bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential Translation Activity Analysis Using Bioorthogonal Noncanonical Amino Acid Tagging (BONCAT) in Archaea
Authors: Kern Michael , Ferreira-Cerca Sébastien
Published: July 2022

The study of protein production and degradation in a quantitative and time-dependent manner is a major challenge to better understand cellular physiological response. Among available technologies bioorthogonal noncanonical amino acid tagging (BONCAT) is an efficient approach allowing for time-dependent labeling of proteins through the incorporation of chemically reactive noncanonical amino acids like l-azidohomoalanine (L-AHA). The azide-containing amino-acid derivative enables a highly efficient and specific reaction termed click chemistry, whereby the azide group of the L-AHA reacts with a reactive alkyne derivate, like dibenzocyclooctyne (DBCO) derivatives, using strain-promoted alkyne–azide cycloaddition (SPAAC). Moreover, available DBCO containing reagents are versatile and can be coupled to fluorophore (e.g., Cy7) or affinity tag (e.g., biotin) derivatives, for easy visualization and affinity purification, respectively.

Here, we describe a step-by-step BONCAT protocol optimized for the model archaeon Haloferax volcanii, but which is also suitable to harness other biological systems. Finally, we also describe examples of downstream visualization, affinity purification of L-AHA-labeled proteins and differential expression analysis.

In conclusion, the following BONCAT protocol expands the available toolkit to explore proteostasis using time-resolved semiquantitative proteomic analysis in archaea.
Specialization of RNA Polymerase I in Comparison to Other Nuclear RNA Polymerases of Saccharomyces cerevisiae
Authors: Merkl Philipp E. , Schächner Christopher , Pilsl Michael , Schwank Katrin , Schmid Catharina , Längst Gernot , Milkereit Philipp , Griesenbeck Joachim , Tschochner Herbert
Published: July 2022

In archaea and bacteria the major classes of RNAs are synthesized by one DNA-dependent RNA polymerase (RNAP). In contrast, most eukaryotes have three highly specialized RNAPs to transcribe the nuclear genome. RNAP I synthesizes almost exclusively ribosomal (r)RNA, RNAP II synthesizes mRNA as well as many noncoding RNAs involved in RNA processing or RNA silencing pathways and RNAP III synthesizes mainly tRNA and 5S rRNA. This review discusses functional differences of the three nuclear core RNAPs in the yeast S. cerevisiae with a particular focus on RNAP I transcription of nucleolar ribosomal (r)DNA chromatin.
Chemical Modifications of Ribosomal RNA
Authors: Sharma Sunny , Entian Karl-Dieter
Published: July 2022

Cellular RNAs in all three kingdoms of life are modified with diverse chemical modifications. These chemical modifications expand the topological repertoire of RNAs, and fine-tune their functions. Ribosomal RNA in yeast contains more than 100 chemically modified residues in the functionally crucial and evolutionary conserved regions. The chemical modifications in the rRNA are of three types—methylation of the ribose sugars at the C2-positionAbstract (Nm), isomerization of uridines to pseudouridines (Ψ), and base modifications such as (methylation (mN), acetylation (acN), and aminocarboxypropylation (acpN)). The modifications profile of the yeast rRNA has been recently completed, providing an excellent platform to analyze the function of these modifications in RNA metabolism and in cellular physiology. Remarkably, majority of the rRNA modifications and the enzymatic machineries discovered in yeast are highly conserved in eukaryotes including humans. Mutations in factors involved in rRNA modification are linked to several rare severe human diseases (e.g., X-linked Dyskeratosis congenita, the Bowen–Conradi syndrome and the William–Beuren disease). In this chapter, we summarize all rRNA modifications and the corresponding enzymatic machineries of the budding yeast.
Race, Eugenics, and the Holocaust
Authors: Anomaly Jonathan
Published: July 2022

This chapter will focus on how the Holocaust shaped the concepts of race and eugenics in bioethics. I will begin with a brief account of how these terms were used before the Second World War, and then discuss how the Nazi eugenics programs and the Holocaust altered how scholars think about race and eugenics. In particular, I will discuss the 1948 United Nations Declaration of Human Rights and 1950 Statement on Race, which signaled a change in how race and eugenics would be used in the second half of the twentieth century. Finally, I will consider how liberal eugenics in contemporary bioethics differs from older forms of eugenics, and how newer views about human populations (as genetic clusters) differ from older views of race. In doing so, I will explore how the Holocaust shaped modern taboos related to human genetics research.
Inclusive rates from smeared spectral densities in the two-dimensional O(3) non-linear σ-model
Authors: Bulava John , Hansen Maxwell T. , Hansen Michael W. , Patella Agostino , Tantalo Nazario
Published: July 2022

Abstract

This work employs the spectral reconstruction approach of ref. [1] to determine an inclusive rate in the 1 + 1 dimensional O(3) non-linear σ-model, analogous to the QCD part of e+e− → hadrons. The Euclidean two-point correlation function of the conserved current j is computed using Monte Carlo lattice field theory simulations for a variety of spacetime volumes and lattice spacings. The spectral density of this correlator is related to the inclusive rate for j → X in which all final states produced by the external current are summed. The ill-posed inverse problem of determining the spectral density from the correlation function is made tractable through the determination of smeared spectral densities in which the desired density is convolved with a set of known smearing kernels of finite width ϵ. The smooth energy dependence of the underlying spectral density enables a controlled ϵ → 0 extrapolation in the inelastic region, yielding the real-time inclusive rate without reference to individual finite-volume energies or matrix elements. Systematic uncertainties due to cutoff effects and residual finite-volume effects are estimated and taken into account in the final error budget. After taking the continuum limit, the results are consistent with the known analytic rate to within the combined statistical and systematic errors. Above energies where 20-particle states contribute, the overall precision is sufficient to discern the four-particle contribution to the spectral density.
Mental health of young informal carers: a systematic review
Authors: Fleitas Alfonzo Ludmila , Singh Ankur , Disney George , Ervin Jennifer , King Tania
Published: July 2022

Purpose

This systematic review aims to assess and evaluate quantitative evidence on the association between informal caregiving and mental health in young people.

