bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between glucagon‐like peptide‐1 receptor agonists and risk of suicidality: A comprehensive analysis of the global pharmacovigilance database
Authors: Kim Tae Hyeon , Lee Kyeongmin , Park Seoyoung , Cho Hanseul , Park Jaeyu , Jo Hyesu , Son Yejun , Kim Soeun , Kang Jiseung , Smith Lee , Rahmati Masoud , Fond Guillaume , Boyer Laurent , Pizzol Damiano , Lee Hayeon , Rhee Sang Youl , Hwang Jiyoung , Sang Hyunji , Yon Dong Keon
Published: August 2024

Aim

To evaluate the potential association between suicidality and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs), as well as other medications used for obesity and diabetes, using comprehensive global data.

Materials and Methods

This study utilized the World Health Organization's pharmacovigilance database, encompassing adverse drug reaction reports from 1967 to 2023, from 170 countries (total reports, N = 131 255 418). We present the reported odds ratios (RORs) with 95% confidence intervals (CIs) and information component (IC) with IC025 regarding the association between GLP‐1RA use and suicidality.

Results

Although reports of GLP‐1RA‐associated suicidality increased gradually from 2005 to 2023 (n = 332), no evidence of an association was observed (ROR 0.15 [95% CI 0.13 to 0.16]; IC −2.77 [IC025 −2.95]). The lack of evidence of an association persisted regardless of whether GLP‐1RAs were used for diabetes treatment (ROR 0.13 [95% CI 0.11 to 0.14]; IC −2.95 [IC025 −3.14]) or obesity treatment (ROR 0.44 [95% CI 0.34 to 0.58]; IC −1.16 [IC025 −1.62]). However, an association was found between suicidality and other diabetes medications excluding GLP‐1RAs (ROR 1.13 [95% CI 1.10 to 1.15]; IC 0.17 [IC025 0.13]). Similarly, the potential association with suicidality was observed in medications used to treat obesity excluding GLP‐1RAs (ROR 1.08 [95% CI 1.01 to 1.14]; IC 0.10 [IC025 0.01]).

Conclusions

The suspected association between GLP‐1RA use and suicidality, as raised by the European Medicines Agency, was not found in our global analysis. This indicates that the sporadic reports of GLP‐1RA‐associated suicidality are likely influenced by factors such as comorbidities present in the GLP‐1RA user population.
Decoding the neural impact of radical complexity in Chinese characters during working memory task
Authors: Li Hongli , Zhao Xin
Published: August 2024

Readers of Chinese characters need to recognize how they are formed in order to identify them correctly. However, our understanding of the cognitive processing of characters in working memory is limited. In Experiment 1, using the character N‐back task paradigm, electrophysiological data were recorded from 26 participants to investigate the effects of the visual feature of radicals on neural activity during the character recognition, updating and maintenance in the N‐back task. Results showed that compound characters required longer response times than single‐component characters. For the event‐related potentials (ERPs), the compound character condition had more negative N2pc and lower P300 amplitudes than the single‐component character condition. In Experiment 2, data from 26 participants were used to analyse the effect of the phonological feature of radicals on neural activity during the character recognition, updating and maintenance in the N‐back task. Results showed that there was a larger P200 in the irregular character condition than in the regular character condition, but there was no difference between the regular and the irregular characters in the N2pc, P300 and slow wave (SW) components. The visual feature and the phonological feature of the radicals may have different effects on the character processing. This study reveals the neural effects of Chinese character radicals on cognitive processing in a working memory task and provides behavioural and electrophysiological evidence for a theoretical model of verbal working memory subprocesses.
Substantial contribution of inorganic carbon sources to CO2 emissions in calcareous vineyard soils in Germany
Authors: Islam Muhammad , Wehrle Ralf , Pätzold Stefan , Brüggemann Nicolas
Published: August 2024

In light of climate change and increasing global temperatures, it is important to equally prioritize the study of inorganic carbon dynamics in calcareous soils within temperate ecosystems, as has been done for arid or semiarid environments. A significant area of vineyards in Germany is established on calcareous soils. However, the potential influence of inorganic carbon on CO2 emissions in these vineyards has not been sufficiently explored when evaluating the carbon footprint of management practices in relation to carbon storage. Therefore, we aimed to differentiate between organic and inorganic sources of CO2 emissions from six vineyard soils located in the southwest of Germany that had previously received organic soil amendments (OA). Inorganic carbon content varied between 8 and 55 g kg−1 across different sites, with variations observed in the inorganic‐to‐organic carbon ratio. Soil samples were incubated under standard laboratory conditions for 48 h, and the source of emitted CO2 was determined using a two‐end‐member mixing model. The contribution of inorganic carbon to CO2 emissions was influenced by the quantity of inorganic carbon, with an increase in contribution with increasing inorganic‐to‐organic carbon ratio. On average, abiotic sources accounted for 5% to 40% of the emitted CO2 at the different sites, with one site showing no significant contribution of inorganic carbon. CO2 production from inorganic carbon was higher in the subsoil compared with the topsoil, likely related to the higher content of inorganic carbon in the subsoil. Notably, there was no discernible influence of OA on carbonate dissolution. This study emphasizes the significance of considering abiotic sources of CO2 emissions in addition to soil respiration in calcareous soils and highlights the need for further investigation to apply these findings at the field scale.
Combined value of interictal markers and stimulated seizures to estimate the seizure onset zone in stereoelectroencephalography
Authors: Rekola Lauri , Peltola Maria , Vanhanen Jukka , Wilenius Juha , Metsähonkala Eeva‐Liisa , Kämppi Leena , Lauronen Leena , Nevalainen Päivi
Published: August 2024

Objective

This study was undertaken to investigate the potential of interictal electroencephalographic (EEG) findings and electrically stimulated seizures during stereo‐EEG (SEEG) as surrogate markers for the spontaneous seizure onset zone (spSOZ). We hypothesized that combining the localizing information of these markers would allow clinically meaningful estimation of the spSOZ.

