere, no strong hydroclimatic anomalies emerge from the 79 precipitation-sensitive chronologies. Although our findings remain spatially biased towards the western US and central Europe, and growth-climate response patterns are not always dominated by a single meteorological factor, this study offers a global proxy framework for the evaluation of paleoclimate model simulations.
Amino acid intake and plasma concentrations and their interplay with gut microbiota in vegans and omnivores in Germany
Authors: Dietrich Stefan , Trefflich Iris , Ueland Per Magne , Menzel Juliane , Penczynski Katharina J. , Abraham Klaus , Weikert Cornelia 
Published: January 2022

Abstract
Purpose
It has been estimated that most vegans meet the total protein requirements, but whether this is also true for individual essential amino acids (AAs) is unclear. Furthermore, a shift in protein intake is suggested to alter microbiota composition, but this association is unknown in terms of veganism or individual AAs. This cross-sectional study compared vegans and omnivores regarding dietary intake and plasma concentration of AAs. The prevalence of insufficient intake of essential AAs among vegans was determined using estimated average requirements (EAR) of WHO. Moreover, correlations between AAs intake and gut microbiota were investigated.

Methods
Data of 36 vegans and 36 omnivores (30–60 years) were analysed. AA intake, AA plasma concentrations and gut microbiota were ascertained by three-day weighed food protocols, gas/liquid chromatography-tandem mass spectrometry and 16S rRNA sequencing, respectively.

Results
At almost the same energy intake, the intake of 9 AAs in vegans was significantly lower than in omnivores, with median differences of − 27.0% to − 51.9%. However, only one female vegan showed total protein and lysine intake below the EAR. Vegans showed lower lysine (− 25.0%), but higher glycine (+ 25.4%) and glutamate (+ 13.1%) plasma concentrations than omnivores. Correlation patterns between AA intake and bacterial microbiota differed between vegans and omnivores. In vegans 19 species and in omnivores 5 species showed correlations with AA intake.

Conclusion
Vegans consumed apparently sufficient but lower AAs than omnivores. In addition, the different AAs intake seems to influence the microbiota composition. The use of short-term dietary data without considering usual intake limits these findings.
Prognostic significance of CTNNB1 mutation in early stage endometrial carcinoma: a systematic review and meta-analysis
Authors: Travaglino Antonio , Raffone Antonio , Raimondo Diego , Reppuccia Sabrina , Ruggiero Alessandro , Arena Alessandro , Casadio Paolo , Zullo Fulvio , Insabato Luigi , Seracchioli Renato , Mollo Antonio 
Published: January 2022

Abstract
Background
In the last years, mutations in the exon 3 of CTNNB1 have emerged as a possible prognostic factor for recurrence in early stage endometrioid endometrial carcinoma, especially in cases with no specific molecular profile (NSMP).

Objective
To define the prognostic value of CTNNB1 mutations in early stage endometrioid endometrial carcinoma, through a systematic review and meta-analysis.

Methods
Electronic databases were searched from their inception to November 2020 for all studies assessing the prognostic value of CTNNB1 mutation in early stage (FIGO I–II) endometrioid endometrial carcinoma. Odds ratio (OR) for tumor recurrence and hazard ratio (HR) for disease-free survival (DFS) were calculated with a significant p value < 0.05.

Results
Seven studies with 1031 patients were included. Four studies were suitable for meta-analysis of OR and showed significant association between CTNNB1 mutation and the absolute number of recurrence (OR = 3.000; p = 0.019); the association became stronger after excluding patients with known molecular status other than NSMP (HR = 5.953; p = 0.012). Three studies were suitable for meta-analysis of HR and showed no significant association between CTNNB1 mutation and decreased DFS (HR = 1.847; p = 0.303); the association became significant after excluding patients with known molecular status other than NSMP (HR = 2.831; p = 0.026).

Conclusion
CTNNB1 mutation is significantly associated with recurrence in early stage endometrioid endometrial carcinomas, especially in the NSMP, appearing potentially useful in directing adjuvant treatment.
Frequency reallocation based on cochlear place frequencies in cochlear implants: a pilot study
Authors: Di Maro Flavia , Carner Marco , Sacchetto Andrea , Soloperto Davide , Marchioni Daniele 
Published: January 2022

Abstract
Purpose
The aim of this study is to evaluate speech perception outcomes after a frequency reallocation performed through the creation of an anatomically based map obtained with Otoplan®, a tablet-based software that allows the cochlear duct length to be calculated starting from CT images.

