bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of pharmacokinetics and tolerability following single‐dose administration of molnupiravir in participants with hepatic or renal impairment
Authors: Duncan Kelly E. , Carstens Russ P. , Butterfield Kristin L. , Jin Yoon , Inbody Laura R. , Schaeffer Andrea K. , Matthews Catherine Z. , Zhao Tian , Patel Shruti , Maas Brian M. , Cheng Mickie H. , Stoch S. Aubrey
Published: November 2024

Individuals with chronic liver or kidney disease are at increased risk of severe COVID‐19. Molnupiravir is an orally administered antiviral authorized for the treatment of mild‐to‐moderate COVID‐19 in adults at risk of progression to severe disease. Two nonrandomized, open‐label, single‐dose, multicenter, phase 1 trials were conducted to investigate the effects of hepatic and renal impairment on the tolerability and pharmacokinetics of molnupiravir (800 mg) and its metabolite β‐D‐N4‐hydroxycytidine (NHC; NCT05386589/NCT05386758). The impact of renal impairment on urinary excretion of NHC was also assessed. The 90% CI for the geometric mean ratio of the plasma NHC area under the concentration–time curve (AUC) from zero to infinity was <2.0 for participants with moderate hepatic or severe renal impairment versus healthy mean‐matched controls. Comparable geometric mean values were observed for other pharmacokinetic parameters—including AUC from 0 to 12 h, AUC from zero to the last measurable concentration, and peak plasma concentration—in participants with moderate hepatic or severe renal impairment and in healthy mean‐matched controls. Urinary excretion of NHC was low in healthy participants and participants with severe renal impairment; renal clearance was numerically lower in those with renal impairment. In both trials, all adverse events were of mild or moderate intensity and resolved by study completion. There were no clinically relevant treatment‐related effects on other safety evaluations. Overall, molnupiravir was generally well‐tolerated, with similar pharmacokinetic profiles in participants with hepatic or renal impairment and healthy participants, supporting its use for treating COVID‐19 in these individuals without the need for dose adjustment.
Combining Real‐Time Neuroimaging With Machine Learning to Study Attention to Familiar Faces During Infancy: A Proof of Principle Study
Authors: Throm Elena , Gui Anna , Haartsen Rianne , da Costa Pedro F. , Leech Robert , Mason Luke , Jones Emily J. H.
Published: November 2024

Looking at caregivers’ faces is important for early social development, and there is a concomitant increase in neural correlates of attention to familiar versus novel faces in the first 6 months. However, by 12 months of age brain responses may not differentiate between familiar and unfamiliar faces. Traditional group‐based analyses do not examine whether these ‘null’ findings stem from a true lack of preference within individual infants, or whether groups of infants show individually strong but heterogeneous preferences for familiar versus unfamiliar faces. In a preregistered proof‐of‐principle study, we applied Neuroadaptive Bayesian Optimisation (NBO) to test how individual infants’ neural responses vary across faces differing in familiarity. Sixty‐one 5–12‐month‐olds viewed faces resulting from gradually morphing a familiar (primary caregiver) into an unfamiliar face. Electroencephalography (EEG) data from fronto‐central channels were analysed in real‐time. After the presentation of each face, the Negative central (Nc) event‐related potential (ERP) amplitude was calculated. A Bayesian Optimisation algorithm iteratively selected the next stimulus until it identified the stimulus eliciting the strongest Nc for that infant. Attrition (15%) was lower than in traditional studies (22%). Although there was no group‐level Nc‐difference between familiar versus unfamiliar faces, an optimum was predicted in 85% of the children, indicating individual‐level attentional preferences. Traditional analyses based on infants’ predicted optimum confirmed NBO can identify subgroups based on brain activation. Optima were not related to age and social behaviour. NBO suggests the lack of overall familiar/unfamiliar‐face attentional preference in middle infancy is explained by heterogeneous preferences, rather than a lack of preference within individual infants.
Coding‐Sequence Evolution Does Not Explain Divergence in Petal Anthocyanin Pigmentation Between Mimulus luteus Var luteus and M. l. variegatus
Authors: Orr Walker E. , Kim Ji Yang , Márquez Iker J. Sánchez , Ryan Caine J. , Raj Tejas , Hom Ellen K. , Person Ashley E. , Vonada Anne , Stratton John A. , Cooley Arielle M.
Published: November 2024

Biologists have long been interested in understanding genetic constraints on the evolution of development. For example, noncoding changes in a gene might be favored over coding changes if they are less constrained by pleiotropic effects. Here, we evaluate the importance of coding‐sequence changes to the recent evolution of a novel anthocyanin pigmentation trait in the monkeyflower genus Mimulus. The magenta‐flowered Mimulus luteus var. variegatus recently gained petal lobe anthocyanin pigmentation via a single‐locus Mendelian difference from its sister taxon, the yellow‐flowered M. l. luteus. Previous work showed that the differentially expressed transcription factor gene MYB5a/NEGAN is the single causal gene. However, it was not clear whether MYB5a coding‐sequence evolution (in addition to the observed patterns of differential expression) might also have contributed to increased anthocyanin production in M. l. variegatus. Quantitative image analysis of tobacco leaves, transfected with MYB5a coding sequence from each taxon, revealed robust anthocyanin production driven by both alleles. Counter to expectations, significantly higher anthocyanin production was driven by the allele from the low‐anthocyanin M. l. luteus, a result that was confirmed through both a replication of the initial study and analysis by an alternative method of spectrophotometry on extracted leaf anthocyanins. Together with previously published expression studies, our findings support the hypothesis that petal pigment in M. l. variegatus was not gained by protein‐coding changes, but instead solely via noncoding cis‐regulatory evolution. Finally, while constructing the transgenes needed for this experiment, we unexpectedly discovered two sites in MYB5a that appear to be post‐transcriptionally edited—a phenomenon that has been rarely reported, and even less often explored, for nuclear‐encoded plant mRNAs.
Giant miniature endplate potentials at vertebrate neuromuscular junctions: A review
Authors: Alkadhi Karim A.
Published: November 2024

