bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of analgesics on executive function and memory in the Alzheimer’s Disease Neuroimaging Initiative Database
Authors: Doan Lisa , Choi Daniel , Kline Richard
Published: February 2024

Background and aims

Pain is common in older adults but may be undertreated in part due to concerns about medication toxicity. Analgesics may affect cognition. In this retrospective cohort study, we used the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database to examine the interaction of cognitive status and medications, especially non-steroidal anti-inflammatory drugs (NSAIDs). We hypothesized NSAID use would be associated with cognition and that this could be mediated through changes in brain structure.

Methods

In this post hoc analysis of the ADNI database, subjects were selected by searching the “concurrent medications log” for analgesic medications. Subjects were included if the analgesic was listed on the medication log prior to enrollment in ADNI and throughout the study. Subjects taking analgesics, particularly NSAIDs, at each study visit were compared to control subjects taking no analgesics. Using descriptive statistics as well as univariate, multivariate and repeated measure ANOVA, we explored the relationship between NSAID use and scores for executive function and memory related cognitive activities. We further took advantage of the extensive magnetic resonance imaging (MRI) data available in ADNI to test whether cognitive change was associated with brain structure. The multitude of imaging variables was compressed into a small number of features (five eigenvectors (EV)) using principal component analysis.

Results

There were 87 NSAID users, 373 controls, and 71 taking other analgesics. NSAID use was associated with higher executive function scores for cognitively normal (NL) subjects as well as subjects with mild cognitive impairment (MCI). NSAID use was also associated with higher memory scores, but for NL females only. We analysed MRI data using principal component analysis to generate a set of five EVs. Examining NL and MCI subjects, one EV had significantly larger values in subjects taking NSAIDs versus control. This EV was one of two EVs which significantly correlated with composite executive function and memory scores as well as cognitive diagnosis.

Conclusions

NSAID use was associated with higher executive function, and memory scores in certain subjects and larger cortical volumes in particular regions. Limitations of the study include secondary analysis of existing data and the possibility of confounding.

Implications

These results suggest it is important to consider the secondary effects of medications when choosing a treatment regimen. Further prospective studies are needed to examine the role of analgesics on cognition and whether NSAIDs act through cortical dimension changes and how they are related to gender and cognitive diagnosis.
Psychoneuroimmunological approach to gastrointestinal related pain
Authors: Toljan Karlo , Vrooman Bruce
Published: February 2024

Graphical Abstract
Comparative Perspectives on the Protection of Food Geographical Indications in Asian Countries
Authors: Datta Sayantani , Manchikanti Padmavati , Bhattacharya Niharika Sahoo
Published: February 2024

The significance of food is beyond its gastronomic value. Food symbolises a community's enriched past and holds cultural expressions and traditional knowledge. The linkage of food with religious beliefs, geo-climatic factors, social standards, and various health benefits builds the reputation of the food, which is essentially attributable to its geographic origin. Following the ratification of the Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS), the contracting states that have enacted Geographical Indications (GI) legislation (particularly those in Asia) have come forward to protect foodstuffs as GI in order to safeguard their communities and their traditional knowledge associated with foodstuffs. Against this background, the present article attempts to compare foodstuff GIs in eight selected Asian countries with a sui generis system of GI protection as TRIPS compliance. The comparative analysis of the evolution and scope of foodstuff protection, pre-registration and post-registration impact, and quality maintenance provides important insights into convergence and divergence among the selected Asian countries. The study further identifies policy implications for the sustenance of GI.
Policy Diffusion, Environmental Federalism, and Economic Efficiency – How Institutions Influence the Implementation of EU Legislation in Two Nordic Countries
Authors: Nerhagen Lena , Jussila Hammes Johanna
Published: February 2024

We explore the changes in central government administration due to European Union (EU) membership and its consequences for policy outcomes and economic efficiency in Finland and Sweden. Both countries became members of the EU in 1995. Upon joining the union, member states are expected to adopt common legislation and are encouraged to develop similar rule-making procedures. The actual implementation of EU directives varies considerably between member states, however. This is also the case for Finland and Sweden. Despite the two Nordic countries for historical reasons having had similar government systems, upon becoming members of the EU, they started to diverge. Using a model of delegation and comparing the more centralized Finnish system with the decentralized institutional setup in Sweden, we show that the Swedish approach leads to a stricter than optimal environmental policy, which in turn makes EU policy non-optimal from a global point of view, ceteris paribus. We also provide empirical support for our findings in the form of some example cases. We focus on environmental policy since this is an area that has been high on the EU agenda.
Developing a shared understanding of translational science within CTSA hubs through facilitated retreats: A case study
Authors: Glauber Kristine M. , Turner Amalia A. , Sperling Jessica , McClernon F. Joseph
Published: February 2024

