bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproducibility and accuracy of microscale thermophoresis in the NanoTemper Monolith: a multi laboratory benchmark study
Authors: López-Méndez Blanca , Baron Bruno , Brautigam Chad A. , Jowitt Thomas A. , Knauer Stefan H. , Uebel Stephan , Williams Mark A. , Sedivy Arthur , Abian Olga , Abreu Celeste , Adamczyk Malgorzata , Bal Wojciech , Berger Sylvie , Buell Alexander K. , Carolis Carlo , Daviter Tina , Fish Alexander , Garcia-Alai Maria , Guenther Christian , Hamacek Josef , Holková Jitka , Houser Josef , Johnson Chris , Kelly Sharon , Leech Andrew , Mas Caroline , Matulis Daumantas , McLaughlin Stephen H. , Montserret Roland , Nasreddine Rouba , Nehmé Reine , Nguyen Quyen , Ortega-Alarcón David , Perez Kathryn , Pirc Katja , Piszczek Grzegorz , Podobnik Marjetka , Rodrigo Natalia , Rokov-Plavec Jasmina , Schaefer Susanne , Sharpe Tim , Southall June , Staunton David , Tavares Pedro , Vanek Ondrej , Weyand Michael , Wu Di 
Published: April 2021

AbstractMicroscale thermophoresis (MST), and the closely related Temperature Related Intensity Change (TRIC), are synonyms for a recently developed measurement technique in the field of biophysics to quantify biomolecular interactions, using the (capillary-based) NanoTemper Monolith and (multiwell plate-based) Dianthus instruments. Although this technique has been extensively used within the scientific community due to its low sample consumption, ease of use, and ubiquitous applicability, MST/TRIC has not enjoyed the unambiguous acceptance from biophysicists afforded to other biophysical techniques like isothermal titration calorimetry (ITC) or surface plasmon resonance (SPR). This might be attributed to several facts, e.g., that various (not fully understood) effects are contributing to the signal, that the technique is licensed to only a single instrument developer, NanoTemper Technology, and that its reliability and reproducibility have never been tested independently and systematically. Thus, a working group of ARBRE-MOBIEU has set up a benchmark study on MST/TRIC to assess this technique as a method to characterize biomolecular interactions. Here we present the results of this study involving 32 scientific groups within Europe and two groups from the US, carrying out experiments on 40 Monolith instruments, employing a standard operation procedure and centrally prepared samples. A protein–small molecule interaction, a newly developed protein–protein interaction system and a pure dye were used as test systems. We characterized the instrument properties and evaluated instrument performance, reproducibility, the effect of different analysis tools, the influence of the experimenter during data analysis, and thus the overall reliability of this method.
Triggers and oncologic outcome of salvage radical prostatectomy, salvage radiotherapy and active surveillance after focal therapy of prostate cancer
Authors: von Hardenberg Jost , Cash Hannes , Koch Daniel , Borkowetz Angelika , Bruendl Johannes , Leyh-Bannurah Sami-Ramzi , Kuru Timur H. , Kowalewski Karl-Friedrich , Schindele Daniel , Mala Katharina S. , Westhoff Niklas , Blana Andreas , Schostak Martin ,   Working Group of Focal and Microtherapy of the German Society of Urology (DGU)
Published: April 2021

Abstract
Purpose
Due to the tissue preserving approach of focal therapy (FT), local cancer relapse can occur. Uncertainty exists regarding triggers and outcome of salvage strategies.

Methods
Patients with biopsy-proven prostate cancer (PCa) after FT for localized PCa from 2011 to 2020 at eight tertiary referral hospitals in Germany that underwent salvage radical prostatectomy (S-RP), salvage radiotherapy (S-RT) or active surveillance (AS) were reported. Prostate specific antigen (PSA) changes, suspicious lesions on mpMRI and histopathological findings on biopsy were analyzed. A multivariable regression model was created for adverse pathological findings (APF) at S-RP specimen. Kaplan–Meier curves were generated to determine oncological outcomes.