Methods

This review was registered in PROSPERO (CRD42021251666). We conducted our search in the following four databases: Medline (PubMed and OVID), EMBASE, PsycInfo and Web of Science. The last search was performed on the 17th of March of 2021. Quantitative studies that focused on carers aged 25 years or less and compared the mental health status of carers and non-carers were eligible for inclusion. Two reviewers independently assessed articles for eligibility and performed the quality assessment using the Risk of Bias tool in Non-Randomised Studies of Exposures (ROBINS-E).

Results

We identified a total of ten eligible articles. Mental health outcomes included depression, anxiety and other mental or emotional problems. Nine out of the ten studies showed that being a young carer was consistently associated with poor mental health. However, the overall quality of evidence was low, and longitudinal data were limited to three articles. The primary sources of bias were confounding and outcome measurement.

Conclusion

Young carers experience poorer mental health outcomes than their non-caring peers. However, we identified an overall lack of quantitative evidence of high methodological rigour. To establish if young caring leads to poor mental health, future research should focus on addressing the identified methodological limitations and understanding the mechanisms explaining these associations. Addressing these gaps can better inform the allocation of appropriate support and resources to optimise the mental health of young carers.
Gerinnungshemmung in Schwangerschaft und Wochenbett
Authors: Studt Jan-Dirk , Trinchero Alice
Published: July 2022

Schwangerschaft und Wochenbett gehen mit einem erhöhten Risiko venöser Thromboembolien (VTE) einher. Dieses Risiko besteht ab dem ersten Trimenon und ist in der frühen Wochenbettzeit am höchsten. In die Bewertung des mütterlichen VTE-Risikos und die Indikationsstellung zur VTE-Prophylaxe gehen anamnestische und klinische Informationen sowie der Beitrag hereditärer und erworbener Thrombophilien ein. Ist eine VTE-Prophylaxe während der Schwangerschaft indiziert, so wird diese frühzeitig im ersten Trimenon begonnen und bis 6 Wochen postpartal fortgesetzt. Die Therapie akuter VTE während der Schwangerschaft sollte mindestens 3 Monate lang und bis 6 Wochen postpartal andauern. Standardpräparat zur Prophylaxe und Therapie schwangerschaftsassoziierter VTE ist niedermolekulares Heparin (NMH).
Periprothetischer Infekt nach Hüftprothesenimplantation
Authors: Dietz J. , Zeidler Anne , Wienke Andreas , Zeh Alexander , Delank Karl-Stefan , Wohlrab David
Published: July 2022

Hintergrund

Die periprothetische Infektion zählt zu den schwerwiegendsten Komplikationen in der Primärendoprothetik. Die in der aktuellen Literatur angegebenen Infektionsraten reichen von 0,36 bis 2,23 %.

Fragestellung

Ziel dieser retrospektiven Fall-Kontroll-Studie war die Ermittlung von präoperativen Risikofaktoren für das Auftreten eines periprothetischen Frühinfektes nach primärer Hüftprothesenimplantation.

Material und Methoden

Es wurden die Einflüsse von Patientenalter, Geschlecht, Body-Mass-Index (BMI), C‑reaktivem Protein, präoperativen Leukozytenwerten und Morbiditätsgrad (American Society of Anaesthesiologists Score) auf das Auftreten einer periprothetischen Frühinfektion am Hüftgelenk geprüft sowie deren Zusammenhang untersucht.

Ergebnisse

Von den 1383 nachuntersuchten Patienten wurde bei 25 Patienten ein Frühinfekt diagnostiziert. Mit Steigerung des BMI um 1 kg/m2 steigt das Risiko eines periprothetischen Frühinfektes um 12,1 % (p < 0,001). Zudem wird mittels „receiver operating characteristic“(ROC)-Kurve ein BMI ≥ 29 kg/m2 als signifikanter Cut-off für die erhöhte Wahrscheinlichkeit einer periprothetischen Hüftgelenkinfektion ermittelt.

Mittels ROC-Kurve kann ein präoperativer CrP-Wert > 5 mg/l als Cut-off-Wert für ein erhöhtes Risiko für eine Frühinfektion validiert werden. Mittels binär logistischer Regression wurde statistisch kein Einfluss des CrP > 5 mg/l auf die Entstehung eines Frühinfektes nachgewiesen (p = 0,065).