Translation of critical and broadly impactful health advancements is stymied by insufficient scientific scrutiny of barriers and roadblocks in the process. The Clinical & Translational Science Award (CTSA) funding opportunity announcement released in July 2021 makes clear the distinction between translational research and translational science (TS) and urges a shift from the former to the latter. This represents a significant shift in the overall scientific direction of the CTSA program and necessitates corresponding shifts in CTSA hub operations. To better support TS, the Team Science Core of the Duke CTSA hub designed and facilitated a virtual retreat for hub personnel that (1) enabled organizational learning about TS and (2) identified anticipated challenges and opportunities. A post-retreat survey was utilized to assess the degree to which the retreat met its stated goals. Our survey received a 62% response rate; 100% of respondents would recommend the session to others. Respondents also reported gains in all areas assessed, with evidence for greater understanding of TS and increased perspective of the value and relevance of TS. In this paper, we provide a roadmap for designing and implementing facilitated TS retreats, which we argue is a key step in TS capacity building through workforce development.
Party-Based Sovereignism in EU Countries: Main Patterns and Their Justification
Authors: Angelucci Davide , Carrieri Luca , Conti Nicolò
Published: February 2024

In this article, we examine party positions on sovereignty issues in European countries based on an analysis of party supply. First, we develop an index of sovereignism reflecting the multidimensional articulation and differentiated emphasis put by parties on sovereignist issues. By applying the index to Chapel Hill Expert Survey (CHES) data, the analysis maps all EU member states. Second, we integrate in the analysis party- and country-level data (including the orientations of domestic public opinion). Through multivariate regression analysis we show how party ideology, contextual factors and public mood favoured the spread of party-based sovereignism in European countries.
“A Ceremony of National and Representative Character”: The Four-Nations Politics of Queen Victoria's Golden Jubilee
Authors: Hight Alison
Published: February 2024

In June 1887, Britons crowded the streets of London to celebrate Queen Victoria's fiftieth year on the throne. It was an opportunity to publicly revel in the social, political, economic, and imperial progress Britain had made during her historic reign. The Lord Chamberlain was tasked with organizing a formal jubilee ceremony at Westminster Abbey representative of the queen's diverse subjects. But this proved a difficult undertaking for a multinational kingdom with a vast overseas empire. Grievances over seating in Westminster Abbey, jubilee honors, and an absent royal family fostered varying degrees of solidarity and rivalry among the United Kingdom's four constituent nations. The Irish Question and imperial expansion—matters in which Victoria was personally invested—heightened four-nations sensibilities and influenced participation in the festivities. The queen's Golden Jubilee both reflected and inspired four-nations thinking, and it revealed public concerns that the British union might exist as a hierarchy of nations rather than as a collaborative venture among equal members. As the institutional embodiment of tiered society, the Crown became an outlet for subjects to explore questions and modes of belonging within the global British world. A four-nations analysis of Victoria's 1887 jubilee shows that despite its unifying function, the modern British monarchy has struggled to harmonize the United Kingdom's multinational perspectives.
Formation and persistence of glaciovolcanic voids explored with analytical and numerical models
Authors: Unnsteinsson Tryggvi , Flowers Gwenn E. , Williams-Jones Glyn
Published: February 2024

One fifth of Earth's volcanoes are covered by snow or ice and many have active geothermal systems that interact with the overlying ice. These glaciovolcanic interactions can melt voids into glaciers, and are subject to controls exerted by ice dynamics and geothermal heat output. Glaciovolcanic voids have been observed to form prior to volcanic eruptions, which raised concerns when such features were discovered within Job Glacier on Qw̓elqw̓elústen (Mount Meager Volcanic Complex), British Columbia, Canada. In this study we model the formation, evolution, and steady-state morphology of glaciovolcanic voids using analytical and numerical models. Analytical steady-state void geometries show cave height limited to one quarter of the ice thickness, while numerical model results suggest the void height h scales with ice thickness H and geothermal heat flux

$\dot {Q}$

as

$h/H = a H^b \dot {Q}^c$

, with exponents b = −n/2 and c = 1/2 where n is the creep exponent. Applying this scaling to the glaciovolcanic voids within Job Glacier suggests the potential for total geothermal heat flux in excess of 10 MW. Our results show that relative changes in ice thickness are more influential in glaciovolcanic void formation and evolution than relative changes in geothermal heat flux.
Analysis of
${\textit{d}}$
-ary tree algorithms with successive interference cancellation
Authors: Vogel Quirin , Deshpande Yash , Stefanović Cedomir , Kellerer Wolfgang
Published: February 2024

We calculate the mean throughput, number of collisions, successes, and idle slots for random tree algorithms with successive interference cancellation. Except for the case of the throughput for the binary tree, all the results are new. We furthermore disprove the claim that only the binary tree maximizes throughput. Our method works with many observables and can be used as a blueprint for further analysis.
Of Foreign Affairs and Foreign Correspondents
Authors: Lebovic Sam
Published: February 2024

