bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum biomarkers and disease progression in CT-negative mild traumatic brain injury
Authors: Jia Xiaoyan , Li Xuan , Ji Qiuyu , Yin Bo , Pan Yizhen , Zhao Wenpu , Zhang Ming , Bai Guanghui , Zhang Jie , Bai Lijun 
Published: November 2023

Abstract
Blood proteins are emerging as potential biomarkers for mild traumatic brain injury (mTBI). Molecular pathology of mTBI underscores the critical roles of neuronal injury, neuroinflammation, and vascular health in disease progression. However, the temporal profile of blood biomarkers associated with the aforementioned molecular pathology after CT-negative mTBI, their diagnostic and prognostic potential, and their utility in monitoring white matter integrity and progressive brain atrophy remain unclear. Thus, we investigated serum biomarkers and neuroimaging in a longitudinal cohort, including 103 CT-negative mTBI patients and 66 matched healthy controls (HCs). Angiogenic biomarker vascular endothelial growth factor (VEGF) exhibited the highest area under the curve of 0.88 in identifying patients from HCs. Inflammatory biomarker interleukin-1β and neuronal cell body injury biomarker ubiquitin carboxyl-terminal hydrolase L1 were elevated in acute-stage patients and associated with deterioration of cognitive function from acute-stage to 6–12 mo post-injury period. Notably, axonal injury biomarker neurofilament light (NfL) was elevated in acute-stage patients, with higher levels associated with impaired white matter integrity in acute-stage and progressive gray and white matter atrophy from 3- to 6–12 mo post-injury period. Collectively, our findings emphasized the potential clinical value of serum biomarkers, particularly NfL and VEGF, in diagnosing mTBI and monitoring disease progression.
Where do we stand on fMRI in awake mice?
Authors: Mandino Francesca , Vujic Stella , Grandjean Joanes , Lake Evelyn M R 
Published: November 2023

Abstract
Imaging awake animals is quickly gaining traction in neuroscience as it offers a means to eliminate the confounding effects of anesthesia, difficulties of inter-species translation (when humans are typically imaged while awake), and the inability to investigate the full range of brain and behavioral states in unconscious animals. In this systematic review, we focus on the development of awake mouse blood oxygen level dependent functional magnetic resonance imaging (fMRI). Mice are widely used in research due to their fast-breeding cycle, genetic malleability, and low cost. Functional MRI yields whole-brain coverage and can be performed on both humans and animal models making it an ideal modality for comparing study findings across species. We provide an analysis of 30 articles (years 2011–2022) identified through a systematic literature search. Our conclusions include that head-posts are favorable, acclimation training for 10–14 d is likely ample under certain conditions, stress has been poorly characterized, and more standardization is needed to accelerate progress. For context, an overview of awake rat fMRI studies is also included. We make recommendations that will benefit a wide range of neuroscience applications.
The temporal dimension of parental employment: Temporary contracts, non-standard work schedules, and children’s education in Germany
Authors: Betthäuser Bastian A , Trinh Nhat An , Fasang Anette Eva 
Published: November 2023

Abstract
The increasing prevalence of non-standard work and its adverse consequences are well documented. However, we still know little about how common non-standard work is amongst parents, and whether its negative consequences are further transmitted to their children. Using data from the German Microcensus, we document the prevalence and concentration of temporary employment and non-standard work schedules in households with children in Germany. Second, we examine the extent to which variation in this temporal dimension of parental employment is associated with children’s school track. Results show that in about half of all German households with children in lower-secondary school at least one parent has a temporary contract or regularly works evenings or Saturdays. We find that children whose mother always works evenings or Saturdays are substantially less likely to transition to the academic school track. By contrast, we find no significant association between fathers’ non-standard work schedules and children’s school track. We also find no evidence of an association between parents’ temporary employment and children’s school track placement. These divergent findings highlight the importance of disaggregating non-standard work into its specific components and differentiating between mothers' and fathers' non-standard work when investigating the consequences of parental non-standard work for children’s educational and life chances.
An investment case analysis for the prevention and treatment of adolescent mental disorders and suicide in England
Authors: Jackson-Morris Angela , Meyer Christina L , Morgan Antony , Stelmach Rachel , Jamison Leah , Currie Candace 
Published: November 2023

Abstract

Background
Adolescent mental health (AMH) needs in England have increased dramatically and needs exceed treatment availability. This study undertook a comparative assessment of the health and economic return on investment (ROI) of interventions to prevent and treat mental disorders among adolescents (10–19 years) and examined intervention affordability and readiness.

Methods
Interventions were identified following a review of published and grey literature. A Markov model followed a simulated adolescent cohort to estimate implementation costs and health, education, and economic benefits. Intervention affordability was assessed, comparing annual cost per adolescent with NHS England per capita spending, and an expert panel assessed intervention readiness using a validated framework.