An unusually large amplitude spontaneous miniature endplate potentials (gMEPPs) occur naturally at low frequency at the vertebrate neuromuscular junction. Unlike the normal miniature endplate potentials (nMEPPs), these gMEPPs have long duration and long time to peak. More strikingly, gMEPPs seem to be independent of extracellular and intracellular Ca+2. and have a greater temperature sensitivity than nMEPPs. They are potentiated by tetrodotoxin but inhibited by acetylcholine (ACh) receptor blockers indicating ACh is the neurotransmitter responsible for gMEPPs. The frequency of gMEPPs is greatly increased in muscles weakened by various drugs, toxins or disease conditions suggesting that gMEPPs may be a part of possible neurotrophic mechanism to preserve effective neuromuscular transmission when the normal function is compromised.
The future of scientific labs: how we are making our research more sustainable
Authors: Monson Ebony A , Rutter Stephanie , Reimann Christopher C , Bueno‐Pedraz Andrea , Vella Caitlin , Pearce Xavier G , Wood Jennifer L , Fanson Kerry V
Published: November 2024

The need for climate action is becoming increasingly urgent, and research labs need to be part of the solution. Scientific labs consume large amounts of energy and water and produce significant waste. Globally, scientific research generates over 5.5 million tons of plastic waste annually, which is ~2% of the world's plastic waste. Recognizing the need for sustainability in research, the La Trobe Green Labs program leads this effort in Australia. Since receiving Australia's first “MyGreenLab” certification in 2021, a dedicated steering committee of volunteers has driven successful green initiatives at La Trobe University. The program ensures proper implementation of sustainable practices, enhanced safety and integration with existing operations. More importantly, these small changes will initiate wide‐scale and long‐term transformations that will improve research into more sustainable options for the future.
iPSCs‐derived iMSCs prevent osteoporotic bone loss and affect bone metabolites in ovariectomized mice
Authors: Wang Wei‐Zhou , Wang Yang‐Hao , Bao Sha‐Sha , He Fei , Li Guoyu , Yang Guang , Chen Jing , Yang Xin‐Yu , Xiao Ya , Tong Ya‐Shuang , Zhao Xue‐Ting , Hu Jun , You Ding‐You
Published: November 2024

Osteoporosis is a metabolic bone disease that seriously jeopardizes the health of middle‐aged and elderly people. Mesenchymal stem cell‐based transplantation for osteoporosis is a promising new therapeutic strategy. Induced mesenchymal stem cells (iMSCs) are a new option for stem cell transplantation therapy. Acquired mouse skin fibroblasts were transduced and reprogrammed into induced pluripotent cells and further induced to differentiate into iMSCs. The iMSCs were tested for pluripotency markers, trilineage differentiation ability, cell surface molecular marker tests, and gene expression patterns. The iMSCs were injected into the tail vein of mice by tail vein injection, and the distribution of cells in various organs was observed. The effect of iMSCs on the bone mass of mice was detected after injection into the mouse osteoporosis model. The effects of iMSCs infusion on metabolites in femoral tissue and peripheral blood plasma were detected based on LC–MS untargeted metabolomics. iMSCs have similar morphology, immunophenotype, in vitro differentiation potential, and gene expression patterns as mesenchymal stem cells. The iMSCs were heavily distributed in the lungs after infusion and gradually decreased over time. The iMSCs in the femoral bone marrow cavity gradually increased with time. iMSCs infusion significantly avoided bone loss due to oophorectomy. The results of untargeted metabolomics suggest that amino acid and lipid metabolic pathways are key factors involved in iMSCs bone protection and prevention of osteoporosis formation. iMSCs obtained by reprogramming‐induced differentiation had cellular properties similar to those of bone marrow mesenchymal stem cells. The iMSCs could promote the remodelling of bone structure in ovariectomy‐induced osteoporotic mice and affect the changes of several key metabolites in bone and peripheral blood. Some of these metabolites can serve as potential biomarkers and therapeutic targets for iMSCs intervention in osteoporosis. Investigating the effects of iMSCs on osteoporosis and the influence of metabolic pathways will provide new ideas and methods for the clinical treatment of osteoporosis.
Effect of Propionate on Citrobacter rodentium Infection in Mice by Regulating NleH Expression
Authors: Li Yingying , Mei Wenjie , Zhang Qinhan , Li Li , Ji Qiaorong
Published: November 2024