Methods

We included all patients (n = 63) who underwent SEEG between January 2013 and March 2020 at Helsinki University Hospital and had spontaneous seizures during the recording. We scored spikes, gamma activity, and background abnormality on each channel visually during a 12‐h epoch containing waking state and sleep. Based on semiology, we classified stimulated seizures as typical or atypical/unclassifiable and estimated the stimulated SOZ (stimSOZ) for typical seizures. To assess which markers increased the odds of channel inclusion in the spSOZ, we fitted mixed effects logistic regression models.

Results

A combined regression model including the stimSOZ and interictal markers scored during sleep performed better in estimating which channels were part of the spSOZ than models based on stimSOZ (p < .001) or interictal markers (p < .001) alone. Of the individual markers, the effect sizes were greatest for inclusion of a channel in the stimSOZ (odds ratio [OR] = 60, 95% confidence interval [CI] = 37–97, p < .001) and for continuous (OR = 25, 95% CI = 12–55, p < .001) and subcontinuous (OR = 36, 95% CI = 21–64, p < .001) interictal spiking. At the individual level, the model's accuracy to predict spSOZ inclusion varied markedly (median accuracy = 85.7, range = 54.4–100), which was not explained by etiology (p > .05).

Significance

Compared to either marker alone, combining visually rated interictal SEEG markers and stimulated seizures improved prediction of which SEEG channels belonged to the spSOZ. Inclusion in the stimSOZ and continuous or subcontinuous spikes increased the odds of spSOZ inclusion the most. Future studies should investigate whether suboptimal sampling of the true epileptogenic zone can explain the model's poor performance in certain patients.
High‐gamma modulation language mapping and cognitive outcomes after epilepsy surgery
Authors: Ervin Brian , Kargol Christina , Byars Anna W. , Buroker Jason , Rozhkov Leonid , Skoch Jesse , Mangano Francesco T. , Greiner Hansel M. , Horn Paul S. , Holland Katherine , Arya Ravindra
Published: August 2024

Objective

We evaluated changes in cognitive domains after neurosurgical lesioning of cortical sites with significant high‐gamma power modulations (HGM) during a visual naming task, although these sites were found language‐negative on standard‐of‐care electrical stimulation mapping (ESM).

Methods

In drug‐resistant epilepsy patients who underwent resection/ablation after stereo‐electroencephalography (SEEG), we computed reliable change indices (RCIs) from a battery of presurgical and 1‐year postsurgical neuropsychological assessments. We modeled RCIs as a function of lesioning even one HGM language site, number of HGM language sites lesioned, and the magnitude of naming‐related HGM. The analyses were adjusted for 1‐year seizure freedom, operated hemispheres, and the volumes of surgical lesions.

Results

In 37 patients with 4455 SEEG electrode contacts (1839 and 2616 contacts in right and left hemispheres, respectively), no ESM language sites were lesioned. Patients with lesioning of even one HGM language site showed significantly lower RCIs for Peabody Picture Vocabulary Test (PPVT), working memory, and verbal learning immediate (VLI) scores. RCI declines with higher number of HGM language sites lesioned were seen in PPVT (slope [β] = −.10), working memory (β = −.10), VLI (β = −.14), and letter–word identification (LWI; β = −.14). No neuropsychological domains improved after lesioning of HGM language sites. Significant effects of the HGM magnitude at lesioned sites were seen on working memory (β = −.31), story memory immediate (β = −.27), verbal learning recognition (β = −.18), LWI (β = −.16), spelling (β = −.49), and passage comprehension (β = −.33). Because working memory was significantly affected in all three analyses, patients with maximal working memory decline were examined post hoc, revealing that all such patients had HGM naming sites lesioned in the posterior quadrants of either hemisphere.

Significance

HGM language mapping should be used as an adjunct to ESM in clinical practice and may help counsel patients/families about postsurgical cognitive deficits.
Linked Selection and Gene Density Shape Genome‐Wide Patterns of Diversification in Peatmosses
Authors: Meleshko Olena , Martin Michael D. , Flatberg Kjell Ivar , Stenøien Hans K. , Korneliussen Thorfinn Sand , Szövényi Péter , Hassel Kristian
Published: August 2024

Genome evolution under speciation is poorly understood in nonmodel and nonvascular plants, such as bryophytes—the largest group of nonvascular land plants. Their genomes are structurally different from angiosperms and likely subjected to stronger linked selection pressure, which may have profound consequences on genome evolution in diversifying lineages, even more so when their genome architecture is conserved. We use the highly diverse, rapidly radiated group of peatmosses (Sphagnum) to characterize the processes affecting genome diversification in bryophytes. Using whole‐genome sequencing data from populations of 12 species sampled at different phylogenetic and geographical scales, we describe high correlation of the genomic landscapes of differentiation, divergence, and diversity in Sphagnum. Coupled with evidence from the patterns of covariation among different measures of genetic diversity, phylogenetic discordance, and gene density, this provides strong support that peatmoss genome evolution has been shaped by the long‐term effects of linked selection, constrained by distribution of selection targets in the genome. Thus, peatmosses join the growing number of animal and plant groups where functional features of the genome, such as gene density, and linked selection drive genome evolution along predetermined and highly similar routes in different species. Our findings demonstrate the great potential of bryophytes for studying the genomics of speciation and highlight the urgent need to expand the genomic resources in this remarkable group of plants.
Trends in the management of horses referred for colic evaluation preceding and during the COVID‐19 pandemic (2013–2023)
Authors: Elane George L. , Blikslager Anthony T. , Mair Tim S.
Published: August 2024

Background

The COVID‐19 pandemic represented a significant source of anxiety and stress for equine veterinarians and clients, with the potential for measurable effects on caseload and owner economics.

