bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogenic tau induces an adaptive elevation in mRNA translation rate at early stages of disease
Authors: Zuniga Gabrielle , Katsumura Sakie , De Mange Jasmine , Ramirez Paulino , Atrian Farzaneh , Morita Masahiro , Frost Bess 
Published: June 2024

AbstractAlterations in the rate and accuracy of messenger RNA (mRNA) translation are associated with aging and several neurodegenerative disorders, including Alzheimer's disease and related tauopathies. We previously reported that error‐containing RNA that are normally cleared via nonsense‐mediated mRNA decay (NMD), a key RNA surveillance mechanism, are translated in the adult brain of a Drosophila model of tauopathy. In the current study, we find that newly‐synthesized peptides and translation machinery accumulate within nuclear envelope invaginations that occur as a consequence of tau pathology, and that the rate of mRNA translation is globally elevated in early stages of disease in adult brains of Drosophila models of tauopathy. Polysome profiling from adult heads of tau transgenic Drosophila reveals the preferential translation of specific mRNA that have been previously linked to neurodegeneration. Unexpectedly, we find that panneuronal elevation of NMD further elevates the global translation rate in tau transgenic Drosophila, as does treatment with rapamycin. As NMD activation and rapamycin both suppress tau‐induced neurodegeneration, their shared effect on translation suggests that elevated rates of mRNA translation are an early adaptive mechanism to limit neurodegeneration. Our work provides compelling evidence that tau‐induced deficits in NMD reshape the tau translatome by increasing translation of RNA that are normally repressed in healthy cells.
Discovery of genomic and transcriptomic pleiotropy between kidney function and soluble receptor for advanced glycation end products using correlated meta‐analyses: The Long Life Family Study
Authors: Feitosa Mary F. , Lin Shiow J. , Acharya Sandeep , Thyagarajan Bharat , Wojczynski Mary K. , Kuipers Allison L. , Kulminski Alexander , Christensen Kaare , Zmuda Joseph M. , Brent Michael R. , Province Michael A. 
Published: June 2024

AbstractPatients with chronic kidney disease (CKD) have increased oxidative stress and chronic inflammation, which may escalate the production of advanced glycation end‐products (AGEs). High soluble receptor for AGE (sRAGE) and low estimated glomerular filtration rate (eGFR) levels are associated with CKD and aging. We evaluated whether eGFR calculated from creatinine and cystatin C share pleiotropic genetic factors with sRAGE. We employed whole‐genome sequencing and correlated meta‐analyses on combined genome‐wide association study (GWAS) p‐values in 4182 individuals (age range: 24–110) from the Long Life Family Study (LLFS). We also conducted transcriptome‐wide association studies (TWAS) on whole blood in a subset of 1209 individuals. We identified 59 pleiotropic GWAS loci (p < 5 × 10−8) and 17 TWAS genes (Bonferroni‐p < 2.73 × 10−6) for eGFR traits and sRAGE. TWAS genes, LSP1 and MIR23AHG, were associated with eGFR and sRAGE located within GWAS loci, lncRNA‐KCNQ1OT1 and CACNA1A/CCDC130, respectively. GWAS variants were eQTLs in the kidney glomeruli and tubules, and GWAS genes predicted kidney carcinoma. TWAS genes harbored eQTLs in the kidney, predicted kidney carcinoma, and connected enhancer‐promoter variants with kidney function‐related phenotypes at p < 5 × 10−8. Additionally, higher allele frequencies of protective variants for eGFR traits were detected in LLFS than in ALFA‐Europeans and TOPMed, suggesting better kidney function in healthy‐aging LLFS than in general populations. Integrating genomic annotation and transcriptional gene activity revealed the enrichment of genetic elements in kidney function and aging‐related processes. The identified pleiotropic loci and gene expressions for eGFR and sRAGE suggest their underlying shared genetic effects and highlight their roles in kidney‐ and aging‐related signaling pathways.
Effects of increasing risk in common resource exploitation under cost asymmetry
Authors: Nkuiya Bruno 
Published: June 2024