Diskussion

Patienten mit einem BMI ≥ 29 kg/m2 sollten auf das erhöhte Risiko einer periprothetischen Frühinfektion nach Hüftprothesenimplantation hingewiesen und es sollte eine Risikoabschätzung durchgeführt werden. Weiterhin sollte die Bestimmung des präoperativen CrP-Wertes als Standard gelten.
A phase I/II study of 10-min dosing of bendamustine hydrochloride (rapid infusion formulation) in patients with previously untreated indolent B-cell non-Hodgkin lymphoma, mantle cell lymphoma, or relapsed/refractory diffuse large B-cell lymphoma in Japan
Authors: Ishizawa Kenichi , Yokoyama Masahiro , Kato Harumi , Yamamoto Kazuhito , Makita Masanori , Ando Kiyoshi , Ueda Yasunori , Tachikawa Yoshimichi , Suehiro Youko , Kurosawa Mitsutoshi , Kameoka Yoshihiro , Nagai Hirokazu , Uoshima Nobuhiko , Ishikawa Takayuki , Hidaka Michihiro , Ito Yoshikiyo , Utsunomiya Atae , Fukushima Koji , Ogura Michinori
Published: July 2022

Purpose

This phase I/II clinical study was conducted to examine the safety, tolerability, pharmacokinetics, and efficacy of 10-min dosing of bendamustine in patients with previously untreated indolent B-cell non-Hodgkin lymphoma (iNHL) or mantle cell lymphoma (MCL) (Group 1) and patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) (Group 2).

Methods

Rituximab 375 mg/m2 was administered intravenously every 28 days to Group 1 patients on day 1 and every 21 days to Group 2 patients on day 1. Bendamustine 90 mg/m2/day was administered to the former on days 1 and 2; bendamustine 120 mg/m2/day was administered to the latter on days 2 and 3. Each regimen was delivered up to six cycles for both groups. The primary endpoints were safety and tolerability in Groups 1 and 2, respectively.

Results

Among 37 enrolled patients, safety was assessed in 36. In Group 1 (n = 30), 27 patients (90%) had follicular lymphoma. Adverse events (AEs) were observed in all 30 patients in Group 1. Dose-limiting toxicities were observed in two of six patients in Group 2. Common AEs included lymphocyte count decreased (86.7%, 100%). In Group 1, overall response and complete response rates were 93.1% (95% confidence interval [CI] 77.2–99.2%) and 75.9% (95% CI 56.5–89.7%), respectively. The Cmax and AUC of bendamustine tended to be higher in Group 2 than in Group 1.

Conclusions

This study showed that bendamustine is safe, well-tolerated and effective for patients with previously untreated iNHL, MCL or rrDLBCL. Pharmacokinetic data were equivalent to those obtained outside of Japan.

Registration numbers

Registration NCT03900377; registered April 3, 2019.
Modelling success after perinatal post-haemorrhagic hydrocephalus: a single-centre study
Authors: Kayhanian Saeed , Funnell Jonathan Perry , Zühlsdorff Katharina , Jalloh Ibrahim
Published: July 2022

Introduction

Post-haemorrhagic hydrocephalus is common amongst premature infants and one of the leading indications for paediatric cerebrospinal fluid (CSF) diversion. Permanent CSF diversion is often delayed until the infant is older but there is no clear consensus on the timing for this. The outcomes for permanent shunting in this patient group are poor, with higher rates of failure and infection compared to other aetiologies of hydrocephalus.

Methods

We conduct a single-centre retrospective review of infants with post-haemorrhagic hydrocephalus requiring a permanent shunt insertion over a 5-year period. Demographic and clinical data from time of shunt insertion were collected and used to generate generalised linear models (GLMs) to predict shunt success at 12 months after insertion.

Results

Twenty-six infants underwent permanent shunting in this period for post-haemorrhagic hydrocephalus, with 10 suffering shunt failure within the first 12 months. The best-performing GLM was able to predict shunt success with a sensitivity of 1 and specificity of 0.90, with head circumference, weight, and corrected age at the time of shunt insertion being the most significantly associated variables for shunt success in this model.

Conclusion

Our proof-of-principle study suggests that highly accurate prediction of shunt success for infants with post-haemorrhagic hydrocephalus is possible using routinely available clinical variables. Further work is required to test this model in larger cohorts and validate whether pre-operative use can improve outcomes for this patient group.
Acute symptomatic seizures and hippocampal sclerosis: the major contributor for post-stroke epilepsy?
Authors: Stancu Patrick , De Stefano Pia , Vargas Maria , Menetre Eric , Carrera Emmanuel , Kleinschmidt Andreas , Seeck Margitta
Published: July 2022

Objective

Hippocampal sclerosis (HS) is a prominent biomarker of epilepsy. If acquired later in life, it usually occurs in the context of degenerative or acute inflammatory-infectious disease. Conversely, acute symptomatic seizures (ASS) are considered a risk factor for developing post-stroke epilepsy, but other factors remain unrecognized. Here, we hypothesize that silent hippocampal injury contributes to the development of post-stroke epilepsy.

Methods

We performed a retrospective observational study of patients hospitalized between 1/2007 and 12/2018 with an acute stroke in the Stroke Center of the Geneva University Hospital. Patients were included if they had a documented normal hippocampal complex at onset and a control MRI at ≥ 2 year interval without new lesion in the meantime.

Results

162 patients fulfilled our inclusion criteria. ASS during the first week (p < 0.0001) and epileptiform abnormalities in electroencephalography (EEG; p = 0.02) were more frequently associated with the development of epilepsy. Hemorrhagic stroke was strongly associated to both ASS and future focal epilepsy (p = 0.00097). Three patients (1.8%) developed hippocampal sclerosis ipsilateral to the cerebrovascular event between 2 and 5 years, all with ASS and hemorrhagic stroke.

