bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term neurocognitive function after whole-brain radiotherapy in patients with melanoma brain metastases in the era of immunotherapy
Authors: Salzmann Martin , Hess Klaus , Lang Kristin , Enk Alexander H. , Jordan Berit , Hassel Jessica C. 
Published: May 2022

AbstractBackgroundWhole-brain radiotherapy (WBRT) used to be standard of care for patients suffering from melanoma brain metastases (MBM) and may still be applicable in selected cases. Deterioration of neurocognitive function (NCF) is commonly seen during and after WBRT. Knowledge on long-term effects in melanoma patients is limited due to short survival rates. With the introduction of immune checkpoint inhibitors, patients may experience ongoing disease control, emphasizing the need for paying more attention to potential long-term adverse effects.MethodsIn this single-center study, we identified in a period of 11 years all long-term survivors of MBM who received WBRT at least 1 year prior to inclusion. NCF was assessed by Neuropsychological Assessment Battery (NAB) screening and detailed neurological exam; confounders were documented.ResultsEight patients (median age 55 years) could be identified with a median follow-up of 5.4 years after WBRT. Six patients reported no subjective neurological impairment. NAB screening revealed an average-range score in 5/8 patients. In 3/8 patients a NAB score below average was obtained, correlating with subjective memory deficits in 2 patients. In these patients, limited performance shown in modalities like memory function, attention, and spatial abilities may be considerably attributed to metastasis localization itself. Six out of 8 patients were able to return to their previous work.ConclusionFive of 8 long-term survivors with MBM after WBRT experienced little to no restriction in everyday activities. In 3 out of 8 patients, cognitive decline was primarily explained by localization of the metastases in functionally relevant areas of the brain. The results of our small patient cohort do not support general avoidance of WBRT for treatment of brain metastases. However, long-term studies including pretreatment NCF tests are needed to fully analyze the long-term neurocognitive effects of WBRT
Effects of alcohol hangover on attentional resources during a verbal memory/psychomotor tracking dual attention task
Authors: Ayre Elizabeth , Benson Sarah , Garrisson Harriet , Cox Katherine H. M. , Verster Joris C. , Scholey Andrew 
Published: May 2022

Abstract
Background
Alcohol hangover (AH) is associated with impaired attention and memory performance. However, whether this effect is related to reduced attentional resources remains unclear.

Aims
A dual-attention paradigm was employed to assess the effects of AH on attentional resources, delayed memory recognition, and the interaction between attentional load and AH. Mental effort and perceived performance during AH and control conditions were also assessed.

Methods
A seminaturalistic, crossover design was used. In total, 25 healthy social drinkers aged 18–35 years, visited the laboratory following a typical night out drinking (Hangover condition) and after alcohol abstinence (control) between 8:30 am and 12:30 pm, with conditions counterbalanced. Attentional load was manipulated via the presence (dual attention) or absence of psychomotor tracking during verbal memory encoding. Perceived mental effort and performance were measured using the NASA-TLX. Participants’ recollected alcohol consumption was used to compute estimated blood alcohol level (eBAC).

Results
Compared with the control visit, AH was associated with reduced recognition accuracy (particularly more false negatives), higher “tracking costs” (poorer accuracy) in the dual attention condition, increased ratings of “mental demand,” “effort,” and “frustration,” and lower ratings of task performance. There was also a significant main effect of attentional load with poorer recognition accuracy and response time in the dual attention condition. There were no significant interaction effects between hangover and attentional load.

Conclusion
These findings suggest that reduced attentional resources contribute to the cognitive deficits associated with AH including impaired memory consolidation. They further suggest that while hungover, participants are aware of these deficits but are unable to compensate.
From sea salt to seawater: a novel approach for the production of water CRMs﻿
Authors: Pagliano Enea , Nadeau Kenny , Mihai Ovidiu , Pihillagawa Gedara Indumathi , Mester Zoltán 
Published: May 2022