Propionate is one of the main short chain fatty acids in the gut. Previously, we found that propionate significantly down‐regulated the expression of NleH. NleH is a virulence effector secreted by Citrobacter rodentium (C. rodentium, C.r.) and is essential for its intestinal colonisation and infection. Therefore, this study intends to explore the effect and mechanism of propionate on C.r. infection by regulating the expression of NleH. Wild‐type C.r. and its NleH mutant (C.r.△NleH), E.coli and its NleH1 mutant (E.coli△NleH1) were co‐cultured with propionate separately, changes in strain growth and invasion adhesion were detected. Meanwhile, C57BL/6J mice were infected with C.r. and C.r.△NleH to establish animal model, and propionate intervention was given. Through detecting the invasive and infectious ability of strains in mice and the changes related to colon inflammation, to analyse the effect of propionate on C.r. infection by regulating NleH expression. The results showed that propionate can reduce the adhesion of C.r. and intestinal damage by down‐regulating NleH expression, meanwhile changes of microbial functional metabolism enhance the resistance to C.r. infection in mice.
Role of m6A Methylation Regulators in the Diagnosis and Subtype Classification of COPD Based on the GEO Database
Authors: Zhang Pingan , Gao Na , Li Xiaoning , Zheng Xudong , Kong Deyu , Wu Jianjun
Published: November 2024

N6‐methyladenosine (m6A) is a prevalent mRNA modifier, yet its role in chronic obstructive pulmonary disease (COPD) remains unexplored. We sourced expression levels of m6A methylation regulators from the GSE76925 dataset. These regulators' differential expression (DEMs) predicted COPD risk via random forest and support vector machine models. Additionally, a nomogram model using DEMs estimated COPD prevalence. We employed consistent cluster analysis of m6A methylation regulators to categorise COPD samples into distinct subtypes. Analyses of immune cell infiltration in these subtypes and differential gene expression (DEGs) across m6A methylation subtypes were conducted. A cell model validated several m6A regulators and their associated pathways. Fifteen m6A methylation regulators showed differential expression and were used in random forest and support vector machine models. Eleven were selected for a nomogram model, which decision curve analysis suggested could benefit patients. Consensus cluster analysis divided the COPD samples into two subtypes: Cluster A and Cluster B. Cluster B was associated with neutrophil and eosinophil‐dominated immunity, while Cluster A was linked with monocyte‐dominated immunity. Validation of some research findings was achieved through cell experiments. m6A methylation regulators appear instrumental in diagnosing and classifying subtypes of COPD.
The Impact of Implementing Virtual Diabetes Group Visits on Staff and Provider Wellbeing, Job Satisfaction, and Burnout: A Mixed Methods Analysis
Authors: Moghe Rohan , Zhu Mengqi , Staab Erin , Nuñez Daisy , Basheer Sana , Wan Wen , Campbell Amanda , Quinn Michael , Schaefer Cynthia T. , Baig Arshiya A.
Published: November 2024

Rationale

Few have assessed the impact of group visits (GVs), or shared medical appointments, on community health centre (CHC) staff and provider burnout, wellness, and job satisfaction.

Aims and Objectives

This study assesses the impact of diabetes GV implementation on staff and provider morale and burnout.

Methods

It is a pre‐post study from a larger cluster randomised trial. Two cohorts of providers and staff from 13 Midwestern CHC clinics implemented in‐person (N = 39) and virtual (N = 31) GVs for adults with diabetes. Semi‐structured interviews (post‐implementation) and surveys (pre and post‐implementation) were conducted with staff and providers in both cohorts to assess changes in burnout, staff morale, and job satisfaction, along with reported benefits and burdens of GVs. Thematic analysis of interview transcripts and significance testing for survey data was then performed.

Results

Interview data came from the in‐person cohort (N = 15) and the virtual cohort (N = 19). Survey data were collected from a total of 70 respondents from the in‐person (N = 39) and virtual (N = 31) cohorts. Key results include reported improved relationships with colleagues (‘it has made our professional relationships stronger and I feel more comfortable talking about other things, as well’.), strengthened connections with patients (‘We were able to help patients on a deeper level and provide more detail and one‐on‐one care’.), and individual reward (‘Morale has increased. They're contributing and doing something positive for the patients’.). When asked about in‐person versus virtual GVs, respondents noted they preferred in‐person care but appreciated the flexibility virtual care afforded. Survey results revealed improved job satisfaction in the 2018 cohort and improved morale in the 2020 cohort, as well as perceived benefits including increased interprofessional collaboration and increased connection to patients.

Conclusions

Implementation of GVs in the CHC setting impacted key areas of burnout, including relationships, job attachment, and feelings of meaningful contribution in the workplace among providers and staff. Future clinic‐based implementation studies may consider measuring staff and provider well‐being as part of the evaluation.
Development and Testing of the Comprehensive Prenatal Care Index: Relationship With Preterm Birth and Small for Gestational Age Across Racial and Ethnic Groups
Authors: Lima dos Santos Sueny P. , Calloway Eric E. , Chertok Ilana R. A. , Haile Zelalem T.
Published: November 2024

Introduction

Preterm birth and small for gestational age (SGA) are significant public health concerns in the United States, with pronounced disparities across racial and ethnic groups. Traditional prenatal care adequacy indices have limitations in fully capturing their multifaceted nature. Our study introduces the Comprehensive Prenatal Care Index (CPCI) to provide a more holistic assessment of prenatal care by integrating key elements of prenatal counseling and health promotion.

