bluuebunny/crossref_metadata_2025 huggingface dataset:
Gesellschaftliche und volkswirtschaftliche Sicht auf die (zukünftige) Finanzierbarkeit von Arzneimitteln
Authors: Wasem Jürgen , Hüer Theresa , Abels Carina
Published: October 2021

Angemessene Preise für patentgeschützte Arzneimittel zu finden ist kein neues Problem. Bei sich ändernden Rahmenbedingungen stellt sich die Frage jeweils wieder neu. Der Markt unterliegt derzeit insbesondere zwei strukturellen Veränderungen. Zum einen werden neue Arzneimittelimmer häufiger auf Basis besonderer Verfahren durch die Europäische Arzneimittel-Agentur (EMA, englisch European Medicines Agency) zugelassen, womit eine geringe Evidenzlage zum Zeitpunkt der Zulassung einhergeht. Zum anderen ergeben sich hauptsächlich durch Arzneimittel für neuartige Therapien transformierte Ausgabenverläufe, da es sich um Einmal-/Impulstherapien handelt, die eine jahre- bis lebenslange Wirkung versprechen. Aus der sich daraus ergebenden Unsicherheit hinsichtlich der (langfristigen) Wirksamkeit unmittelbar nach der Zulassung ergibt sich ein Spannungsfeld im Rahmen der Preisfindung. Um diesem Spannungsfeld in der derzeitigen Arzneimittelpreisbildung im deutschen System zu begegnen, werden in diesem Beitrag international diskutierte innovative Preis- und Erstattungsmechanismen betrachtet und in Bezug auf ihre Anwendbarkeit im deutschen Preisbildungssystem bewertet. Gleichzeitig wird darauf eingegangen, dass möglicherweise ein stärkerer Fokus auf Kosten-Nutzen-Bewertungen im Rahmen der Preisbildung gelegt wird, um die (zukünftige) Finanzierbarkeit von Arzneimitteln sicherzustellen.
Ethische Sichtweise auf hochpreisige Arzneimittel
Authors: Nagel Eckhard , Henzler Dennis , Lauerer Michael
Published: October 2021

Die Zulassung und Preisbildung neuer Arzneimittel ist in Deutschland, wie in vielen anderen Ländern, reglementiert. Damit fügen sie sich in die umfänglichen Vorgaben zur Strukturierung des Gesundheitswesens ein, die im Wesentlichen das Ziel haben, die Interessen des Leistungsanbieters, der Versichertengemeinschaft als Kostenträger sowie der behandlungsbedürftigen Personen adäquat zu berücksichtigen. Diese Ausgleichsfunktionen sind einer Reihe ethischer Normen unterworfen, die zum Teil explizit das Gesundheitswesen charakterisieren oder häufig auch implizit das genannte Ziel realisieren sollen. Der Artikel rekapituliert relevante ethische Grundlagen der Gesundheitsversorgung, welche einen engeren Bezug zur Preisfindung bei Medikamenten aufweisen. Dabei bedient er sich zweier Fallstudien anhand derer erkennbar wird, wie sich die Zusammenhänge zwischen Normensetzung und Verantwortung auf diesem Gebiet darstellen.
Hochpreisigkeit bei Onkologika
Authors: Ludwig Wolf-Dieter , Vokinger Kerstin Noëlle
Published: October 2021

Onkologikasind seit mehreren Jahren die umsatzstärkste Arzneimittelgruppe in Deutschland. Während 2014 unter den 30 umsatzstärksten patentgeschützten Arzneimitteln nur drei Onkologika mit Nettokosten zwischen 184 Mio. € und 259 Mio. € je Arzneimittel waren, befinden sich unter den führenden 20 Arzneimitteln nach Nettokosten im Jahr 2020 bereits neun Onkologika. Sie sind deshalb inzwischen die mit weitem Abstand umsatzstärkste Arzneimittelgruppe mit 9,5 Mrd. € Nettokosten insgesamt. Verantwortlich hierfür sind die sehr hohen Preise, die heute von pharmazeutischen Unternehmern (pU) für neuartige Wirkstoffe zur Behandlung hämatologischer Neoplasien und solider Tumore (z. B. Proteinkinaseinhibitoren und monoklonale Antikörper) verlangt werden. Im Zusammenhang mit der Auswertung von Verordnungen ist zu berücksichtigen, dass für GKV-Patient:innen 2020 insgesamt nur 8,1 Mio. Verordnungen von Onkologika erfolgten, die nur 1,2 % aller verordneten Arzneimittel des GKV-Arzneimittelmarktes ausmachten. Anhand aktueller Untersuchungen konnte inzwischen gezeigt werden, dass die Kosten für Forschung & Entwicklung (F & E)neuer Wirkstoffe, die von pU häufig als Begründung für die sehr hohen Preise der Onkologika genannt wurden, deutlich niedriger liegen als früher behauptet (im Median circa 548 Mio. €), sodass Onkologika heute sehr hohe Erträge generieren, die die Kosten für F & E deutlich übersteigen. Darüber hinaus belegen sowohl aktuelle Studien aus den USA und Europa als auch die Ergebnisse der seit 2011 in Deutschland durchgeführten frühen Nutzenbewertung von Onkologika, dass ein Zusammenhang zwischen deren klinischem Nutzen und den Behandlungskosten meist nicht besteht.
Beschleunigte Zulassung von Arzneimitteln: Herausforderungen für Patient:innen, Datenqualität und faire Preise
Authors: Haas Antje , Mayer Thomas , Tebinka-Olbrich Anja , Blindzellner Maximilian , Beggerow Elisa , Nickel Andreas
Published: October 2021