If the owl of Minerva flies only at dusk, what are we to make of the recent flurry of popular histories about foreign correspondents? In 2021, with You Don't Belong Here, Elizabeth Becker told us “How Three Women Rewrote the Story of War” in Vietnam, and Judith Mackrell gave us the stories of “Six Women Writers on the Front Lines of World War II” in The Correspondents.1 The year before, Nancy Cott, the pioneering scholar of U.S. gender history, explored the intertwined biographies of interwar journalists Dorothy Thompson, Vincent Sheean, Rayna Raphaelson, and John Gunther in Fighting Words.2 And then, in 2022, Deborah Cohen, an acclaimed historian of British and European cultural politics, subbed the relatively obscure Raphaelson out of Cott's quartet and added in H. R. Knickerbocker, the Pulitzer Prize–winning European correspondent in Last Call at the Hotel Imperial.3 (Cohen also elevates the role of Frances Gunther, John's wife, who suffered from crippling writer's block but was perhaps the most interesting thinker of the bunch.) When two leading, accomplished historians at the height of their games write essentially the same book, you know that something is in the air. So what era's eclipse are these works marking?
What Is Existence?
Authors: Cottingham John
Published: February 2024

This paper argues that being there, actually existing, is a notion that cannot be explicated by formal logicians, cannot be defined in terms of conscious perception, and cannot be satisfactorily explained using the theories of mathematics or natural science. So, must we turn to theology to make up for the deficiencies of the methods so far canvassed? The paper concludes by considering the Thomistic identification of God with existence itself, but argues that it would be a mistake to suppose that the mystery of actual existence is thereby dispelled.
Tropical vegetation productivity and atmospheric methane over the last 40,000 years from model simulations and stalagmites in Sulawesi, Indonesia
Authors: Krause Claire E. , Kimbrough Alena K. , Gagan Michael K. , Hopcroft Peter O. , Dunbar Gavin B. , Hantoro Wahyoe S. , Hellstrom John C. , Cheng Hai , Edwards R. Lawrence , Wong Henri , Suwargadi Bambang W. , Valdes Paul J. , Rifai Hamdi
Published: February 2024

Recent research has shown the potential of speleothem δ13C to record a range of environmental processes. Here, we report on 230Th-dated stalagmite δ13C records for southwest Sulawesi, Indonesia, over the last 40,000 yr to investigate the relationship between tropical vegetation productivity and atmospheric methane concentrations. We demonstrate that the Sulawesi stalagmite δ13C record is driven by changes in vegetation productivity and soil respiration and explore the link between soil respiration and tropical methane emissions using HadCM3 and the Sheffield Dynamic Global Vegetation Model. The model indicates that changes in soil respiration are primarily driven by changes in temperature and CO2, in line with our interpretation of stalagmite δ13C. In turn, modelled methane emissions are driven by soil respiration, providing a mechanism that links methane to stalagmite δ13C. This relationship is particularly strong during the last glaciation, indicating a key role for the tropics in controlling atmospheric methane when emissions from high-latitude boreal wetlands were suppressed. With further investigation, the link between δ13C in stalagmites and tropical methane could provide a low-latitude proxy complementary to polar ice core records to improve our understanding of the glacial–interglacial methane budget.
Does sweetness exposure drive ‘sweet tooth’?
Authors: Mela David J. , Risso Davide
Published: February 2024

It is widely believed that exposure to sweetened foods and beverages stimulates the liking and desire for sweetness. Here we provide an updated review of the empirical evidence from human research examining whether exposure to sweet foods or beverages influences subsequent general liking for sweetness (‘sweet tooth’), based on the conclusions of existing systematic reviews and more recent research identified from a structured search of literature. Prior reviews have concluded that the evidence for a relationship between sweet taste exposure and measures of sweet taste liking is equivocal, and more recent primary research generally does not support the view that exposure drives increased liking for sweetness, in adults or children. In intervention trials using a range of designs, acute exposure to sweetness usually has the opposite effect (reducing subsequent liking and desire for sweet taste), while sustained exposures have no significant effects or inconsistent effects. Recent longitudinal observational studies in infants and children also report no significant associations between exposures to sweet foods and beverages with measures of sweet taste preferences. Overall, while it is widely assumed that exposure to sweetness stimulates a greater liking and desire for sweetness, this is not borne out by the balance of empirical evidence. While new research may provide a more robust evidence base, there are also a number of methodological, biological and behavioural considerations that may underpin the apparent absence of a positive relationship between sweetness exposure and liking.
Before Stockholm: Emotions and Victimhood in Mediterranean Kidnapping Narratives, 1866–1921
Authors: Hornung Juliane
Published: February 2024

Fifty years ago, the infamous bank robbery and ensuing hostage crisis that took place in a Stockholm bank gave rise to the so-called ‘Stockholm syndrome’. Though never recognized as a valid medical diagnosis, the (allegedly) pathological relationship between kidnapper and hostage has become an omnipresent media phenomenon that inspires movies and television series to this day. However, this forced bond was not always seen as problematic. The years between 1860 and 1910 witnessed the rise of kidnappings in the Mediterranean world (Southern Italy, Greece, the Ottoman Balkan region, and Morocco) involving English, American, and European hostages. Today, we know about these incidents from autobiographical narratives by the former captives. They painted a surprisingly favourable picture of their captors – and found enthusiastic audiences for their stories. Looking at the interplay of feelings, coercion, and empowerment, the article opens up a new perspective on the history of emotions that brings both victims and perpetrators into the picture.
The Interplay between Hereditary Traditional Leaders, Democratically Elected Leaders and Succession: A Case Study from Makapanstad, North West Province, South Africa
Authors: Manthwa Aubrey , Ntsoane Lefa
Published: February 2024