Results
A total of 90 men were included. Cancer relapse after FT was detected at a median of 12 months (IQR 9–16). Of 50 men initially under AS 13 received S-RP or S-RT. In total, 44 men underwent S-RP and 13 S-RT. At cancer relapse 17 men (38.6%) in the S-RP group [S-RT n = 4 (30.8%); AS n = 3 (6%)] had ISUP > 2. APF (pT ≥ 3, ISUP ≥ 3, pN + or R1) were observed in 23 men (52.3%). A higher ISUP on biopsy was associated with APF [p = 0.006 (HR 2.32, 97.5% CI 1.35–4.59)] on univariable analysis. Progression-free survival was 80.4% after S-RP and 100% after S-RT at 3 years. Secondary therapy-free survival was 41.7% at 3 years in men undergoing AS. Metastasis-free survival was 80% at 5 years for the whole cohort.

Conclusion
With early detection of cancer relapse after FT S-RP and S-RT provide sufficient oncologic control at short to intermediate follow-up. After AS, a high secondary-therapy rate was observed.
Einfluss des COVID-19-Shutdowns auf die Arbeitsleistung einer Universitäts-Augenpoliklinik
Authors: Framme C. , Gottschling J. , Buley P. , Rohwer-Mensching K. , Junker B. , Dittberner M. , Volkmann I. 
Published: April 2021

Zusammenfassung
Hintergrund
Die Coronaviruserkrankung COVID-19 hat im Frühjahr 2020 zu einer deutlichen Minderleistung der elektiven Medizin in den Krankenhäusern geführt, wobei es für universitäre Polikliniken bisher keine entsprechenden Daten über das Ausmaß dieser Reduktion und die damit verbundenen Erlösminderungen gibt.

Material und Methode
Mithilfe der Daten des aus dem Krankenhausinformationssystems (IS-H/i.s.h.med unter SAP, Cerner Corporation, North Kansas City, MO, Vereinigte Staaten von Amerika und SAP SE, Walldorf, Deutschland) und der an unserer Klinik mitentwickelten Zeiterfassungs- und Managementsoftware TimeElement (Medizinische Hochschule Hannover, Hannover, Deutschland) wurden alle Patientenkontakte des COVID-19-Shutdowns über ca. 7 Wochen vom 18.03.2020 bis zum 08.05.2020 evaluiert und mit dem Vorjahreszeitraum 2019 verglichen. Zudem wurden die Fallzahlen für das erste und zweite Quartal 2019 und 2020 in Relation gesetzt.

Ergebnisse
Im COVID-19-Zeitraum reduzierte sich die Gesamtzahl der Patientenkontakte um 59,5 % gegenüber dem Vorjahr. Die Anzahl der abrechenbaren Fälle reduzierte sich um 74,8 %.
Insbesondere der Hochschulambulanz‑/Selbstzahlerbereich verzeichnete mit einer Reduktion der Patientenkontakte auf 17,2 % des Ausgangswertes von 2019 den größten Patientenwegfall. Aus der reduzierten Arbeitsleistung resultierte ein Erlösverlust von mindestens 218.000 €. Über TimeElement ergab sich ein Rückgang aller diagnostischen Spezialleistungen von 69,4 %, wobei gerade auch Gesichtsfelduntersuchungen um ca. 75,3 % reduziert waren. OCT-Messungen verzeichneten einen Rückgang um 60,3 %. Das Patiententracking ergab allerdings auch eine Reduktion der durchschnittlichen Anwesenheitszeiten der Patienten um ca. 23 % (COVID-19: 145,8 ± 88,8 min vs. 2019: 189,6 ± 97,2 min).