Interpretation

ASS and epileptiform EEG abnormalities are strong predictors of post-stroke epilepsy. HS develops in a minority of patients after hemorrhagic lesions, leading to focal epilepsy. Prospective studies are required, including follow-up with EEG and if characterized by epileptiform discharges, with MRI, to determine the true frequency of HS and to better understand predictors of post-stroke epilepsy (AAS, stroke type, and HS), and their impact on stroke recovery.
Exploring the long-term colonisation and persistence of probiotic-prophylaxis species on the gut microbiome of preterm infants: a pilot study
Authors: Westaway Jacob A. F. , Huerlimann Roger , Kandasamy Yoga , Miller Catherine M. , Norton Robert , Watson David , Infante-Vilamil Sandra , Rudd Donna
Published: July 2022

Preterm infants suffer from a higher incidence of acute diseases such as necrotising enterocolitis and sepsis. This risk can be mitigated through probiotic prophylaxis during admission. This reduction in risk is likely the result of acute modulation of the gut microbiome induced by probiotic species, which has been observed to occur up until discharge. We aimed to determine if this modulation, and the associated probiotic species, persisted beyond discharge. We conducted both a cross-sectional analysis (n = 18), at ~ 18 months of age, and a longitudinal analysis (n = 6), from admission to 18 months of the gut microbiome of preterm infants using both shotgun metagenomics and 16S rRNA profiling respectively. The 16S amplicon sequencing revealed that the microbial composition of the probiotic-supplemented infants changed dramatically over time, stabilising at discharge. However, species from the probiotic Infloran®, as well as positive modulatory effects previously associated with supplementation, do not appear to persist beyond discharge and once prophylaxis has stopped.

   Conclusions: Although differences exist between supplemented and non-supplemented groups, the implications of these differences remain unclear. Additionally, despite a lack of long-term colonisation, the presence of probiotics during early neonatal life may still have modulatory effects on the microbiome assembly and immune system training.What is Known:• Evidence suggests modulation of the microbiome occurs during probiotic prophylaxis, which may support key taxa that exert positive immunological benefits.• Some evidence suggests that this modulation can persist post-prophylaxis.What is New:• We present support for long-term modulation in association with probiotic prophylaxis in a cohort of infants from North Queensland Australia.• We also observed limited persistence of the probiotic species post-discharge.
Der technische Beckenpass – eine hydraulische und biotische Gegenüberstellung mit konventionellen beckenartigen Fischaufstiegshilfen
Authors: Seidl Georg , Haslwanter Markus , Schneider Josef
Published: July 2022

Beckenartige Fischaufstiegshilfen lassen sich auf Basis ihrer Charakteristik grundsätzlich in Schlitzpässe mit einheitlicher Sohlneigung und Beckenpässe, welche durch Anrampung im Übergang errichtet werden, unterteilen. Dabei gelten der Vertical-Slot-Schlitzpass und der naturnahe Beckenpass als beprobte Bautypen. Im Zuge der Umsetzung der Wasserrahmenrichtlinie wurden zahlreiche Beckenpässe, entgegen der naturnahen Variante, welche sich durch die Gestaltung der Übergänge mit Wasserbausteinen auszeichnet, mit technischen, betonierten Übergängen errichtet. Da technische Beckenpässe baulich-wirtschaftliche Vorteile gegenüber der naturnahen Variante bieten sowie mit einer exakten Bemessungs- bzw. Errichtungsmöglichkeit gegenüber dem naturnahen Beckenpass punkten und daher vermehrt zur Ausführung kommen, widmet sich der vorliegende Beitrag der hydraulischen und biotischen Analyse dieser Variante.
Dating of polyhalite: a difficult 40Ar/39Ar dating tool of diagenetic to very low-grade metamorphic processes
Authors: Leitner C. , Neubauer F. , Genser J. , Bernroider M.
Published: July 2022

Halite already deforms at surface temperatures. A valuable universal dating tool to constrain the timing of sedimentary, diagenetic, or deformational structures is still missing. The evaporite mineral polyhalite can be dated by the40Ar/39Ar method. On the example of the extremely deformed halite deposits of the Eastern Alps, polyhalite was tested to date early diagenetic stages of the deposits. The sedimentological investigation of the present study indicates that some of the macrostructures of polyhalite had a syn-depositional origin during the late Permian. It is supposed that polyhalite originated during reflux of brines. All samples selected for age dating represent characteristic microfabric types of euhedral to subhedral polyhalite crystals. Intact macro- and non-recrystallized looking microstructures of polyhalite can be expected to give plateau ages. However, nearly all measurements produced overdispersed data that do not define an age. The oldest age steps thus represent only minimum ages. A closer look revealed grain boundary migration, subgrain rotation recrystallization, twinning, and fluid-supported grain size increase. These recovery processes obscured the original ages and/or reflect the origin of new polyhalite in place of the original individuals. Based on these microstructures, the age data are supposed to reflect the circulation of aqueous fluids. Just extremely careful separation of individual crystals or in situ age dating under the microscope will be successful in dating polyhalite. Nevertheless, polyhalite can potentially serve to date deformational events of halite deposits due to its easy recrystallization property.
Restore politics in societal debates on new genomic techniques
Authors: Poort Lonneke M. , Swart Jac. A. A. , Mampuys Ruth , Waarlo Arend J. , Struik Paul C. , Hanssen Lucien
Published: July 2022

