bluuebunny/crossref_metadata_2025_split huggingface dataset:
Steroids' Neuroprotective Potential in Severe Cerebral Venous Thrombosis: Experimental and Clinical Exploration of NLRP3 Inflammasome Inhibition
Authors: Hu Shuyuan , Gu Yaqin , Hou Limin , Liu Jia , Zhao Haiping , Luo Yumin , Wang Chunxiu , Ji Xunming , Liu Guiyou , Duan Jiangang 
Published: November 2024

ABSTRACTBackgroundNLRP3 inflammasome‐related inflammation might play an important role in the pathophysiology of severe CVT. The use of steroids as anti‐inflammatory agents in improving severe CVT prognosis remains controversial.MethodsA total of 94 male Sprague–Dawley rats were used. We evaluated the dynamic and association between NLRP3 inflammasome in brain, blood, and CSF and severity in severe CVT rats and/or patients. We also explored the effect of steroids on NLRP3 activation, neurological injury, and CSF circulation disturbance after CVT in animals and/or patients.ResultsIn rats, compared with the sham group, NLRP3‐related factors rose on day 1, peaked on day 2 (NLRP3, Sham: 0.79 ± 0.22; day 2: 1.25 ± 0.08, p < 0.01; pro‐Caspase‐1, Sham: 0.58 ± 0.13, day 2: 1.20 ± 0.44, p < 0.05; GSDMD, Sham: 0.94 ± 0.22, day 2: 1.72 ± 0.46, p < 0.05; pro‐IL‐1β, Sham: 0.74 ± 0.15, day 2: 1.35 ± 0.09, p < 0.01), decreased on day 7 in rats (n = 4 per group). Thrombus (Sham: 0.00 ± 0.00, day 2: 3.44 ± 0.70, p < 0.0001), infarct size (Sham: 0.00 ± 0.00, day 2: 11.99 ± 6.26, p < 0.01) and neurological deficits appeared similar trend. In 50 patients, serum NLRP3 and IL‐6 levels correlated positively with NIHSS (r = 0.4273, p = 0.0020; r = 0.4938, p = 0.0029) and mRS (r = 0.5349, p = 0.0125; r = 0.6213, p = 0.026), while CSF IL‐6 correlated positively with mRS on admission (r = 0.5349, p = 0.0125). Compared with baseline, NLRP3 (0.36 (0.36, 0.36) vs. 0.41 (0.37, 0.84), p < 0.0001) and IL‐6 decreased (4.06 ± 1.48 vs. 12.03 ± 7.80, p < 0.05), accompanying by improvement of neurological deficits and CSF circulation (all p < 0.01) after steroids therapy in severe CVT patients at discharge and 3 months follow‐up. No significant steroid‐related adverse effects were observed.ConclusionShort‐term steroid therapy may improve prognosis of severe CVT by suppressing NLRP3 inflammasome‐related inflammation.
The Pseudoinflammatory Pattern Revisited
Authors: Shea Christopher R. 
Published: November 2024

ABSTRACTIn 1973, Dr. Martin C. Mihm, Jr. presented the finding that congenital melanocytic nevi, when viewed at low magnification, resemble superficial and deep perivascular dermatitis, forming the so‐called “pseudoinflammatory” pattern. One year earlier, Dr. Richard A. Sagebiel had put forward the concept of “pseudovascular spaces” in melanocytic nevi. A retrospective look at these early studies confirms that alert observation at the microscope can lead to a deeper understanding of the fundamental biology underlying melanocytic tumors.
Genotype‐by‐environment interactions for mean performance and trait variation in house fly larvae reared on two diets
Authors: Laursen Stine Frey , Hansen Laura Skrubbeltrang , Bahrndorff Simon , Nielsen Hanne Marie , Sahana Goutam , Sørensen Jesper Givskov , Ørsted Michael , Kristensen Torsten Nygaard 
Published: November 2024