Diskussion
Der COVID-19-Shutdown ließ die Arbeitsleistung unserer Poliklinik auf nur noch ca. 40 % der Patientenkontakte und die der funktionsdiagnostischen Untersuchungen auf nur noch ca. 30 %, verglichen zur Leistung aus dem Jahr 2019, einbrechen. Die Reduktion der Patientenzahl führte allerdings auch dazu, dass die Anwesenheitszeiten der Patienten deutlich geringer als bei regulärer Auslastung ausfielen. Die damit verbundenen finanziellen Verluste sind durchaus erheblich und offensichtlich nicht über gesetzlich geregelte Ausgleichszahlungen wie im stationären Bereich kompensiert.
TREM2 expression in the brain and biological fluids in prion diseases
Authors: Diaz-Lucena Daniela , Kruse Niels , Thüne Katrin , Schmitz Matthias , Villar-Piqué Anna , da Cunha Jose Eriton Gomes , Hermann Peter , López-Pérez Óscar , Andrés-Benito Pol , Ladogana Anna , Calero Miguel , Vidal Enric , Riggert Joachim , Pineau Hailey , Sim Valerie , Zetterberg Henrik , Blennow Kaj , del Río Jose Antonio , Marín-Moreno Alba , Espinosa Juan Carlos , Torres Juan María , Sánchez-Valle Raquel , Mollenhauer Brit , Ferrer Isidre , Zerr Inga , Llorens Franc 
Published: April 2021

AbstractTriggering receptor expressed on myeloid cells 2 (TREM2) is an innate immune cell surface receptor that regulates microglial function and is involved in the pathophysiology of several neurodegenerative diseases. Its soluble form (sTREM2) results from shedding of the TREM2 ectodomain. The role of TREM2 in prion diseases, a group of rapidly progressive dementias remains to be elucidated. In the present study, we analysed the expression of TREM2 and its main sheddase ADAM10 in the brain of sporadic Creutzfeldt-Jakob disease (sCJD) patients and evaluated the role of CSF and plasma sTREM2 as a potential diagnostic marker of prion disease. Our data indicate that, compared to controls, TREM2 is increased in sCJD patient brains at the mRNA and protein levels in a regional and subtype dependent fashion, and expressed in a subpopulation of microglia. In contrast, ADAM10 is increased at the protein, but not the mRNA level, with a restricted neuronal expression. Elevated CSF sTREM2 is found in sCJD, genetic CJD with mutations E200K and V210I in the prion protein gene (PRNP), and iatrogenic CJD, as compared to healthy controls (HC) (AUC = 0.78–0.90) and neurological controls (AUC = 0.73–0.85), while CSF sTREM2 is unchanged in fatal familial insomnia. sTREM2 in the CSF of cases with Alzheimer’s disease, and multiple sclerosis was not significantly altered in our series. CSF sTREM2 concentrations in sCJD are PRNP codon 129 and subtype-related, correlate with CSF 14-3-3 positivity, total-tau and YKL-40, and increase with disease progression. In plasma, sTREM2 is increased in sCJD compared with HC (AUC = 0.80), displaying positive correlations with plasma total-tau, neurofilament light, and YKL-40. We conclude that comparative study of TREM2 in brain and biological fluids of prion diseases reveals TREM2 to be altered in human prion diseases with a potential value in target engagement, patient stratification, and disease monitoring.
Aminopeptidase A contributes to biochemical, anatomical and cognitive defects in Alzheimer’s disease (AD) mouse model and is increased at early stage in sporadic AD brain
Authors: Valverde Audrey , Dunys Julie , Lorivel Thomas , Debayle Delphine , Gay Anne-Sophie , Lacas-Gervais Sandra , Roques Bernard. P. , Chami Mounia , Checler Frédéric 
Published: April 2021