Methods

This cross‐sectional study used the Pregnancy Risk Assessment Monitoring System 2016‐2021 data. The CPCI was developed based on a comprehensive literature review, incorporating components such as timing, frequency, and content of prenatal visits. The index was validated using Item Response Theory (IRT) and compared with the Kotelchuck and Kessner Indices.

Results

The study included 139,181 pregnant women. The CPCI demonstrated strong internal consistency (Cronbach's α, 0.75; ω total, 0.81). IRT analysis confirmed the index's ability to capture variability in the quality of prenatal care, with item difficulty parameters ranging from −2.93 to +2.10. CPCI scores were significantly associated with reduced odds of adverse birth outcomes. Adequate CPCI care was linked to a 63% reduction in the odds of preterm birth among non‐Hispanic White women, with similar reductions observed in Hispanic women (odds ratio [OR], 0.59) and Asian women (OR, 0.38). For SGA, adequate care was protective among non‐Hispanic White (OR, 0.86) and Hispanic women (OR, 0.82) but showed mixed results in other groups.

Discussion

The CPCI provides a more inclusive measure of the quality of prenatal care compared with traditional indices. The study's findings suggest a significant role of comprehensive prenatal care in reducing adverse birth outcomes and addressing racial and ethnic disparities. Future research should focus on refining the CPCI and exploring its applicability in diverse populations to inform targeted and culturally sensitive prenatal care strategies.
Consumer Acceptance of Baked Products Containing Various Probiotic Strains
Authors: Payne Jessie , Bellmer Danielle , Holt Brooke
Published: November 2024

A consumer central location test explored the effect of adding probiotics to baked products. Lactobacillus acidophilus and two Bacillus subtilis strains were incorporated into plain cookies and crackers. Consumer acceptability and the sensory characteristics of these products were then evaluated. The addition of Bacillus probiotics significantly affected the color, appearance, flavor, texture, and overall liking of both cookies and crackers. However, the sensory profiles of the L. acidophilus cookies and crackers were not significantly different from those of the control samples. In contrast, the B. subtilis samples were significantly less liked by consumers. Overall, consumers liked the control samples over those samples containing B. subtilis spores.
Quantifying the predation impact of an expanding mesocarnivore on declining small‐game species
Authors: Descalzo E. , Jiménez J. , Villafuerte R. , Delibes‐Mateos M. , Díaz‐Ruiz F. , Ferreras P.
Published: November 2024

Human‐wildlife conflicts have increased and are particularly acute when predators are involved. A frequent source of conflict is some people's misbeliefs related to the alleged impact of predators on game species and livestock. In this context, quantifying the impact of expanding predators on their prey can be useful in designing conflict mitigation strategies. We estimated the predation impact of the Egyptian mongoose (Herpestes ichneumon), an expanding mesocarnivore in southwestern Europe, on European rabbit (Oryctolagus cuniculus) and red‐legged partridge (Alectoris rufa) populations, two declining prey species highly valued by hunters. We estimated mongoose densities in three areas of central Spain through live capture, GPS/VHF tagging, camera‐trapping and spatial mark‐resight models. Rabbit and partridge densities were estimated through transect counts and distance sampling. We quantified the mongoose diet by scat analysis. Finally, we compared the number of individuals consumed by the predator population with the estimated total prey populations. European rabbits were the most important mongoose food in two of the study areas, whereas red‐legged partridges were rarely consumed in all the areas. Rabbit density varied widely among study areas (14.0–881.4 rabbits/km2), while partridge density was low in all the areas (2.3–6.9 partridges/km2). The predation impact on rabbits was low in the area with the highest rabbit density (1.9–3.8% of estimated population) and higher (5.6–29%) in the other areas. In contrast, the predation impact on partridge populations was low (<9%) in all the study areas. This is the first study that estimates the Egyptian mongoose impact on small‐game species, a necessary step to deal with the conflicts over the management of this expanding species. The study of predation impact may contribute to the effective management of human‐wildlife conflicts involving predators, by improving the understanding of where additional management may take place to protect prey species or deter predator populations.
Unveiling the nature of philosophical problems: Formal and conceptual aspects
Authors: Harbecke Jens
Published: November 2024

This paper approximates an intensional definitional distinction between philosophical problems and non‐philosophical problems. It contends that a philosophical problem consists of an inconsistent set M of propositions that satisfies certain characteristics. Among these are its minimality, the plausibility of its individual propositions, the non‐empirical character of some of these propositions, and the fact that a discursive context exists within which some of M's non‐mathematical non‐empirical propositions are challenged by argument. The extrinsic and pragmatic criterion marks the key novelty of the presented definition. Building on the analysed concept of a philosophical problem, the paper explores the question of how the definition relates to philosophy as a discipline, whether it should be interpreted as descriptively adequate and exclusive, and whether there is space for genuine philosophical research that does not deal with philosophical problems in the presented sense.
The top‐down nature of ontological inquiry: Against pluralism about top‐down and bottom‐up approaches
Authors: van der Merwe Ragnar
Published: November 2024