End of April 2021, the European Commission published its study on New Genomic Techniques (NGTs). The study involved a consultation of Member States and stakeholders. This study reveals a split on whether current legislation should be maintained or adapted to take account of scientific progress and the risk level of NGT products. This split was predictable. New technological developments challenge both ethical viewpoints and regulatory institutions; and contribute to the growing divide between science and society that value ‘technological innovations’ differently. Such controversies are often characterized as ‘unstructured’ because of nearly unbridgeable positions on entangled scientific and value-laden issues. Initiatives for stakeholder involvement, such as consultation or participation, often focus on reaching a ‘shared vision’ without exploring the diverse societal concerns and values behind these positions. To resolve the EU stalemate in NGT regulation, we advocate to bring back politics in the EU decision-making process instead of hiding it under the veil of science, the need for regulatory change and public support. A more productive and justified use of genuine stakeholder participation is possible, if participants and deliberation design meet the criteria of what we call participation ethics. Drawing from our applied experience exploring the ethics of genetic modification, we believe that this approach can lead to more robust political decision-making and restore societal confidence in the governance of contested issues such as NGTs.
Dyadic analysis for multi-block data in sport surveys analytics
Authors: Iannario Maria , Romano Rosaria , Vistocco Domenico
Published: July 2022

Analyzing sports data has become a challenging issue as it involves not standard data structures coming from several sources and with different formats, being often high dimensional and complex. This paper deals with a dyadic structure (athletes/coaches), characterized by a large number of manifest and latent variables. Data were collected in a survey administered within a joint project of University of Naples Federico II and Italian Swimmer Federation. The survey gathers information about psychosocial aspects influencing swimmers’ performance. The paper introduces a data processing method for dyadic data by presenting an alternative approach with respect to the current used models and provides an analysis of psychological factors affecting the actor/partner interdependence by means of a quantile regression. The obtained results could be an asset to design strategies and actions both for coaches and swimmers establishing an original use of statistical methods for analysing athletes psychological behaviour.
Flux–Gradient Relationships Below 2 m Over a Flat Site in Complex Terrain
Authors: Martí B. , Martínez-Villagrasa D. , Cuxart J.
Published: July 2022

The surface–atmosphere turbulent exchange fluxes are experimentally determined using the eddy-covariance method. Their estimation using profiles of the variables of interest is a less costly alternative, although restricted to certain ranges of stability and assumed to hold for relatively flat and homogeneous terrain. It relays usually on the prescription of the roughness lengths for momentum, heat and matter, the latter two being adjustable parameters with unclear physical significance. The relations are derived with data from screen level to a few tens of metres upward. The application of these expressions using data only at one level in the surface layer implies assuming zero wind speed and the land surface temperature at their respective roughness lengths. The latter is a quantity that experimentally can only be determined radiatively with a substantial uncertainty. In this work the flux-profile relationships for momentum and sensible heat are assessed over a flat site in moderately inhomogeneous complex terrain in the southern pre-Pyrenees, using data between 2 m and the surface. The main findings are that (i) the classical expressions hold in the daytime for most of the dataset, (ii) the iterative estimations using the Obukhov length and the direct ones using the bulk Richardson number provide very similar results, (iii) using a second observation of temperature avoids a radiometric measure of land surface temperature and the prescription of a thermal roughness length value, (iv) the estimations over wet terrain with high irradiance depart largely from observations.
3D cell cultures, as a surrogate for animal models, enhance the diagnostic value of preclinical in vitro investigations by adding information on the tumour microenvironment: a comparative study of new dual-mode HDAC inhibitors
Authors: Bär Sofia I. , Biersack Bernhard , Schobert Rainer
Published: July 2022

Anchorage-independent 3D-cultures of multicellular tumour spheroids (MCTS) and in vitro microtumours of cancer cells can provide upfront information on the effects of anticancer drug candidates, tantamount to that obtained from animal xenograft studies. Unlike 2D cancer cell cultures, 3D-models take into account the influence of the tumour microenvironment and the location dependence of drug effects and accumulation. We exemplified this by comparison of the effects of two new dual-mode anticancer agents, Troxbam and Troxham, and their monomodal congeners SAHA (suberoylanilide hydroxamic acid) and CA-4 (combretastatin A-4). We assessed the growth of MCTS of HCT116wt human colon carcinoma cells exposed to these compounds, as well as the spatial distribution of dead HCT116wt cells in these MCTS. Also, fluorescence imaging of live and fixed MCTS was used to assess the type of cellular death induced by test compounds. Furthermore, an innovative perfusion bioreactor system was used to grow microtumours in the presence or absence of test compounds. Both new investigational compounds led to significant reductions of the size of such MCTS and also of corresponding in vitro microtumours by inducing caspase-9 dependent apoptosis and elevated levels of reactive oxygen species. 3D multicellular tumour spheroids are easy to grow and employ for compound tests in the familiar well-plate set-up. Together with 3D microtumours grown at scaffolds in continuously perfused bioreactors they allow to study, early on in the course of drug evaluations, the communication of tumour cells with their microenvironment to an extent hitherto available only in animal experiments.
Digital technologies: students’ expectations and experiences during their transition from high school to university
Authors: Keane Therese , Linden Tanya , Hernandez-Martinez Paul , Molnar Andreea , Blicblau Aaron
Published: July 2022