Objective

To compare the number of horses presenting for emergency colic evaluation and treatment, as well as costs at two equine referral hospitals.

Study design

Retrospective cohort.

Methods

Medical records of horses admitted to North Carolina State University (NCSU) and Bell Equine Veterinary Clinic (BEVC) were compared. Total equine accessions, number of horses referred for colic and patient age were recorded over an 11‐year period (2013–2023). Horses were categorised based on treatment as medical, surgical treatment with recovery, surgical exploration with intraoperative euthanasia, or euthanasia without surgery. Total invoice of each case was also recorded.

Results

Total equine accessions, total number and proportion of horses presenting for evaluation of colic, and number of horses recovering from colic surgery at NCSU increased following onset of the pandemic, while they remained similar to pre‐pandemic levels at BEVC. The proportion of horses presenting for colic that received surgery decreased at both hospitals over the study period. Mean invoice totals for horses surviving colic surgery increased at both hospitals over the study period, but was not significantly associated with euthanasia. Age was not significantly different between categories of colic.

Main limitations

Retrospective study design, differences in academic and private practices.

Conclusions

The decreasing proportion of horses admitted for colic that received surgery is likely due to the increased caseload of first‐opinion care at referral practices during the pandemic, as fewer options were available to owners. The increasing number of horses euthanised intraoperatively or euthanised without receiving surgery may be due to the dramatically rising costs of medical care, particularly surgery.
Net primary productivity and litter decomposition rates in two distinct Amazonian peatlands
Authors: Dargie G. C. , del Aguila‐Pasquel J. , Córdova Oroche C. J. , Irarica Pacaya J. , Reyna Huaymacari J. , Baker T. R. , Hastie A. , Honorio Coronado E. N. , Lewis S. L. , Roucoux K. H. , Mitchard E. T. , Williams M. , Draper F. C. H. , Lawson I. T.
Published: August 2024

Measurements of net primary productivity (NPP) and litter decomposition from tropical peatlands are severely lacking, limiting our ability to parameterise and validate models of tropical peatland development and thereby make robust predictions of how these systems will respond to future environmental and climatic change. Here, we present total NPP (i.e., above‐ and below‐ground) and decomposition data from two floristically and structurally distinct forested peatland sites within the Pastaza Marañón Foreland Basin, northern Peru, the largest tropical peatland area in Amazonia: (1) a palm (largely Mauritia flexuosa) dominated swamp forest and (2) a hardwood dominated swamp forest (known as ‘pole forest’, due to the abundance of thin‐stemmed trees). Total NPP in the palm forest and hardwood‐dominated forest (9.83 ± 1.43 and 7.34 ± 0.84 Mg C ha−1 year−1, respectively) was low compared with values reported for terra firme forest in the region (14.21–15.01 Mg C ha−1 year−1) and for tropical peatlands elsewhere (11.06 and 13.20 Mg C ha−1 year−1). Despite the similar total NPP of the two forest types, there were considerable differences in the distribution of NPP. Fine root NPP was seven times higher in the palm forest (4.56 ± 1.05 Mg C ha−1 year−1) than in the hardwood forest (0.61 ± 0.22 Mg C ha−1 year−1). Above‐ground palm NPP, a frequently overlooked component, made large contributions to total NPP in the palm‐dominated forest, accounting for 41% (14% in the hardwood‐dominated forest). Conversely, Mauritia flexuosa litter decomposition rates were the same in both plots: highest for leaf material, followed by root and then stem material (21%, 77% and 86% of mass remaining after 1 year respectively for both plots). Our results suggest potential differences in these two peatland types' responses to climate and other environmental changes and will assist in future modelling studies of these systems.
Beyond resilience: Responses to changing climate and disturbance regimes in temperate forest landscapes across the Northern Hemisphere
Authors: Dollinger Christina , Rammer Werner , Suzuki Kureha F. , Braziunas Kristin H. , Keller Timon T. , Kobayashi Yuta , Mohr Johannes , Mori Akira S. , Turner Monica G. , Seidl Rupert
Published: August 2024