This article examines the interplay between traditional leaders, democratically elected leaders and succession in Makapanstad Village, North West Province, South Africa. The article stems from community-based participatory action research conducted in Makapanstad in 2018. The article uses research data, in the form of community dialogue, together with desktop literature on the same subject. The article analyses the significance and role of traditional leadership in a democratic South Africa. It considers traditional leadership and democratically elected leadership in conjunction with succession and the demarcation of roles and responsibilities. The article analyses participants’ views to explore the form of leadership preferred by the residents of Makapanstad. It argues that, despite the recognition of traditional leadership in South Africa's Constitution, the roles and responsibilities of traditional leaders in local and provincial arms of government are limited, in contrast to those of democratically elected leaders.
Longitudinal development of second language utterance fluency, cognitive fluency, and their relationship
Authors: Kahng Jimin
Published: February 2024

The development of L2 utterance fluency has been extensively researched, whereas that of cognitive fluency has rarely been examined. This study investigated the longitudinal development of L2 utterance and cognitive fluency and their relationship. Thirty-one Chinese learners of English completed speaking tasks and a set of tasks for cognitive fluency before and after 5 months’ study abroad. The results showed that participants made a significant improvement in mean syllable duration, end-clause pause frequency, and the speed of syntactic encoding and articulation but not in mid-clause pause frequency or lexical retrieval speed. Mixed-effects modeling confirmed a significant relationship between syntactic encoding speed and mean syllable duration and mid-clause pausing. Furthermore, the significant relationships were maintained over time. The findings highlight (a) the differences between mid-clause and end-clause pausing in terms of their developmental patterns and relationship with cognitive fluency and (b) a significant role of syntactic encoding speed in L2 utterance fluency.
Viral Interstitiality and Unlikely Resources: Gender and Labour in Turkish Public Theatre During the Covid-19 Pandemic
Authors: BANALOPOULOU CHRISTINA
Published: February 2024

The growing literature on Covid-19 and theatre has demonstrated how the pandemic has intensified gendered precarities in theatrical labour.1 However, the pandemic has also provided feminist theatre makers with unexpected or unlikely resources, albeit with limitations. The Istanbul Municipal Theatre's (İstanbul Büyükşehir Belediyesi Şehir Tiyatroları or İBBŞT) production of Melek that premiered in 2020 is an indicative example of such rare and largely invisible cases of pandemic theatre. Critically engaging with the archives and repertoires of tuberculosis (TB) melodrama and the Turkish lives of the genre, Melek conducts an experiential mapping of the performativity of death and the porous borders between everyday performance and artistic performance. The production offered independent feminist theatre practitioners, who otherwise maintain a precarious existence in Turkey's theatre world, access to new spaces, resources and audiences. Combining archival with ethnographic research, I will demonstrate how, in the case of Melek, the intersections between actual and fictive viral contagion – what I define as viral interstitiality – constitute inclusive economies amidst the Covid-19 pandemic. In somatics, the interstitial is theorized and enacted as suspensions of static schisms that shape relational empowerment.2 Drawing upon this grasp of the interstitial as connective thresholds, viral interstitiality sheds light on the practices and the economies of care that emerge from the porous dynamism between the viral and the theatrical.
Subway Crush
Authors: HOLLEY KELLEY
Published: February 2024

An attendant exerts all his strength to squeeze in as many passengers as possible into a car at the 28th Street Station in New York. The most prominent passenger feature is the contorting face of a Black man. He is surrounded by white riders, one of whom is trying his best to read the newspaper, a little girl, who stands with her legs akimbo, and a white woman, obscured by the window. The hectic scene muddles the identity of body parts, more akin to a game of Twister than a fantasy of public mobility across an urban landscape. Reduced to limbs and faces, the diverse passengers portrayed in Bernard Brussel-Smith's 1940 lithograph demonstrate its title: Subway Crush.1
‘We Will Teach Them How to Use This Building’: Acts of Accountability from South African Artists
Authors: LEVER CARLA
Published: February 2024

On 3 March 2021, almost a full year after South Africa's theatres were closed due to Covid-19 restrictions, renowned opera soprano Sibongile Mngoma walked into the Johannesburg offices of the South African National Arts Council (NAC) to meet with senior department officials. She was there to demand accountability over their non-payment of promised Covid-19 artist relief funds to the tune of R300 million (roughly USD 16.6 million). When it became apparent that no official would honour the meeting, Mngoma announced her intention to wait. She did not leave the building for another sixty days.
Evolution of ice rises in the Fimbul Ice Shelf, Dronning Maud Land, over the last millennium
Authors: Goel Vikram , Martín Carlos , Matsuoka Kenichi
Published: February 2024

