bluuebunny/crossref_metadata_2025 huggingface dataset:
Locus coeruleus in the pathogenesis of Alzheimer's disease: A systematic review
Authors: Chen Yuqing , Chen Teng , Hou Ruihua
Published: March 2022

The locus coeruleus (LC) is a nucleus in the brain stem producing noradrenaline. While cognitive decline in Alzheimer's disease (AD) has primarily been related to cholinergic depletion, evidence indicates extensive LC degeneration as its earliest pathological marker. The current study aimed to systematically evaluate current evidence investigating the role of the LC in the pathogenesis of AD. A systematic search of the literature was performed on electronic databases including PubMed and Web of Science. Twelve animal, human post mortem, and human imaging studies were included in this review. Screening, data extraction, and quality assessment were undertaken following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines for preferred reporting of systematic reviews. Significant associations were identified between LC changes and cognitive decline. Significant reductions in fiber density, neuronal number, and LC volume were seen to correlate with other pathological degenerative markers. Current evidence indicates an important role of the LC in pathogenesis of AD and suggests its potential in both diagnosis and treatment of AD. This systematic review advances our understanding of the role of the LC in AD by synthesizing available evidence, identifying research gaps, highlighting methodological challenges, and making recommendations for future work.
Insights from the first International Water Policy Lab Champions' Forum: Developing modalities for cocreating knowledge, policy, and practice
Authors: Icyimpaye Adeline , Sharifi Sayed Saber , Anyanwu Ifeanyi Emmanuel , Aletoum Ehab , Tiwari Deepanker , Kanyunge Claydon Mumba , Otekpo Lémonla Armel , Malemba Edith , Adhiambo Betha , Itenya Wendy , Camkin Jeff
Published: March 2022

Solving water problems requires new ways of harnessing dialogs, reflections, empathy, research, and visions. Too often, water policies and practices tend to take shortcuts, missing out on the benefits these powerful social learning processes can bring towards water justice and sustainability. The question is: How do we apply and nurture an interactive approach to implement water management decisions that benefit both people and the environment, now and into the future? Tackling this question requires a transdisciplinary, practice‐focused, and policy‐oriented approach to learning and governing, embracing the idea of coproduction of knowledge, practice, and policy. The first International Water Policy Lab (WPL) Champions' Forum was organized by the Institute for Study and Development Worldwide (IFSD), the Australia India Water Centre, and World Water Policy Journal on July 16, 2021, bringing together a range of factors to share experience and lessons on processes and practices of the coproduction of policy, knowledge, and practice in water governance. Out of a group of 10 IFSD water policy and management interns under the guidance of Prof. Jeff Camkin, three participated in the WPL Forum and subsequently shared their learnings with the broader group. This discussion paper presents the ideas of all 10 IFSD interns, who come from nine different countries, about how WPL processes can support their efforts towards improving water policy and management around the world. The first WPL forum emphasized that interactive methods are needed to achieve successful water governance policies. It is due to this fact that policy development and implementation both require involvement, integration, and cooperation among all concerned stakeholders (government, researchers, local communities, businesses, etc.) at each stage. A key message from this forum was that boosting the community's role in water governance and its capability to contribute to water management can enhance the development and implementation of policies and the sustainability of water‐related projects.
Developmental life stages of the Pickersgill's reed frog (Hyperolius pickersgilli) in an ex‐situ environment at Johannesburg Zoo's captive breeding facility, South Africa
Authors: du Plessis Ian , Armstrong Adrian , Malepa Piet L. , Kanengoni Arnold T. , Price Cormac , Downs Colleen T.
Published: March 2022

Globally, the threats of habitat loss and disease on amphibian survival have necessitated the creation of ex‐situ insurance populations as a conservation tool. We initiated a captive breeding project to create an insurance population for the endangered Pickersgill's reed frog (Hyperolius pickersgilli Raw, 1982) at the Johannesburg Zoo from parents collected from KwaZulu‐Natal Province, South Africa, in 2017. We found that this species has seven developmental life stages, each with unique management requirements. The quiescent tadpoles hatched 6–8 days after the eggs were laid and remained at this stage for 2 days. The next stage, the developing tadpoles, showed no form of cannibalism or carrion feeding. The external appearance of the first leg (the right hind) occurred 5–6 weeks after the tadpoles hatched, and the metamorph stage was reached after 7–8 weeks. The metamorph stage lasted 3–5 days, after which tail resorption was complete and the froglet stage reached. Froglets could not be sexed externally, although body color changed based on the amount of light present at the resting place. Sub‐adults were 6 months and older with adult coloration and sex differentiation visible even with color change. Adults were older than 18 months and fully developed and sexually mature, displaying amplexus, oviposition, and external fertilization. A greater understanding of Pickersgill's reed frog's developmental stages and physiological and environmental needs can improve captive breeding and subsequent release of the frogs, facilitate captive breeding elsewhere, and improve the species’ conservation status.
„Resuscitative endovascular balloon occlusion of the aorta“ bei schwer verletzten Patienten im Schockraum: eine Fallserie
Authors: Knapp Jürgen , Jakob Dominik A. , Haltmeier Tobias , Lehmann Beat , Hautz Wolf E.
Published: March 2022