Some philosophical pluralists argue that a top‐down and a bottom‐up approach serve as equally justified methods for engaging in ontological inquiry. In the top‐down approach, we start with an analysis of theory and extrapolate from there to the world. In the bottom‐up approach, we begin with an empirical investigation of the world and let our theory respond accordingly. The idea is that ontological conclusions arrived at via these two equally justified methods are then also equally justified. This paper argues that top‐down/bottom‐up methodological pluralism inadvertently grants primacy to the top‐down approach. It goes on to suggest that this is, in fact, unavoidable because it applies to ontological inquiry in general. Ontological inquiry invariably prioritises the top‐down approach because (a) ontological conclusions are not revealed during empirical investigations; instead, they are conceptual (that is, theoretical) posits asserted top‐down and (b) even if we consider both top‐down and bottom‐up approaches during ontological inquiry, such a consideration itself occurs from within theory (that is, top‐down).
Three‐Dimensional Comparative Analysis of Root Parallelism in First Premolar Extraction Cases: Clear Aligner Versus Fixed Orthodontic Appliance
Authors: Al‐Gumaei Waseem S. , Jian Fan , Zhang Xiaoqi , Tang Yufei , Yang Yi , Zhang Haoxin , Lai Wenli , Long Hu
Published: November 2024

Objective

To compare the three‐dimensional root parallelism (mesiodistally and buccolingually) between orthodontic therapy with the Invisalign clear aligners (CA) and fixed appliances (FA) among the first premolar‐extraction patients, using cone‐beam computed tomography (CBCT).

Materials and Methods

Sixty participants with similar American Board of Orthodontics discrepancy index scores as baseline characteristics were included and divided into CA and FA groups (30 per group). Post‐treatment mesiodistal and buccolingual root parallelisms were analysed through CBCT using Invivo 6.0.3 software. Descriptive and analytical statistics were performed with a p < 0.05, considered statistically significant.

Results

Mesiodistal dental root parallelism in the U1‐U2 and L1‐L2 pairings between CA and FA groups were found to be significantly different with inferior parallelism in the CA group (p < 0.05). Conversely, the U3‐U5 and L5‐L6 pairings exhibited superior parallelism in the CA group (p < 0.05). However, other pairings, including U1‐U1, U2‐U3, U5‐U6, U6‐U7, L1‐L1, L2‐L3, L3‐L5, and L6‐L7, showed no significant differences in mesiodistal parallelism between groups (p > 0.05). Regarding the buccolingual dental root parallelism, significant differences were also noted in the U5‐U6 and L5‐L6 pairings with superior parallelism in the CA group (p < 0.05). However, in the U1‐U1, U2‐U3, U3‐U5, U6‐U7, L1‐L1, L2‐L3, L3‐L5, and L6‐L7 pairings, no significant differences in buccolingual parallelism were observed (p > 0.05).

Conclusion

In this study, our findings indicate that in cases involving the extraction of first premolars, Invisalign clear aligners may offer comparable or even superior three‐dimensional root parallelism compared to fixed orthodontic appliances, with the exception of the mesiodistal dimension in upper and lower incisors, where their performance is less effective.
Intensive Kinship, Development, and Demography: Why Pakistan has the Highest Rates of Cousin Marriage in the World
Authors: Shenk Mary K. , Naz Saman , Chaudhry Theresa
Published: November 2024

Pakistan has the highest rates of consanguinity in the world, with nearly two‐thirds marrying cousins. To understand this pattern, we adopt the theoretical framework of intensive and extensive kinship that allows us to predict correlates of consanguineous marriages and logically connect patterns in Pakistan with those in other regions. Using data from the Punjab Consanguinity Survey, we examine indicators of economic development, fertility, cultural norms, and marriage payments as potential correlates of cousin marriage. Consistent with the intensive kinship framework, we find that number of cousins, parental consanguinity, spousal proximity, and caste or clan endogamy are associated with higher likelihood of consanguinity. In contrast, the likelihood of cousin marriage decreases with extensive kinship indicators including husband's education, co‐education, and large wedding expenditures. For women, cousin marriages are often “marrying down” financially, keeping women's wealth in the family. Comparison of Pakistan to other countries highlights the importance of low levels of literacy and female education, high fertility, and rapid population growth. We conclude that high rates of cousin marriage persist in Pakistan due to slow economic development which maintains motivations for cooperation with kin, and high fertility rates which sustain the large numbers of cousins that enable high levels of consanguinity.
An Intraspecific Negative Correlation Between the Repair Capacity of Photoinhibition of Cold Acclimated Plants and the Habitat Temperature
Authors: Oguchi Riichi , Nagano Soichiro , Pfleger Ana , Ozaki Hiroshi , Hikosaka Kouki , Osmond Barry , Chow Wah Soon
Published: November 2024

Both the activity of photosynthesis and the repair of damaged photosystems decline in cold environments, which may increase the extent of the damage of photosynthetic machinery by light, namely photoinhibition. We hypothesized that plants in colder habitats may possess greater tolerance to photoinhibition, especially in low‐temperature conditions.