AbstractNatural water certified reference materials (CRMs) are mostly available in a liquid form, and they are produced starting from suitable environmental samples. Many precautions are usually needed to avoid biological or physical degradation, including filtration, acidification, and sterilization. In this study, the drawbacks associated with liquid-based seawater CRMs were tackled by developing a salt-based seawater proxy for nutrients that could be reconstituted in water solution just before use. Phosphate, silicate, and nitrate were chosen as target analytes. Sea salt mimicking the composition of seawater was spiked with an aqueous solution of the analytes and homogenized using a high-energy planetary ball mill (uhom < 1.2%). The salt powder CRM SALT-1 (https://doi.org/10.4224/crm.2022.salt-1) demonstrated good short- and long-term stability for nutrients. When the SALT-1 was reconstituted in water at the 4.0% w/w level, the resulting solution had similar properties with respect to typical seawater in terms of major constituents (± 20%), trace metals, density (1.023 g/mL), pH (8.8–9.0), and optical properties relevant to the photometric characterization. Phosphate and silicate were quantified by photometry (molybdenum blue method, batch mode), whereas nitrate was quantified by isotope dilution GC−MS (uchar < 1.2%). In the SALT-1 reconstituted seawater solution at the 4.0% w/w salt level, the nutrient amount concentration was w(phosphate, PO43−) = 1.615 ± 0.030 μmol/L, w(silicate as SiO2) = 8.89 ± 0.31 μmol/L, and w(nitrate, NO3−) = 18.98 ± 0.45 μmol/L at the 95% confidence (k = 2). Overall, the SALT-1 CRM exhibits similar nutrient profile and general analytical characteristics as the MOOS-3 CRM. However, the SALT-1 has much reduced preparation, storage, and distribution cost, likely much better long-term stability, and it could enable the production of lower cost and more accessible seawater reference materials.
Graphical abstract
Factors influencing downstaging after neoadjuvant long-course chemoradiotherapy in rectal carcinoma
Authors: Kohl Valerie K. B. , Weber Klaus , Brunner Maximilian , Geppert Carol I. , Fietkau Rainer , Grützmann Robert , Semrau Sabine , Merkel Susanne 
Published: May 2022

Abstract

Purpose
This single-centre cohort study was designed to identify factors that can predict primary tumour downstaging by neoadjuvant chemoradiotherapy (nCRT) in rectal carcinoma.

Methods
Prospectively collected data from 555 patients with clinical T category (cT) cT3-4 rectal carcinoma treated between 1995 and 2019 were retrospectively analysed. All patients received long-term neoadjuvant chemoradiotherapy followed by surgery with curative intent at the Department of Surgery, University Hospital Erlangen, Germany. Patient-, tumour- and treatment-related factors with a potential impact on the downstaging of rectal carcinoma to pathological T category (pT) ≤ ypT2 and ypT0 were analysed in univariate and multivariate logistic regression analyses. The prognosis of patients with and without downstaging of the primary tumour was compared.

Results
A total of 288 (51.9%) patients showed downstaging to ≤ ypT2. Eighty-six (15.5%) patients achieved clinical complete regression (ypT0). In the multivariate logistic regression analysis, the factors cT category, BMI, ECOG score, CEA, histological type, extension in the rectum and year of the start of treatment were found to be independent factors for predicting downstaging to ≤ ypT2 after neoadjuvant chemoradiotherapy. The year of treatment initiation also remained an independent significant predictor for pathological complete regression. The prognosis was superior in patients with downstaging to ≤ ypT2 in terms of locoregional and distant recurrence as well as disease-free and overall survival.

Conclusion
Factors predicting downstaging after long-term nCRT could be identified. This may be helpful for counselling patients and selecting the optimal treatment for patients with advanced rectal carcinoma.
Identifying predictive signalling networks for Vedolizumab response in ulcerative colitis
Authors: Singh Amrinder , Fenton Christopher G. , Anderssen Endre , Paulssen Ruth H. 
Published: May 2022

Abstract
Background
In ulcerative colitis (UC), the molecular mechanisms that drive disease development and patient response to therapy are not well understood. A significant proportion of patients with UC fail to respond adequately to biologic therapy. Therefore, there is an unmet need for biomarkers that can predict patients’ responsiveness to the available UC therapies as well as ascertain the most effective individualised therapy. Our study focused on identifying predictive signalling pathways that predict anti-integrin therapy response in patients with UC.