Eine Hämorrhagie ist in 30–40 % der Patienten, die im Rahmen eines Traumas versterben, todesursächlich und die häufigste vermeidbare Todesursache. Für nichtkomprimierbare Blutungen im Bereich des Abdomens oder des Beckens wird in den letzten Jahren zunehmend (wieder) die Anwendung der „resuscitative endovascular balloon occlusion of the aorta“ (REBOA) zur temporären Blutungskontrolle diskutiert. Seit August 2020 steht im Schockraum des Universitären Notfallzentrums des Universitätsspital Bern die REBOA als Therapieoption im Rahmen der Schwerverletztenversorgung zur Verfügung. Wir berichten in dieser Fallserie unsere Erfahrungen aus allen 7 Anwendungen im Laufe des ersten Jahres.
Harnessing the diversity of wild emmer wheat for genetic improvement of durum wheat
Authors: Balla Mohammed Yousif , Gorafi Yasir Serag Alnor , Kamal Nasrein Mohamed , Abdalla Modather Galal Abdeldaim , Tahir Izzat Sidahmed Ali , Tsujimoto Hisashi
Published: March 2022

Key message

The multiple derivative lines (MDLs) characterized in this study offer a promising strategy for harnessing the diversity of wild emmer wheat for durum and bread wheat improvement.

Crop domestication has diminished genetic diversity and reduced phenotypic plasticity and adaptation. Exploring the adaptive capacity of wild progenitors offer promising opportunities to improve crops. We developed a population of 178 BC1F6 durum wheat (Triticum turgidum ssp. durum) lines by crossing and backcrossing nine wild emmer wheat (T. turgidum ssp. dicoccoides) accessions with the common durum wheat cultivar ‘Miki 3’. Here, we describe the development of this population, which we named as multiple derivative lines (MDLs), and demonstrated its suitability for durum wheat breeding. We genotyped the MDL population, the parents, and 43 Sudanese durum wheat cultivars on a Diversity Array Technology sequencing platform. We evaluated days to heading and plant height in Dongola (Sudan) and in Tottori (Japan). The physical map length of the MDL population was 9 939 Mb with an average of 1.4 SNP/Mb. The MDL population had greater diversity than the Sudanese cultivars. We found high gene exchange between the nine wild emmer accessions and the MDL population, indicating that the MDL captured most of the diversity in the wild emmer accessions. Genome-wide association analysis identified three loci for days to heading on chromosomes 1A and 5A in Dongola and one on chromosome 3B in Tottori. For plant height, common genomic loci were found on chromosomes 4A and 4B in both locations, and one genomic locus on chromosome 7B was found only in Dongola. The results revealed that the MDLs are an effective strategy towards harnessing wild emmer wheat diversity for wheat genetic improvement.
Linear programming feedrate optimization
Authors: Petráček Petr , Vlk Bořivoj , Švéda Jiří
Published: March 2022

This paper focuses on two aspects of feedrate optimization via linear programming methods. Namely, the effect of curve sampling on time optimality of the resultant feedrate profile and a method of feedrate profile adaptation in response to a feedrate override command. A comparison of three distinct curve sampling approaches (uniform in parameter, uniform in arc length and curvature adaptive) is performed on a series of standard tool path curves. Results show that the curvature-adaptive sampling approach leads to substantial machining time reduction for tool path curves displaying high degree of curvature variation. Secondly, a method by which a new feedrate profile can be calculated in response to a feedrate override command is developed. The method formulates a new set of boundary conditions on the control point sequence of the feedrate curve in such a way that the resulting profile is guaranteed to coincide with the currently active profile up to the moment of override command, while minimizing the arc length necessary for transition to the newly commanded feedrate.
The p-adic Corlette–Simpson correspondence for abeloids
Authors: Heuer Ben , Mann Lucas , Werner Annette
Published: March 2022

For an abeloid variety A over a complete algebraically closed field extension K of $$\mathbb {Q}_p$$

Q
p

, we construct a p-adic Corlette–Simpson correspondence, namely an equivalence between finite-dimensional continuous K-linear representations of the Tate module and a certain subcategory of the Higgs bundles on A. To do so, our central object of study is the category of vector bundles for the v-topology on the diamond associated to A. We prove that any pro-finite-étale v-vector bundle can be built from pro-finite-étale v-line bundles and unipotent v-bundles. To describe the latter, we extend the theory of universal vector extensions to the v-topology and use this to generalise a result of Brion by relating unipotent v-bundles on abeloids to representations of vector groups.
Care reality of menopausal women in Germany: healthcare research using quantitative (SHI claims data) and qualitative (survey) data collection
Authors: Stute Petra , Eversheim Helena , Ortius-Lechner Diethe , May Melanie , Feig Chiara
Published: March 2022

Purpose

The transition from the fertile phase of life to menopause is associated with numerous physical changes. Hormone replacement therapy (HRT), as the most effective and efficient form of drug treatment, involves the use of oestrogens and progestins with the aim of increasing health-related quality of life through symptom reduction, sleep improvement and affect enhancement.

Methods

The medical care situation and disease burden of menopausal women was investigated by means of a survey of 1000 women aged 45–60 years on the topics of quality of life, menopause and HRT and a quantitative, longitudinal healthcare study based on an anonymised and age- and sex-adjusted Statutory Health Insurance (SHI) routine data set with approximately four million anonymous insured persons per year.