AbstractOne of the main components of senile plaques in Alzheimer’s disease (AD)-affected brain is the Aβ peptide species harboring a pyroglutamate at position three pE3-Aβ. Several studies indicated that pE3-Aβ is toxic, prone to aggregation and serves as a seed of Aβ aggregation. The cyclisation of the glutamate residue is produced by glutaminyl cyclase, the pharmacological and genetic reductions of which significantly alleviate AD-related anatomical lesions and cognitive defects in mice models. The cyclisation of the glutamate in position 3 requires prior removal of the Aβ N-terminal aspartyl residue to allow subsequent biotransformation. The enzyme responsible for this rate-limiting catalytic step and its relevance as a putative trigger of AD pathology remained yet to be established. Here, we identify aminopeptidase A as the main exopeptidase involved in the N-terminal truncation of Aβ and document its key contribution to AD-related anatomical and behavioral defects. First, we show by mass spectrometry that human recombinant aminopeptidase A (APA) truncates synthetic Aβ1-40 to yield Aβ2-40. We demonstrate that the pharmacological blockade of APA with its selective inhibitor RB150 restores the density of mature spines and significantly reduced filopodia-like processes in hippocampal organotypic slices cultures virally transduced with the Swedish mutated Aβ-precursor protein (βAPP). Pharmacological reduction of APA activity and lowering of its expression by shRNA affect pE3-42Aβ- and Aβ1-42-positive plaques and expressions in 3xTg-AD mice brains. Further, we show that both APA inhibitors and shRNA partly alleviate learning and memory deficits observed in 3xTg-AD mice. Importantly, we demonstrate that, concomitantly to the occurrence of pE3-42Aβ-positive plaques, APA activity is augmented at early Braak stages in sporadic AD brains. Overall, our data indicate that APA is a key enzyme involved in Aβ N-terminal truncation and suggest the potential benefit of targeting this proteolytic activity to interfere with AD pathology.
Auditory and visual short-term memory: influence of material type, contour, and musical expertise
Authors: Talamini Francesca , Blain Salomé , Ginzburg Jérémie , Houix Olivier , Bouchet Patrick , Grassi Massimo , Tillmann Barbara , Caclin Anne 
Published: April 2021

AbstractShort-term memory has mostly been investigated with verbal or visuospatial stimuli and less so with other categories of stimuli. Moreover, the influence of sensory modality has been explored almost solely in the verbal domain. The present study compared visual and auditory short-term memory for different types of materials, aiming to understand whether sensory modality and material type can influence short-term memory performance. Furthermore, we aimed to assess if music expertise can modulate memory performance, as previous research has reported better auditory memory (and to some extent, visual memory), and better auditory contour recognition for musicians than non-musicians. To do so, we adapted the same recognition paradigm (delayed-matching to sample) across different types of stimuli. In each trial, participants (musicians and non-musicians) were presented with two sequences of events, separated by a silent delay, and had to indicate whether the two sequences were identical or different. The performance was compared for auditory and visual materials belonging to three different categories: (1) verbal (i.e., syllables); (2) nonverbal (i.e., that could not be easily denominated) with contour (based on loudness or luminance variations); and (3) nonverbal without contour (pink noise sequences or kanji letters sequences). Contour and no-contour conditions referred to whether the sequence can entail (or not) a contour (i.e., a pattern of up and down changes) based on non-pitch features. Results revealed a selective advantage of musicians for auditory no-contour stimuli and for contour stimuli (both visual and auditory), suggesting that musical expertise is associated with specific short-term memory advantages in domains close to the trained domain, also extending cross-modally when stimuli have contour information. Moreover, our results suggest a role of encoding strategies (i.e., how the material is represented mentally during the task) for short-term-memory performance.
Victimization by traditional bullying and cyberbullying and the combination of these among adolescents in 13 European and Asian countries
Authors: Chudal Roshan , Tiiri Elina , Brunstein Klomek Anat , Ong Say How , Fossum Sturla , Kaneko Hitoshi , Kolaitis Gerasimos , Lesinskiene Sigita , Li Liping , Huong Mai Nguyen , Praharaj Samir Kumar , Sillanmäki Lauri , Slobodskaya Helena R. , Srabstein Jorge C. , Wiguna Tjhin , Zamani Zahra , Sourander Andre ,   the Eurasian Child Mental Health Study (EACMHS) Group, Akhondzadeh Shahin , Fung Daniel S. S. , Giannakopoulos George , Grimland Meytal , Hamada Shoko , Heinonen Emmi , Ismail Raden Irawati , Jain Praveen A. , Kamath Avinash G. , Khong Jerrine Z. N. , Kyrrestad Henriette , Lempinen Lotta , Limawan Albert Prabowo , Mohseni Maryam , Najafi Ali , Ngoc Minh Thanh , Ogura Masayoshi , Peng Zhekuan , Rippinen Tatiana O. , Sekartini Rini , Semenova Nadezhda B. , Skokauskas Norbert , Tan Yi Ren , Triantafyllou Kalliopi , Zaravinos-Tsakos Phevous 
Published: April 2021