Beschleunigte Zulassungen stellen die Nutzenbewertung und Erstattung von Arzneimitteln vor besondere Herausforderungen. Der Artikel setzt sich in Form eines narrativen Reviews mit den Auswirkungen dieser Zulassungen auf Patient:innen, Angehörige der Gesundheitsberufe und die Solidargemeinschaft sowie mit den möglichen Lösungsstrategien auseinander. Die Autor:innen geben dazu anhand aktueller Literatur zunächst einen Überblick über die Zulassung von Arzneimitteln mit „conditional marketing authorisation“, „approval under exceptional circumstances“ sowie Orphan Drugs. Anschließend stellen sie den Einfluss beschleunigter Zulassungen auf die Nutzenbewertung dar und bewerten diesen. Zum Schluss beschreiben sie in diesem Zusammenhang Herausforderungen im Hinblick auf Arzneimittelpreise.
Initial experience with AcQMap catheter for treatment of persistent atrial fibrillation and atypical atrial flutter
Authors: Liebregts M. , Wijffels M. C. E. F. , Klaver M. N. , van Dijk V. F. , Balt J. C. , Boersma L. V. A.
Published: October 2021

Introduction

The AcQMap High Resolution Imaging and Mapping System was recently introduced. This system provides 3D maps of electrical activation across an ultrasound-acquired atrial surface.

Methods

We evaluated the feasibility and the acute and short-term efficacy and safety of this novel system for ablation of persistent atrial fibrillation (AF) and atypical atrial flutter.

Results

A total of 21 consecutive patients (age (mean ± standard deviation) 62 ± 8 years, 23% female) underwent catheter ablation with the use of the AcQMap System. Fourteen patients (67%) were treated for persistent AF and 7 patients (33%) for atypical atrial flutter. Eighteen patients (86%) had undergone at least one prior ablation procedure. Acute success, defined as sinus rhythm without the ability to provoke the clinical arrhythmia, was achieved in 17 patients (81%). At 12 months, 4 patients treated for persistent AF (29%) and 4 patients treated for atypical flutter (57%) remained in sinus rhythm. Complications included hemiparesis, for which intra-arterial thrombolysis was given with subsequent good clinical outcome (n = 1), and complete atrioventricular block, for which a permanent pacemaker was implanted (n = 2). No major complications attributable to the mapping system occurred.

Conclusion

The AcQMap System is able to provide fast, high-resolution activation maps of persistent AF and atypical atrial flutter. Despite a high acute success rate, the recurrence rate of persistent AF was relatively high. This may be due to the selection of the patients with therapy-resistant arrhythmias and limited experience in the optimal use of this mapping system that is still under development.
Comparison of 2D 4K vs. 3D HD laparoscopic imaging systems using a pelvitrainer model: a randomized controlled study
Authors: Zwimpfer Tibor A. , Wismer Claudine , Fellmann-Fischer Bernhard , Geiger James , Schötzau Andreas , Heinzelmann-Schwarz Viola
Published: October 2021

Laparoscopic surgery provides well-known benefits, but it has technological limitations. Depth perception is particularly crucial, with three-dimensional (3D) imaging being superior to two-dimensional (2D) HD imaging. However, with the introduction of 4K resolution monitors, 2D rendering is capable of providing higher-quality visuals. Therefore, this study aimed to compare 3D HD and 2D 4K imaging using a pelvitrainer model. Eight experts and 32 medical students were performing the same four standardized tasks using 2D 4K and 3D HD imaging systems. Task completion time and the number of errors made were recorded. The Wilcoxon test and mixed-effects models were used to analyze the results. Students were significantly faster in all four tasks when using the 3D HD perspective. The median difference ranged from 18 s in task 3 (P < 0.003) up to 177.5 s in task 4 (P < 0.001). With the exception of task 4, students demonstrated significantly fewer errors in all tasks involving 3D HD imaging. The experts’ results confirmed these findings, as they were also faster in all four tasks using 3D HD, which was significant for task 1 (P < 0.001) and task 4 (P < 0.006). The expert group also achieved better movement accuracy using the 3D HD system, with fewer mistakes made in all four tasks, which was significant in task 4 (P < 0.001). Participants in both groups achieved better results with the 3D HD imaging system than with the 2D 4K system. The 3D HD image system should be used when available. Trial registration: this trial is registered at research registry under the identifier researchregistry6852.
Observation and Maneuver Detection for Cislunar Vehicles
Authors: Greaves Jesse A. , Scheeres Daniel J.
Published: October 2021

International interest in the sustained development of cislunar space will generate traffic and debris in the region which requires monitoring; similar to how current space situation awareness is necessary for the traffic and debris near Earth. There are many challenges associated with developing a cislunar situation awareness program, but 2 primary issues addressed by this paper are observational strategies and maneuver detection methods. This work proposes an observational strategy that utilizes the ballistic Optimal Control Based Estimator (OCBE) to filter measurements from cislunar optical observers. To reduce numerical issues associated with filtering, new modifications to the ballistic Optimal Control Based Estimator (OCBE) are introduced that preserve the OCBE update equations in Square Root Information (SRI) space. This new derivation produces a more stable version of the ballistic OCBE which is beneficial for filtering larger data sets with non-linear motion and measurements. Applying the SRI OCBE to the estimation problem it was found that only a single L2 observer with angle and angle-rate measurements provided sufficient information for consistent estimation. Then a newly developed maneuver detection method is presented to statistically identify maneuvers. The method applies a binary hypothesis test to the optimal control policy of the ballistic OCBE to quantify mismodeling. This method was tested given a impulsive maneuver policy with a mean of 50 mm/s and standard deviation of 15 mm/s, and 194 out of 200 tests correctly identified if a maneuver occurred. The OCBE control policy also provided appropriate impulse estimates of mismodeling, which may be used to reconstruct maneuvers in future work. Together, the proposed observation and maneuver detection methodology yields reliable tracking and provides a statistical framework to detect maneuvers.
Efficacy of the Orally Disintegrating Strip Sildenafil for the Treatment of Erectile Dysfunction: A Prospective, Randomized Trial
Authors: Sangkum Premsant , Sirisopana Kun , Matang Wijittra , Phengsalae Yada , Lertsithichai Panuwat , Ketsuwan Chinnakhet , Kochakarn Wachira , Kongchareonsombat Wisoot
Published: October 2021