We investigate two ice rises, Kupol Moskovskij and Kupol Ciolkovskogo, in the Fimbul Ice Shelf, East Antarctica, situated ~60 km from each other but differing in their glaciological settings. We apply a thermo-mechanically coupled Elmer/Ice model to profiles going across these ice rises and use it to investigate their past evolution covering present to several millennia ago. We constrain the model results using field measurements, including surface-velocity measurements, and surface mass balance estimated by isochronous radar stratigraphy dated with firn cores. We find that the ice rises are thickening at present (2012–2014), which started only in recent decades. Investigation of deeper radar reflectors suggests a stronger upwind-downwind contrast in surface mass balance in the past for both ice rises, with varying details. This result matches what was previously found on Blåskimen Island ice rise, which is also in the Fimbul Ice Shelf. Moreover, Kupol Moskovskij, situated at a shear margin, shows signs of recent changes in its ice-divide position, while Kupol Ciolkovskogo shows a more stable divide position. This study highlights the long-term influence of surface mass balance on ice rises, as well as the strong influence of local glaciological settings on their evolution.
Humanitarian principles and humanitarian disarmament: An operator's perspective
Authors: Dresner Josephine , Labianco Riccardo
Published: February 2024

Conceptually rooted in the efforts to ban indiscriminate weapons and both their immediate and long-term effects, humanitarian mine action and humanitarian disarmament operations have developed significantly since 1988, when the United Nations first took on work on mine action operations for the protection and benefit of local communities. A large part of those operations has been carried out by humanitarian disarmament NGOs such as the Mines Advisory Group (MAG), one of the first organizations to be established on this issue. Drawing on MAG's experience and perspective, this article explores how the humanitarian principles apply to humanitarian disarmament operations. The aim of the article is to show that as an operator on the humanitarian–development nexus, MAG considers the four humanitarian principles as a critical and necessary part of its reference framework due to the influence of the humanitarian disarmament framework, even when operating in the development space. All in all, the case of humanitarian disarmament and MAG's experience are good examples to illustrate where the humanitarian horizon is extended because of long-terms serious needs, and that humanitarian principles remain essential to keep the focus on the needs of affected populations.
An Analytical Model of Active Layer Depth Under Changing Ground Heat Flux
Authors: Zhu Modi , Wang Jingfeng , Ivanov Valeriy , Sheshukov Aleksey , Zhou Wenbo , Zhang Liujing , Mazepa Valeriy , Sokolov Alexandr , Valdayskikh Victor
Published: February 2024

Improved modeling of permafrost active layer freeze‐thaw plays a crucial role in understanding the response of the Arctic ecosystem to the accelerating warming trend in the region over the past decades. However, modeling the dynamics of the active layer at diurnal time scale remains challenging using the traditional models of freeze‐thaw processes. In this study, a physically based analytical model is formulated to simulate the thaw depth of the active layer under changing boundary conditions of soil heat flux. Conservation of energy for the active layer leads to a nonlinear integral equation of the thaw depth using a temperature profile approximated from the analytical solution of the heat transfer equation forced by ground heat flux. Temporally variable ground heat flux is estimated using non‐gradient models when field observations are not available. Validation of the proposed model conducted against field data obtained from three Arctic forest and tundra sites demonstrates that the model is able to simulate both thaw depth and soil temperature profiles accurately. The model has the potential to estimate regional variability of the thaw depth for permafrost related applications.
Photonic neuromorphic architecture for tens-of-task lifelong learning
Authors: Cheng Yuan , Zhang Jianing , Zhou Tiankuang , Wang Yuyan , Xu Zhihao , Yuan Xiaoyun , Fang Lu
Published: February 2024

Scalable, high-capacity, and low-power computing architecture is the primary assurance for increasingly manifold and large-scale machine learning tasks. Traditional electronic artificial agents by conventional power-hungry processors have faced the issues of energy and scaling walls, hindering them from the sustainable performance improvement and iterative multi-task learning. Referring to another modality of light, photonic computing has been progressively applied in high-efficient neuromorphic systems. Here, we innovate a reconfigurable lifelong-learning optical neural network (L2ONN), for highly-integrated tens-of-task machine intelligence with elaborated algorithm-hardware co-design. Benefiting from the inherent sparsity and parallelism in massive photonic connections, L2ONN learns each single task by adaptively activating sparse photonic neuron connections in the coherent light field, while incrementally acquiring expertise on various tasks by gradually enlarging the activation. The multi-task optical features are parallelly processed by multi-spectrum representations allocated with different wavelengths. Extensive evaluations on free-space and on-chip architectures confirm that for the first time, L2ONN avoided the catastrophic forgetting issue of photonic computing, owning versatile skills on challenging tens-of-tasks (vision classification, voice recognition, medical diagnosis, etc.) with a single model. Particularly, L2ONN achieves more than an order of magnitude higher efficiency than the representative electronic artificial neural networks, and 14× larger capacity than existing optical neural networks while maintaining competitive performance on each individual task. The proposed photonic neuromorphic architecture points out a new form of lifelong learning scheme, permitting terminal/edge AI systems with light-speed efficiency and unprecedented scalability.
Ghrelin decreases sensitivity to negative feedback and increases prediction-error related caudate activity in humans, a randomized controlled trial
Authors: Pietrzak Michal , Yngve Adam , Hamilton J. Paul , Asratian Anna , Gauffin Emelie , Löfberg Andreas , Gustavson Sarah , Persson Emil , Capusan Andrea J. , Leggio Lorenzo , Perini Irene , Tinghög Gustav , Heilig Markus , Boehme Rebecca
Published: February 2024