Climate change has profound impacts on forest ecosystem dynamics and could lead to the emergence of novel ecosystems via changes in species composition, forest structure, and potentially a complete loss of tree cover. Disturbances fundamentally shape those dynamics: the prevailing disturbance regime of a region determines the inherent variability of a system, and its climate‐mediated change could accelerate forest transformation. We used the individual‐based forest landscape and disturbance model iLand to investigate the resilience of three protected temperate forest landscapes on three continents—selected to represent a gradient from low to high disturbance activity—to changing climate and disturbance regimes. In scenarios of sustained strong global warming, natural disturbances increased across all landscapes regardless of projected changes in precipitation (up to a sevenfold increase in disturbance rate over the 180‐year simulation period). Forests in landscapes with historically high disturbance activity had a higher chance of remaining resilient in the future, retaining their structure and composition within the range of variability inherent to the system. However, the risk of regime shift and forest loss was also highest in these systems, suggesting forests may be vulnerable to abrupt change beyond a threshold of increasing disturbance activity. Resilience generally decreased with increasing severity of climate change. Novelty in tree species composition was more common than novelty in forest structure, especially under dry climate scenarios. Forests close to the upper tree line experienced high novelty in structure across all three study systems. Our results highlight common patterns and processes of forest change, while also underlining the diverse and context‐specific responses of temperate forest landscapes to climate change. Understanding past and future disturbance regimes can anticipate the magnitude and direction of forest change. Yet, even across a broad gradient of disturbance activity, we conclude that climate change mitigation is the most effective means of maintaining forest resilience.
An invasive prey and changing climate interact to shape the breeding phenology of an endangered predator
Authors: Fletcher Robert J. , Beatty Meghan A. , Elmquist Lara , Jeffery Brian M. , Poli Caroline L. , Robertson Ellen P.
Published: August 2024

Changes in phenology are occurring from global climate change, yet the impacts of other types of global change on the phenology of animals remain less appreciated. Understanding the potential for synergistic effects of different types of global change on phenology is needed, because changing climate regimes can have cascading effects, particularly on invasive species that vary in their thermal tolerances. Using 25 years of data from 5963 nests and 4675 marked individuals across the entire US breeding range of an endangered predator, the snail kite (Rostrhamus sociabilis plumbeus), we isolated the effects of an invasion of novel prey and warming temperatures on breeding phenology and its demographic consequences. Over this time period, breeding season length doubled, increasing by approximately 14 weeks. Both temperature and the establishment of invasive prey interacted to explain the timing of nest initiation. Temperature and invasive prey played distinct roles: earlier nest initiation occurred with increasing temperatures, whereas late nesting increased with invasion. Ultimately, both nest survival and juvenile survival declined later in the year, such that effects from invasive prey, but not warming temperatures, have the apparent potential for mistiming in breeding phenology by some individuals. Nonetheless, relatively few nesting events occurred during late fall when nest survival was very low, and seasonal declines in nest survival were weaker and renesting was more frequent in invaded wetlands, such that total reproductive output increased with invasion. Variation in demographic effects illustrate that considering only particular components of demography (e.g., nest survival rates) may be inadequate to infer the overall consequences of changes in phenology, particularly the potential for mistiming of phenological events. These results emphasize that species invasions may profoundly alter phenology of native species, such effects are distinct from climate effects, and both interact to drive population change.
Spatially Heterogeneous Responses of Planktonic Foraminiferal Assemblages Over 700,000 Years of Climate Change
Authors: Mathes Gregor H. , Reddin Carl J. , Kiessling Wolfgang , Antell Gawain S. , Saupe Erin E. , Steinbauer Manuel J.
Published: August 2024

Aim

To determine the degree to which assemblages of planktonic foraminifera track thermal conditions.

Location

The world's oceans.

Time Period

The last 700,000 years of glacial–interglacial cycles.

Major Taxa Studied

Planktonic foraminifera.

Methods

We investigate assemblage dynamics in planktonic foraminifera in response to temperature changes using a global dataset of Quaternary planktonic foraminifera, together with a coupled Atmosphere–Ocean General Circulation Model (AOGCM) at 8000‐year resolution. We use ‘thermal deviance’ to assess assemblage responses to climate change, defined as the difference between the temperature at a given location and the bio‐indicated temperature (i.e., the abundance‐weighted average of estimated temperature optima for the species present).

Results

Assemblages generally tracked annual mean temperature changes through compositional turnover, but thermal deviances are evident under certain conditions. The coldest‐adapted species persisted in polar regions during warming but were not joined by additional immigrants, resulting in minimal assemblage turnover. The warmest‐adapted species persisted in equatorial regions during cooling with similarly minimal assemblage change. Assemblages at mid‐latitudes mostly tracked temperature cooling and warming.

Main Conclusions

Planktonic foraminiferal assemblages were generally able to track or endure temperature changes: as climate warmed or cooled, bio‐indicated temperature also became warmer or cooler, although to a variable degree. At polar sites under warming and at equatorial sites under cooling, the change in bio‐indicated temperature was less than, or even opposite to, what would be expected from estimated environmental change. Nevertheless, all studied species persisted across the study interval, regardless of thermal deviance—a result that highlights the resilience and inertia of planktonic foraminifera on an assemblage level to the last 700,000 years of climate change.
Core collections: Essential titles for health libraries
Authors: Hawker Lynsey , Blacklock Claire
Published: August 2024

Core collections have been produced by CILIP's Health Libraries Group, then called the Library Association's Medical Section, since 1952. Maintained by a Working Group of health librarians based in the UK NHS, higher education and specialist libraries, the collections provide an up‐to‐date curated list of reliable titles essential to health libraries. The core collections currently include nursing, midwifery, medicine and dentistry. The newest core collection is being developed in collaboration with the African Hospital Libraries to provide a list of key resources relevant to sub‐Saharan Africa. Expressions of interest to help develop this latest collection are invited.
Probiotic‐rich bean sprouts alleviate oxidative stress and inflammation induced by a diet with an increased fat‐to‐carbohydrate energy ratio
Authors: Świeca Michał , Reguła Julita , Michalska Agata , Sierocka Małgorzata , Jarocki Piotr , Kordowska‐Wiater Monika , Drzewiecka Beata , Kapusta Ireneusz
Published: August 2024