AbstractIn their in situ habitat, renewable resource populations are subject to stochastic growth caused by environmental variability such as fluctuations in upwelling conditions or temperature. In this paper, we examine the effects of this type of uncertainty on the noncooperative harvest decisions made by harvesters exploiting a common‐pool renewable resource. To do this, we extend the related literature on dynamic resource extraction games based on Markov strategies to allow for asymmetric extraction costs and general economic, biological, and environmental conditions. We find equilibrium behaviors that can reverse conventional wisdom. For example, in response to increasing risk caused by anticipated higher variability in biological growth, a harvester may choose to enhance conservation efforts, whereas another harvester diminishes his escapement. Increasing risk can lead to conflicts as it may increase a harvester's payoff while causing a loss to another harvester. In response to an increase in the discount rate, we find that strategic interactions can give rise to greater conservation efforts. Overall, this paper highlights the importance of adequately accounting for uncertainty and strategic behaviors in renewable resource management.
Effect of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation: A retrospective cohort study
Authors: Zhang Kan , Sun Ying , Ding Jiancao , Ma Qing , Zhang Dai , Huang Wei , Xing Yunli 
Published: June 2024

AbstractObjectiveTo explore the influence of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation.MethodsThis retrospective observational cohort study included 196 patients, 75–102‐years‐old, with nonvalvular atrial fibrillation, hospitalized in our hospital. The nutritional status was assessed using Mini‐Nutritional Assessment—Short Form (MNA‐SF). Patients with MNA‐SF scores of 0–11 and 12–14 were included in the malnutrition and nonmalnutrition groups, respectively.ResultsThe average age of the malnutrition group was higher than that of the nonmalnutrition group, and the levels of body mass index (BMI), hemoglobin (HGB), and albumin (ALB) were significantly lower than those of the nonmalnutrition group, with statistical significance (p < .05). The incidence of all‐cause death in the malnutrition group was higher than that in the nonmalnutrition group (p = .007). Kaplan–Meier curve indicated that malnutrition patients have a higher risk of all‐cause death (log‐rank test, p = .001) and major bleeding events (p = .017). Multivariate Cox proportional hazard regression analysis corrected for confounders showed that malnutrition was an independent risk factor of all‐cause death (HR = 1.780, 95%CI:1.039–3.050, p = .036). The malnutrition group had a significantly high incidence of major bleeding than the nonmalnutrition group (p = .026), and there was no significant difference in the proportion of anticoagulation therapy (p = .082) and the incidence of ischemic stroke/systemic embolism (p = .310) between the two groups.ConclusionsMalnutrition is an independent risk factor of all‐cause death in elderly patients with atrial fibrillation. The incidence of major bleeding in malnourished elderly patients with atrial fibrillation is high, and the benefit of anticoagulation therapy is not obvious.
Dose rationale for the use of meropenem/vaborbactam combination in paediatric patients with Gram‐negative bacterial infections
Authors: Fornari Chiara , Arrieta Antonio , Bradley John S. , Tout Mira , Magalhaes Paulo , Auriol Faten Koraichi , Borella Elisa , Piana Chiara , Della Pasqua Oscar , Vallespir Bartomeu Piza , Mazzei Paolo , Bokesch Paula M. , Hoover Randall , Capriati Angela , Habboubi Nassir 
Published: June 2024

AimsMeropenem/vaborbactam combination is approved in adults by FDA and EMA for complicated urinary tract infections and by EMA also for other Gram‐negative infections. We aimed to characterise the pharmacokinetics of both moieties in an ongoing study in children and use a model‐based approach to inform adequate dosing regimens in paediatric patients.MethodsOver 4196 blood samples of meropenem and vaborbactam (n = 414 subjects) in adults, together with 114 blood samples (n = 39) in paediatric patients aged 3 months to 18 years were available for this analysis. Data were analysed using a population with prior information from a pharmacokinetic model in adults to inform parameter estimation in children. Simulations were performed to assess the suitability of different dosing regimens to achieve adequate probability of target attainment (PTA).ResultsMeropenem/vaborbactam PK was described with two‐compartment models with first‐order elimination. Body weight and CLcr were significant covariates on the disposition of both drugs. A maturation function was evaluated to explore changes in clearance in neonates. PTA ≥90% was derived for children aged ≥3 months after 3.5‐h IV infusion of 40 mg/kg Q8h of both meropenem and vaborbactam and 2 g/2 g for those ≥50 kg. Extrapolation of disposition parameters suggest that adequate PTA is achieved after a 3.5‐h IV infusion of 20 mg/kg for neonates and infants (3 months).ConclusionsAn integrated analysis of adult and paediatric data allowed accurate description of sparsely sampled meropenem/vaborbactam PK in paediatric patients and provided recommendations for the dosing in neonates and infants (3 months).
Identifying subtypes in persons, situations and person–situation interactions: Categorical latent state–trait modelling approaches
Authors: Liu Qimin , Cole David A. 
Published: June 2024