AbstractSome insect species have been proposed as a sustainable alternative to traditional animal‐based food and feed sources. Optimisation of insect production can generally be achieved using two main approaches: optimising environmental conditions and improving traits of interest through selective breeding. These avenues are not inseparable as performance of a genotype might differ between environments due to phenotypic plasticity and because genotypes can respond differently to environmental changes, that is genotype‐by‐environment interactions (G × E). In insect production, diets can be of variable quality and consist of waste‐ and by‐products of low nutritional value, which might result in decreased performance and/or increased trait variability within a population. Therefore, it is of interest to investigate how genotypes perform across various diets. Here, we investigated plasticity and G × E for mean performance and trait variation, which we define as the ability of a genotype to produce consistent phenotypes within and across environments. We did this by rearing 190 full‐sib families of house fly larvae, Musca domestica L. (Diptera: Muscidae), on two diets based on either alfalfa, Medicago sativa L. (Fabales: Fabaceae), or deproteinated grass. Four larval traits were assessed: egg‐to‐larva viability, surface area, dry weight and relative lipid content. Reaction norms were used to investigate the effects of diet on full‐sib family mean and trait variation within and across environments. We found that families reared on the grass‐based diet had higher performance across all investigated traits than families reared on the alfalfa‐based diet. For both mean performance and trait variation, we found G × E for all investigated traits. These findings suggest that there is genetic variation for plasticity (slope of reaction norms) for both trait mean and trait variation, and thus that there is a potential to breed for genotypes with high performance as well as for genotypes with low trait variation within and across diets.
Loss of neuropeptide signalling alters temporal expression of mouse suprachiasmatic neuronal state and excitability
Authors: Wegner Sven , Belle Mino D. C. , Chang Pi‐Shan , Hughes Alun T. L. , Conibear Alexandra E. , Muir Charlotte , Samuels Rayna E. , Piggins Hugh D. 
Published: November 2024

AbstractIndividual neurons of the hypothalamic suprachiasmatic nuclei (SCN) contain an intracellular molecular clock that drives these neurons to exhibit day‐night variation in excitability. The neuropeptide vasoactive intestinal polypeptide (VIP) and its cognate receptor, VPAC2, are synthesized by SCN neurons and this intercellular VIP‐VPAC2 receptor signal facilitates coordination of SCN neuronal activity and timekeeping. How the loss of VPAC2 receptor signalling affects the electrophysiological properties and states of SCN neurons as well as their responses to excitatory inputs is unclear. Here we used patch‐clamp electrophysiology and made recordings of SCN neurons in brain slices prepared from transgenic animals that do not express VPAC2 receptors (Vipr2−/− mice) as well as animals that do (Vipr2+/+ mice). We report that while Vipr2+/+ neurons exhibit coordinated day‐night variation in their electrical state, Vipr2−/− neurons lack this and instead manifest a range of states during both day and night. Further, at the population level, Vipr2+/+ neurons vary the membrane threshold potential at which they start to fire action potentials from day to night, while Vipr2−/− neurons do not. We provide evidence that Vipr2−/− neurons lack a component of voltage‐gated sodium currents that contribute to SCN neuronal excitability. Moreover, we determine that this aberrant temporal control of neuronal state and excitability alters neuronal responses to a neurochemical mimic of the light‐input pathway to the SCN. These results highlight the critical role VIP‐VPAC2 receptor signalling plays in the temporal expression of individual neuronal states as well as appropriate ensemble activity and input gating of the SCN neural network.
Behavioural phenotypes of Dicer knockout in the mouse SCN
Authors: Du Ngoc‐Hien , Kompotis Konstantinos , Sato Miho , Pedron Erica , Androvic Sabrina , Brown Steven 
Published: November 2024

AbstractThe suprachiasmatic nucleus (SCN) is the master clock that directly dictates behavioural rhythms to anticipate the earth's light/dark cycles. Although post‐transcriptional regulators called microRNAs have been implicated in physiological SCN function, how the absence of the entire mature miRNome impacts SCN output has not yet been explored. To study the behavioural consequences of miRNA depletion in the SCN, we first generated a mouse model in which Dicer is inactivated in the SCN by crossing Syt10Cre mice with Dicerflox mice to study behavioural consequences of miRNA depletion in the SCN. Loss of all mature miRNAs in the SCN shortened the circadian period length by ~37 minutes at the tissue level and by ~45 minutes at the locomotor activity level. Moreover, knockout animals exhibited a reduction in the precision of the circadian rhythm with more variable activity onsets under both LD 12:12 and DD conditions. We also observed that knockouts with higher onset variations were inclined to develop ultradian rhythms under constant light. In a second mouse model, recombination of Dicerflox via Cre delivery specifically in the SCN resulted in loss of behavioural rhythms in some animals depending on the injection efficiency. Together, our observations highlight the importance of microRNAs for a physiological SCN function and their pivotal role in robust circadian oscillations.
The political and economic environment promoting growth in American wealth inequality
Authors: Ackert Lucy F. , Ramirez Gabriel G. 
Published: November 2024