The rat's model evaluated the function of sprouted beans enriched with probiotic Lactiplantibacillus plantarum 299v in alleviating dyslipidaemia, inflammation and disturbed redox homeostasis caused by a high‐lard diet. Sprouted beans improved the total antioxidant capacity of serum and liver, regardless of whether the feeds had a higher content of low‐molecular antioxidants or were additionally enriched with probiotics. The reduction of inflammation (lowered level of C‐reactive protein) and restoration of triglycerides and total cholesterol to the levels recorded in the control group (AIN‐93M) were especially observed in the group supplemented with the control adzuki bean. Introducing sprouted legumes (both the control and probiotic‐rich) improved microbiota activity affected by a high‐lard diet. The highest, desirable reduction of urease (by 80%) and tryptophanase (by 78%) activity was found in the groups fed with probiotic‐rich adzuki and mung bean sprouts respectively. Sprouted beans improve the metabolism of individuals subjected to a diet with an increased fat‐to‐carbohydrate energy ratio, especially concerning oxidative stress injury and microbiota activity.
Beyond the precariat: Trajectories of precarious work and its determinants in South Korea
Authors: Lee Sophia Seung‐yoon , Baek Seung‐ho
Published: August 2024

This study examines the evolving patterns of precarious work in South Korea over a 20‐year period, challenging conventional understandings of labour market segmentation and class formation. Using group‐based trajectory modelling on Korean Labour and Income Panel Study data (2002–2021), we identify five distinct trajectories of labour market experiences. Our findings reveal that 34.4% of the sample, categorised into persistently high precariousness and persistent precariousness groups, provides evidence for an emerging, heterogeneous precariat class. This new class formation transcends traditional occupational boundaries and challenges existing class theories. Multinomial logistic regression shows that low‐skilled service workers and women are more likely to belong to precarious groups. Our study contributes by (1) providing empirical evidence for a diverse precariat class, (2) demonstrating the need for a multidimensional approach to precarious work, and (3) highlighting the dynamic nature of precarious work over time. We argue for bringing class discussion back into labour market inequality analysis through a new theoretical framework that synthesises traditional class theory with contemporary precariat discourse, offering insights for policy and theoretical development in understanding modern labour markets.
A newborn's perspective on immune responses to food
Authors: Verhasselt Valerie
Published: August 2024

In this review, we will highlight infants' immune responses to food, emphasizing the unique aspects of early‐life immunity and the critical role of breast milk as a food dedicated to infants. Infants are susceptible to inflammatory responses rather than immune tolerance at the mucosal and skin barriers, necessitating strategies to promote oral tolerance that consider this susceptibility. Breast milk provides nutrients for growth and cell metabolism, including immune cells. The content of breast milk, influenced by maternal genetics and environmental exposures, prepares the infant's immune system for the outside world, including solid foods. To do this, breast milk promotes immune system development through antigen‐specific and non‐antigen‐specific immune education by exposing the newborn to food and respiratory allergens and acting on three key targets for food allergy prevention: the gut microbiota, epithelial cells, and immune cells. Building knowledge of how the maternal exposome and human milk composition influence offspring's healthy immune development will lead to recommendations that meet the specific needs of the developing immune system and increase the chances of promoting an appropriate immune response to food in the long term.
Antibody‐mediated control mechanisms of viral infections
Authors: Mackin Samantha R. , Sariol Alan , Diamond Michael S.
Published: August 2024

Antibodies generated after vaccination or natural pathogen exposure are essential mediators of protection against many infections. Most studies with viruses have focused on antibody neutralization, in which protection is conferred by the fragment antigen binding region (Fab) through targeting of different steps in the viral lifecycle including attachment, internalization, fusion, and egress. Beyond neutralization, the fragment crystallizable (Fc) region of antibodies can integrate innate and adaptive immune responses by engaging complement components and distinct Fc gamma receptors (FcγR) on different host immune cells. In this review, we discuss recent advances in our understanding of antibody neutralization and Fc effector functions, and the assays used to measure them. Additionally, we describe the contexts in which these mechanisms are associated with protection against viruses and highlight how Fc‐FcγR interactions can improve the potency of antibody‐based therapies.
Manufacturer encroachment in a vertically differentiated market with competing retailers and counterfeiter
Authors: Huang Song , Chen Yuqing
Published: August 2024

This study investigates the encroachment strategy of a manufacturer with multiple competing retailers in the presence of a counterfeiter who produces an imitated product in a vertically differentiated market wherein the counterfeits and authentic products differ in quality. We derive some intriguing results that uncover the strategic effects among manufacturer encroachment, counterfeiting, and retailer competition. First, having the option to encroach may hurt the manufacturer himself but benefit the counterfeiter in the presence of competing retailers. Second, increased counterfeit similarity shrinks the beneficial encroachment region for the manufacturer but may widen the beneficial region for the retailer. However, the intensified retailer competition always shrinks the beneficial region for them. Third, the individual retailer's (manufacturer's) profit increases (decreases) with counterfeit similarity when the manufacturer chooses encroachment. Conversely, consumer surplus (social welfare) exhibits an inverted U‐shaped (U‐shaped) pattern with counterfeit similarity under encroachment threat. Moreover, the profits and welfare may jump with counterfeit similarity because of the change in the encroachment strategy wherein retailer competition alters the jump points.
Rattling effect in YbaCabSi7.5Al4.5O1.5N14.5 α‐SiAlON ceramics
Authors: Zhang Shijia , Li Fei , Du Songmo , Chen Zhanglin , Zhao Shuo , Zhao Dengke , Fan Binbin , Wang Bohan , Chen Kexin , Liu Guanghua
Published: August 2024