University students’ expectations of digital technologies in their studies are greatly influenced by their previous exposure both within the secondary school classroom and in their private lives. These expectations often play a powerful role in their approaches and learning strategies in their first-year university classes. In this work, we investigated students’ expectations and utilisation of digital technologies in their transition from high school to tertiary studies. A survey encompassing the Expectancy-Disconfirmation Paradigm was conducted amongst second year students across the university. The results showed students expected to use advanced IT technologies and equipment at university. The high expectations were similar regardless of demographic parameters, such as gender, school type or field of studies. The findings also indicated that most students perceived little disconnection between the technology they used in high school and that of university. The majority of students seemed satisfied and even positively surprised by the use of technology in their university courses.
Technology Adoption and Early Network Infrastructure Provision in the Market for Electric Vehicles
Authors: van Dijk Jeremy , Delacrétaz Nathan , Lanz Bruno
Published: July 2022

We document non-linear stock effects in the relationship linking emerging technology adoption and network infrastructure increments. We exploit 2010–2017 data covering nascent to mature electric vehicle (EV) markets across 422 Norwegian municipalities together with two complementary identification strategies: control function regressions of EV sales on flexible polynomials in the stock of charging stations and charging points, and synthetic control methods to quantify the impact of initial infrastructure provision in municipalities that previously had none. Our results are consistent with indirect network effects and the behavioral bias called “range anxiety,” and support policies targeting early infrastructure provision to incentivize EV adoption.
Probabilities and Certainties Within a Causally Symmetric Model
Authors: Sutherland Roderick I.
Published: July 2022

This paper is concerned with the causally symmetric version of the familiar de Broglie–Bohm interpretation, this version allowing the spacelike nonlocality and the configuration space ontology of the original model to be avoided via the addition of retrocausality. Two different features of this alternative formulation are considered here. With regard to probabilities, it is shown that the model provides a derivation of the Born rule identical to that in Bohm’s original formulation. This derivation holds just as well for a many-particle, entangled state as for a single particle. With regard to “certainties”, the description of a particle’s spin is examined within the model and it is seen that a statistical description is no longer necessary once final boundary conditions are specified in addition to the usual initial state, with the particle then possessing a definite (but hidden) value for every spin component at intermediate times. These values are consistent with being the components of a single, underlying spin vector. The case of a two-particle entangled spin state is also examined and it is found that, due to the retrocausal aspect, each particle possesses its own definite spin during the entanglement, independent of the other particle. In formulating this picture, it is demonstrated how such a realistic model can preserve Lorentz invariance in the face of Bell’s theorem and avoid the need for a preferred reference frame.
‘Living at work’: COVID-19, remote-working and the spatio-relational reorganisation of professional services in UK universities
Authors: Watermeyer Richard , Knight Cathryn , Crick Tom , Borras Mar
Published: July 2022

The COVID-19 pandemic has been the source of large-scale disruption to the work practices of university staff, across the UK and globally. This article reports the experiences of n = 4731 professional services staff (PSS) working in UK universities and their experiences of pandemic-related work disruption. It specifically focuses on a transition to remote-working as a consequence of social restrictions and campus closures, presenting both quantitative and qualitative findings that speak to the various spatio-relational impacts of PSS working at distance from university campuses. These survey findings contribute to a new narrative of work organisation in higher education which addresses the potential of remote-working as a means for boundary crossing, social connectedness and trust relationships in universities in the immediate context and strongly anticipated post-pandemic future.
Null Function of Npr1 Disturbs Immune Response in Colonic Inflammation During Early Postnatal Stage
Authors: Long Changkun , Liu Hongfei , Zhan Wenxing , Chen Liping , Wu Andong , Yang Lin , Chen Shenghan
Published: July 2022

Abstract

Natriuretic peptide receptor 1 (NPR1) is conventionally known as a regulator of vascular homeostasis. Here, we generated an Npr1 knockout mouse model with CRISPR/Cas9 technology and found that homozygous mice (Npr1−/−) exhibited weight loss and poor survival rate during early postnatal stage. Careful examination revealed unexpectedly that Npr1−/− mice developed colitis characterized by shortened colon, evident colonic mucosal damage, increased histopathological score, and higher colonic expression of proinflammatory cytokines interleukin-1B (IL1B) and -6 (IL6). RNA-sequencing analysis revealed that differentially expressed genes were prominently enriched in the biological pathways related to immune response in both spleen and colon of Npr1−/− mice. Cytofluorimetric analysis demonstrated that leukocytes in the spleen were significantly increased, particularly, the populations of neutrophil and CD3+ T cell were elevated but CD4+ T cells were decreased in Npr1−/− mice. Administration of 8-Br-cGMP, a downstream activator of NPR1, restored these immune-cell populations disturbed in Npr1−/− mice and lessened the colitis-related phenotypes. To validate the involvement of Npr1 in colitis, we examined another mouse model induced by dextran sodium sulfate (DSS) and found a decreased Npr1 expression and shifted immune-cell populations as well. Importantly, 8-Br-cGMP treatment exhibited a similar effect in the restoration of immune-cell populations and attenuation of colonic inflammation in DSS mice. Our data indicate that loss of Npr1 possibly interrupts immune response, which is critical to the pathogenesis of colitis in the early life.
Tetrahydrocannabinol and cannabidiol medicines for chronic pain and mental health conditions
Authors: Henson Jeremy D. , Vitetta Luis , Hall Sean
Published: July 2022