Introduction

Phosphodiesterase 5 inhibitors are the predominant treatment option for erectile dysfunction.

Aim

This study evaluates the efficacy and safety of sildenafil orally disintegrating strips for the treatment of erectile dysfunction.

Methods

One hundred twenty erectile dysfunction patients were enrolled in a prospective, randomized, controlled crossover study and allocated into 2 groups of 60 participants. Patients were either treated with sildenafil strips or tablets for 8 weeks after which they crossed over into the alternate treatment formulation for another 8 weeks following a 4-week wash-out period. Each participant was assessed 8 times throughout the study period and their formulation preference registered at the end of the study.

Main outcomes and measures

Changes in the abridged International Index of Erectile Function (IIEF-5) score and Erection Hardness Score (EHS) resulting from sildenafil orally disintegrating strip or tablet treatments were the primary end points, with differences in onset of action, duration of action, and incidence of adverse events between the 2 formulations included as secondary end points.

Results

Both sildenafil formulations were effective in treating patients with erectile dysfunction. There was significant improvement of erectile function in term of IIEF-5 score and EHS from both formulations. The number and type of adverse events were also comparable. Likewise, there were no statistically significant differences between the earliest onset of action times and longest duration of action times. However, the results showed a 7.1-minute earlier onset of action time for orally disintegrating strips that may be considered as clinically meaningful by some patients.

Conclusion

Sildenafil orally disintegrating strips are a safe and effective alternative to the conventional tablet formulation for the treatment of erectile dysfunction.
Essential Interoperability Standards
Authors: Brinsmead Simon
Published: October 2021

A new international instrument is needed to address access to interoperability standards and standards-essential intellectual property, which are critical to maintaining technological advancement and promoting cost-effective solutions for consumers. Applying law and economics methodologies, Simon Brinsmead systematically explores how international and domestic law deals with these matters. This important book includes an examination of the technical and economic nature of interoperability standards; a detailed analysis of the issues arising under intellectual property and competition law; an analysis of whether liability or exclusive property rules should apply with respect to interoperability standards and SEIP; and consideration of feasible international approaches. Finally, Brinsmead includes a draft of his proposed international soft law instrument as a starting point for future discussions in the field. Of interest to lawyers, regulators and scholars, this work offers a meaningful contribution to international governance, harmonization of laws and technological advancement.
Pas encore classiques: La fabrique des antiquités américaines au xixe siècle
Authors: Achim Miruna , Gänger Stefanie
Published: October 2021

Pas encore classiques: La fabrique des antiquités américaines au xixe siècle

Les antiquités précolombiennes sont devenues une catégorie esthétique, scientifique, commerciale et juridique reconnaissable au cours du xixe siècle. Cet article présente les acteurs, les sites et les configurations matérielles et idéologiques qui jouèrent un rôle dans sa construction et son développement. La première section examine la tradition antiquaire ibérique qui, vers le milieu du xviie siècle, a mis en circulation les artefacts d’avant la conquête en tant qu’objets épistémiques, dans le contexte de la pertinence croissante des vestiges matériels comme objets d’investigation. L’article se penche ensuite sur les scènes de collecte dans les pays d’Amérique hispanique nouvellement indépendants, où les élites créoles, les musées locaux et les étrangers, mus par leurs propres intérêts, se sont disputé les antiquités. La troisième section explore la manière dont, au milieu du xixe siècle, les « technologies du papier » ont fonctionné comme des outils heuristiques pour connaître, organiser et interpréter les antiquités, conférant une densité ontologique à des objets et groupes d’objets spécifiques et conduisant à la construction de régimes de savoirs et d’expertises dédiés. Enfin, la quatrième section reconstruit les processus nationaux et internationaux d’institutionnalisation du passé d’avant la conquête à la fin des années 1800 et au début des années 1900 – à travers la consolidation des musées nationaux et la constitution de l’archéologie et de l’ethnographie comme disciplines scientifiques – afin d’examiner comment ceux-ci ont renforcé l’importance et la signification des antiquités.
Parliamentary Representation in Modern Britain: Past, Present, and Future
Authors: Taylor Miles
Published: October 2021

A series of recent books all attest to a revival of interest in the theory and practice of parliamentary representation in the modern era as a scholarly discipline. This review surveys eight different aspects of that history since the early nineteenth century: the spatial dimension of the Palace of Westminster; the comparative framework offered by the history of parliaments in Europe; ideas of parliamentary representation; the history of parliamentary procedure; women in parliament; the House of Lords; the history of corruption; and the Brexit crisis. Insights and perspectives are drawn from recent historical research as well as from political science and intellectual history. The review concludes by observing that the history of parliamentary representation in the modern era is in good shape. Some older interpretive paradigms still lurk, especially an obsession with ‘democratization’. However, more is now known about individual MPs and constituencies than ever before. The digitization of the records of parliament is expediting the kind of longitudinal analysis which was impossible back in the 1960s and 1970s. And the intellectual history and public policy literature around the idea of representation is enjoying a renaissance.
Vaccination rates in cochlear implant patients: a review of paediatric recipients
Authors: Rose O , Moriarty R , Brown C , Teagle H , Neeff M
Published: October 2021

Objective

This study aimed to investigate whether children with cochlear implants received the recommended vaccinations according to New Zealand national immunisation guidelines and to report the incidence of meningitis in this population after intervention.