Results
Over 10- and 80-year horizons, interventions to treat mild anxiety and mild depression were most cost-effective, with the highest individual lifetime ROI (GBP 5822 GBP 1 and GBP 257: GBP 1). Preventing anxiety and depression was most affordable and ‘implementation ready’ and offered the highest health and economic benefits. A priority package (anxiety and depression prevention; mild anxiety and mild depression treatment) would avert 5 million disability-adjusted life-years (DALYS) and achieve an ROI of GBP 15: GBP 1 over 10 years or 11.5 million DALYs (ROI of GBP 55: GBP 1) over 80 years.

Conclusion
The economic benefits from preventing and treating common adolescent mental disorders equivalent to 25% of NHS England’s annual spending in 2021 over 10 years and 91% over 80 years. Preventing and early treatment for anxiety and depression had the highest ROIs and strong implementation readiness.
The effects of arginine phosphate (ArGrow® Granulat) on growth of Scots pine and Norway spruce seedlings planted in varying soil layer structures simulating site preparation
Authors: Luoranen Jaana , Saksa Timo 
Published: November 2023

Abstract
The pressure to plant seedlings in unprepared instead of prepared soil in forest regeneration is increasing, although seedlings’ growth in unprepared soil is poorer. One way to improve seedlings’ growth could be to add arginine phosphate to the planting hole at the time of planting. In field studies, abiotic and biotic damage normally disturbs studies which seek to determine growth effects, especially in unprepared soil. The study’s aims were (i) to clarify whether it was possible to investigate the differences between varying soil layer structures mimicking site preparation methods and seedling treatments in simulated planting places in partly controlled conditions; and (ii) to investigate the effects of arginine phosphate (arGrow® Granulat) on the growth, especially root growth, of Norway spruce (Picea abies (L.) H. Karst.) and Scots pine (Pinus sylvestris L.) container seedlings in those simulated planting places. Seedlings of both tree species were planted in 40 l pots sunk partly into the soil in a sandy field. Before planting, pots were filled with soil layers mimicking layers in soil without any site preparation treatment and in spot mounds. After one growing season, the differences in growth parameters between treatments were small in Norway spruce seedlings, and no significant benefits of arginine phosphate were observed. The soil in the spruce pots was fine-textured and contained a thick organic layer. More studies in more common forest soil types suitable for Norway spruce seedlings are needed to be sure about the growth responses. In Scots pine seedlings, adding arginine phosphate granules to the planting holes improved the growth of seedlings at least in the first summer after planting in soil layers mimicking no mechanical site preparation situation, and the growth improvement may even have compensated the mounding effects. In conclusion, mimicking site preparation methods in large pots was a promising method by which the differences between site preparations methods as well as effects of seedling treatments, in our case arginine phosphate, on the growth of conifer seedlings, can be tested.
Lipophorin receptors genetically modulate neurodegeneration caused by reduction of Psn expression in the aging Drosophila brain
Authors: Kang Jongkyun , Zhang Chen , Wang Yuhao , Peng Jian , Berger Bonnie , Perrimon Norbert , Shen Jie 
Published: November 2023

Abstract
Mutations in the Presenilin (PSEN) genes are the most common cause of early-onset familial Alzheimer's disease (FAD). Studies in cell culture, in vitro biochemical systems, and knockin mice showed that PSEN mutations are loss-of-function mutations, impairing γ-secretase activity. Mouse genetic analysis highlighted the importance of Presenilin (PS) in learning and memory, synaptic plasticity and neurotransmitter release, and neuronal survival, and Drosophila studies further demonstrated an evolutionarily conserved role of PS in neuronal survival during aging. However, molecular pathways that interact with PS in neuronal survival remain unclear. To identify genetic modifiers that modulate PS-dependent neuronal survival, we developed a new Drosophila Psn model that exhibits age-dependent neurodegeneration and increases of apoptosis. Following a bioinformatic analysis, we tested top ranked candidate genes by selective knockdown (KD) of each gene in neurons using two independent RNAi lines in Psn KD models. Interestingly, 4 of the 9 genes enhancing neurodegeneration in Psn KD flies are involved in lipid transport and metabolism. Specifically, neuron-specific KD of lipophorin receptors, lpr1 and lpr2, dramatically worsens neurodegeneration in Psn KD flies, and overexpression of lpr1 or lpr2 does not alleviate Psn KD-induced neurodegeneration. Furthermore, lpr1 or lpr2 KD alone also leads to neurodegeneration, increased apoptosis, climbing defects, and shortened lifespan. Lastly, heterozygotic deletions of lpr1 and lpr2 or homozygotic deletions of lpr1 or lpr2 similarly lead to age-dependent neurodegeneration and further exacerbate neurodegeneration in Psn KD flies. These findings show that LpRs modulate Psn-dependent neuronal survival and are critically important for neuronal integrity in the aging brain.
The statistical complexity of early-stopped mirror descent
Authors: Kanade Varun , Rebeschini Patrick , Vaškevičius Tomas 
Published: November 2023