Results

Out of more than half a million women aged 35–70 years, and with statutory health insurance, (n = 613,104), 14% (n = 82,785) had climacteric disorder documented as a first diagnosis in 2014. The proportion of women with the climacteric disorder, who were prescribed HRT on an outpatient basis, was 21%; according to the forsa survey, 50% of the women surveyed felt moderate to poorly/very poorly informed about treatment options.

Conclusion

Findings from the health insurance research conducted with different data sources (survey and SHI claims data) indicate the need for increasing awareness and providing an early and informative education on HRT and its risks and benefits.
Outcomes and complications of cataract surgery in patients with chronic ocular graft-versus-host-disease—a multicenter, retrospective analysis
Authors: Gehlsen Uta , Faust Christiane , Blecha Christiane , Dietrich-Ntoukas Tina , Eberwein Philipp , Issleib Susanne , Meyer-ter-Vehn Tobias , Braun Regine , Westekemper Henrike , Steven Philipp
Published: March 2022

Purpose

To evaluate the outcome of phacoemulsification in patients with chronic ocular Graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplantation (aHSCT).

Methods

Retrospective, observational multicenter study from 1507 oGVHD patients. From the patient files, data were collected including best-corrected visual acuity (BCVA), intraocular pressure (IOP), Schirmer’s test I, tear film break-up time (TFBUT), corneal fluorescein staining score, postoperative complications, and pre- and post-operative topical therapy.

Results

Seventy-three patients underwent cataract surgery in 104 eyes. In n = 84 eyes, the oGVHD NIH grade was documented; 12% (n = 12) of analyzed eyes were staged oGVHD NIH grade 1, 31% (n = 32) NIH 2 and 39% (n = 41) NIH 3. The mean BCVA improved in 82% of the eyes (n = 86 eyes). BCVA significantly increased from 0.7 ± 0.5 to 0.4 ± 0.4 LogMAR after surgery independent from oGVHD severity. The mean IOP decreased from 14 ± 4 to 13 ± 4 mmHg after surgery. Visual acuity was moderately correlated to the pre-operative degree of corneal staining (Pearson p = 0.26, p = 0.002, Cohen’s effect size f = 0.29). The visual acuity decreased by 0.078 LogMar units (95% CI = 0.027–0.141) with each increase of corneal staining by one grade (p = 0.05). After surgery, corneal epitheliopathy increased significantly in 42% (n = 44) of the eyes. Postoperative complications included corneal perforation (n = 6, 6%), cystoid macular edema (n = 4, 4%), and endophthalmitis (n = 1, 1%).

Conclusion

Phacoemulsification in patients with chronic oGVHD significantly improves visual acuity, but is associated with an increased risk of complications in particular corneal epitheliopathy and corneal perforations.
Carbazochrome sodium sulfonate is not effective for prevention of post-gastric endoscopic submucosal dissection bleeding: A retrospective study
Authors: Takahashi Keitaro , Sasaki Takahiro , Ueno Nobuhiro , Uehara Kyoko , Kobayashi Yu , Sugiyama Yuya , Murakami Yuki , Kunogi Takehito , Ando Katsuyoshi , Kashima Shin , Moriichi Kentaro , Tanabe Hiroki , Okumura Toshikatsu , Fujiya Mikihiro
Published: March 2022

Background

Carbazochrome sodium sulfonate (CSS) is conventionally administered to prevent post-endoscopic submucosal dissection (ESD) bleeding in many institutions, but research on its preventive efficacy is lacking. Therefore, we investigated the risk of post-ESD bleeding and the preventive efficacy of CSS administration.

Methods

We retrospectively reviewed 304 lesions in 259 patients with gastric neoplasms who underwent ESD at Asahikawa Medical University Hospital from 2014 to 2021. In the CSS group, CSS 100 mg/day was intravenously infused with maintenance fluid replacement on postoperative days 0–2. The risk factors of post-ESD bleeding, including CSS administration, were investigated.

Results

The overall rate of post-ESD bleeding was 4.6% (14/304). The univariate analysis showed that atrial fibrillation (Af), warfarin intake, heparin replacement, and tumor location in the lower third were significant risk factors for increasing the likelihood of postoperative bleeding. In the multivariate analysis, Af (odds ratio [OR] 3.83, 95% CI 1.02–14.30; p < 0.05), heparin replacement (OR 4.60, 95% CI 1.02–20.70; p < 0.05), and tumor location in the lower third of the stomach (OR 6.67, 95% CI 1.43–31.00; p < 0.05) were independent factors for post-ESD bleeding. Post-ESD bleeding was observed in 5.2% (9/174) of the CSS group and 3.8% (5/130) of the non-CSS group, with no significant difference between the two groups (p = 0.783). Additionally, CSS was not shown to have preventive effects in groups with higher-risk factors, such as Af diagnosis, warfarin use, heparin replacement, and tumor location in the lower third of the stomach.

Conclusion

CSS administration was not effective for the prevention of the post-ESD bleeding in the overall patient population as well as in higher-risk patients. This suggests that the administration of CSS for post-ESD bleeding prevention may need to be reconsidered.
FDG-PET/CT for oral focus assessment in head and neck cancer patients
Authors: Schwaninger Dominic Raphael , Hüllner Martin , Bichsel Dominique , Giacomelli-Hiestand Barbara , Stutzmann Nicole Selina , Balermpas Panagiotis , Valdec Silvio , Stadlinger Bernd
Published: March 2022

Objectives

To compare oral and maxillo-mandibular inflammatory foci on standard oral radiographs (OPT, periapical radiograph) with available fluorine-18-labelled fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) data and to discuss whether additional metabolic information derived from FDG-PET/CT can support oral care specialists when performing oral focus examinations.