AbstractThe latent state–trait theory posits that a psychological construct may reflect stable influences specific to a person (i.e., trait), ephemeral influences from situations (i.e., state), and interactions between them (i.e., state–trait interactions). Researchers conventionally apply mixture modelling to explore heterogeneity in variables by identifying homogenous classes with respect to the measured variable, yet rarely distinguishing between person‐ and situation‐specific classes. The current study introduces novel categorical latent state–trait models to identify subgroups in states and traits, quantifying the effects of person‐specific classes, situation‐specific classes, and person–situation interactions. The proposed models are applied to an empirical dataset. We discuss statistical inference, effect size measures, and model visualization for the proposed models. Based on realistic parameter values from the empirical dataset, preliminary simulation studies were conducted to investigate models’ performances. Bayesian estimation in the proposed models allows flexible testing of a wide range of hypotheses related to state, trait, and interaction effects. We discuss limitations and future directions.
Functionally distinct pericyte subsets differently regulate amyloid‐β deposition in patients with Alzheimer's disease
Authors: Bohannon Diana G. , Long Danielle , Okhravi Hamid R. , Lee Sunhee C. , De Jesus Christopher Lawrence , Neubert Thomas A. , Rostagno Agueda A. , Ghiso Jorge A. , Kim Woong‐Ki 
Published: June 2024

AbstractAlthough the concept that the blood–brain barrier (BBB) plays an important role in the etiology and pathogenesis of Alzheimer's disease (AD) has become increasingly accepted, little is known yet about how it actually contributes. We and others have recently identified a novel functionally distinct subset of BBB pericytes (PCs). In the present study, we sought to determine whether these PC subsets differentially contribute to AD‐associated pathologies by immunohistochemistry and amyloid beta (Aβ) peptidomics. We demonstrated that a disease‐associated PC subset (PC2) expanded in AD patients compared to age‐matched, cognitively unimpaired controls. Surprisingly, we found that this increase in the percentage of PC2 (%PC2) was correlated negatively with BBB breakdown in AD patients, unlike in natural aging or other reported disease conditions. The higher %PC2 in AD patients was also correlated with a lower Aβ42 plaque load and a lower Aβ42:Aβ40 ratio in the brain as determined by immunohistochemistry. Colocalization analysis of multicolor confocal immunofluorescence microscopy images suggests that AD patient with low %PC2 have higher BBB breakdown due to internalization of Aβ42 by the physiologically normal PC subset (PC1) and their concomitant cell death leading to more vessels without PCs and increased plaque load. On the contrary, it appears that PC2 can secrete cathepsin D to cleave and degrade Aβ built up outside of PC2 into more soluble forms, ultimately contributing to less BBB breakdown and reducing Aβ plaque load. Collectively our data shows functionally distinct mechanisms for PC1 and PC2 in high Aβ conditions, demonstrating the importance of correctly identifying these populations when investigating the contribution of neurovascular dysfunction to AD pathogenesis.
FoxG1/BNIP3 axis promotes mitophagy and blunts cisplatin resistance in osteosarcoma
Authors: Pan Baolong , Li Yan , Han Huiyun , Zhang Lu , Hu Xuemei , Pan Yanyu , Peng Zhuohui 
Published: June 2024

AbstractCisplatin (CDDP) is a commonly used chemotherapeutic for osteosarcoma (OS) patients, and drug resistance remains as a major hurdle to undermine the treatment outcome. Here, we investigated the potential involvement of FoxG1 and BNIP3 in CDDP resistance of OS cells. FoxG1 and BNIP3 expression levels were detected in the CDDP‐sensitive and CDDP‐resistant OS tumors and cell lines. Mitophagy was observed through transmission electron microscope analysis. The sensitivity to CDDP in OS cells upon FoxG1 overexpression was examined in cell and animal models. We found that FoxG1 and BNIP3 showed significant downregulation in the CDDP‐resistant OS tumor samples and cell lines. CDDP‐resistant OS tumor specimens and cells displayed impaired mitophagy. FoxG1 overexpression promoted BNIP3 expression, enhanced mitophagy in CDDP‐resistant OS cells, and resensitized the resistant cells to CDDP treatment in vitro and in vivo. Our data highlighted the role of the FoxG1/BNIP3 axis in regulating mitophagy and dictating CDDP resistance in OS cells, suggesting targeting FoxG1/BNIP3‐dependent mitophagy as a potential strategy to overcome CDDP resistance in OS.
Premature pubarche in Prader‐Willi syndrome: Risk factors and consequences
Authors: Griffing Emily , Halpin Kelsee , Lee Brian R. , Paprocki Emily 
Published: June 2024