Method

A retrospective review of the vaccination coverage of paediatric patients receiving cochlear implants between 2005 and 2019 was performed.

Results

Data were collected on 203 children. Evidence of immunisation against Haemophilus influenza B was documented in 94.1 per cent of this cohort and 21.2 per cent received the seasonal influenza vaccine. The pneumococcal conjugate vaccine was fully administered in 81.8 per cent of children; however, only 16.9 per cent of eligible children had received the pneumococcal polysaccharide vaccine. There was marked improvement in compliance to the pneumococcal conjugate vaccine once it became fully funded for cochlear implant patients.

Conclusion

Despite established guidelines, the paediatric vaccination rates were less than expected. Work is in progress to address this.
Adaptation, adjudication, and private ordering: Contractual Relations through the Williamson Lens
Authors: Masten Scott E.
Published: October 2021

Williamson's legacy will be permanently, and deservedly, linked with the theory of the firm. As important, however, is his contribution to our understanding of contracting. My aim here is to describe Williamson's conception of contracting, how it differs from other approaches to contracting, and some implications of that approach for contract design and enforcement. I argue that Williamson's ‘process orientation’ – in which the main dimension along which contracts vary is the extent to which contract adjustments are effected through court ordering versus private ordering – provides alternative interpretations of some conventional contract terms but also sheds light on some otherwise puzzling contractual phenomena.
Simulation of Crop Water Demand and Consumption Considering Irrigation Effects Based on Coupled Hydrology‐Crop Growth Model
Authors: Zhang Yuliang , Wu Zhiyong , Singh Vijay P. , Su Qiong , He Hai , Yin Hao , Zhang Yaxin , Wang Fang
Published: October 2021

Hydrological models are widely used in regional drought assessments. Usually, the spatiotemporal development of droughts is evaluated only via drought indexes based on simulated soil moisture. However, the physiological status of crops is key to accurately assessing the effect of drought, and hydrological models either do not consider crop physiological status or oversimplify it. In addition, the effects of reservoirs, irrigation, and crop rotation are generally not considered. To overcome the oversimplification of crop and irrigation modules in hydrological models, the variable infiltration capacity (VIC) model was coupled with the Environmental Policy Integrated Climate model. Irrigation and reservoir modules were introduced into the coupled hydrology‐crop growth (CHC) model. The CHC model was built for the watershed upstream of Heilin hydrological station on the Qingkou River on the border of Jiangsu and Shandong Provinces, China. The model performance was compared with simulation results of the Soil and Water Assessment Tool and VIC, which showed that the CHC model was more accurate. The temporal variation of water consumption and demand of three crop rotations, namely spring peanuts, summer peanuts‐winter wheat, and summer corn‐winter wheat, in the study area was analyzed. Drought area data obtained from Junan County yearbooks were consistent with the simulated water deficit and drought index considering the effect of irrigation. Crop irrigation increased soil water content and evapotranspiration and decreased crop water deficit. Therefore, crop irrigation was considered in hydrological simulations. The CHC model reliably simulated crop water consumption, soil moisture, and drought index, and the model simulated data could be used as basic data for water resources management and drought mitigation measures.
Selective and competitive functions of the AAR and UPR pathways in stress-induced angiogenesis
Authors: Zhang Fan , Zeng Qi-Yu , Xu Hao , Xu Ai-Ning , Liu Dian-Jia , Li Ning-Zhe , Chen Yi , Jin Yi , Xu Chun-Hui , Feng Chang-Zhou , Zhang Yuan-Liang , Liu Dan , Liu Na , Xie Yin-Yin , Yu Shan-He , Yuan Hao , Xue Kai , Shi Jing-Yi , Liu Ting Xi , Xu Peng-Fei , Zhao Wei-Li , Zhou Yi , Wang Lan , Huang Qiu-Hua , Chen Zhu , Chen Sai-Juan , Zhou Xiao-Long , Sun Xiao-Jian
Published: October 2021

The amino acid response (AAR) and unfolded protein response (UPR) pathways converge on eIF2α phosphorylation, which is catalyzed by Gcn2 and Perk, respectively, under different stresses. This close interconnection makes it difficult to specify different functions of AAR and UPR. Here, we generated a zebrafish model in which loss of threonyl-tRNA synthetase (Tars) induces angiogenesis dependent on Tars aminoacylation activity. Comparative transcriptome analysis of thetars-mutant and wild-type embryos with/without Gcn2- or Perk-inhibition reveals that only Gcn2-mediated AAR is activated in thetars-mutants, whereas Perk functions predominantly in normal development. Mechanistic analysis shows that, while a considerable amount of eIF2α is normally phosphorylated by Perk, the loss of Tars causes an accumulation of uncharged tRNAThr, which in turn activates Gcn2, leading to phosphorylation of an extra amount of eIF2α. The partial switchover of kinases for eIF2α largely overwhelms the functions of Perk in normal development. Interestingly, although inhibition of Gcn2 and Perk in this stress condition both can reduce the eIF2α phosphorylation levels, their functional consequences in the regulation of target genes and in the rescue of the angiogenic phenotypes are dramatically different. Indeed, genetic and pharmacological manipulations of these pathways validate that the Gcn2-mediated AAR, but not the Perk-mediated UPR, is required fortars-deficiency induced angiogenesis. Thus, the interconnected AAR and UPR pathways differentially regulate angiogenesis through selective functions and mutual competitions, reflecting the specificity and efficiency of multiple stress response pathways that evolve integrally to enable an organism to sense/respond precisely to various types of stresses.
Kinetic and structural roles for the surface in guiding SAS-6 self-assembly to direct centriole architecture
Authors: Banterle Niccolò , Nievergelt Adrian P. , de Buhr Svenja , Hatzopoulos Georgios N. , Brillard Charlène , Andany Santiago , Hübscher Tania , Sorgenfrei Frieda A. , Schwarz Ulrich S. , Gräter Frauke , Fantner Georg E. , Gönczy Pierre
Published: October 2021