Materials and methods

Data from 23 patients with head and neck cancer who underwent FDG-PET/CT and panoramic and periapical radiography in close succession before first-line radiotherapy and/or chemotherapy were included in this exploratory retrospective study. Periapical lesions and marginal periodontal inflammation on FDG-PET/CT scans and standard oral radiographs were analysed and compared with regard to metabolic activity on FDG-PET/CT in comparison to recorded clinical symptoms and radiological scores. Additionally, inflammatory maxillo-mandibular pathologies were analysed using FDG-PET/CT.

Results

The maximum standardised uptake value (SUVmax) in FDG-avid marginal periodontal sites could not be conclusively associated with the radiologically recorded severity of marginal bone loss, but a potential positive correlation was identified. No association was found either between the metabolic activity of periapical lesions and their extent, as recorded on standard oral radiographs, or regarding clinical symptoms (percussion test). Most maxillo-mandibular pathologies did not show increased FDG uptake.

Conclusions

FDG-PET/CT provided additional metabolic information that can help clinicians identify lesions with increased inflammatory activity. The incorporation of available oral FDG-PET/CT findings into the primary oral focus assessment may allow for more accurate oral focus treatment.

Clinical relevance

FDG-PET/CT provides valuable metabolic information for oral care specialists. The detection of inflammatory oral processes using FDG-PET/CT facilitates treatment.
A Bayesian approach to model individual differences and to partition individuals: case studies in growth and learning curves
Authors: Mezzetti Maura , Borzelli Daniele , d’Avella Andrea
Published: March 2022

The first objective of the paper is to implement a two stage Bayesian hierarchical nonlinear model for growth and learning curves, particular cases of longitudinal data with an underlying nonlinear time dependence. The aim is to model simultaneously individual trajectories over time, each with specific and potentially different characteristics, and a time-dependent behavior shared among individuals, including eventual effect of covariates. At the first stage inter-individual differences are taken into account, while, at the second stage, we search for an average model. The second objective is to partition individuals into homogeneous groups, when inter individual parameters present high level of heterogeneity. A new multivariate partitioning approach is proposed to cluster individuals according to the posterior distributions of the parameters describing the individual time-dependent behaviour. To assess the proposed methods, we present simulated data and two applications to real data, one related to growth curve modeling in agriculture and one related to learning curves for motor skills. Furthermore a comparison with finite mixture analysis is shown.
Semantic feature activation takes time: longer SOA elicits earlier priming effects during reading
Authors: Hofmann Markus J. , Kleemann Mareike A. , Roelke-Wellmann André , Vorstius Christian , Radach Ralph
Published: March 2022

While most previous studies of “semantic” priming confound associative and semantic relations, here we use a simple co-occurrence-based approach to examine “pure” semantic priming, while experimentally controlling for associative relations. We define associative relations by the co-occurrence of words in the sentences of a large text corpus. Contextual-semantic feature overlap, in contrast, is defined by the number of common associates that the prime shares with the target. Then we revisit the spreading activation theory and examine whether a long vs. short time available for semantic feature activation leads to early vs. late viewing time effects on the target words of a sentence reading experiment. We independently manipulate contextual-semantic feature overlap of two primes with one target word in sentences of the form pronoun, verb prime, article, adjective prime and target noun, e. g., "She rides the gray elephant." The results showed that long-SOA (verb-noun) overlap reduces early single and first fixation durations of the target noun, and short-SOA (adjective-noun) overlap reduces late go-past durations. This result pattern can be explained by the spreading activation theory: The semantic features of the prime words need some time to become sufficiently active before they can reliably affect target processing. Therefore, the verb can act on the target noun's early eye-movement measures presented three words later, while the adjective is presented immediately prior to the target—thus a difficult adjective-noun semantic integration leads to a late sentence re-examination of the preceding words.
An atomistic view on the uptake of aromatic compounds by cyclodextrin immobilized on mesoporous silica
Authors: Kraus Hamzeh , Hansen Niels
Published: March 2022

The effect of immobilized $$\upbeta$$
β
-cyclodextrin (bCD) molecules inside a mesoporous silica support on the uptake of benzene and p-nitrophenol from aqueous solution was investigated using all-atom molecular dynamics (MD) simulations. The calculated adsorption isotherms are discussed with respect to the free energies of binding for a 1:1 complex of bCD and the aromatic guest molecule. The adsorption capacity of the bCD-containing material significantly exceeds the amount corresponding to a 1:1 binding scenario, in agreement with experimental observations. Beside the formation of 1:2 and, to a lesser extent, 1:3 host:guest complexes, also host–host interactions on the surface as well as more unspecific host–guest interactions govern the adsorption process. The demonstrated feasibility of classical all-atom MD simulations to calculate liquid phase adsorption isotherms paves the way to a molecular interpretation of experimental data that are too complex to be described by empirical models.
Global Poverty and Kantian Hope
Authors: Blöser Claudia
Published: March 2022