AbstractThere has been a lack of studies on bullying in non-western low-income and middle-income countries. This study reported the prevalence of traditional victimization, cybervictimization, and the combination of these, in 13 European and Asian countries, and explored how psychiatric symptoms were associated with victimization. The data for this cross-sectional, school-based study of 21,688 adolescents aged 13–15 were collected from 2011 to 2017. The main outcomes were traditional and cybervictimization obtained from student self-reports. The Strengths and Difficulties Questionnaire was used to assess psychiatric symptoms. Generalized estimating equation and logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). The mean prevalence of any victimization was 28.9%, of traditional victimization only, this was 17.7%, and for cybervictimization only this was 5.1%. Cybervictimization occurred both independently, and in combination with, traditional victimization. The mean prevalence of combined victimization was 6.1%. The mean proportion of those who were cyberbullied only among those who were either cyberbullied only or bullied both traditionally and in cyber was 45.1%. The rates of prevalence varied widely between countries. In the total sample, those who experienced combined victimization, reported the highest internalizing symptoms (girls, OR 1.25, 95% CI 1.22–1.29; boys, OR 1.29, 95% CI 1.25–1.33). The study findings suggest that anti-bullying interventions should include mental health components and target both traditional and cyberbullying. Due to the overlap between these, targeting bullying should primarily focus on how to reduce bullying behavior rather than just focusing on where bullying takes place.
Reference ranges for clinical electrophysiology of vision
Authors: Davis C. Quentin , Hamilton Ruth 
Published: April 2021

AbstractIntroductionEstablishing robust reference intervals for clinical procedures has received much attention from international clinical laboratories, with approved guidelines. Physiological measurement laboratories have given this topic less attention; however, most of the principles are transferable.MethodsHerein, we summarise those principles and expand them to cover bilateral measurements and one-tailed reference intervals, which are common issues for those interpreting clinical visual electrophysiology tests such as electroretinograms (ERGs), visual evoked potentials (VEPs) and electrooculograms (EOGs).ResultsThe gold standard process of establishing and defining reference intervals, which are adequately reliable, entails collecting data from a minimum of 120 suitable reference individuals for each partition (e.g. sex, age) and defining limits with nonparametric methods. Parametric techniques may be used under some conditions. A brief outline of methods for defining reference limits from patient data (indirect sampling) is given. Reference intervals established elsewhere, or with older protocols, can be transferred or verified with as few as 40 and 20 suitable reference individuals, respectively. Consideration is given to small numbers of reference subjects, interpretation of serial measurements using subject-based reference values, multidimensional reference regions and age-dependent reference values. Bilateral measurements, despite their correlation, can be used to improve reference intervals although additional care is required in computing the confidence in the reference interval or the reference interval itself when bilateral measurements are only available from some of subjects.DiscussionGood quality reference limits minimise false-positive and false-negative results, thereby maximising the clinical utility and patient benefit. Quality indicators include using appropriately sized reference datasets with appropriate numerical handling for reporting; using subject-based reference limits where appropriate; and limiting tests for each patient to only those which are clinically indicated, independent and highly discriminating.
The EU Child Cohort Network’s core data: establishing a set of findable, accessible, interoperable and re-usable (FAIR) variables
Authors:   for the LifeCycle Project Group, Pinot de Moira Angela , Haakma Sido , Strandberg-Larsen Katrine , van Enckevort Esther , Kooijman Marjolein , Cadman Tim , Cardol Marloes , Corpeleijn Eva , Crozier Sarah , Duijts Liesbeth , Elhakeem Ahmed , Eriksson Johan G. , Felix Janine F. , Fernández-Barrés Sílvia , Foong Rachel E. , Forhan Anne , Grote Veit , Guerlich Kathrin , Heude Barbara , Huang Rae-Chi , Järvelin Marjo-Riitta , Jørgensen Anne Cathrine , Mikkola Tuija M. , Nader Johanna L. T. , Pedersen Marie , Popovic Maja , Rautio Nina , Richiardi Lorenzo , Ronkainen Justiina , Roumeliotaki Theano , Salika Theodosia , Sebert Sylvain , Vinther Johan L. , Voerman Ellis , Vrijheid Martine , Wright John , Yang Tiffany C. , Zariouh Faryal , Charles Marie-Aline , Inskip Hazel , Jaddoe Vincent W. V. , Swertz Morris A. , Nybo Andersen Anne-Marie 
Published: April 2021