AbstractRecently there has been a surge of interest in understanding implicit regularization properties of iterative gradient-based optimization algorithms. In this paper, we study the statistical guarantees on the excess risk achieved by early-stopped unconstrained mirror descent algorithms applied to the unregularized empirical risk. We consider the set-up of learning linear models and kernel methods for strongly convex and Lipschitz loss functions while imposing only boundedness conditions on the unknown data-generating mechanism. By completing an inequality that characterizes convexity for the squared loss, we identify an intrinsic link between offset Rademacher complexities and potential-based convergence analysis of mirror descent methods. Our observation immediately yields excess risk guarantees for the path traced by the iterates of mirror descent in terms of offset complexities of certain function classes depending only on the choice of the mirror map, initialization point, step size and the number of iterations. We apply our theory to recover, in a clean and elegant manner via rather short proofs, some of the recent results in the implicit regularization literature while also showing how to improve upon them in some settings.
Impact of pH on the activity of novel cephalosporin cefiderocol in human urine
Authors: Nussbaumer-Pröll Alina Karoline , Eberl Sabine , Schober Christine , Zeitlinger Markus 
Published: November 2023

Abstract

Background
Antimicrobial activity of antibiotics can be impacted by pH, enhancing or reducing their bactericidal properties. Cefiderocol, a novel cephalosporin antibiotic that is among others indicated for the treatment of complicated urinary tract infections (cUTIs), lacks data on activity in urine.

Methods
Pooled human urine (iron levels ∼0.05 mg/L/24 h), CAMHB and iron-depleted CAMHB (ID-CAMHB) at pH 5, 7 and 8 served as media. MIC testing was done according to EUCAST with the broth microdilution method for 17 clinical isolates of Escherichia coli and ATCC 25922 (including isolates with ESBL activity), 17 clinical isolates of Klebsiella pneumoniae and ATCC 700603 (also with ESBL), and 6 clinical isolates of Pseudomonas aeruginosa and ATCC 27853. Time–kill curves (TKCs) were performed for selected strains at pH 5, 7 and 8 in urine.

Results
MIC values in urine, CAMHB and ID-CAMHB exhibited isolate-specific variations when assessed under identical pH conditions, ranging from a 1-fold dilution to changes of up to 4-fold dilutions in either direction. Median MICs of cefiderocol were up to 50-fold higher in pH 5 than in pH 7 for P. aeruginosa isolates and 32-fold higher in E. coli and K. pneumoniae isolates. TKCs with 650 and 1300 mg/L cefiderocol in urine showed that ATCC strains were efficiently eradicated despite the pH set.

Conclusions
Acidic pH had a significant negative impact on cefiderocol activity. Yet, after a recommended IV administration of 2 g cefiderocol every 8 h, a concentration of approximately 1300 mg/L can be achieved in urine, suggesting that efficient killing of all tested pathogens could have been possible even under acidic conditions in vivo.
Effects of high levels of zinc oxide and dietary zinc/copper ratios on the metabolism of iron in weaned pigs
Authors: Dalto Danyel Bueno , Audet Isabelle , Matte Jean-Jacques , Lapointe Jérôme 
Published: November 2023

AbstractThe present study compares the use different levels of dietary zinc oxide and zinc/copper ratios on the metabolism of iron (Fe) in weaned pigs. Two experiments were conducted using 120 and 160 weanling piglets (7.96 ± 1.17 kg and 7.81 ± 0.25 kg body weight, respectively) that were randomly assigned to the experimental treatments. Experiment I: diets supplemented with 100, 1,000, and 3,000 mg/kg of zinc (Zn) as ZnO (LZn, MZn, HZn) and 130 mg/kg of copper (Cu) as CuSO4; experiment II: diets supplemented with 100 or 3,000 mg/kg of Zn as ZnO (LZn and HZn) in combination with 6 or 130 mg/kg of Cu as CuSO4 (LCu and HCu). In both experiments, diets had similar levels of supplemental Fe (100 mg/kg of Fe as FeSO4). Piglets were slaughtered at d21 (weaning), d23 (experiment I), d28 (experiment II), d35, and d42 to assess whole blood, serum, and liver Fe concentrations, hemoglobin concentration, and the relative expression of key genes associated with Fe metabolism in jejunum and liver. Whole blood Fe and hemoglobin concentrations (experiment I) as well as serum Fe concentrations (experiments I and II) were not affected by dietary treatments (P ≥ 0.11). Liver Fe concentrations (experiment II) and total liver Fe content (experiments I and II) were lower (P ≤ 0.05) in HZn compared to LZn groups at d42. In both experiments, the mRNA expression of jejunal DMT1 was lowest and that of jejunal FTH1 was highest at d42 (P ≤ 0.04) for HZn piglets. In experiment II only, jejunal FTH1 and FPN1 expression were greater (P ≤ 0.04) in HCu compared to LCu groups at d42. The highest expression of hepatic FTH1 and FPN1 at d35 and d42 (P ≤ 0.02) was detected in HZn piglets in both experiments. For hepatic HAMP, expression values were greater (P = 0.04) at d42 in HZn groups. In conclusion, high dietary ZnO levels impair Fe metabolism but the effects are not intense enough to impact circulating Fe and hemoglobin concentrations.
Feeling the Heat. Mapping the Epigenetic Modifications of Histone during Burn Wound Healing
Authors: Rolim Larissa S A , Nascente Patricia da S , Castilho Rogerio M , Squarize Cristiane H 
Published: November 2023