Discovering mechanisms governing organelle assembly is a fundamental pursuit in biology. The centriole is an evolutionarily conserved organelle with a signature 9-fold symmetrical chiral arrangement of microtubules imparted onto the cilium it templates. The first structure in nascent centrioles is a cartwheel, which comprises stacked 9-fold symmetrical SAS-6 ring polymers emerging orthogonal to a surface surrounding each resident centriole. The mechanisms through which SAS-6 polymerization ensures centriole organelle architecture remain elusive. We deploy photothermally-actuated off-resonance tapping high-speed atomic force microscopy to decipher surface SAS-6 self-assembly mechanisms. We show that the surface shifts the reaction equilibrium by ~104 compared to solution. Moreover, coarse-grained molecular dynamics and atomic force microscopy reveal that the surface converts the inherent helical propensity of SAS-6 polymers into 9-fold rings with residual asymmetry, which may guide ring stacking and impart chiral features to centrioles and cilia. Overall, our work reveals fundamental design principles governing centriole assembly.
Selection on adaptive and maladaptive gene expression plasticity during thermal adaptation to urban heat islands
Authors: Campbell-Staton Shane C. , Velotta Jonathan P. , Winchell Kristin M.
Published: October 2021

Phenotypic plasticity enables a single genotype to produce multiple phenotypes in response to environmental variation. Plasticity may play a critical role in the colonization of novel environments, but its role in adaptive evolution is controversial. Here we suggest that rapid parallel regulatory adaptation ofAnolislizards to urban heat islands is due primarily to selection for reduced and/or reversed heat-induced plasticity that is maladaptive in urban thermal conditions. We identify evidence for polygenic selection across genes of the skeletal muscle transcriptome associated with heat tolerance. Forest lizards raised in common garden conditions exhibit heat-induced changes in expression of these genes that largely correlate with decreased heat tolerance, consistent with maladaptive regulatory response to high-temperature environments. In contrast, urban lizards display reduced gene expression plasticity after heat challenge in common garden and a significant increase in gene expression change that is congruent with greater heat tolerance, a putatively adaptive state in warmer urban environments. Genes displaying maladaptive heat-induced plasticity repeatedly show greater genetic divergence between urban and forest habitats than those displaying adaptive plasticity. These results highlight the role of selection against maladaptive regulatory plasticity during rapid adaptive modification of complex systems in the wild.
A reasonable approach for the generation of hollow icosahedral kernels in metal nanoclusters
Authors: Kang Xi , Wei Xiao , Liu Xiaokang , Wang Sicong , Yao Tao , Wang Shuxin , Zhu Manzhou
Published: October 2021

Although the hollow icosahedral M12 kernel has been extensively observed in metal nanoclusters, its origin remains a mystery. Here we report a reasonable avenue for the generation of the hollow icosahedron: the kernel collapse from several small nano-building blocks to an integrated hollow icosahedron. On the basis of the Au alloying processes from Ag28Cu12(SR)24 to the template-maintained AuxAg28-xCu12(SR)24 and then to the template-transformed Au12CuyAg32-y(SR)30, the kernel evolution/collapse from “tetrahedral Ag4 + 4∗Ag3” to “tetrahedral Au4 + 4∗M3 (M = Au/Ag)” and then to “hollow icosahedral Au12” is mapped out. Significantly, the “kernel collapse” from small-sized nano-building blocks to large-sized nanostructures not only unveils the formation of hollow icosahedral M12 in this work, but also might be a very common approach in constructing metallic kernels of nanoclusters and nanoparticles (not limited to the M12 structure).
Fronto-striatal dopamine D2 receptor availability is associated with cognitive variability in older individuals with low dopamine integrity
Authors: Korkki Saana M. , Papenberg Goran , Karalija Nina , Garrett Douglas D. , Riklund Katrine , Lövdén Martin , Lindenberger Ulman , Nyberg Lars , Bäckman Lars
Published: October 2021