We measured the rate of photoinhibition, rate of photoinhibition repair and other thylakoid activities in cold environments using 298 Arabidopsis thaliana ecotypes and studied the relationships among the indicators of photoinhibition tolerance and climatic data of the habitat of each ecotype. The plants acclimated to cold conditions (12°C) for 3 days showed a negative correlation between the rate of photoinhibition repair at 5°C and the mean annual temperature of habitats, although we could not see this correlation with the control plants grown at 22°C. This result would indicate that the acclimation capacity of photoinhibition tolerance in cold conditions can affect the distribution of plants, especially in colder regions.
“China” and the Emergence of Religious Toleration in Enlightenment Philosophers, Part II: Voltaire's Project of Universal Toleration and the Legacy of Intercultural Self‐Critique
Authors: Hui Xianzhe , Wenning Mario
Published: November 2024

This article explores the significance of engaging in intercultural reversals of perspectives by reconstructing Voltaire's reflections on the relationship between China and Europe. It highlights the ensuing ethics of universal religious tolerance in this civilizational comparison. Voltaire employed China as a heuristic model primarily to criticize the intolerance and fanaticism of French Catholics. He also used the methodology of intercultural reversals of perspectives to articulate his arguments for universal religious toleration. This paper's focus on the philosophical reception of China reveals the emergence of what we call “intercultural self‐critique” and an important conception of religious toleration during the European Enlightenment.
Dynamics of a Nonlocal Dispersal Population Model With Annually Synchronized Emergence of Adults
Authors: Li Zhenzhen , Dai Binxiang , Zou Xingfu
Published: November 2024

This paper is devoted to studying the spatial dynamics of a nonlocal dispersal species model with annually synchronized emergence of adults. In the situation of a bounded domain, we show threshold dynamics of the adult population, and provide exact persistence criterion. In the situation of a spatially homogeneous unbounded domain, we obtain the existence and computation formula of spreading speeds, which coincide with the minimal wave speed for the traveling waves. The above results are obtained in both monotone and nonmonotone cases of maturation impulse function. Numerical simulations are carried out to demonstrate the theoretical results.
Computational Analysis of Linguistic Markers Reveals Group Identification Patterns During a Global Public Health Crisis
Authors: Ma Mac Zewei
Published: November 2024

Using a computational social science approach integrating evolutionary psychology, social psychology, and intergroup relations, this research examined associations between disease threats and group identification across cultures by analyzing the relationship between COVID‐19 threats (actual and perceived) and first‐person plural versus singular pronoun usage—a linguistic marker of collective identity. Two studies analyzed epidemiological and Google Trends search data over 154 weeks: Study 1 established baseline patterns using U.S. data, while Study 2 investigated cross‐cultural variations globally. Through transfer function methodology to pre‐whiten time series data for cross‐correlation function analysis and random‐slope‐random‐intercept multilevel modeling, the research explored temporal dynamics of threat‐identification relationships. Results indicated that perceived COVID‐19 threat, measured through pandemic‐related search volumes, exhibited consistent correlations with increased first‐person plural pronoun usage across both studies. While COVID‐19 cases demonstrated non‐significant relationships globally but positive associations in the U.S., mortality rates showed negative correlations with first‐person plural pronoun usage globally, differing from U.S. patterns. Cultural collectivism emerged as a moderating factor in the global analysis, with individualistic cultures displaying stronger associations between perceived threat and collective linguistic markers. These findings contribute to our understanding of the relationship between collective threats and group identification processes across cultures while demonstrating the potential of computational linguistic analysis for monitoring real‐time collective responses to pandemics, offering insights relevant to preparedness strategies for future global challenges.
Understanding the effect of abortion attitudes on elections after Dobbs: Evidence from cross‐sectional and panel surveys in Texas
Authors: Ferguson Grant , Gimpel James , Owens Mark , Shaw Daron
Published: November 2024

Objective

We investigate the nature of abortion opinion after the Dobbs decision's reversal of Roe v. Wade with attention to the evaluation of incumbents and vote preference.

Method

We relied on pre‐ and post‐election cross‐sectional and panel survey data from Texas. Texas is an important case because (1) the ruling placed abortion policy squarely on the shoulders of the states and (2) each state has different laws regarding abortion (including so‐called “trigger” laws restricting abortion after Roe was overturned).

Results

The data suggest that state abortion policy context affects voter attitudes and that incumbent evaluations and the vote in Texas were largely insulated from an anti‐Dobbs backlash in 2022.

Conclusion

It is unrealistic to assume that a unidimensional response occurred to the Dobbs decision. The response to subnational policy changes has reflected a similar shift in the intensity of policy views that was found nationally after the Roe decision. We develop a broader thematic approach to understand the nature of abortion opinion and its impact on the evaluation of incumbents and on vote preference in 2022.
Plasma exchange using peripheral arterial and venous access in the pediatric intensive care unit
Authors: Kaplan Eytan , Weissbach Avichai , Kadmon Gili , Nahum Elhanan , Stein Jerry
Published: November 2024

Objective

Therapeutic plasma exchange (TPE) is a vital therapeutic modality in pediatric intensive care units (PICU) for various indications. Traditionally, pediatric TPE is performed via a large bore, double lumen catheter, whose insertion necessitates deep sedation, and poses risk of hemorrhagic and thrombotic complications. Building on our previous success utilizing percutaneous radial artery catheters (ALs) for apheresis procedures, we present our experience with ALs for TPE procedures in the PICU.

Methods

A retrospective cohort study, conducted in the PICU of a tertiary, university affiliated pediatric hospital, including all children aged 19 years and younger, who underwent TPE using an AL for vascular access, between 2018 and 2023. TPE procedures were evaluated for utility (the procedure was performed as planned) and safety.