When a small atom is induced into a larger lattice, new phonon scattering modes are aroused and thermal conductivity is significantly reduced by increased anharmonicity. This effect, called “rattling,” has been reported in pyrochlores and some cage compounds, but not in α‐SiAlON. In this study, we reveal that in (Yb+Ca) co‐doped α‐SiAlON ceramics (YbaCabSi7.5Al4.5O1.5N14.5, x = a/[a+b]), the rattling effect plays a crucial role in reducing thermal conductivity. Samples with different Yb/Ca ratios (x = 0, 0.1, 0.2, 0.3…, 1.0) were sintered by spark plasma sintering (SPS) at 1600°C and their thermal diffusivity/conductivity were measured by the laser‐flash method. We found that substituting Ca2+ with smaller Yb3+ cations in Ca‐α‐SiAlON caused significant reduction in thermal conductivity. On the contrary, substituting Yb3+ with larger Ca2+ cations in Yb‐α‐SiAlON caused only slight reduction in thermal conductivity. A lowest thermal conductivity of 3.3 W/(m·K) was achieved, when x = 0.3 rather than x = 0.5 or 0.7. Further analysis of phonon scattering intensity confirmed that both intrinsic and extrinsic scatterings are enhanced in the sample of x = 0.3. This study demonstrates that by utilization of the rattling effect, α‐SiAlON, well‐known for its excellent mechanical properties, can be tuned to exhibit low thermal conductivity comparable to that of La2Zr2O7 and 8YSZ.
Automatic identification of ablation targets in persistent atrial fibrillation: Initial experience with a new mapping tool
Authors: Lațcu Decebal Gabriel , Enache Bogdan , Lerebours Chloe , Milanese Sofia , Benhenda Nazih , Canepa Silvia , Kingston Amanda , Meo Marianna , Saoudi Nadir
Published: August 2024

Introduction

Strategies beyond pulmonary vein isolation (PVI) in persistent atrial fibrillation (persAF) are debated. A novel mapping tool provides algorithmic detection of ablation targets based on electrogram (EGM) properties specific to stable localized rotational activations.

Methods

The mapping tool was used on 31 patients (20 de novo). The algorithm was used to optimize PVI line placement and guide additional ablations. Targets were detected by calculating local cycle length (L‐CL) and local spread of activation within that L‐CL (Duty Cycle; DC) for EGMs with consistent morphology and activation. At least two left atrial (LA) maps (pre‐PVI and post‐PVI) were acquired in atrial fibrillation (AF) in all patients (except those with AF termination during PVI). Extra‐pulmonary vein (PV) targets were compared between the two LA maps in each patient. Follow‐up included Holter monitoring every 3 months.

Results

Patients had a median of 3 extra‐PV drivers/targets. The majority (81%) were localized in the same areas between the two LA maps. All patients had progressive AF organization demonstrated by global activation slowing: histogram peak L‐CL increased from 162 to 171 ms (post‐PVI; p = .0003) than to 175 ms (posttarget ablation; p = .04). Moreover, L‐CL dispersion was reduced by ablation; in 50% their values tended to cluster around two dominant cycles. In de novo patients AF terminated to sinus rhythm or atrial tachycardia (AT) within 48 h postprocedure in 88% of cases, and at 18 months mean follow‐up recurrence occurred in only five (25%) patients (three persAF, two AT). There were no complications.

Conclusion

The algorithmic detection of EGMs consistent with localized reentry during sequential mapping of persAF provided reproducible targets for ablation. This allowed personalized PVI and limited, highly‐selective, extra‐PV ablation. Results of this initial experience included progressive organization of AF with ablation and a low recurrence rate after a single procedure.
Prognostic value of morning blood pressure surge in chronic kidney disease
Authors: Ma Zhilan , Wang Yan , Guo Xiaoyan , Ma Lan , Liu Yonghua , Zhou Xiaoling
Published: August 2024

This was a retrospective study. This study investigated the occurrence of a composite endpoints (cardiovascular and cerebrovascular events, end‐stage renal disease, and death) in 153 patients (aged ≥ 18 years) with a diagnosis of in chronic kidney disease (CKD). Based on morning blood pressure surge (MBPS) defined as ≥35 mm Hg, patients were divided into two groups: with MBPS (n = 50) and without MBPS (n = 103). All patients were followed up for at least 1 year. Baseline demographic, laboratory and follow‐up data were collected. The clinical characteristics of the two groups were compared. The relationships between MBPS and endpoint events were analyzed using the Kaplan–Meier method and Cox regression model. In total, 153 patients (mean age 41.8 years; 56.86% males) were included in this study. During the follow‐up period (mean 4.3 years), 34 endpoint events occurred. After adjustment for the covariates, the risk of cardiovascular and cerebrovascular events, end‐stage renal disease and death remained significantly higher in patients with MBPS (hazard ratio [HR] and 95% confidence interval [CI] 3.124 [1.096–9.130]]) Among the other variables, systolic blood pressure, and night‐time and daytime pulse pressures remained significantly associated with outcome in patients of CKD (1.789 [1.205–2.654], 1.710 [1.200–2.437], and 1.318 [1.096–1.586], respectively]. In conclusions, MBPS was identified as an independent prognostic factor for composite endpoint events (cardiovascular and cerebrovascular events, end‐stage renal disease and death) patients with chronic kidney disease patients.
Genetic variants of m6A modification genes are associated with survival of HBV‐related hepatocellular carcinoma
Authors: Liu Shuyan , Li Jianxu , Qiu Moqin , Liu Yingchun , Wen Qiuping , Lin Qiuling , Jiang Yanji , Zhou Zihan , Liang Xiumei , Wei Xiaoxia , Yu Hongping , Chen Peiqin
Published: August 2024