AbstractObjectivesChildren with Prader‐Willi Syndrome (PWS) may develop premature pubarche (PP). We investigated the frequency of PP, and its potential precursors and sequelae, in PWS.Design, Patients and MeasurementsA chart review of children with PWS treated at our institution between 1990 and 2021 was performed. PP was defined as Tanner stage 2 (TS2) pubic hair in girls <8 and boys <9 years old. Demographic, anthropometric, and laboratory data were collected to assess predisposing factors and consequences of PP in comparison to patients with PWS who had normal pubarche (NP).ResultsAnalysis included 43 children with PWS, 23 (53.5%) with PP and 20 (46.5%) with NP. Median age at pubarche was 7.0 years in PP group and 10.0 years in NP group. Age at pubarche was not correlated with age of recombinant human growth hormone (rhGH) initiation, body mass index (BMI) z‐score, or homeostasis model assessment of insulin resistance (HOMA‐IR) at pubarche. BMI z‐score at pubarche was modestly correlated with degree of pubarchal BA advancement (p = 0.033). Those with PP were more likely to have a lower high‐density lipoprotein (HDL) (1.05 mmol/L vs. 1.41 mmol/L in the NP group, p = 0.041). The difference between target and final height did not differ between groups (p = 0.507).ConclusionPP is common in PWS but does not compromise final height in comparison to the NP group. Obesity and insulin resistance were not associated with PP in children with PWS, contrary to what has been seen in obese children without PWS.
Generalized lymphatic anomaly: A case report and review of literature
Authors: Hofny Eman R. M. , Ahmed Asmaa M. , Ghazally Alaa , Salah Yasmin , Mahran Ayman 
Published: June 2024

AbstractGeneralized lymphatic anomaly (GLA), previously known as lymphangiomatosis, is a rare developmental disease characterized by abnormal proliferation of lymphatic vascular structures that may involve the dermis, soft tissue, bone, and visceral parenchyma. Being an uncommon condition and the lack of specific symptoms often result in a delayed diagnosis or even misdiagnosis, which, in addition to its progressive nature, can lead to dysfunction of vital organs, and ultimately, a poor prognosis. In this report, we present a unique case of GLA in an upper Egyptian female child. Increasing awareness of the possible phenotypic presentations of such anomalies can lead to early diagnosis and possibly more effective management before significant organ damage ensues.
1100. Corallorhiza trifida Châtel.
Authors: Fay Michael F. , Raistrick Reinhild , Freudenstein John V. 
Published: June 2024

SummaryCorallorhiza trifida Châtel., illustrated here as Plate 1100, is a widely distributed orchid, occurring in temperate and subarctic regions of Eurasia and North America [Correction added on 14 August 2024, after first online publication: In Summary section, ‘Plate 2000’ has been corrected to ‘Plate 1100’.]. It is an inconspicuous species that can be difficult to spot due to its lack of leaves and predominantly subterranean life history. Although it produces some chlorophyll, it is a mycoheterotroph dependent on its fungal associates for much of its nutrition, and it is difficult or impossible to cultivate.
The ‘means’ and the ‘ends’ of economic calculation: The missing aspect of an epochal dispute
Authors: Trubnikov Dmitrii 
Published: June 2024

AbstractCurrent technological advances have revived the old socialist calculation debate. While the arguments on the socialist side appear to be backed by exciting technological developments, the pro‐market camp still mainly relies on the classical thinking of the Austrian school. A reasonable way to reinvigorate the free‐market thesis is to look at the ends of economic calculations, intentionally overlooked during the classical period of the debate. A valuable supplement to the contemporary pro‐market position could be found in the ordoliberal vision that emphasised the interdependence of various spheres and the power problem.
Susceptibility of Orius insidiosus to Beauveria bassiana, Akanthomyces muscarius, and Cordyceps fumosorosea and their effects on predator behavior
Authors: Manfrino Romina G. , Rocca Margarita 
Published: June 2024