Methods
We retrieved and pre-processed two publicly accessible gene expression datasets (GSE73661 and GSE72819) of UC patients treated with anti-integrin therapies: (1) 12 non-IBD controls and 41 UC patients treated with Vedolizumab therapy, and (2) 70 samples with 58 non-responder and 12 responder UC patient samples treated with Etrolizumab therapy without non-IBD controls. We used a diffusion-based signalling model which is mainly focused on the T-cell receptor signalling network. The diffusion model uses network connectivity between receptors and transcription factors.

Results
The network diffusion scores were able to separate VDZ responder and non-responder patients before treatment better than the original gene expression. On both anti-integrin treatment datasets, the diffusion model demonstrated high predictive performance for discriminating responders from non-responders in comparison with ‘nnet’. We have found 48 receptor-TF pairs identified as the best predictors for VDZ therapy response with AUC ≥ 0.76. Among these receptor-TF predictors pairs, FFAR2-NRF1, FFAR2-RELB, FFAR2-EGR1, and FFAR2-NFKB1 are the top best predictors. For Etrolizumab, we have identified 40 best receptor-TF pairs and CD40-NFKB2 as the best predictor receptor-TF pair (AUC = 0.72). We also identified subnetworks that highlight the network interactions, connecting receptors and transcription factors involved in cytokine and fatty acid signalling. The findings suggest that anti-integrin therapy responses in cytokine and fatty acid signalling can stratify UC patient subgroups.

Conclusions
We identified signalling pathways that may predict the efficacy of anti-integrin therapy in UC patients and personalised therapy alternatives. Our results may lead to the advancement of a promising clinical decision-making tool for the stratification of UC patients.
Pilot study of a new freely available computer-aided polyp detection system in clinical practice
Authors: Lux Thomas J. , Banck Michael , Saßmannshausen Zita , Troya Joel , Krenzer Adrian , Fitting Daniel , Sudarevic Boban , Zoller Wolfram G. , Puppe Frank , Meining Alexander , Hann Alexander 
Published: May 2022

Abstract
Purpose
Computer-aided polyp detection (CADe) systems for colonoscopy are already presented to increase adenoma detection rate (ADR) in randomized clinical trials. Those commercially available closed systems often do not allow for data collection and algorithm optimization, for example regarding the usage of different endoscopy processors. Here, we present the first clinical experiences of a, for research purposes publicly available, CADe system.

Methods
We developed an end-to-end data acquisition and polyp detection system named EndoMind. Examiners of four centers utilizing four different endoscopy processors used EndoMind during their clinical routine. Detected polyps, ADR, time to first detection of a polyp (TFD), and system usability were evaluated (NCT05006092).

Results
During 41 colonoscopies, EndoMind detected 29 of 29 adenomas in 66 of 66 polyps resulting in an ADR of 41.5%. Median TFD was 130 ms (95%-CI, 80–200 ms) while maintaining a median false positive rate of 2.2% (95%-CI, 1.7–2.8%). The four participating centers rated the system using the System Usability Scale with a median of 96.3 (95%-CI, 70–100).

Conclusion
EndoMind’s ability to acquire data, detect polyps in real-time, and high usability score indicate substantial practical value for research and clinical practice. Still, clinical benefit, measured by ADR, has to be determined in a prospective randomized controlled trial.
Admissible Reversing and Extended Symmetries for Bijective Substitutions
Authors: Bustos Álvaro , Luz Daniel , Mañibo Neil 
Published: May 2022

AbstractIn this paper, we deal with reversing and extended symmetries of subshifts generated by bijective substitutions. We survey some general algebraic and dynamical properties of these subshifts and recall known results regarding their symmetry groups. We provide equivalent conditions for a permutation on the alphabet to generate a reversing/extended symmetry, and algorithms how to compute them. Moreover, for any finite group H and any subgroup P of the d-dimensional hyperoctahedral group, we construct a bijective substitution which generates an aperiodic subshift with symmetry group $${\mathbb {Z}}^{d}\times H$$