Combination tetrahydrocannabinol (THC)/cannabidiol (CBD) medicines or CBD-only medicines are prospective treatments for chronic pain, stress, anxiety, depression, and insomnia. THC and CBD increase signaling from cannabinoid receptors, which reduces synaptic transmission in parts of the central and peripheral nervous systems and reduces the secretion of inflammatory factors from immune and glial cells. The overall effect of adding CBD to THC medicines is to enhance the analgesic effect but counteract some of the adverse effects. There is substantial evidence for the effectiveness of THC/CBD combination medicines for chronic pain, especially neuropathic and nociplastic pain or pain with an inflammatory component. For CBD-only medication, there is substantial evidence for stress, moderate evidence for anxiety and insomnia, and minimal evidence for depression and pain. THC/CBD combination medicines have a good tolerability and safety profile relative to opioid analgesics and have negligible dependence and abuse potential; however, should be avoided in patients predisposed to depression, psychosis and suicide as these conditions appear to be exacerbated. Non-serious adverse events are usually dose-proportional, subject to tachyphylaxis and are rarely dose limiting when patients are commenced on a low dose with gradual up-titration. THC and CBD inhibit several Phase I and II metabolism enzymes, which increases the exposure to a wide range of drugs and appropriate care needs to be taken. Low-dose CBD that appears effective for chronic pain and mental health has good tolerability and safety, with few adverse effects and is appropriate as an initial treatment.
Autistic Traits and College Adjustment
Authors: McLeod Jane D. , Anderson Elizabeth M.
Published: July 2022

This study evaluated the association of autistic traits (RAADS-14) with academic and social outcomes among college students using data from an online survey (N = 2,736). In the academic domain, the total trait score and all subscale scores (mentalizing deficits, social anxiety, sensory reactivity) were associated with course failure and academic difficulties independent of an autism diagnosis; the total score and mentalizing deficits also predicted lower grade point average (GPA). In the social domain, the total trait score and subscale scores were associated with lower odds of having a confidant, lower friendship quality, and higher odds of social exclusion. Subgroup analyses revealed that autistic traits had more consistently negative associations with social outcomes for students without an autism diagnosis than for students with a diagnosis. Associations were also more often significant for women than men. These results support the development of programs and services for students with autistic traits regardless of diagnostic status.
The Role of Supportive Parenting and Stress Reactivity in the Development of Self-Regulation in Early Childhood
Authors: Kok Rianne , Luijk Maartje P. C. M. , Lucassen Nicole , Prinzie Peter , Jongerling Joran , van IJzendoorn Marinus H. , Tiemeier Henning , Bakermans-Kranenburg Marian J.
Published: July 2022

Maternal sensitivity and supportive discipline are important determinants of child self-regulation. Some evidence suggests that specific genetic or temperamental markers determine children’s susceptibility to the impact of maternal parenting on child self-regulation. Cortisol reactivity as a susceptibility marker moderating the relation between maternal parenting and child self-regulation has not yet been studied. In this longitudinal population-based study (N = 258), the moderating role of infant cortisol stress response to the Strange Situation Procedure at age 1 was examined in the association between parenting (sensitivity and supportive discipline) at age 3 and child self-regulation at age 3 and 4. Maternal sensitivity and supportive discipline were related to child immediate and prolonged delay of gratification at age 3, and maternal sensitivity was related to working memory skills at age 4. No evidence of differential susceptibility to maternal parenting was found, based on differences in infant cortisol stress response.
Use of a novel integrated dilator-needle system in cryoballoon procedures: a zero-exchange approach
Authors: Yap Sing-Chien , Bhagwandien Rohit E. , Szili-Torok Tamas
Published: July 2022

Background

Recently, a novel integrated dilator-needle system (AcQCross Qx, Acutus Medical) was introduced to reduce the number of exchanges for a transseptal access. This system can be used in combination with large bore sheaths. In this pilot study, we evaluated the safety and efficacy of a zero-exchange approach with the AcQCross system in cryoballoon procedures.

Methods

In this retrospective single-center study, we included 40 patients (AcQCross: n = 20; control group: n = 20) who underwent a cryoballoon procedure for the treatment of atrial fibrillation. In the AcQCross and control group, patients underwent ablation with POLARx (Boston Scientific) and Arctic Front Advance Pro (AFA-Pro, Medtronic) in equal numbers (n = 10). In the AcQCross group, the AcQGuide Max sheath (Acutus Medical) was used in all POLARx cases.

Results

The baseline characteristics of the study population were comparable between groups. In the AcQCross group, there was a reduction in procedure time (49.7 ± 9.0 min vs. 59.6 ± 8.1 min, P < 0.001) and time from puncture until balloon delivery (15.5 ± 6.8 min vs. 21.5 ± 7.4 min, P = 0.01) in comparison with the control group. The balloon in body time, fluoroscopy time, number of cryoapplications, and biophysical parameters were similar between groups. There was one temporary phrenic nerve injury in the AcQCross group. Importantly, no signs of air embolism were noted with the AcQGuide Max sheath.