Within-person, moment-to-moment, variability in behavior increases with advancing adult age, potentially reflecting the influence of reduced structural and neurochemical brain integrity, especially that of the dopaminergic system. We examined the role of dopamine D2 receptor (D2DR) availability, grey-, and white-matter integrity, for between-person differences in cognitive variability in a large sample of healthy older adults (n = 181; 64–68 years) from the Cognition, Brain, and Aging (COBRA) study. Intra-individual variability (IIV) in cognition was measured as across-trial variability in participants’ response times for tasks assessing perceptual speed and working memory, as well as for a control task of motor speed. Across the whole sample, no associations of D2DR availability, or grey- and white-matter integrity, to IIV were observed. However, within-person variability in cognition was increased in two subgroups of individuals displaying low mean-level cognitive performance, one of which was characterized by low subcortical and cortical D2DR availability. In this latter group, fronto-striatal D2DR availability correlated negatively with within-person variability in cognition. This finding suggests that the influence of D2DR availability on cognitive variability may be more easily disclosed among individuals with low dopamine-system integrity, highlighting the benefits of large-scale studies for delineating heterogeneity in brain-behavior associations in older age.
Analysis of whole exome sequencing in severe mental illness hints at selection of brain development and immune related genes
Authors: Mahadevan Jayant , Pathak Ajai Kumar , Vemula Alekhya , Nadella Ravi Kumar , Viswanath Biju , Jain Sanjeev ,   Accelerator Program for Discovery in Brain disorders using Stem cells (ADBS) Consortium, Rao Naren P. , Narayanaswamy Janardhanan C. , Viswanath Biju , Sivakumar Palanimuthu T. , Kandasamy Arun , Kesavan Muralidharan , Mehta Urvakhsh Meherwan , Venkatasubramanian Ganesan , John John P. , Purushottam Meera , Mukherjee Odity , Kannan Ramakrishnan , Mehta Bhupesh , Kandavel Thennarasu , Binukumar B. , Saini Jitender , Jayarajan Deepak , Shyamsundar A. , Moirangthem Sydney , Kumar K. G. Vijay , Holla Bharath , Mahadevan Jayant , Thirthalli Jagadisha , Chandra Prabha S. , Gangadhar Bangalore N. , Murthy Pratima , Panicker Mitradas M. , Bhalla Upinder S. , Chattarji Sumantra , Benegal Vivek , Varghese Mathew , Reddy Janardhan Y. C. , Jain Sanjeev , Raghu Padinjat , Rao Mahendra , Purushottam Meera , Mondal Mayukh
Published: October 2021

Evolutionary trends may underlie some aspects of the risk for common, non-communicable disorders, including psychiatric disease. We analyzed whole exome sequencing data from 80 unique individuals from India coming from families with two or more individuals with severe mental illness. We used Population Branch Statistics (PBS) to identify variants and genes under positive selection and identified 74 genes as candidates for positive selection. Of these, 20 were previously associated with Schizophrenia, Alzheimer’s disease and cognitive abilities in genome wide association studies. We then checked whether any of these 74 genes were involved in common biological pathways or related to specific cellular or molecular functions. We found that immune related pathways and functions related to innate immunity such as antigen binding were over-represented. We also evaluated for the presence of Neanderthal introgressed segments in these genes and found Neanderthal introgression in a single gene out of the 74 candidate genes. However, the introgression pattern indicates the region is unlikely to be the source for selection. Our findings hint at how selection pressures in individuals from families with a history of severe mental illness may diverge from the general population. Further, it also provides insights into the genetic architecture of severe mental illness, such as schizophrenia and its link to immune factors.
A silent epidemic of major congenital malformations in Tigray, northern Ethiopia: hospital-based study
Authors: Mekonen Hayelom Kebede , Berhe Yibrah , Berihu Birhane Alem , Teka Hale , Hadgu Abera , Gebregziabher Letekirstos , Berhe Etenat Halefom , Magana Tony , Mulugeta Afework
Published: October 2021

Congenital malformations are defects of the morphogenesis of organs or body during the pregnancy period and are identifiable at pre- or postnatal. They are identified as the major cause of child mortality worldwide. There is a need to understand the prevalence of congenital malformations in Tigray and Ethiopia in general as surveillance data are lacking. Hence, this study was designed to investigate the burden of major congenital malformations in the Tigray Region, Northern Ethiopia. Hospital-based cross-sectional study was conducted to identify neonates with major congenital anomalies in the labor ward admitted at six major public hospitals of Tigray region, Ethiopia between January 2018 and 2019. All newborns/neonates delivered in all study hospitals during the study period were considered as the study population. The prevalence of major congenital anomalies and the distribution of each type of major congenital anomalies within total birth were calculated. Data on maternal, and newborn demographic characteristics was collected. Statistical analysis was done using SPSS and p value < 0.05 was considered significant. A total of 12,225 births and terminations were recorded in the six hospitals during the study period. Of total 12,225 births and terminations examined, 383 births had major congenital malformations and the overall prevalence of congenital malformations was 3.13% of the total births examined. Congenital anomalies (CAs) of the central nervous system specifically neural tube defects (NTDs) were the commonest anomalies in this study, found in 68.7% (263NTDs/383 CAs) of the neonates with CAs. The overall prevalence of NTDs was 2.15% (263/12,225 births) of the total births examined. Maternal factors such as women 20 years of age or younger (p < 0.0001) and women older than 35 years of age (p < 0.0001), abortion history (p < 0.0001), gravidity above 4 (p = 0.005), were more likely associated with an increased risk of babies with congenital anomalies. Fetal factors including gestational ages below 28 weeks (p < 0.0001) and above 40 weeks (p < 0.0001) were strongly associated with an increased risk of babies with congenital anomalies. However, these associated factors were not resulted from multivariable logistic regression analysis. Thus, the result might be affected by possible confounding factors. This study has shown a high prevalence of major congenital anomalies in the study community. Of the total congenital anomalies observed, most of neonates are affected with neural tube defects, a birth defect with well–established evidence having folic acid deficiency or insufficiency is the predominant cause of spina bifida and anencephaly. This just screams urgency to implement effective/mandatory/ programs to get all women of reproductive age an adequate folic acid to prevent spina bifida and anencephaly.
Detailed phylogenetic analysis tracks transmission of distinct SARS-COV-2 variants from China and Europe to West Africa
Authors: Wruck Wasco , Adjaye James
Published: October 2021