AbstractWealth inequality around the world is high and rising. In this paper, we argue that wealth inequality in the United States has been exacerbated by an environment favourable to the ultra‐wealthy. Three distinctive changes in the economic and political landscape have fostered the increase in inequality. First, campaign finance law abruptly changed after the Citizens United Supreme Court decision. This decision gave the ultra‐wealthy an outsized influence on American politics. Second, an increase in competition for executive talent drove CEO salaries to new heights. Demand increased for executives with general leadership skills as corporations grew larger, increasing competition in the market for executive talent. Third, because tax policy in the United States is subject to lobbying influences, those at the top of the wealth distribution are favoured, leading to further concentration in wealth. Our empirical results are consistent with the view that these changes resulted in an increase in disparity, shifting wealth from the 99% to the 1%.
Changing Bird Migration Patterns Have Potential to Enhance Dispersal of Alien Plants From Urban Centres
Authors: Deshpande Purabi , Johansson Niko , Kluen Edward , Lehikoinen Aleksi , Thorogood Rose 
Published: November 2024

ABSTRACTThere is increasing recognition that alien species may be ‘sleepers’, becoming invasive with favourable changes in conditions, yet these changes remain difficult to predict. As populations of frugivorous birds shift with urbanisation and climate change, they could provide dispersal services for introduced fruiting plants that have previously been considered benign. This is likely to be especially problematic at higher latitudes where bird migration phenologies are altering rapidly. However, any consequences for fruit dispersal have not yet been explored. Here, we use Helsinki, Finland, to investigate whether (i) streetscapes provide birds with a fruit resource that differs from urban forest fragments and (ii) the chances for dispersal of alien species (i.e., preferential consumption of native fruits). While there were both more fruits and birds in streetscapes (replicated across multiple years), fruits were not consumed preferentially according to origin. Additionally, seed analysis from faecal samples of blackbird Turdus merula L., a previously migratory but increasingly resident species, suggested that alien and native plants are equally likely to be dispersed. These results indicate that birds could be dispersing alien species more frequently than previously thought and highlight the complex effects of changing climates on potentially invasive species.
A Proposed Coupling Framework of Biological Invasions: Quantifying the Management Prioritization in Mealybugs Invasion
Authors: Zhao Haoxiang , Xian Xiaoqing , Yang Nianwan , Chen Ting , Li Jianyu , Sheppard Andy , Wan Fanghao , Qi Guojun , Liu Wanxue 
Published: November 2024

ABSTRACTPrioritizing potential invasive alien species, introduction pathways, and likely places susceptible to biological invasions is collectively critical for developing the targeting of management strategies at pre‐border, border, and post‐border. A framework for prioritizing the invasion management that considered all these elements in combination is lacking, particularly in the context of potential coinvasion scenarios of multispecies. Here, for the first time, we have constructed a coupling framework of biological invasions to evaluate and prioritize multiple invasion risks of 35 invasive alien mealybugs (IAMs) that posed a significant threat to the agri‐horticultural crops in China. We found that the imported tropical fruits from free trade areas of the Association of Southeast Asian Nations to entry ports of southern China were the primary introduction pathway for IAMs, vectored on various fruit commodities. There was also a high probability for cointroductions of potential multi‐IAMs with a single imported tropical fruit. The potential distribution of such IAMs with dissimilar net relatedness were mainly located in southern China. These distributions, however, are likely to expand to the higher latitudes of northern China under future climate and land use/land cover changes. Temperature and anthropogenic factors were both independently and collectively determining factors for the diversity and distribution patterns of imported IAMs under near‐current climate conditions. Our findings highlight that these multiple components of global change have and will continue to facilitate the introduction and establishment risks of IAMs in southern China, as well as the spread risk into northern China. Additionally, our findings, for the first time, demonstrated management prioritization across the continuous invasion stages of 35 IAMs in China, and provide additional insights into the development of targeting of their biosecurity and management decisions.
Shared Decision‐Making and Body Mass Index in Australian Antenatal Care: An Exploratory OPTION12 Evaluation
Authors: Hawke Madeline , Sweet Linda , Considine Julie 
Published: November 2024