Z

d

×
H

and extended symmetry group $$({\mathbb {Z}}^{d} \rtimes P)\times H$$

(

Z

d

⋊
P
)
×
H

. A similar construction with the same symmetry group, but with extended symmetry group $$({\mathbb {Z}}^{d} \times H) \rtimes P$$

(

Z

d

×
H
)
⋊
P

is also provided under a mild assumption on the dimension.
Second primary malignancies in patients with clinical T1bN0 esophageal squamous cell carcinoma after definitive therapies: supplementary analysis of the JCOG trial: JCOG0502
Authors: Mitani Seiichiro , Kato Ken , Daiko Hiroyuki , Ito Yoshinori , Nozaki Isao , Kojima Takashi , Yano Masahiko , Nakagawa Satoru , Ueno Masaki , Watanabe Masaya , Tsunoda Shigeru , Abe Tetsuya , Kadowaki Shigenori , Kadota Tomohiro , Sasaki Keita , Machida Ryunosuke , Kitagawa Yuko 
Published: May 2022

Abstract
Background
Previous studies have suggested that patients with esophageal squamous cell carcinoma (ESCC) are still at a high risk of developing second primary malignancies (SPMs) after definitive therapies. We evaluated the development of SPMs and explored its risk factors in patients with clinical T1bN0 ESCC.

Methods
JCOG0502 prospectively compared esophagectomy with definitive chemo-radiotherapy for clinical T1bN0 ESCC. Here, we reviewed all JCOG0502 patients’ data for SPMs and investigated the risk factors for SPMs using uni-variable and multivariable analyses by Fine and Gray model.

Results
Among 379 enrolled patients, 213 underwent esophagectomy and 166 received chemo-radiotherapy. Patient characteristics were male (85%); median age [63 (range 41–75) years; location of the primary tumor (upper/middle/lower thoracic esophagus, 11%/63%/27%, respectively]; alcohol consumption history (79%); smoking history (66%); prevalence of no/several/many/unknown Lugol-voiding lesions (LVLs) (45%/36%/8%/11%, respectively). In a median follow-up of 7.1 years, 118 SPMs occurred in 99 (26%) patients. Cumulative incidences of SPMs after 3, 5, and 10 years were 9%, 15%, and 36%, respectively. The most common primary tumor sites were the head and neck (35%), stomach (20%) and lungs (14%). In multivariable analyses, compared to no LVLs, several LVLs [hazard ratio (HR) 2.24, 95% confidential interval (CI) 1.32–3.81] and many LVLs (HR 2.88, 95% CI 1.27–6.52) were significantly associated with the development of SPMs. Sixteen patients died due to the SPMs.

Conclusion
The incidence of SPMs was high. The presence of LVLs, which was a predictive factor for SPMs, may be useful for surveillance planning.
Tests of stochastic dominance with repeated measurements data
Authors: Angelov Angel G. , Ekström Magnus 
Published: May 2022

AbstractThe paper explores a testing problem which involves four hypotheses, that is, based on observations of two random variables X and Y, we wish to discriminate between four possibilities: identical survival functions, stochastic dominance of X over Y, stochastic dominance of Y over X, or crossing survival functions. Four-decision testing procedures for repeated measurements data are proposed. The tests are based on a permutation approach and do not rely on distributional assumptions. One-sided versions of the Cramér–von Mises, Anderson–Darling, and Kolmogorov–Smirnov statistics are utilized. The consistency of the tests is proven. A simulation study shows good power properties and control of false-detection errors. The suggested tests are applied to data from a psychophysical experiment.
TFEB controls integrin-mediated endothelial cell adhesion by the regulation of cholesterol metabolism
Authors: Ariano Camilla , Riganti Chiara , Corà Davide , Valdembri Donatella , Mana Giulia , Astanina Elena , Serini Guido , Bussolino Federico , Doronzo Gabriella 
Published: May 2022