SARS-CoV-2, the virus causing the COVID-19 pandemic emerged in December 2019 in China and raised fears it could overwhelm healthcare systems worldwide. Mutations of the virus are monitored by the GISAID database from which we downloaded sequences from four West African countries Ghana, Gambia, Senegal and Nigeria from February 2020 to April 2020. We subjected the sequences to phylogenetic analysis employing the nextstrain pipeline. We found country-specific patterns of viral variants and supplemented that with data on novel variants from June 2021. Until April 2020, variants carrying the crucial Europe-associated D614G amino acid change were predominantly found in Senegal and Gambia, and combinations of late variants with and early variants without D614G in Ghana and Nigeria. In June 2021 all variants carried the D614G amino acid substitution. Senegal and Gambia exhibited again variants transmitted from Europe (alpha or delta), Ghana a combination of several variants and in Nigeria the original Eta variant. Detailed analysis of distinct samples revealed that some might have circulated latently and some reflect migration routes. The distinct patterns of variants within the West African countries point at their global transmission via air traffic predominantly from Europe and only limited transmission between the West African countries.
The effect of shape and size in the stability of triangular Janus MoSSe quantum dots
Authors: Paez-Ornelas J. I. , Ponce-Pérez R. , Fernández-Escamilla H. N. , Hoat D. M. , Murillo-Bracamontes E. A. , Moreno-Armenta María G. , Galván Donald H. , Guerrero-Sánchez J.
Published: October 2021

Asymmetric Janus transition metal dichalcogenide MoSSe is a promising catalytic material due to the intrinsic in-plane dipole of its opposite faces. The atomic description of the structures observed by experimental techniques is relevant to tuning and optimizing its surface reaction processes. Furthermore, the experimentally observed triangular morphologies in MoSSe suggest that an analysis of the chemical environment of its edges is vital to understand its reactivity. Here we analyze the size-shape stability among different triangular structures-quantum- dots proposed from the ideal S(-1010) and Mo(10-10) terminations. Our stability analysis evidenced that the S–Se termination is more stable than Mo; moreover, as the size of the quantum dot increases, its stability increases as well. Besides, a trend is observed, with the appearance of elongated Mo-S/Se bonds at symmetric positions of the edges. Tersoff–Hamann scanning tunneling microscopy images for both faces of the stablest models are presented. Electrostatic potential isosurfaces denote that the basal plane on the S face of both configurations remains the region with more electron density concentration. These results point toward the differentiated activity over both faces. Finally, our study denotes the exact atomic arrangement on the edges of MoSSe quantum dots corresponding with the formation of S/Se dimers who decorates the edges and their role along with the faces as catalytic sites.
Insulin resistance and muscle weakness are synergistic risk factors for silent lacunar infarcts: the Bunkyo Health Study
Authors: Someya Yuki , Tamura Yoshifumi , Kaga Hideyoshi , Sugimoto Daisuke , Kadowaki Satoshi , Suzuki Ruriko , Aoki Shigeki , Hattori Nobutaka , Motoi Yumiko , Shimada Kazunori , Daida Hiroyuki , Ishijima Muneaki , Kaneko Kazuo , Nojiri Shuko , Kawamori Ryuzo , Watada Hirotaka
Published: October 2021

Insulin resistance and muscle weakness are risk factors for silent lacunar infarcts (SLI), but it is unclear whether they are still independent risk factors when adjusted for each other. In addition, the effect of their combination on SLI is completely unknown. We evaluated SLI, insulin sensitivity, and knee extensor muscle strength by magnetic resonance imaging, PREDIM, and dynamometer, respectively, in 1531 elderly people aged 65–84 years living in an urban area of Tokyo. Among the study subjects, 251 (16.4%) had SLI. Impaired insulin sensitivity (High; 1.00 [reference], Medium; 1.53 [95% confidence interval (CI) 0.94–2.48], Low; 1.86 [1.02–3.39], p for trend 0.047) and reduced muscle strength (High; 1.00 [reference], Medium; 1.40 [0.98–2.02], Low; 1.49 [1.04–2.15], p for trend 0.037) were independently associated with increased risk for SLI in the fully adjusted model. In terms of combined, subjects classified as having the lowest insulin sensitivity and lowest strength were 4.33 times (95% CI 1.64–11.45) more likely to have a SLI than those classified as having the highest insulin sensitivity and highest strength. Impaired insulin sensitivity and reduced muscle strength were independently associated with higher risk of SLI in elderly subjects, and their combination synergistically increased this risk.
Development and validation of a scoring system for pre-surgical and early post-surgical prediction of bariatric surgery unsuccess at 2 years
Authors: Bioletto Fabio , Pellegrini Marianna , D’Eusebio Chiara , Boschetti Stefano , Rahimi Farnaz , De Francesco Antonella , Arolfo Simone , Toppino Mauro , Morino Mario , Ghigo Ezio , Bo Simona
Published: October 2021