ABSTRACTBackgroundShared decision‐making is recommended as a person‐centred approach to decision‐making in antenatal care. Little is known about the implementation of shared decision‐making in antenatal care.ObjectiveAn exploratory study to understand how shared decision‐making is implemented in antenatal clinics and whether body mass index influences maternity clinicians’ use of shared decision‐making when providing antenatal care for women.MethodsTwenty‐six antenatal clinic consultations were audio‐recorded with maternity clinicians and women with body mass index ≥ 35 kg/m2, and a comparison group of women with body mass index 18.5–24.9 kg/m2. Data were analysed quantitatively using the OPTION12 scale. Narrative case studies are presented to compare shared decision‐making behaviour related to induction of labour.ResultsTwelve clinicians and 26 pregnant women were recruited to the study. The total scores ranged from 0 to 24, with a mean score of 9 and a median of 9.5 indicating low implementation of shared decision‐making by clinicians and limited involvement of women in decision‐making. No difference was observed in OPTION12 scores in decision‐making for women by body mass index.ConclusionThis study suggests that shared decision‐making is limited in the antenatal clinic setting for all women, regardless of body mass index. Further research is required to confirm the findings of this exploratory study.Patient or Public ContributionThe perspectives of women with body mass index ≥ 35 kg/m2 informed many aspects of this study including the language/terminology adopted by researchers. A consumer group reviewed the language used in the study materials, to ensure readability and avoidance of stigmatising terminology.
Gender‐specific genetic influence of rs1111875 on diabetes risk: Insights from the Taiwan biobank study
Authors: Chiang Chih‐Wei , Chou Ying‐Hsiang , Huang Chien‐Ning , Lu Wen‐Yu , Liaw Yung‐Po 
Published: November 2024

ABSTRACTBackgroundThis study investigates the gender‐specific genetic influence of the single nucleotide polymorphism (SNP) rs1111875 on diabetes risk within the Taiwanese population using data from the Taiwan Biobank. Diabetes mellitus, particularly type 2 diabetes (T2D), is influenced by genetic factors, and the rs1111875 SNP near the hematopoietically expressed homeobox (HHEX) gene has been linked to T2D susceptibility.MethodsThe study included 69,272 participants after excluding those from arsenic‐polluted areas and those with incomplete data. Logistic regression models were used for analyses.ResultsThe analyses revealed that the CT genotype of rs1111875 was associated with an increased risk of diabetes (OR = 1.092, 95% CI = 1.030–1.157, P = 0.003), as was the TT genotype (OR = 1.280, 95% CI = 1.165–1.407, P < 0.001). The effect was more pronounced in women (CT: OR = 1.118, 95% CI = 1.036–1.207, P = 0.004; TT: OR = 1.404, 95% CI = 1.243–1.585, P < 0.001). Men exhibited a higher overall risk of diabetes (OR = 1.565, 95% CI = 1.445–1.694, P < 0.001) and had a higher prevalence (12.71% vs 7.80%, P < 0.001) compared to women.ConclusionsThe findings underscore the importance of considering gender differences in genetic studies of diabetes and suggest that personalized diabetes management strategies should account for both genetic and gender‐specific risk factors. This research contributes to the broader understanding of genetic determinants of diabetes and their interaction with gender, aiming to enhance personalized healthcare strategies for diabetes prevention and treatment.
Inhibition of iron‐induced cofilin activation and inflammation in microglia by a novel cofilin inhibitor
Authors: Shehjar Faheem , James Antonisamy William , Mahajan Reetika , Shah Zahoor A. 
Published: November 2024

AbstractNeuroinflammatory conditions linked to iron dysregulation pose significant challenges in neurodegenerative diseases. Iron‐loaded microglia are observed in the brains of patients with various neuroinflammatory conditions, yet how iron overload affects microglial function and contributes to various neuroinflammatory processes is poorly understood. This in vitro study elucidates the relationship between excess iron, cofilin activation, and microglial function, shedding light on potential therapeutic avenues. Iron overload was induced in Human Microglial Clone 3 cells using ferrous sulfate, and the expressions of ferritin heavy chain, ferritin light chain, divalent metal transporter 1, cofilin, p‐cofilin, nuclear factor‐κB (NF‐κB), and various inflammatory cytokines were analyzed using real‐time quantitative polymerase chain reaction, immunocytochemistry, Western blotting, and enzyme‐linked immunosorbent assay. Results revealed a notable increase in cofilin, NF‐κB, and inflammatory cytokine expression levels following excess iron exposure. Moreover, treatment with deferoxamine (DFX), a known iron chelator, and a novel cofilin inhibitor (CI) synthesized in our laboratory demonstrate a mitigating effect on iron‐induced cofilin expression. Furthermore, both DFX and CI exhibit promising outcomes in mitigating the inflammatory consequences of excess iron, including the expression of pro‐inflammatory cytokines and NF‐κB activation. These findings suggest that both DFX and CI can potentially alleviate microglia‐induced neuroinflammation by targeting both iron dysregulation and cofilin‐mediated pathways. Overall, this study provides valuable insights into iron‐induced cofilin activation and microglial activation, offering avenues for potential targeted therapies for neuroinflammatory conditions associated with iron and cofilin dysregulation in neurodegenerative diseases.image
QuPath Edu and OpenMicroanatomy: Open‐source virtual microscopy tools for medical education
Authors: Yli‐Hallila Aaron , Bankhead Peter , Arends Mark J. , Lehenkari Petri , Palosaari Sanna 
Published: November 2024