Methods
Ten postlingually deafened patients who underwent cochlear implantation with MED-EL company devices from 2015 to 2019 in the Tertiary referral center University Hospital of Verona have been included in a retrospective study. The postoperative CT scans were evaluated with Otoplan®; the position of the intracochlear electrodes was obtained, an anatomical mapping was carried out and then it was submitted to the patients.
All patients underwent pure tonal and speech audiometry before and after the reallocation and the audiological results were processed considering the Speech Recognition Threshold (SRT), the Speech Awareness Threshold (SAT) and the Pure Tone Average (PTA). The differences in the PTA, SAT and SRT values before and after the reallocation were determined. The results were statistically processed using the software Stata with a significance value of α < 0.05.

Results
The mean values of SRT (61.25 dB versus 51.25 dB) and SAT (49 dB versus 41 dB) were significantly lower (p: 0.02 and p: 0.04, respectively) after the reallocation. No significant difference was found between PTA values (41.5 dB versus 39.25 dB; p: 0.18).

Conclusions
Our preliminary results demonstrate better speech discrimination and rapid adaptation in implanted postlingually deaf patients after anatomic mapping and subsequent frequency reallocation.
Efficacy and safety of VNS therapy or continued medication management for treatment of adults with drug-resistant epilepsy: systematic review and meta-analysis
Authors: Batson Sarah , Shankar Rohit , Conry Joan , Boggs Jane , Radtke Rodney , Mitchell Stephen , Barion Francesca , Murphy Joanna , Danielson Vanessa 
Published: January 2022

AbstractVagus nerve stimulation (VNS) Therapy® is an adjunctive neurostimulation treatment for people with drug-resistant epilepsy (DRE) who are unwilling to undergo resective surgery, have had unsuccessful surgery or are unsuitable for surgery. A systematic review and meta-analysis were conducted to determine the treatment effects of VNS Therapy as an adjunct to anti-seizure medications (ASMs) for the management of adults with DRE. A literature search was performed in August 2020 of the Medline®, Medline® Epub Ahead of Print, Embase, and the Cochrane library databases. Outcomes examined included reduction in seizure frequency, seizure freedom, ASM load, discontinuations, and serious adverse events (SAEs). Comparators included best medical practice, ASMs, low-stimulation or sham VNS Therapy. Four RCTs and six comparative observational studies were identified for inclusion. Against comparators, individuals treated with VNS had a significantly better odds of experiencing a ≥ 50% reduction in seizure frequency (OR: 2.27 [95% CI 1.47, 3.51]; p = 0.0002), a ≥ 75% reduction in seizure frequency (OR: 3.56 [95% CI 1.59, 7.98]; p = 0.002) and a reduced risk for increased ASM load (risk ratio: 0.36 [95% CI 0.21, 0.62]; p = 0.0002). There was no difference in the odds of discontinuation or the rate of SAEs between VNS versus comparators. This meta-analysis demonstrated the benefits of VNS Therapy in people with DRE, which included improvement in seizure frequency without an increase in the rate of SAEs or discontinuations, thereby supporting the consideration of VNS Therapy for people who are not responding to ASMs and those unsuitable or unwilling to undergo surgery.
New kids on the CPET: age-appropriate outdoor cardiopulmonary exercise testing in preschoolers
Authors: Rottermann Kathrin , Weigelt Annika , Stäbler Tim , Ehrlich Benedikt , Dittrich Sven , Schöffl Isabelle 
Published: January 2022

Abstract
Purpose
Cardiopulmonary exercise testing (CPET) in preschoolers (4–6 years) represents a challenge. Most studies investigating CPET have been limited to older children (> 8 year). However, knowledge of the performance of small children is essential for evaluating their cardiorespiratory fitness. This study strives to compare a modified Bruce protocol with a new age-appropriate incremental CPET during natural movement running outdoors, using a mobile device.

Methods
A group of 22 4–6-year-old healthy children was tested indoor on a treadmill (TM) using the modified Bruce protocol. The results were compared with a self-paced incremental running test, using a mobile CPET device in an outdoor park. The speeds were described as (1) slow walking, (2) slow running, (3) regular running, and (4) running with full speed as long as possible.