AbstractThe use of pathogens and other natural enemies to suppress pest populations is a key component of integrated pest management (IPM) strategies. As biocontrol agents may interact synergistically, additively, or antagonistically, it is crucial to assess their interactions for effective pest management. In this study, we investigated the effect of three entomopathogenic fungus (EPF) species—Beauveria bassiana (Bals.‐Criv.) Vuill. CEP 091, Akanthomyces muscarius (Petch) Spatafora, Kepler & B. Shrestha CEP 182, and Cordyceps fumosorosea (Wize) Kepler, B. Shrestha & Spatafora CEP 315 (all Hypocreales)—on the survival, fecundity, and searching behavior of Orius insidiosus (Say) (Hemiptera: Anthocoridae). All three EPF species were found to be pathogenic to O. insidiosus, resulting in a significant decrease in survival compared with the control group. Fecundity remained unaffected by the fungal treatments. No effect of EPF on searching behavior of the predator was found. In relation to the searching behavior, individuals of 2 days post‐infections remained in the food patch longer than individuals of 7 days post‐infections, regardless of treatment. These findings provide valuable insights into the compatibility of EPF and O. insidiosus as combined biocontrol agents for managing whiteflies, aphids, and thrips. Understanding the interactions between EPF and predatory insects is crucial for developing IPM strategies that maximize pest control efficacy. Further studies should explore the long‐term effects of EPF on O. insidiosus populations and their overall impact on pest management in agricultural systems.
Effect of the mGlu2 positive allosteric modulator biphenyl‐indanone A as a monotherapy and as adjunct to a low dose of L‐DOPA in the MPTP‐lesioned marmoset
Authors: Kang Woojin , Frouni Imane , Kwan Cynthia , Bédard Dominique , Nuara Stephen G. , Hamadjida Adjia , Gourdon Jim C. , Huot Philippe 
Published: June 2024

AbstractActivation of metabotropic glutamate 2 (mGlu2) receptors is a potential novel therapeutic approach for the treatment of parkinsonism. Thus, when administered as monotherapy or as adjunct to a low dose of L‐3,4‐dihydroxyphenylalanine (L‐DOPA), the mGlu2 positive allosteric modulator (PAM) LY‐487,379 alleviated parkinsonism in 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐lesioned primates. Here, we sought to investigate the effect of biphenyl‐indanone A (BINA), a highly selective mGlu2 PAM whose chemical scaffold is unrelated to LY‐487,379, to determine if a structurally different mGlu2 PAM would also confer anti‐parkinsonian benefit. In monotherapy experiments, MPTP‐lesioned marmosets were injected with either vehicle, L‐DOPA/benserazide (15/3.75 mg/kg, positive control) or BINA (0.1, 1, 10 mg/kg). In adjunct to a low L‐DOPA dose experiments, MPTP‐lesioned marmosets were injected with L‐DOPA/benserazide (7.5/1.875 mg/kg) in combination with vehicle or BINA (0.1, 1, 10 mg/kg). Parkinsonism, dyskinesia and psychosis‐like behaviours (PLBs) were then quantified. When administered alone, BINA 1 and 10 mg/kg decreased parkinsonism severity by ~22% (p < 0.01) and ~47% (p < 0.001), when compared with vehicle, which was comparable with the global effect of a high L‐DOPA dose. When administered in combination with a low L‐DOPA dose, BINA 1 and 10 mg/kg decreased global parkinsonism by ~38% (p < 0.001) and ~53% (p < 0.001). BINA 10 mg/kg decreased global dyskinesia by ~94% (p < 0.01) and global PLBs by ~92% (p < 0.01). Our results provide additional evidence that mGlu2 positive allosteric modulation elicits anti‐parkinsonian effects. That this benefit is not related to a particular chemical scaffold suggests that it may be a class effect rather than the effect of a specific molecule.
Conflicting cognitive decisions: Does egg retrieval modify egg rejection in a host of an obligate brood parasite?
Authors: Peer Brian D. , Vozza Nicholas 
Published: June 2024

AbstractEgg retrieval is an ancient behaviour displayed by birds in which a displaced egg is transferred back into the nest. Egg rejection, in contrast, is a recently evolved adaptation by hosts of brood parasites in which an egg is removed from a nest. These conflicting behaviours are both adaptive because they prevent reproductive losses, but egg retrieval may benefit brood parasites if hosts retrieve parasitic eggs into their nests. We examined these conflicting cognitive processes in the prothonotary warbler (Protonotaria citrea), a cavity‐nesting host of the brown‐headed cowbird (Molothrus ater). Eggs and nestlings are occasionally found on the rims of warbler nest cavities. We determined how this happened using video cameras and tested whether warblers retrieved their own eggs more often than cowbird eggs. We also determined if shape affects retrieval and rejection by placing cylinders inside nest cups or onto nest rims. We found that eggs were displaced by rapidly departing warblers whose nests are constantly prospected by nest competitors and brood parasites. Warblers retrieved their eggs (29%) and cowbird eggs (19%) at similar rates, and never rejected cowbird eggs after retrieval. Warblers removed most cylinders from nest rims and cups (89% and 78%, respectively), and never retrieved them. Warblers have retained egg retrieval at a low level and its expression is costly because they only retrieve a low level of their own eggs and also retrieve cowbird eggs, which benefits the brood parasite.