Results

A total of 72 procedures were performed on 20 children, using ALs for inlet access and peripheral intra‐venous catheters for blood return. Procedure success rate was 94%, with AL malfunction causing transient delays in 6%. All were successfully completed following AL replacement. ALs were mostly 20 and 22 gauge, predominantly located in the radial artery. AL gauge did not significantly affect flow rate or procedure duration.

Conclusions

Our findings support AL use for vascular access, as a viable alternative to the traditional large bore, double lumen catheters most often used for TPE in children. Benefits of AL use may include a decrease in sedation requirements and a lower risk of vascular complications. Further investigation is warranted, for consideration as routine practice in PICUs.
Corrigendum: Deformative magnetic marked length spectrum rigidity
Authors: Marshall Reber James
Published: November 2024

We describe a mistake in Corollary 3.2 as well as a mistake in Lemma 3.4 of Reber [Bull. London Math. Soc. 55 (2023), no. 6, 3077–3096], and give an alternative proof of the main result.
Acute oral digoxin in healthy adults hastens fatigue and increases plasma K+ during intense exercise, despite preserved skeletal muscle Na+,K+‐ATPase
Authors: Atanasovska Tania , Farr Trevor , Smith Robert , Petersen Aaron C. , Garnham Andrew , Andersen Mitchell J. , Krum Henry , Wong Chiew , McKenna Michael J.
Published: November 2024

We investigated acute effects of the Na+,K+‐ATPase (NKA) inhibitor, digoxin, on muscle NKA content and isoforms, arterial plasma [K+] ([K+]a) and fatigue with intense exercise. In a randomised, crossover, double‐blind design, 10 healthy adults ingested 0.50 mg digoxin (DIG) or placebo (CON) 60 min before cycling for 1 min at 60% then at 95% until fatigue. Pre‐ and post‐exercise muscle biopsies were analysed for [3H]‐ouabain binding site content without (OB‐Fab) and after incubation in digoxin antibody (OB+Fab) and NKA α1‐2 and β1‐2 isoform proteins. In DIG, pre‐exercise serum [digoxin] reached 3.36 (0.80) nM [mean (SD)] and muscle NKA–digoxin occupancy was 8.2%. Muscle OB‐Fab did not differ between trials, whereas OB+Fab was higher in DIG than CON (8.1%, treatment main effect, P = 0.001), whilst muscle NKA α1‐2 and β1‐2 abundances were unchanged by digoxin. Fatigue occurred earlier in DIG than CON [−7.7%, 2.90 (0.77) vs. 3.14 (0.86) min, respectively; P = 0.037]. [K+]a increased during exercise until 1 min post‐exercise (P = 0.001), and fell below baseline at 3–10 (P = 0.001) and 20 min post‐exercise (P = 0.022, time main effect). In DIG, [K+]a (P = 0.035, treatment effect) and [K+]a rise pre‐fatigue were greater [1.64 (0.73) vs. 1.55 (0.73), P = 0.016], with lesser post‐exercise [K+]a decline than CON [−2.55 (0.71) vs. −2.74 (0.62) mM, respectively, P = 0.003]. Preserved muscle OB‐Fab with digoxin, yet increased OB+Fab with unchanged NKA isoforms, suggests a rapid regulatory assembly of existing NKA α and β subunits exists to preserve muscle NKA capacity. Nonetheless, functional protection against digoxin was incomplete, with earlier fatigue and perturbed [K+]a with exercise.

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Key points

Intense exercise causes marked potassium (K+) shifts out of contracting muscle cells, which may contribute to muscle fatigue.

Muscle and systemic K+ perturbations with exercise are largely regulated by increased activity of Na+,K+‐ATPase in muscle, which can be specifically inhibited by the cardiac glycoside, digoxin.

We found that acute oral digoxin in healthy adults reduced time to fatigue during intense exercise, elevated the rise in arterial plasma K+ concentration during exercise and slowed K+ concentration decline post‐exercise.

Muscle functional Na+,K+‐ATPase content was not reduced by acute digoxin, despite an 8.2% digoxin occupancy, and was unchanged at fatigue. Muscle Na+,K+‐ATPase isoform protein abundances were unchanged by digoxin or fatigue. These suggest possible rapid assembly of existing subunits into functional pumps.

Thus, acute digoxin impaired performance and exacerbated plasma K+ disturbances with intense, fatiguing exercise in healthy participants. These occurred despite the preservation of functional Na+,K+‐ATPase in muscle.
Incretin impact on gastric function in obesity: physiology, and pharmacological, surgical and endoscopic treatments
Authors: Camilleri Michael
Published: November 2024

The aims of this review are to appraise the role of the stomach in satiation, the effects of incretin and other hormone agonists on weight loss and the role of altered gastric functions in their effects on obesity or glycaemic control. In addition to the gut in its role in enzymatic digestion and hormonal responses to nutrient ingestion, gastric motor functions include accommodation, trituration and emptying [gastric emptying (GE)] of food and elicitation of postprandial satiation and satiety. The postprandially released hormones most extensively studied and utilized therapeutically are glucagon‐like peptide 1 (GLP‐1) and glucose‐dependent insulinotropic peptide (GIP). Their mechanisms of action include stimulation of pancreatic β cells to produce insulin. However, GLP‐1 reduces glucagon and slows GE, whereas GIP increases glucagon and does not alter GE. Molecular modifications of GLP‐1 (which has a T1/2 of 3 min) led to the development of long‐acting subcutaneous or oral pharmacological agents that have been approved for the treatment of obesity, and their effects on gastric function are documented. Other medications in development target other molecular mechanisms, including glucagon and amylin. Small‐molecule GLP‐1 receptor agonists are promising for the treatment of obesity and may also slow GE. Bariatric surgery and endoscopy increase satiation by restricting gastric size; in addition Roux‐en‐Y gastric bypass and to a lesser extent sleeve gastrectomy (but not endoscopic gastroplasty) increase postprandial circulating incretins, reducing appetite. In conclusion the stomach's function is integral to the impact of the most effective pharmacological and procedural reversal of obesity related to the incretin revolution.