Development economists have suggested that the hopes of the poor are a relevant factor in overcoming poverty. I argue that Kant’s approach to hope provides an important complement to the economists’ perspective. A Kantian account of hope emphasizes the need for the rationality of hope and thereby guards against problematic aspects of the economists’ discourse on hope. Section 1 introduces recent work on hope in development economics. Section 2 clarifies Kant’s question “What may I hope?” and presents the outlines of his answer. Crucially, hope is rational if it is rational to trust in the structures of reality on which the realization of one’s hope depends. Section 3 argues that central tenets of Kant’s account of what makes hope rational can be applied to the context of poverty. It becomes apparent that the poor often have good reason to be hopeless since they may not trust fundamental structures that are necessary for realizing their hope. Thus, the insight that the poor need more hope must go hand in hand with a commitment to establishing trustworthy political structures, such that their hope can be rational. Section 4 highlights the relevance of the secular highest good for a better understanding of the justification and scope of our duties to the poor in a Kantian framework.
Underground LoRa Sensor Node for Bushfire Monitoring
Authors: Herring Ben , Sharp Tony , Roberts Tim , Fastier-Wooller Jarred , Kelly Greg , Sahin Oz , Thiel David , Dao Dzung , Woodfield Peter L.
Published: March 2022

The feasibility of an underground LoRaWAN bushfire temperature sensing node from the point of view of survivability in a bushfire event is considered. Thermal penetration into the soil is modelled using a one-dimensional analytical formulation for a semi-infinite solid. A working prototype of the sensor unit was tested experimentally beneath a relatively small (400 mm × 400 mm base) timber fire. A buried LoRa radio (depth 100 mm) with a k-type thermocouple monitored the temperature from beneath the fire. The analysis demonstrates that under dry soil conditions, the time that the sensor node under the fire base can endure is proportional to the square of the depth of burial of the electronic components and inversely proportional to the thermal diffusivity of the soil. The original contribution of the work is in the practical demonstration of the durability of a LoRa sensing node beneath a fire front for bushfire sensing applications.
sMARE: a new paradigm to evaluate and understand query performance prediction methods
Authors: Faggioli Guglielmo , Zendel Oleg , Culpepper J. Shane , Ferro Nicola , Scholer Falk
Published: March 2022

Query performance prediction (QPP) has been studied extensively in the IR community over the last two decades. A by-product of this research is a methodology to evaluate the effectiveness of QPP techniques. In this paper, we re-examine the existing evaluation methodology commonly used for QPP, and propose a new approach. Our key idea is to model QPP performance as a distribution instead of relying on point estimates. To obtain such distribution, we exploit the scaled Absolute Ranking Error (sARE) measure, and its mean the scaled Mean Absolute Ranking Error (sMARE). Our work demonstrates important statistical implications, and overcomes key limitations imposed by the currently used correlation-based point-estimate evaluation approaches. We also explore the potential benefits of using multiple query formulations and ANalysis Of VAriance (ANOVA) modeling in order to measure interactions between multiple factors. The resulting statistical analysis combined with a novel evaluation framework demonstrates the merits of modeling QPP performance as distributions, and enables detailed statistical ANOVA models for comparative analyses to be created.
Why Indirect Harms do not Support Social Robot Rights
Authors: Sweeney Paula
Published: March 2022

There is growing evidence to support the claim that we react differently to robots than we do to other objects. In particular, we react differently to robots with which we have some form of social interaction. In this paper I critically assess the claim that, due to our tendency to become emotionally attached to social robots, permitting their harm may be damaging for society and as such we should consider introducing legislation to grant social robots rights and protect them from harm. I conclude that there is little evidence to support this claim and that legislation in this area would restrict progress in areas of social care where social robots are a potentially valuable resource.
Engaging communities to prepare for natural hazards: a conceptual model
Authors: Johnston Kim A. , Taylor Maureen , Ryan Barbara
Published: March 2022

Natural hazard preparation by communities reduces disaster-induced physical health problems and adverse experiences, lowers potential for post-traumatic stress disorders, and aids faster recovery. However, approaches to community engagement for preparedness vary widely leaving those responsible confused and often overwhelmed. This study builds on natural hazards behavior, community development, participatory, and codesign research to understand current community engagement approaches in an Australian context. Key principles for engaging communities were operationalized from document analysis and interviews with 30 community engagement practitioners from 25 Australian emergency management agencies. A thematic analysis of the agency documents and interviews led to a visualization of the pathway to community-led preparedness with the iterative community-centered engagement model for preparedness. The model reflects both current practice and aspirations. It contributes theoretically to a collaborative community-led engagement approach for risk personalization and protective action by highlighting the need to develop a deep understanding of the specific features of local communities. The model maps a pathway through different levels of community engagement toward the ultimate aim of a community-led approach to natural hazards preparation. It recognizes the changing circumstances and the situation of communities within their environment, and the barriers and enablers to support community-led preparedness. The model is significant in that it delivers a practical framework for engagement practitioners to build capacity in their communities and support their local communities to prepare for natural hazards and build relational capital for longer-term resilience.
Pharmacoproteomics of Brain Barrier Transporters and Substrate Design for the Brain Targeted Drug Delivery
Authors: Huttunen Kristiina M. , Terasaki Tetsuya , Urtti Arto , Montaser Ahmed B. , Uchida Yasuo
Published: March 2022