Conclusions

The use of the novel AcQCross system improves procedural efficacy in cryoballoon procedures by reducing the number of exchanges.
Do higher alarm thresholds for arterial blood pressure lead to less perioperative hypotension? A retrospective, observational cohort study
Authors: Meidert Agnes S. , Hornung Roman , Christmann Tina , Aue Elisa , Dahal Chetana , Dolch Michael E. , Briegel Josef
Published: July 2022

Arterial blood pressure is one of the vital signs monitored mandatory in anaesthetised patients. Even short episodes of intraoperative hypotension are associated with increased risk for postoperative organ dysfunction such as acute kidney injury and myocardial injury. Since there is little evidence whether higher alarm thresholds in patient monitors can help prevent intraoperative hypotension, we analysed the blood pressure data before (group 1) and after (group 2) the implementation of altered hypotension alarm settings. The study was conducted as a retrospective observational cohort study in a large surgical centre with 32 operating theatres. Alarm thresholds for hypotension alarm for mean arterial pressure (MAP) were altered from 60 (before) to 65 mmHg for invasive measurement and 70 mmHg for noninvasive measurement. Blood pressure data from electronic anaesthesia records of 4222 patients (1982 and 2240 in group 1 and 2, respectively) with 406,623 blood pressure values undergoing noncardiac surgery were included. We analysed (A) the proportion of blood pressure measurements below the threshold among all measurements by quasi-binomial regression and (B) whether at least one blood pressure measurement below the threshold occurred by logistic regression. Hypotension was defined as MAP < 65 mmHg. There was no significant difference in overall proportions of hypotensive episodes for mean arterial pressure before and after the adjustment of alarm settings (mean proportion of values below 65 mmHg were 6.05% in group 1 and 5.99% in group 2). The risk of ever experiencing a hypotensive episode during anaesthesia was significantly lower in group 2 with an odds ratio of 0.84 (p = 0.029). In conclusion, higher alarm thresholds do not generally lead to less hypotensive episodes perioperatively. There was a slight but significant reduction of the occurrence of intraoperative hypotension in the presence of higher thresholds for blood pressure alarms. However, this reduction only seems to be present in patients with very few hypotensive episodes.
The Child-to-Parent Violence Functions Scale (CPV-F): Development and Validation
Authors: Harries Travis , Curtis Ashlee , Skvarc David , Walker Arlene , Mayshak Richelle
Published: July 2022

Purpose

The function (i.e., the motivation) of child-to-parent violence (CPV) is an important consideration for intervention but under researched, primarily due to a lack of appropriate measurement tools. The current study aimed to develop and validate a caregiver-report measure of the function of CPV (the Child-to-Parent Violence Functions Scale [CPV-F]).

Methods

One-hundred-and-twenty-one caregivers (94% female) ranging from 27 to 68 years of age (M = 45.36, SD = 8.35) completed an online survey reporting on experiences of CPV from a young person, who were mostly male (63%) and aged between 5 and 24 years (M = 12.71, SD = 4.77).

Results

The current study shows that the motivation for CPV varies across three related but distinct functions: Reactive (i.e., in response to perceived or actual threat, transgression, or intrusion), Affective (i.e., driven by internal frustration, fear, or emotional conflict), and Proactive (i.e., instrumental, callous, and planned). The CPV-F demonstrated predictive and concurrent validity, as well as adequate reliability across subscales.

Conclusions

Future research should consider the function of CPV, as it may impact the relevance of risk factors. Moving forward, the CPV-F could be used for comprehensive investigative profiling, with a focus on parent and dyadic factors, to resolve heterogeneity in the field. Such factors are crucial to intervention yet under explored. As a caregiver-report measure, the CPV-F is well-positioned to aid in these investigations.
Microbial Mediated Synthesis of Zinc Oxide Nanoparticles, Characterization and Multifaceted Applications
Authors: Gomaa Eman Zakaria
Published: July 2022

Nanoparticles have gained considerable importance compared to bulk counterparts due to their unique properties. Due to their high surface to volume ratio and high reactivity, metallic and metal-oxide nanostructures have shown great potential applications. Among them, zinc oxide nanoparticles (ZnONPs) have gained tremendous attention attributed to their unique properties such as low toxicity, biocompatibility, simplicity, easy fabrication, and environmental friendly. Remarkably, ZnONPs exhibit optical, physical, antimicrobial, anticancer, anti-inflammatory and wound healing properties. These nanoparticles have been applied in various fields such as in biomedicine, biosensors, electronics, food, cosmetic industries, textile, agriculture and environment. The synthesis of ZnONPs can be performed by chemical, physical and biological methods. Although the chemical and physical methods suffer from some disadvantages such as the involvement of high temperature and pressure conditions, high cost and not environmentally friendly, the green synthesis of ZnONPs offers a promising substitute to these conventional methods. On that account, the microbial mediated synthesis of ZnONPs is clean, eco-friendly, nontoxic and biocompatible method. This paper reviews the microbial synthesis of ZnONPs, parameters used for the optimization process and their physicochemical properties. The potential applications of ZnONPs in biomedical, agricultural and environmental fields as well as their toxic aspects on human beings and animals have been reviewed.
Analytical Models for the Pulse Shape of a Superconductor-Ferromagnet Tunnel Junction Thermoelectric Microcalorimeter
Authors: Geng Z. , Maasilta I. J.
Published: July 2022

The superconductor-ferromagnet thermoelectric detector (SFTED) is a novel ultrasensitive radiation detector based on the giant thermoelectric effect in superconductor-ferromagnet tunnel junctions. We demonstrate analytical models and solutions in the time domain for a SFTED operated as a microcalorimeter (pulse excitation), in the linear small-signal limit. Based on these solutions, the signal current and temperature pulse response were studied for two different electrical circuit models, providing design conditions for stable and non-oscillatory response.Kindly check and confirm whether the corresponding author is correctly identified.The corresponding author is correct.