The stomach-derived hormone ghrelin plays not only a role in feeding, starvation, and survival, but it has been suggested to also be involved in the stress response, in neuropsychiatric conditions, and in alcohol and drug use disorders. Mechanisms related to reward processing might mediate ghrelin’s broader effects on complex behaviors, as indicated by animal studies and mostly correlative human studies. Here, using a within-subject double-blind placebo-controlled design with intravenous ghrelin infusion in healthy volunteers (n = 30), we tested whether ghrelin alters sensitivity to reward and punishment in a reward learning task. Parameters were derived from a computational model of participants’ task behavior. The reversal learning task with monetary rewards was performed during functional brain imaging to investigate ghrelin effects on brain signals related to reward prediction errors. Compared to placebo, ghrelin decreased punishment sensitivity (t = −2.448, p = 0.021), while reward sensitivity was unaltered (t = 0.8, p = 0.43). We furthermore found increased prediction-error related activity in the dorsal striatum during ghrelin administration (region of interest analysis: t-values ≥ 4.21, p-values ≤ 0.044). Our results support a role for ghrelin in reward processing that extends beyond food-related rewards. Reduced sensitivity to negative outcomes and increased processing of prediction errors may be beneficial for food foraging when hungry but could also relate to increased risk taking and impulsivity in the broader context of addictive behaviors.
Moiré effect enables versatile design of topological defects in nematic liquid crystals
Authors: Wang Xinyu , Jiang Jinghua , Chen Juan , Asilehan Zhawure , Tang Wentao , Peng Chenhui , Zhang Rui
Published: February 2024

Recent advances in surface-patterning techniques of liquid crystals have enabled the precise creation of topological defects, which promise a variety of emergent applications. However, the manipulation and application of these defects remain limited. Here, we harness the moiré effect to engineer topological defects in patterned nematic liquid crystal cells. Specifically, we combine simulation and experiment to examine a nematic cell confined between two substrates of periodic surface anchoring patterns; by rotating one surface against the other, we observe a rich variety of highly tunable, novel topological defects. These defects are shown to guide the three-dimensional self-assembly of colloids, which can conversely impact defects by preventing the self-annihilation of loop-defects through jamming. Finally, we demonstrate that certain nematic moiré cells can engender arbitrary shapes represented by defect regions. As such, the proposed simple twist method enables the design and tuning of mesoscopic structures in liquid crystals, facilitating applications including defect-directed self-assembly, material transport, micro-reactors, photonic devices, and anti-counterfeiting materials.
Persistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection
Authors: Lam Ivan Chun Hang , Zhang Ran , Man Kenneth Keng Cheung , Wong Carlos King Ho , Chui Celine Sze Ling , Lai Francisco Tsz Tsun , Li Xue , Chan Esther Wai Yin , Lau Chak Sing , Wong Ian Chi Kei , Wan Eric Yuk Fai
Published: February 2024

The persisting risk of long-term health consequences of SARS-CoV-2 infection and the protection against such risk conferred by COVID-19 vaccination remains unclear. Here we conducted a retrospective territory-wide cohort study on 1,175,277 patients with SARS-CoV-2 infection stratified by their vaccination status and non-infected controls to evaluate the risk of clinical sequelae, cardiovascular and all-cause mortality using a territory-wide public healthcare database with population-based vaccination records in Hong Kong. A progressive reduction in risk of all-cause mortality was observed over one year between patients with SARS-CoV-2 infection and controls. Patients with complete vaccination or have received booster dose incurred a lower risk of health consequences including major cardiovascular diseases, and all-cause mortality than unvaccinated or patients with incomplete vaccination 30-90 days after infection. Completely vaccinated and patients with booster dose of vaccines did not incur significant higher risk of health consequences from 271 and 91 days of infection onwards, respectively, whilst un-vaccinated and incompletely vaccinated patients continued to incur a greater risk of clinical sequelae for up to a year following SARS-CoV-2 infection. This study provided real-world evidence supporting the effectiveness of COVID-19 vaccines in reducing the risk of long-term health consequences of SARS-CoV-2 infection and its persistence following infection.
A wireless battery-free eye modulation patch for high myopia therapy
Authors: Zhong Tianyan , Yi Hangjin , Gou Jiacheng , Li Jie , Liu Miao , Gao Xing , Chen Sizhu , Guan Hongye , Liang Shan , He Qianxiong , Lin Rui , Long Zhihe , Wang Yue , Shi Chuang , Zhan Yang , Zhang Yan , Xing Lili , Zhong Jie , Xue Xinyu
Published: February 2024