One of the major reasons why central nervous system (CNS)-drug development has been challenging in the past, is the barriers that prevent substances entering from the blood circulation into the brain. These barriers include the blood-brain barrier (BBB), blood-spinal cord barrier (BSCB), blood-cerebrospinal fluid barrier (BCSFB), and blood-arachnoid barrier (BAB), and they differ from each other in their transporter protein expression and function as well as among the species. The quantitative expression profiles of the transporters in the CNS-barriers have been recently revealed, and in this review, it is described how they affect the pharmacokinetics of compounds and how these expression differences can be taken into account in the prediction of brain drug disposition in humans, an approach called pharmacoproteomics. In recent years, also structural biology and computational resources have progressed remarkably, enabling a detailed understanding of the dynamic processes of transporters. Molecular dynamics simulations (MDS) are currently used commonly to reveal the conformational changes of the transporters and to find the interactions between the substrates and the protein during the binding, translocation in the transporter cavity, and release of the substrate on the other side of the membrane. The computational advancements have also aided in the rational design of transporter-utilizing compounds, including prodrugs that can be actively transported without losing potency towards the pharmacological target. In this review, the state-of-art of these approaches will be also discussed to give insights into the transporter-mediated drug delivery to the CNS.
Affective Polarization: Over Time, Through the Generations, and During the Lifespan
Authors: Phillips Joseph
Published: March 2022

The continual rise of affective polarization in the United States harms trust in democratic institutions. Scholars cite processes of ideological and social sorting of the partisan coalitions in the electorate as contributing to the rise of affective polarization, but how do these processes relate to one another? Most scholarship implicitly assumes period effects—that people change their feelings toward the parties uniformly and contemporaneously as they sort. However, it is also possible that sorting and affective polarization link with one another as a function of age or cohort effects. In this paper, I estimate age, period and cohort effects on affective polarization, partisan strength, and ideological sorting. I find that affective polarization increases over time, but also as people age. Age-related increases in affective polarization occur as a function of increases in partisan strength, and for Republicans, social sorting. Meanwhile, sorting only partially explains period effects. These effects combine such that each cohort enters the electorate more affectively polarized than the last.
The structure of mean equicontinuous group actions
Authors: Fuhrmann Gabriel , Gröger Maik , Lenz Daniel
Published: March 2022

We study mean equicontinuous actions of locally compact σ-compact amenable groups on compact metric spaces. In this setting, we establish the equivalence of mean equicontinuity and topo-isomorphy to the maximal equicontinuous factor and provide a characterization of mean equicontinuity of an action via properties of its product. This characterization enables us to show the equivalence of mean equicontinuity and the weaker notion of Besicovitch-mean equicontinuity in fairly high generality, including actions of abelian groups as well as minimal actions of general groups. In the minimal case, we further conclude that mean equicontinuity is equivalent to discrete spectrum with continuous eigenfunctions. Applications of our results yield a new class of non-abelian mean equicontinuous examples as well as a characterization of those extensions of mean equicontinuous actions which are still mean equicontinuous.
A Narrative Review of Pathogenetic and Histopathologic Aspects, Epidemiology, Classification Systems, and Disease Outcome Measures in Systemic Sclerosis
Authors: Lazzaroni Maria-Grazia , Piantoni Silvia , Angeli Fabrizio , Bertocchi Stefania , Franceschini Franco , Airò Paolo
Published: March 2022

Systemic sclerosis (SSc) is a rare systemic autoimmune disease, characterized by the presence of three main actors: vasculopathy, immune activation, and fibrosis. This pathologic process is then translated in a clinical picture with great variability among different patients in terms of type of organ involvement, disease severity and prognosis. This heterogeneity is a main feature of SSc, which, in addition to the presence of early phases of the disease characterized by mild symptoms, can explain the high difficulty in establishing classification criteria, and in defining patients’ subsets and disease outcomes. The definition of disease outcomes is particularly relevant in the setting of clinical trials, where the aim is to provide reliable endpoints, able to measure the magnitude of the efficacy of a certain drug or intervention. For this reason, in the last years, increasing efforts have been done to design measures of disease activity, damage, severity, and response to treatment, often in the context of composite indexes. When considering disease outcomes, the experience of the patient represents a relevant and complementary aspect. The tools able to capture this experience, the patient-reported outcomes, have been increasingly used in the last years in clinical practice and in clinical trials, both as primary and secondary endpoints. This comprehensive narrative review on SSc will therefore cover pathogenetic and histopathologic aspects, epidemiology, classification systems, and disease outcome measures, in order to focus on issues that are relevant for clinical research and design of clinical trials.
A Mutant Variant of E2F4 Triggers Multifactorial Therapeutic Effects in 5xFAD Mice
Authors: López-Sánchez Noelia , Ramón-Landreau Morgan , Trujillo Cristina , Garrido-García Alberto , Frade José M.
Published: March 2022