Bariatric surgery (BS) is an effective treatment for morbid obesity. However, a simple and easy-to-use tool for the prediction of BS unsuccess is still lacking. Baseline and follow-up data from 300 consecutive patients who underwent BS were retrospectively collected. Supervised regression and machine-learning techniques were used for model development, in which BS unsuccess at 2 years was defined as a percentage of excess-weight-loss (%EWL) < 50%. Model performances were also assessed considering the percentage of total-weight-loss (%TWL) as the reference parameter. Two scoring systems (NAG-score and ENAG-score) were developed. NAG-score, comprising only pre-surgical data, was structured on a 4.5-point-scale (2 points for neck circumference ≥ 44 cm, 1.5 for age ≥ 50 years, and 1 for fasting glucose ≥ 118 mg/dL). ENAG-score, including also early post-operative data, was structured on a 7-point-scale (3 points for %EWL at 6 months ≤ 45%, 1.5 for neck circumference ≥ 44 cm, 1 for age ≥ 50 years, and 1.5 for fasting glucose ≥ 118 mg/dL). A 3-class-clustering was proposed for clinical application. In conclusion, our study proposed two scoring systems for pre-surgical and early post-surgical prediction of 2-year BS weight-loss, which may be useful to guide the pre-operative assessment, the appropriate balance of patients’ expectations, and the post-operative care.
Gaze facilitates responsivity during hand coordinated joint attention
Authors: Caruana Nathan , Inkley Christine , Nalepka Patrick , Kaplan David M. , Richardson Michael J.
Published: October 2021

The coordination of attention between individuals is a fundamental part of everyday human social interaction. Previous work has focused on the role of gaze information for guiding responses during joint attention episodes. However, in many contexts, hand gestures such as pointing provide another valuable source of information about the locus of attention. The current study developed a novel virtual reality paradigm to investigate the extent to which initiator gaze information is used by responders to guide joint attention responses in the presence of more visually salient and spatially precise pointing gestures. Dyads were instructed to use pointing gestures to complete a cooperative joint attention task in a virtual environment. Eye and hand tracking enabled real-time interaction and provided objective measures of gaze and pointing behaviours. Initiators displayed gaze behaviours that were spatially congruent with the subsequent pointing gestures. Responders overtly attended to the initiator’s gaze during the joint attention episode. However, both these initiator and responder behaviours were highly variable across individuals. Critically, when responders did overtly attend to their partner’s face, their saccadic reaction times were faster when the initiator’s gaze was also congruent with the pointing gesture, and thus predictive of the joint attention location. These results indicate that humans attend to and process gaze information to facilitate joint attention responsivity, even in contexts where gaze information is implicit to the task and joint attention is explicitly cued by more spatially precise and visually salient pointing gestures.
Stereotactic navigation versus ultrasound guidance in placing IRE applicators in a liver phantom
Authors: Stillström David , Eigl Benjamin , Freedman Jacob
Published: October 2021

The aim of this study was to compare the accuracy of stereotactic CT-guided navigation and ultrasound guided navigation for placing electrodes in Irreversible electroporation in a liver phantom. A liver phantom with multiple tumours was used and interventionists placed four IRE electrodes around each tumour guided either by stereotactic CT-guided navigation or ultrasound. The goal was to place them in a perfect 20 × 20 mm square with parallel electrodes. After each treatment, a CT-scan was performed. The accuracy in pairwise electrode distance, pairwise parallelism and time per tumour was analysed. Eight interventionists placed four electrodes around 55 tumours, 25 with ultrasound and 30 with stereotactic CT-guided navigation. 330 electrode pairs were analysed, 150 with ultrasound and 180 with stereotactic CT-navigation. The absolute median deviation from the optimal distance was 1.3 mm (range 0.0 to 11.3 mm) in the stereotactic CT-navigation group versus 7.1 mm (range 0.3 to 18.1 mm) in the Ultrasound group (p < 0.001). The mean angle between electrodes in each pair was 2.7 degrees (95% CI 2.4 to 3.1 degrees) in the stereotactic CT-navigation group and 5.5 degrees (95% CI 5.0 to 6.1 degrees) in the Ultrasound group (p < 0.001). The mean time for placing the electrodes was 15:11 min (95% CI 13:05 to 17:18 min) in the stereotactic CT-navigation group and 6:40 min (95% CI 5:28 to 7:52 min) in the Ultrasound group. The use of stereotactic CT-navigation in placing IRE-electrodes in a liver phantom is more accurate, but more time consuming, compared to ultrasound guidance.
Convergent community structure of algal–bacterial consortia and its effects on advanced wastewater treatment and biomass production
Authors: Qi Feng , Jia Yantian , Mu Ruimin , Ma Guixia , Guo Qingyang , Meng Qianya , Yu Gejiang , Xie Jun
Published: October 2021

Microalgal-bacterial consortium is an effective way to meet increasingly stringent standards in wastewater treatment. However, the mechanism of wastewater removal effect has not been properly explained in community structure by phycosphere. And little is known about that the concept of macroecology was introduced into phycosphere to explain the phenomenon. In the study, the algal–bacterial consortia with different ratios of algae and sludge were cultured in same aerobic wastewater within 48 h in photobioreactors (PSBRs). Community structure at start and end was texted by metagenomic analysis. Bray–Curtis similarities analysis based on microbial community showed that there was obvious convergent succession in all consortia, which is well known as “convergence” in macroecology. The result showed that Bray–Curtis similarities at End (overall above 0.88) were higher than these at Start (almost less than 0.66). In terms of community structure, the consortium with 5:1 ratio at Start are the more similar with the consortia at End by which the maximum removal of total dissolved nitrogen (TDN, 73.69%), total dissolved phosphorus (TDP, 94.40%) and NH3-N (93.26%) in wastewater treatment process and biomass production (98.2%) higher than other consortia, according with climax community in macroecology with the highest resource utilization than other communities. Therefore, the macroecology can be introduced into phycosphere to explain the consortium for advanced wastewater treatment and optimization community structure. And the study revealed a novel insight into treatment effect and community structure of algal–bacterial consortia for advanced wastewater treatment, a new idea for to shortening the culture time of consortium and optimize predicting their ecological community structure and predicting ecological community.