AbstractThe Horizon2020 LifeCycle Project is a cross-cohort collaboration which brings together data from multiple birth cohorts from across Europe and Australia to facilitate studies on the influence of early-life exposures on later health outcomes. A major product of this collaboration has been the establishment of a FAIR (findable, accessible, interoperable and reusable) data resource known as the EU Child Cohort Network. Here we focus on the EU Child Cohort Network’s core variables. These are a set of basic variables, derivable by the majority of participating cohorts and frequently used as covariates or exposures in lifecourse research. First, we describe the process by which the list of core variables was established. Second, we explain the protocol according to which these variables were harmonised in order to make them interoperable. Third, we describe the catalogue developed to ensure that the network’s data are findable and reusable. Finally, we describe the core data, including the proportion of variables harmonised by each cohort and the number of children for whom harmonised core data are available. EU Child Cohort Network data will be analysed using a federated analysis platform, removing the need to physically transfer data and thus making the data more accessible to researchers. The network will add value to participating cohorts by increasing statistical power and exposure heterogeneity, as well as facilitating cross-cohort comparisons, cross-validation and replication. Our aim is to motivate other cohorts to join the network and encourage the use of the EU Child Cohort Network by the wider research community.
Transmission of SARS-CoV-2 before and after symptom onset: impact of nonpharmaceutical interventions in China
Authors: Bushman Mary , Worby Colin , Chang Hsiao-Han , Kraemer Moritz U. G. , Hanage William P. 
Published: April 2021

AbstractNonpharmaceutical interventions, such as contact tracing and quarantine, have been the primary means of controlling the spread of SARS-CoV-2; however, it remains uncertain which interventions are most effective at reducing transmission at the population level. Using serial interval data from before and after the rollout of nonpharmaceutical interventions in China, we estimate that the relative frequency of presymptomatic transmission increased from 34% before the rollout to 71% afterward. The shift toward earlier transmission indicates a disproportionate reduction in transmission post-symptom onset. We estimate that, following the rollout of nonpharmaceutical interventions, transmission post-symptom onset was reduced by 82% whereas presymptomatic transmission decreased by only 16%. The observation that only one-third of transmission was presymptomatic at baseline, combined with the finding that NPIs reduced presymptomatic transmission by less than 20%, suggests that the overall impact of NPIs was driven in large part by reductions in transmission following symptom onset. This implies that interventions which limit opportunities for transmission in the later stages of infection, such as contact tracing and isolation, are particularly important for control of SARS-CoV-2. Interventions which specifically reduce opportunities for presymptomatic transmission, such as quarantine of asymptomatic contacts, are likely to have smaller, but non-negligible, effects on overall transmission.