Alzheimer’s disease (AD) has a complex etiology, which requires a multifactorial approach for an efficient treatment. We have focused on E2 factor 4 (E2F4), a transcription factor that regulates cell quiescence and tissue homeostasis, controls gene networks affected in AD, and is upregulated in the brains of Alzheimer’s patients and of APPswe/PS1dE9 and 5xFAD transgenic mice. E2F4 contains an evolutionarily conserved Thr-motif that, when phosphorylated, modulates its activity, thus constituting a potential target for intervention. In this study, we generated a knock-in mouse strain with neuronal expression of a mouse E2F4 variant lacking this Thr-motif (E2F4DN), which was mated with 5xFAD mice. Here, we show that neuronal expression of E2F4DN in 5xFAD mice potentiates a transcriptional program consistent with the attenuation of the immune response and brain homeostasis. This correlates with reduced microgliosis and astrogliosis, modulation of amyloid-β peptide proteostasis, and blocking of neuronal tetraploidization. Moreover, E2F4DN prevents cognitive impairment and body weight loss, a known somatic alteration associated with AD. We also show that our finding is significant for AD, since E2F4 is expressed in cortical neurons from Alzheimer patients in association with Thr-specific phosphorylation, as evidenced by an anti-E2F4/anti-phosphoThr proximity ligation assay. We propose E2F4DN-based gene therapy as a promising multifactorial approach against AD.
Clinical impact of delays in the management of lung cancer patients in the last decade: systematic review
Authors: Guirado María , Fernández Martín Elena , Fernández Villar Alberto , Navarro Martín Arturo , Sánchez-Hernández Alfredo
Published: March 2022

Introduction

Due to the importance of lung cancer early treatment because of its severity and extent worldwide a systematic literature review was conducted about the impact of delays in waiting times on the disease prognosis.

Materials and Methods

We conducted a systematic search of observational studies (2010-2020) including adult patients diagnosed with lung cancer and reporting healthcare timelines and their clinical consequences.

Results

We included 38 articles containing data on waiting times and prognosis; only 31 articles linked this forecast to a specific waiting time. We identified 41 healthcare time intervals and found medians of 6-121 days from diagnosis to treatment and 4-19.5 days from primary care to specialist visit: 37.5% of the intervals indicated better prognosis with longer waiting times.

Conclusions

All articles emphasized that waiting times must be reduced to achieve good management and prognosis of lung cancer. Further prospective studies are needed on the relationship between waiting times and prognosis of lung cancer.
A Metric Version of Poincaré’s Theorem Concerning Biholomorphic Inequivalence of Domains
Authors: Lemmens Bas
Published: March 2022

We show that if$$Y_j\subset \mathbb {C}^{n_j}$$Yj⊂Cnjis a bounded strongly convex domain with$$C^3$$C3-boundary for$$j=1,\dots ,q$$j=1,⋯,q, and$$X_j\subset \mathbb {C}^{m_j}$$Xj⊂Cmjis a bounded convex domain for$$j=1,\ldots ,p$$j=1,…,p, then the product domain$$\prod _{j=1}^p X_j\subset \mathbb {C}^m$$∏j=1pXj⊂Cmcannot be isometrically embedded into$$\prod _{j=1}^q Y_j\subset \mathbb {C}^n$$∏j=1qYj⊂Cnunder the Kobayashi distance, if$$p>q$$p>q. This result generalises Poincaré’s theorem which says that there is no biholomorphic map from the polydisc onto the Euclidean ball in$$\mathbb {C}^n$$Cnfor$$n\ge 2$$n≥2. The method of proof only relies on the metric geometry of the spaces and will be derived from a more general result for products of proper geodesic metric spaces with the sup-metric. In fact, the main goal of the paper is to establish a general criterion, in terms of certain asymptotic geometric properties of the individual metric spaces, that yields an obstruction for the existence of an isometric embedding between product metric spaces.
Accurate Determination of Zr Isotopic Ratio in Zircons by Femtosecond Laser Ablation MC-ICP-MS with “Wet” Plasma Technique
Authors: Zhang Wen , Hu Zhaochu , Feng Lanping , Wang Zaicong , Liu Yongsheng , Feng Yantong , Liu Hong
Published: March 2022

This work evaluates the use of femtosecond laser ablation multiple collector inductively coupled plasma mass spectrometry (fs-LA-MC-ICP-MS) for Zr isotopic analysis in zircons. The mass fractionation caused by instrumental mass discrimination was corrected by a combination of internal correction using Sr as an internal standard (coming from a NIST SRM 987 standard solution) and external correction using a matrix-matched standard. Several important instrument parameters were investigated, such as the effect of the addition of N2 and “wet” plasma condition, the mass fractionation behaviors between Zr isotopes and Sr isotopes, the position effect in laser ablation cell and the effect of laser ablation parameters (laser spot size and energy density). The Zr isotope compositions of seven zircons (GJ-1, 91500, Plešovice, Rak-17, Paki, Aus and Mala) were determined by the developed fs-LA-MC-ICP-MS and thermal ionization mass spectrometry (TIMS). Our fs-LA-MC-ICP-MS results for Zr isotope compositions agreed with TIMS analyses within analytical uncertainties, indicating the presented method is a suitable tool to resolve isotopic zoning in natural zircons. The results also suggest that GJ-1, 91500, Plešovice, Paki, Aus and Mala had the homogenous Zr isotope composition and could be considered as the potential candidates for the Zr isotope analysis in zircons, except Rak-17 which presented the large Zr isotope variation.
Multiple-Stage Mineralization in the Huayangchuan U−REE−Mo−Cu−Fe Ore Belt of the Qinling Orogen, Central China: Geological and Re−Os Geochronological Constraints
Authors: Jiang Hongjun , Yang Chunsi , Wang Dequan , Zheng Hui , Li Jie , Chen Huayong
Published: March 2022