N6‐methyladenosine (m6A) is a dynamic and reversible modification process involving in a series of important biological and pathophysiological processes, including the progression of cancers. Herein, we aimed to assess the relationships of genetic variants in m6A modification genes with the survival of hepatitis B virus ‐related hepatocellular carcinoma (HBV‐HCC). We performed a two‐stage survival analysis to investigate the associations of 4425 single nucleotide polymorphisms (SNPs) in 36 m6A modification genes with the overall survival (OS) of HBV‐HCC patients. Then, the identified SNPs were further used to functionally annotate. We identified that METTL3 rs1263790 (A > G) and ADARB1 rs57884102 (C > T) were significantly associated with the HBV‐HCC OS (hazard ratios [HR] = 0.68, 95% confidence interval [CI] = 0.52–0.89, p = 0.004; and HR = 1.70, 95% CI = 1.33–2.18, p < 0.001, respectively). Combined analysis revealed that patients carrying more risk genotypes of two variants had a progressively poorer OS. Moreover, the expression quantitative trait loci (eQTL) analysis indicated that rs1263790 G allele decreased mRNA expression levels of METTL3 in 483 cell‐cultured fibroblasts samples. And we found the mRNA expression levels of METTL3 and ADARB1 in HCC tissues were higher than in normal tissues, and the higher METTL3 and the lower ADARB1 were associated with poorer HCC OS. Our results demonstrated that two novel genetic variants (METTL3 rs1263790 and ADARB1 rs57884102) may be potential prognostic markers for HBV‐HCC, but these results need larger different ethnic cohorts and functional experiments to validate in the future.
Interleukin‐6 positively correlates with cardiovascular disease predictor algorithms and biomarker in rheumatoid arthritis patients
Authors: Roghani Seyed Askar , Shamsi Afsaneh , Jalili Cyrus , Jalili Farnaz , Lotfi Ramin , Garman Nima , Rostampour Rezvan , Taghadosi Mahdi
Published: August 2024

Chronic inflammation is believed as the main culprit of the link between cardiovascular disease (CVD) and rheumatoid arthritis (RA). Interleukin‐6 (IL‐6) is a pro‐inflammatory cytokine with a key role in RA pathophysiology and also correlates with joint destruction and disease activity. This study evaluates the association between IL‐6 plasma level and cardiac biomarker NT‐proBNP, HS‐CRP, CVD predictor algorithms, Framingham Risk Score (FRS) and Systematic Coronary Risk Evaluation (SCORE), as well as with CXCL9 and its receptor, CXCR3 in RA patients compared to the controls. Sixty RA patients (30 early and 30 late) and 30 healthy persons were included in this study. IL‐6 and NT‐proBNP plasma levels were measured by the ELISA. Also, HS‐CRP plasma levels were quantified using the immunoturbidimetric assay. The CVD risk was assessed by the FRS and SCORE. IL‐6 plasma levels were significantly higher in the early and late RA patients compared to the controls (p < 0.001). There was a positive correlation between IL‐6 with DAS‐28 (p = 0.007, r = 0.346), BPS (p = 0.002, r = 0.396), BPD (p = 0.046, r = 0.259), SCORE (p < 0.001, r = 0.472), and FRS (p < 0.001, r = 0.553), and a negative association with HDL (p = 0.037, r = −0.270), in the patients. Also, IL‐6 plasma level positively correlated with HS‐CRP (p = 0.021, r = 0.297) and NT‐proBNP (p = 0.045, r = 0.260) in the patients. Furthermore, a positive association was found between IL‐6 plasma levels and CXCL9 (p = 0.002, r = 0.386), and CXCR3 (p = 0.018, r = 0.304) in the patients. Given the interesting association between IL‐6 with various variables of CVD, IL‐6 may be considered a biomarker for assessing the risk for future cardiovascular events in RA patients.
Utilizing Oral Neutrophil Counts as an Indicator of Oral Inflammation Associated With Periodontal Disease: A Blinded Multicentre Study
Authors: Elebyary Omnia , Sun Chunxiang , Batistella Elis Angela , Van Dyke Thomas E. , Low Samuel B. , Singhal Sonica , Tenenbaum Howard , Glogauer Michael
Published: August 2024

Background

Periodontal diseases are chronic inflammatory conditions that require early screening for effective long‐term management. Oral neutrophil counts (ONCs) correlate with periodontal inflammation. This study investigates a point‐of‐care test using a neutrophil enzyme activity (NEA) colorimetric strip for measuring periodontal inflammation.

Methods

This prospective study had two phases. Phase 1 validated the relationship between ONCs and periodontal inflammation with 90 participants. Phase 2 examined the test's applicability in a real‐world setting through a multicentre clinical trial with 375 participants at four sites. ONCs were quantified in oral rinses using laboratory‐based methods, and the NEA strip was used for ONC stratification. Clinical measures included bleeding on probing (BoP), probing depth (PD) and clinical attachment loss (CAL).