Results
Mean exercise time outdoors (6,57 min) was significantly shorter than on the treadmill (11,20 min), $$\dot{V}{O}_{2peak}$$

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(51.1 ml/min/kg vs. 40.1 ml/min/kg), RER (1.1 vs. 0.98) and important CPET parameters such as $$\dot{V}E$$

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max, O2pulse, heart rate and breath rate were significantly higher outdoors. The submaximal parameter OUES was comparable between both the tests.

Conclusions
Testing very young children with a mobile device is a new alternative to treadmill testing. With a significantly shorter test duration, significantly higher values for almost all cardiopulmonary variables can be achieved without losing the ability to determine VT1 and VT2. It avoids common treadmill problems and allows for individualized exercise testing. The aim is to standardize exercise times with individual protocols instead of standardizing protocols with individual exercise times, allowing for better comparability.
Aortic haemodynamics: the effects of habitual endurance exercise, age and muscle sympathetic vasomotor outflow in healthy men
Authors: Wakeham Denis J. , Dawkins Tony G. , Lord Rachel N. , Talbot Jack S. , Lodge Freya M. , Curry Bryony A. , Simpson Lydia L. , Pugh Christopher J. A. , Shave Robert E. , Moore Jonathan P. 
Published: January 2022

Abstract
Purpose
We determined the effect of habitual endurance exercise and age on aortic pulse wave velocity (aPWV), augmentation pressure (AP) and systolic blood pressure (aSBP), with statistical adjustments of aPWV and AP for heart rate and aortic mean arterial pressure, when appropriate. Furthermore, we assessed whether muscle sympathetic nerve activity (MSNA) correlates with AP in young and middle-aged men.

Methods
Aortic PWV, AP, aortic blood pressure (applanation tonometry; SphygmoCor) and MSNA (peroneal microneurography) were recorded in 46 normotensive men who were either young or middle-aged and endurance-trained runners or recreationally active nonrunners (10 nonrunners and 13 runners within each age-group). Between-group differences and relationships between variables were assessed via ANOVA/ANCOVA and Pearson product-moment correlation coefficients, respectively.

Results
Adjusted aPWV and adjusted AP were similar between runners and nonrunners in both age groups (all, P > 0.05), but higher with age (all, P < 0.001), with a greater effect size for the age-related difference in AP in runners (Hedges’ g, 3.6 vs 2.6). aSBP was lower in young (P = 0.009; g = 2.6), but not middle-aged (P = 0.341; g = 1.1), runners compared to nonrunners. MSNA burst frequency did not correlate with AP in either age group (young: r = 0.00, P = 0.994; middle-aged: r = − 0.11, P = 0.604).

Conclusion
There is an age-dependent effect of habitual exercise on aortic haemodynamics, with lower aSBP in young runners compared to nonrunners only. Statistical adjustment of aPWV and AP markedly influenced the outcomes of this study, highlighting the importance of performing these analyses. Further, peripheral sympathetic vasomotor outflow and AP were not correlated in young or middle-aged normotensive men.
Cold stress and freezing tolerance negatively affect the fitness of Arabidopsis thaliana accessions under field and controlled conditions
Authors: Boinot Maximilian , Karakas Esra , Koehl Karin , Pagter Majken , Zuther Ellen 
Published: January 2022

Abstract
Main conclusion
Higher acclimated freezing tolerance improved winter survival, but reduced reproductive fitness of Arabidopsis thaliana accessions under field and controlled conditions.

Abstract
Low temperature is one of the most important abiotic factors influencing plant fitness and geographical distribution. In addition, cold stress is known to influence crop yield and is therefore of great economic importance. Increased freezing tolerance can be acquired by the process of cold acclimation, but this may be associated with a fitness cost. To assess the influence of cold stress on the fitness of plants, long-term field trials over 5 years were performed with six natural accessions of Arabidopsis thaliana ranging from very tolerant to very sensitive to freezing. Fitness parameters, as seed yield and 1000 seed mass, were measured and correlation analyses with temperature and freezing tolerance data performed. The results were compared with fitness parameters from controlled chamber experiments over 3 years with application of cold priming and triggering conditions. Winter survival and seed yield per plant were positively correlated with temperature in field experiments. In addition, winter survival and 1000 seed mass were correlated with the cold-acclimated freezing tolerance of the selected Arabidopsis accessions. The results provide strong evidence for a trade-off between higher freezing tolerance and reproductive fitness in A. thaliana, which might have ecological impacts in the context of global warming.