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On the Application of Background Oriented Schlieren to a Transonic Low-Reynolds Turbine Cascade
Authors: Halby Alexandre , Cakir Bora O. , Da Valle Lorenzo , Lopes Gustavo , Okada Mizuki , Lavagnoli Sergio
Published: November 2024

Qualitative and quantitative visualizations of transonic turbomachinery flows provide essential information on compressibility and Mach number effects on boundary layer development, shock-boundary layer interactions, and trailing edge flows. Background oriented Schlieren (BOS) is a relatively new optical technique that allows capturing unsteady density gradient fields through turbomachinery cascades and thus quantitative experimental data to validate transonic and supersonic blade designs. However, only very few experimental works in the open literature have successfully applied BOS to transonic turbine or compressor flows. The current study presents the application of BOS to a transonic low-pressure turbine cascade, the VKI SPLEEN C1 cascade for a range of Reynolds numbers (70,000–140,000) and transonic Mach numbers (0.90–1.00). The linear turbine cascade is tested at the von Karman Institute in the S-1/C high-speed wind tunnel. The test section is instrumented with different BOS optical setups to visualize the time-resolved density gradients through the turbine passage and at the trailing edge plane with dedicated field of views. The BOS images are processed using the classical cross-correlation algorithm, and the optical flow approach, recently introduced in BOS applications to gain spatial resolution and increased sensitivity. Steady-state density gradients of the cascade flow characterize the airfoil boundary layers, wakes, and shock waves. The results from the two data reduction methods are assessed and compared against available RANS CFD predictions. Time-resolved measurements reveal the low-frequency motion of weak shock waves generated in the blade passage using proper orthogonal decomposition (POD) and spectra analysis.
Numerical Simulations and Sensitivity Analysis of Ice Formation on Fan Blades
Authors: Müller Katja , Flassig Peter , Flassig Robert
Published: November 2024

In-flight icing, the formation of ice during flight, poses risks to the safety and reliability of aircraft. Due to environmental conditions, ice accumulation occurs on the low-pressure compressor blades of an engine, diminishing aerodynamic performance and potentially causing damage to the engine. Numerical simulations of ice accretion are conducted on the blades of the NASA Rotor 67 utilizing the computational fluid dynamics software ansys cfx and the in-flight icing software fensap-ice. One-dimensional and two-dimensional sensitivity studies aim to analyze the influences of temperature, droplet diameter, and liquid water content (LWC) on the resulting ice buildup on the blade. The analyses reveal that ice accumulates predominantly at the leading edge of the blade, where collection efficiency is maximal. Additionally, an ice layer forms at the blade root on the pressure side. While LWC and temperature exert a significant influence on the ice mass, only a marginal impact on droplet diameter is observed.
Efficacy and
in vitro
pharmacological assessment of novel
N
-hydroxypyridinediones as hepatitis B virus ribonuclease H inhibitors
Authors: Woodson Molly E. , Walden Holly F. , Mottaleb M. Abdul , Makri Maria , Prifti Georgia-Myrto , Moianos Dimitrios , Pardali Vasiliki , Zoidis Grigoris , Tavis John E.
Published: November 2024

We previously reported
N
-hydroxypyridinedione (HPD) compounds with mid-nanomolar efficacy and selectivity indexes around 300 against hepatitis B virus (HBV) replication. However, they lack pharmacological evaluation. Here, we report
in vitro
anti-HBV efficacy, cytotoxicity, and pharmacological characterization of 29 novel HPDs within seven subgroups. The best two compounds had EC
50
s of 61 and 190 nM and selectivity indexes of 526 and 1,071. Compounds with one halogen on the major R group were most effective and compounds with large ether R groups were most cytotoxic. Compounds were not cytotoxic in primary human hepatocytes. All compounds were freely soluble in pHs reflecting plasma (7.4) and the gastrointestinal tract (5 and 6.5). Almost all highly soluble compounds were passively permeable at pH 5.0 and 7.4. Only 2 of 11 compounds tested were likely to be effluxed by p-glycoprotein. The most potent HPDs inhibited HBV replication over human ribonuclease H1 activity by 10-fold. Four of 19 compounds inhibited CYP2D6 >50%, but their CYP2D6 IC
50
s were >8× higher than their anti-HBV EC
50
. No compound substantially inhibited CYP3A4. Thirteen of 15 compounds had human microsomal half-lives >30 min with medium to low rates of intrinsic clearance. Eleven of 12 compounds bound plasma proteins by ≥80%; however, effects against HBV replication for only one would likely be physiologically relevant. These results identify two lead candidate HPDs with pharmacological characteristics resembling commercially available drugs that are suitable for
in vivo
pharmacological and efficacy studies.