AbstractThe dynamic integrin-mediated adhesion of endothelial cells (ECs) to the surrounding ECM is fundamental for angiogenesis both in physiological and pathological conditions, such as embryonic development and cancer progression. The dynamics of EC-to-ECM adhesions relies on the regulation of the conformational activation and trafficking of integrins. Here, we reveal that oncogenic transcription factor EB (TFEB), a known regulator of lysosomal biogenesis and metabolism, also controls a transcriptional program that influences the turnover of ECM adhesions in ECs by regulating cholesterol metabolism. We show that TFEB favors ECM adhesion turnover by promoting the transcription of genes that drive the synthesis of cholesterol, which promotes the aggregation of caveolin-1, and the caveolin-dependent endocytosis of integrin β1. These findings suggest that TFEB might represent a novel target for the pharmacological control of pathological angiogenesis and bring new insights in the mechanism sustaining TFEB control of endocytosis.
Effects of Measurement Height and Low-Pass-Filtering Corrections on Eddy-Covariance Flux Measurements Over a Forest Clearing with Complex Vegetation
Authors: Reitz Oliver , Graf Alexander , Schmidt Marius , Ketzler Gunnar , Leuchner Michael 
Published: May 2022

AbstractFlux measurements over heterogeneous surfaces with growing vegetation and a limited fetch are a difficult task, as measurement heights that are too high or too low above the canopy adversely affect results. The aim of this study is to assess implications from measurement height in regard to low-pass filtering, footprint representativeness, and energy balance closure for a clear-cut site with regrowing vegetation of varying height. For this, measurements from two open-path eddy-covariance systems at different heights are compared over the course of one growing season. Particular attention is paid to low-pass-filtering corrections, for which five different methods are compared. Results indicate significant differences between fluxes from the upper and lower systems, which likely result from footprint differences and an insufficient spectral correction for the lower system. Different low-pass-filtering corrections add an uncertainty of 3.4% (7.0%) to CO2 fluxes and 1.4% (3.0%) to H2O fluxes for the upper (lower) system, also leading to considerable differences in cumulative fluxes. Despite limitations in the analysis, which include the difficulty of applying a footprint model at this study site and the likely influence of advection on the total exchange, the analysis confirms that information about the choice of spectral correction method and measurement-height changes are critical for interpreting data at complex sites.
Amending China’s Notion of a “Consumer”: Lessons from Comparative Analysis of the PRC Consumer Protection Law
Authors: Thomas K. 
Published: May 2022

AbstractWho does the law treat as a “consumer” and why does it matter? How should China’s notion of a “consumer” best be articulated within the law and applied in practice? This article will attempt to answer these intriguing questions by first focusing on the approach taken to define a “consumer” in China’s Law on the Protection of Consumer Rights and Interests before examining the legal notion of a “consumer” in comparative perspective, in order to further understand the competing rationales behind the consumer protection law. This article will explore this Chinese definition of a “consumer” to propose how China’s vague and unworkable statutory definition of a ‘consumer’ should be amended in future.
The Effects of Attentional Deployment on Reinterpretation in Depressed Adolescents: Evidence from an Eye-Tracking Study
Authors: Piechaczek Charlotte Elisabeth , Schröder Pia-Theresa , Feldmann Lisa , Schulte-Körne Gerd , Greimel Ellen 
Published: May 2022

Abstract
Background
Individuals with major depression have difficulties employing cognitive reappraisal. Most prior studies have not accounted for attentional deployment, which seems to be involved in this process.

Methods
We investigated the cognitive reappraisal tactic reinterpretation in 20 depressed and 28 healthy youths and assessed regulation success in response to negative pictures via self-report. To investigate attentional deployment during reinterpretation, we applied eye-tracking and manipulated gaze focus by instructing participants to direct their attention towards/away from emotional picture aspects.

Results
Depressed adolescents, compared with healthy youths, had a diminished regulation success when their gaze was focused on emotional aspects. Both depressed and healthy adolescents spent less time fixating on emotional facets of negative pictures when using reinterpretation as compared with simply attending to the pictures.

Conclusions
Results from this study suggest that adolescents with major depression have emotion regulation deficits when being confronted with negative emotional facets, while showing intact overt attentional processes. The findings provide important starting points for future research investigating the role of other factors which might impact on emotion regulation processes in this patient group, such as cognitive control deficits.