The proper axial length of the eye is crucial for achieving emmetropia. In this study, we present a wireless battery-free eye modulation patch designed to correct high myopia and prevent relapse. The patch consists of piezoelectric transducers, an electrochemical micro-actuator, a drug microneedle array, μ-LEDs, a flexible circuit, and biocompatible encapsulation. The system can be wirelessly powered and controlled using external ultrasound. The electrochemical micro-actuator plays a key role in precisely shortening the axial length by driving the posterior sclera inward. This ensures accurate scene imaging on the retina for myopia eye. The drug microneedle array delivers riboflavin to the posterior sclera, and μ-LEDs’ blue light induces collagen cross-linking, reinforcing sclera strength. In vivo experiments demonstrate that the patch successfully reduces the rabbit eye’s axial length by ~1217 μm and increases sclera strength by 387%. The system operates effectively within the body without the need for batteries. Here, we show that the patch offers a promising avenue for clinically treating high myopia.
Remote-carbonyl-directed sequential Heck/isomerization/C(sp2)–H arylation of alkenes for modular synthesis of stereodefined tetrasubstituted olefins
Authors: Luan Runze , Lin Ping , Li Kun , Du Yu , Su Weiping
Published: February 2024

Modular and regio-/stereoselective syntheses of all-carbon tetrasubstituted olefins from simple alkene materials remain a challenging project. Here, we demonstrate that a remote-carbonyl-directed palladium-catalyzed Heck/isomerization/C(sp2)–H arylation sequence enables unactivated 1,1-disubstituted alkenes to undergo stereoselective terminal diarylation with aryl iodides, thus offering a concise approach to construct stereodefined tetrasubstituted olefins in generally good yields under mild conditions; diverse carbonyl groups are allowed to act as directing groups, and various aryl groups can be introduced at the desired position simply by changing aryl iodides. The stereocontrol of the protocol stems from the compatibility between the E/Z isomerization and the alkenyl C(sp2)–H arylation, where the vicinal group-directed C(sp2)–H arylation of the Z-type intermediate product thermodynamically drives the reversible E to Z isomerization. Besides, the carbonyl group not only promotes the Pd-catalyzed sequential transformations of unactivated alkenes by weak coordination, but also avoids byproducts caused by other possible β-H elimination.
Quiescence enables unrestricted cell fate in naive embryonic stem cells
Authors: Khoa Le Tran Phuc , Yang Wentao , Shan Mengrou , Zhang Li , Mao Fengbiao , Zhou Bo , Li Qiang , Malcore Rebecca , Harris Clair , Zhao Lili , Rao Rajesh C. , Iwase Shigeki , Kalantry Sundeep , Bielas Stephanie L. , Lyssiotis Costas A. , Dou Yali
Published: February 2024

Quiescence in stem cells is traditionally considered as a state of inactive dormancy or with poised potential. Naive mouse embryonic stem cells (ESCs) can enter quiescence spontaneously or upon inhibition of MYC or fatty acid oxidation, mimicking embryonic diapause in vivo. The molecular underpinning and developmental potential of quiescent ESCs (qESCs) are relatively unexplored. Here we show that qESCs possess an expanded or unrestricted cell fate, capable of generating both embryonic and extraembryonic cell types (e.g., trophoblast stem cells). These cells have a divergent metabolic landscape comparing to the cycling ESCs, with a notable decrease of the one-carbon metabolite S-adenosylmethionine. The metabolic changes are accompanied by a global reduction of H3K27me3, an increase of chromatin accessibility, as well as the de-repression of endogenous retrovirus MERVL and trophoblast master regulators. Depletion of methionine adenosyltransferase Mat2a or deletion of Eed in the polycomb repressive complex 2 results in removal of the developmental constraints towards the extraembryonic lineages. Our findings suggest that quiescent ESCs are not dormant but rather undergo an active transition towards an unrestricted cell fate.
Dopamine and serotonin in human substantia nigra track social context and value signals during economic exchange
Authors: Batten Seth R. , Bang Dan , Kopell Brian H. , Davis Arianna N. , Heflin Matthew , Fu Qixiu , Perl Ofer , Ziafat Kimia , Hashemi Alice , Saez Ignacio , Barbosa Leonardo S. , Twomey Thomas , Lohrenz Terry , White Jason P. , Dayan Peter , Charney Alexander W. , Figee Martijn , Mayberg Helen S. , Kishida Kenneth T. , Gu Xiaosi , Montague P. Read
Published: February 2024

Dopamine and serotonin are hypothesized to guide social behaviours. In humans, however, we have not yet been able to study neuromodulator dynamics as social interaction unfolds. Here, we obtained subsecond estimates of dopamine and serotonin from human substantia nigra pars reticulata during the ultimatum game. Participants, who were patients with Parkinson’s disease undergoing awake brain surgery, had to accept or reject monetary offers of varying fairness from human and computer players. They rejected more offers in the human than the computer condition, an effect of social context associated with higher overall levels of dopamine but not serotonin. Regardless of the social context, relative changes in dopamine tracked trial-by-trial changes in offer value—akin to reward prediction errors—whereas serotonin tracked the current offer value. These results show that dopamine and serotonin fluctuations in one of the basal ganglia’s main output structures reflect distinct social context and value signals.
The astrocyte-produced growth factor HB-EGF limits autoimmune CNS pathology
Authors: Linnerbauer Mathias , Lößlein Lena , Vandrey Oliver , Peter Anne , Han Yanan , Tsaktanis Thanos , Wogram Emile , Needhamsen Maria , Kular Lara , Nagel Lisa , Zissler Julia , Andert Marie , Meszaros Lisa , Hanspach Jannis , Zuber Finnja , Naumann Ulrike J. , Diebold Martin , Wheeler Michael A. , Beyer Tobias , Nirschl Lucy , Cirac Ana , Laun Frederik B. , Günther Claudia , Winkler Jürgen , Bäuerle Tobias , Jagodic Maja , Hemmer Bernhard , Prinz Marco , Quintana Francisco J. , Rothhammer Veit
Published: February 2024