AbstractVirtual microscopy is becoming increasingly common in both medical education and routine clinical practice. Virtual microscopy software is typically designed either for (1) training students in anatomy, histology, and histopathology, or (2) quantitative analysis—but not both simultaneously. QuPath is one of the most widely used software applications for histopathology image analysis in research and provides a comprehensive set of computational tools to evaluate histology slides. We have enhanced QuPath by developing a new extension, QuPath Edu, which adapts the software to function as an intuitive microanatomy learning environment. Additionally, we have created an entirely new, complementary software platform called OpenMicroanatomy, which provides an alternative way to access QuPath Edu teaching content through a web interface. These tools have been used in teaching of first year medical and dentistry students at the University of Oulu Medical Faculty, and we conducted a user survey for the Class of 2023 to assess the usability and student experience. In general, the introduced annotation and quiz features were appreciated by the students and the system usability of OpenMicroanatomy was considered excellent (SUS score 84.8). Together, these freely available tools enable teachers to develop and deploy innovative training material for anatomy, histopathology, quantitative analysis, and artificial intelligence in a wide range of contexts. This unique combination can provide the next generation of students with essential multidisciplinary skills.
Cyclin‐dependent kinase 13 is indispensable for normal mouse heart development
Authors: Waheed‐Ullah Qazi , Wilsdon Anna , Abbad Aseel , Rochette Sophie , Bu'Lock Frances , Saed Asma Ali , Hitz Marc‐Phillip , Brook J. David , Loughna Siobhan 
Published: November 2024

AbstractCongenital heart disease (CHD) has an incidence of approximately 1%. Over the last decade, sequencing studies including large cohorts of individuals with CHD have begun to unravel the genetic mechanisms underpinning CHD. This includes the identification of variants in cyclin‐dependent kinase 13 (CDK13), in individuals with syndromic CHD. CDK13 encodes a serine/threonine protein kinase. The cyclin partner of CDK13 is cyclin K; this complex is thought to be important in transcription and RNA processing. Pathogenic variants in CDK13 cause CDK13‐related disorder in humans, characterised by intellectual disability and developmental delay, recognisable facial features, feeding difficulties and structural brain defects, with 35% of individuals having CHD. To obtain a greater understanding for the role that this essential protein kinase plays in embryonic heart development, we have analysed a presumed loss of function Cdk13 transgenic mouse model (Cdk13tm1b). The homozygous mutants were embryonically lethal in most cases by E15.5. X‐gal staining showed Cdk13 expression localised to developing facial regions, heart and surrounding areas at E10.5, whereas at E12.5, it was more widely present. In the E15.5 heart, staining was seen throughout. RT‐qPCR showed significant reduction in Cdk13 transcript expression in homozygous compared with WT and heterozygous hearts at E10.5 and E12.5. Detailed morphological 3D analysis of embryonic and postnatal hearts was performed using high‐resolution episcopic microscopy, which affords a more detailed analysis of structures such as cardiac valve leaflets and endocardial cushions, compared with more traditional histological techniques. We show that both the homozygous and heterozygous Cdk13tm1b mutants exhibit a range of CHD, including ventricular septal defects, bicuspid aortic valve, double outlet right ventricle and atrioventricular septal defects. 100% (n = 4) of homozygous hearts displayed CHD. Differential expression was seen in Cdk13tm1b homozygous mutants for two genes known to be necessary for normal heart development. The types of defects, and the presence of CHD in heterozygous mice (17.02%, n = 8/47), are consistent with the CDK13‐related disorder phenotype in humans. This study provides important insights into the effects of reduced function of CDK13 in the mouse heart and contributes to our understanding of the mechanism behind this disorder as a cause of CHD.