Results

ONCs were significantly elevated in patients with Grade B periodontitis and deep periodontal pockets (PD ≥ 5 mm, CAL ≥ 5 mm). The NEA strip accurately classified patients into high or low ONC categories, showing 80% sensitivity, 82.5% specificity and an AUC of 0.89. It also assessed the effectiveness of periodontal therapy in reducing ONC and inflammation. The test was user‐friendly, with no reported discomfort among patients.

Conclusion

The NEA strip is a user‐friendly and rapid screening tool for detecting high ONCs associated with periodontal inflammation and for evaluating the effectiveness of periodontal therapy.
Targeting PI3K/AKT and MEK/ERK pathways for synergic effects on improving features of peripheral diabetic neuropathy
Authors: Pham Vuong M.
Published: August 2024

Diabetic neuropathy is one of the most serious and common complications of diabetes with a wide spectrum, affecting 30–50% of diabetic patients. However, the current treatments of this disorder, mainly based on controlling blood glucose level, show an inadequate clinical outcome. Better approaches are needed. In this fashion, it is noted that promoting nerve regeneration and preventing nerve degeneration should be focused on equally and appropriately. In this mini review, how more effective approaches are in targeting PI3K/AKT and MEK/ERK pathways in the treatment of peripheral diabetic neuropathy is discussed. Future treatment of peripheral diabetic neuropathy should consider these approaches.
Cancer‐associated fibroblasts promote the proliferation and metastasis of colon cancer by mediating the RLIM/PML axis through paracrine COMP
Authors: Chen Zhenfeng , Chen Weirong , Lin Kaihuang , Chen Xigui , Lin Guangrong , Li Yanchong , Cui Chunhui
Published: August 2024

Background and Aim

Cancer‐associated fibroblasts (CAFs) are abundant in colon cancer (CC) patients with a poor prognosis. Here, the molecular regulatory mechanism of CAFs on CC growth and metastasis was explored.

Methods

The genes' expression was monitored using RT‐qPCR, immunoblotting, and immunohistochemistry. Cell viability and proliferation were found using CCK‐8 and clone formation assays. The cell migration and invasion were probed using wound healing and Transwell. Co‐IP was utilized for ascertaining the interaction between AKT and the ring finger protein, LIM domain interacting (RLIM). The in vivo murine subcutaneous tumor model and the metastasis model were built to further ascertain the axis.

Results

The result showed that CAFs motivate the growth and activate the PI3K/AKT pathway of CC cells via paracrine cartilage oligomeric matrix protein (COMP). Moreover, RLIM promoted the growth of CC cells, and its protein stability was regulated by AKT through its phosphorylation. Further, RLIM facilitated the ubiquitination and degradation of promyelocytic leukemia protein (PML). The in vitro and in vivo tests found that PML overexpression could inhibit CC's growth and metastasis, which were enhanced by CAFs.

Conclusion

The COMP excreted from CAFs enhances the CC's growth and metastasis through regulating the RLIM/PML axis, supplying a new potential target for the cure of CC.
Washed microbiota transplantation improved the level of serum vitamin D in ulcerative colitis
Authors: Zhang Hui , Xiao Yuyan , Wen Quan , Zhang Sheng , Li Pan , Marcella Cicilia , Hu Bo , Liu Hui , Zhang Faming , Cui Bota
Published: August 2024

Background and Aim

Vitamin D (VD) deficiency was reported to correlate with ulcerative colitis (UC) activity, which might be closely related to gut microbiota dysbiosis. This study aims to investigate the effects of washed microbiota transplantation (WMT) on VD metabolism in UC.

Methods

The serum levels of 25‐hdroxyvitamin D [25(OH)D] in 121 patients with UC and 53 healthy controls (HC) were detected. Subsequently, a non‐randomized control trial (non‐RCT) was conducted. Patients with UC were non‐randomly assigned to undergo WMT (n = 28) vs. conventional treatment (5‐aminosalicylic acid, 5‐ASA, n = 10). Serum levels of 25(OH)D, fecal microbiota, and the expression of vitamin D receptor (VDR) in patients with UC were evaluated with a 3‐month follow‐up.

Results

Serum VD levels collected in the clinic practice indicated that patients with UC had significantly lower VD levels than HC (P < 0.001). In the non‐RCT, serum 25(OH)D level and VDR expression significantly increased (P = 0.011, 0.026, respectively) in the WMT group, while no noticeable changes were observed in the non‐WMT group. Microbiome profiling revealed that the increase in VD levels after WMT was positively associated with the abundances of Adlercreutzia_equolifaciens, Ruminococcus_obeum, and Dorea but negatively correlated with Escherichia.

Conclusions

The study suggested that WMT increases the levels of VD with characteristic changes of specific microbiota, which indicated the association between the VD and the activity of UC might be regulated by gut microbiota.
Estimating the Ideas' Production Function Using Macro‐Economic Persistence
Authors: MA XIAOHAN , SAMANIEGO ROBERTO
Published: August 2024

If productivity stems from the accumulation of ideas, then the ideas' production function can cause productivity and macro‐economic aggregates to be persistent. We use this insight to estimate the parameters of the ideas' production function in a general equilibrium model. We find that ideas become harder to produce as they accumulate. We quantitatively explore the propagation of different kinds of shocks through the ideas' production function, finding that nonpersistent shocks that affect R&D decisions may lead to persistent productivity changes as a result. The use of capital in R&D is important for propagation.