The Huayangchuan ore belt is located in the western segment of Xiaoqinling Orogen in the southern margin of the North China Craton (NCC), and hosts voluminous magmatism and significant U−REE−Mo−Cu−Fe polymetallic mineralization. However, geochronological framework of the various mineralization phases in this region is poorly understood. Here, we present new Re−Os isochron ages on magnetite from the Caotan Fe deposit (2 675 ± 410 Ma, MSWD = 0.55), and on pyrite from the Jialu REE deposit (2 127 ± 280 Ma, MSWD = 1.9) and Yuejiawa Cu deposit (418 ± 23 Ma, MSWD = 11.5), and Re−Os weighted average model age on pyrite from the Taoyuan Mo−U deposit (235 ± 14 Ma, MSWD = 0.17). These ages, combined with regional geology and mineralization ages from other deposits, suggest that mineralization in the Huayangchuan ore belt lasted from the Neoarchean to the Late Mesozoic. The mineralization corresponds to regional tectono-magmatic events, including the Neoar-chean alkali magmatism (REE mineralization), Paleoproterozoic plagioclase-amphibolite emplacement (Fe mineralization), Paleoproterozoic pegmatite magmatism (U mineralization), Paleozoic Shangdan oceanic slab subduction-related arc magmatism (Cu mineralization), Early Mesozoic Paleo-Tethys Ocean subduction-related arc magmatism (Mo−U mineralization), and Late Mesozoic Paleo-Pacific oceanic plate subduction direction change-related Mo(-Pb) mineralization. We proposed that the Huayang-chuan ore belt has undergone prolonged metallogenic evolution, and the magmatism and associated mineralization were controlled by regional geodynamic events.
Is acetamiprid really not that harmful to bumblebees (Apidae: Bombus spp.)?
Authors: Varga-Szilay Zsófia , Tóth Zoltán
Published: March 2022

Due to recent changes in regulation, acetamiprid has become the only neonicotinoid that can be applied without restrictions and in open field cultivations in the EU from 2021. We provide an overview of the current knowledge on the effects of this insecticide on bumblebees and assessed whether available empirical evidence supports the claim that acetamiprid poses negligible risk to these pollinators. We found that there is limited data on the lethal and sublethal effects of this pesticide on bumblebees. While risk assessment results suggest that field-realistic concentrations of acetamiprid have minor acute and chronic toxicity, detrimental sublethal effects, including reduced reproductive output, have been observed when bumblebees were exposed to high doses of this insecticide. We propose that further research on the topic is warranted as the more extensive application of acetamiprid may lead to such high concentrations in the field.
Structure of Fejes Tóth cells in natural honey bee combs
Authors: Yang Shunhua , Gong Xueyang , Zhou Danyin , Zhang Xuan , Kuang Haiou , Dong Kun
Published: March 2022

We present an analysis of the structure of Fejes Tóth cells in the natural combs of the Chinese bee, Apis cerana cerana (Hymenoptera: Apidae), and the Italian bee, Apis mellifera ligustica (Hymenoptera: Apidae). The proportion of Fejes Tóth cells in the natural combs built by bee colonies was determined. Molds of Fejes Tóth cells and three-rhombus cells were used to measure various structural parameters, such as the diameter and depth of Fejes Tóth cells and three-rhombus cells. Both Chinese bees and Italian bees built an average of no more than 18% Fejes Tóth cells on natural combs. The dihedral angle of the two hexagonal planes at the bottom of the Fejes Tóth cells was significantly less than 120°. No significant differences in the diameter and depth of Fejes Tóth cells and three-rhombus cells were observed. The results of this study clarified the structural characteristics of Fejes Tóth cells in natural combs. These data will aid the manufacture of Fejes Tóth wax comb foundations specifically and the growth of the beekeeping industry more generally.
Genetic diversity and population genetic structure analysis of Apis mellifera subspecies in Algeria and Europe based on complementary sex determiner (CSD) gene
Authors: FRIDI Riad , TABET AOUL Nacera , CATAYS Guillaume , BASSO Benjamin , BIENEFELD Kaspar , GREGORC Aleš , VIGNAL Alain , CANALE-TABET Kamila
Published: March 2022

In honeybees, the mechanism of sex determination depends on genetic variation at the complementary sex determiner (CSD) locus, which has a large allelic diversity. In this study, we examined the population genetic structure and genetic diversity within the highly variable region (HVR) of CSD in five Apis mellifera subspecies, in addition to Buckfast and unknown mixed ancestry bees. We sequenced CSD in 329 drones, 146 from Algeria (A. m. intermissa and A. m. sahariensis subspecies) and 183 from Europe (A. m. ligustica, A. m. carnica, A. m. mellifera subspecies, Buckfast samples, and individuals of unknown mixed ancestry). A total of 119 nucleotide haplotypes were detected. These corresponded to 119 protein haplotypes, of which 81 were new. The analysis of these haplotypes showed that HVR diversity levels were comparable with those in other populations of honeybee worldwide. Paradoxically, this high level of diversity at the locus did not allow for a separation of the samples according to their subspecies origin, which suggested either an evolutionary convergence or a conservation of alleles across subspecies, and an absence of genetic drift. Our results can be used to provide more information about the CSD diversity to include in breeding programs of honeybee populations.