Central nervous system (CNS)-resident cells such as microglia, oligodendrocytes and astrocytes are gaining increasing attention in respect to their contribution to CNS pathologies including multiple sclerosis (MS). Several studies have demonstrated the involvement of pro-inflammatory glial subsets in the pathogenesis and propagation of inflammatory events in MS and its animal models. However, it has only recently become clear that the underlying heterogeneity of astrocytes and microglia can not only drive inflammation, but also lead to its resolution through direct and indirect mechanisms. Failure of these tissue-protective mechanisms may potentiate disease and increase the risk of conversion to progressive stages of MS, for which currently available therapies are limited. Using proteomic analyses of cerebrospinal fluid specimens from patients with MS in combination with experimental studies, we here identify Heparin-binding EGF-like growth factor (HB-EGF) as a central mediator of tissue-protective and anti-inflammatory effects important for the recovery from acute inflammatory lesions in CNS autoimmunity. Hypoxic conditions drive the rapid upregulation of HB-EGF by astrocytes during early CNS inflammation, while pro-inflammatory conditions suppress trophic HB-EGF signaling through epigenetic modifications. Finally, we demonstrate both anti-inflammatory and tissue-protective effects of HB-EGF in a broad variety of cell types in vitro and use intranasal administration of HB-EGF in acute and post-acute stages of autoimmune neuroinflammation to attenuate disease in a preclinical mouse model of MS. Altogether, we identify astrocyte-derived HB-EGF and its epigenetic regulation as a modulator of autoimmune CNS inflammation and potential therapeutic target in MS.
Nanoparticles synthesis in microwave plasmas: peculiarities and comprehensive insight
Authors: Ouaras Karim , Lombardi Guillaume , Hassouni Khaled
Published: February 2024

Low-pressure plasma processes are routinely used to grow, functionalize or etch materials, and thanks to some of its unique attributes, plasma has become a major player for some applications such as microelectronics. Plasma processes are however still at a research level when it comes to the synthesis and functionalization of nanoparticles. Yet plasma processes can offer a particularly suitable solution to produce nanoparticles having very peculiar features since they enable to: (i) reach particle with a variety of chemical compositions, (ii) tune the size and density of the particle cloud by acting on the transport dynamics of neutral or charged particles through a convenient setting of the thermal gradients or the electric field topology in the reactor chamber and (iii) manipulate nanoparticles and deposit them directly onto a substrate, or codeposit them along with a continuous film to produce nanocomposites or (iv) use them as a template to produce 1D materials. In this article, we present an experimental investigation of nanoparticles synthesis and dynamics in low-pressure microwave plasmas by combining time-resolved and in-situ laser extinction and scattering diagnostics, QCL absorption spectroscopy, mass spectrometry, optical emission spectroscopy and SEM along with a particle transport model. We showed for the first time the thermophoresis-driven dynamic of particle cloud in electrodless microwave plasmas. We showed that this effect is linked to particular fluctuations in the plasma composition and results in the formation of a void region in the bulk of the plasma surrounded by a particle cloud in the peripherical post-discharge. We also reveals and analyze the kinetics of precursor dissociation and molecular growth that result in the observed nanoparticle nucleation.
The optimal cut-off values of Klotho for predicting all-cause and cardiovascular mortality among chronic kidney disease: results from NHANES
Authors: Liu Lili , Jia Junya , Cheng Xi , Gao Shan , Yan Tiekun
Published: February 2024

To explore the optimal cut-off values of Klotho for predicting all-cause and cardiovascular mortality among chronic kidney disease (CKD) patients. Klotho was measured in 40–79-year-old individuals in the NHANES 2007–2016. A total of 2418 patients with stage 1–4 CKD were included. The optimal cut-off values of Klotho were utilized using receiver operator characteristic (ROC) curves and be verified on the effects of all-cause and cardiovascular mortality. Restricted cubic splines were used to examine the relationship between Klotho and all-cause and cardiovascular mortality with the optimal cutpoints as the reference. After a mean follow-up period of 87.9 months, 535 deaths occurred and 188 died of cardiovascular disease. Cubic splines showed that the risk of all-cause and cardiovascular mortality increased gradually for Klotho < 700 pg/ml. ROC curves revealed that the optimal cut-off values of Klotho for all-cause and cardiovascular mortality are 548.8 pg/ml and 660.9 pg/ml, respectively. Compared to patients with higher levels of Klotho, HRs (95% CIs) for all-cause and cardiovascular mortality were 1.52 (1.23, 1.87) and 1.58 (1.13, 2.22) among patients with lower levels of Klotho, respectively, in the multivariate model (P < .0001 and P = 0.008). Our findings revealed the optimal cut-off values of Klotho for all-cause and cardiovascular mortality in CKD.