Abstract
Burn injuries are observed throughout a wide range of ages, with over 1.1 million Americans suffering burns yearly, and half of these require hospitalization. Epigenetic modifications are fast-acting mechanisms that allow the human body to respond and adapt to environmental changes, including burn injuries. There is a lack of understanding of the epigenetic role during burn-induced tissue repair. Here, we characterize the histone modifications that follow burn injury, aiming at future pharmacological intervention using drugs capable of targeting epigenetic events. A clinically relevant porcine burn model was used to recapitulate the skin healing process after the burn. Isolated skin tissues at different time points were used to detect the acetylation levels of histones H3K27, H4K5, H4K8, and H4K12 as significant players of gene transcription using MetaXpress High-Content Imaging Analysis. We observed that the acetylation of histones is dynamically adjusted throughout healing, and its modifications are uniquely expressed according to the anatomical location and time of healing. We also observed that histone H4K5 is the most widely expressed during healing, followed by histone H3K27. We observed that histones expressed in intact skin tissue adjacent to the burn site could sense the burn injury by changing its histone acetylation pattern compared to control skin from uninjured and distant skin. Using a clinically relevant animal model, we have generated a comprehensive landscape of epigenetic modifications during burn healing. Our data will help us identify novel epi-drugs capable of manipulating histone modifications during healing to accelerate the healing process.
Unexpected legacies
Authors: Richards Candace 
Published: November 2023

Abstract
William J. Woodhouse was honorary curator of the Nicholson Museum, University of Sydney, from 1904 until 1937. During his curatorship he undertook a significant acquisition of plaster casts to enhance the representation of Greek and Italian sculpture alongside the existing ceramics collection. At its height the collection included well over 250 plaster casts and reproductions. Today the majority of the cast collection has been deaccessioned and, instead, his personal collections of ceramic sherds and photography, donated after her father’s death by his daughter Liska Woodhouse, have become Woodhouse’s curatorial legacy. This paper introduces Woodhouse’s role as curator, and examines each of his unique collections to analyse how Woodhouse himself conceived of his legacy and the reality represented in the Nicholson collection today. Central to this paper is an exploration of how collecting priorities and the perception of authenticity and narrative value changed in museums of antiquities during the twentieth century.
Stepwise prolongation of overall survival from first to third generation EGFR-TKIs for EGFR mutation-positive non-small-cell lung cancer: the Tokushukai REAl-world Data project (TREAD 01)
Authors: Uryu Kiyoaki , Imamura Yoshinori , Shimoyama Rai , Mase Takahiro , Fujimura Yoshiaki , Hayashi Maki , Ohtaki Megu , Otani Keiko , Hibino Makoto , Horiuchi Shigeto , Fukui Tomoya , Fukai Ryuta , Chihara Yusuke , Iwase Akihiko , Yamada Noriko , Tamura Yukihiro , Harada Hiromasa , Shinozaki Nobuaki , Tsuya Asuka , Fukuoka Masahiro , Minami Hironobu 
Published: November 2023

Abstract

Objective
The introduction of new-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has afforded promising overall survival outcomes in clinical trials for non-small-cell lung cancer. We aim to investigate the current adoption rate of these agents and the real-world impact on overall survival among institutions.

Methods
In a nationwide retrospective cohort study of 46 Tokushukai Medical Group hospitals in Japan, we analyzed clinical data of consecutive patients with non-small-cell lung cancer receiving EGFR-TKIs between April 2010 and March 2020. Univariate and multivariate Cox regression analyses examined the associations between overall survival and patient/tumor-related factors and first-line EGFR-TKIs.

Results
A total of 758 patients (58.5% females; median age, 73 years) were included. Of 40 patients diagnosed in 2010, 72.5% received gefitinib, whereas 81.3% of 107 patients diagnosed in 2019 received osimertinib as the first-line EGFR-TKI. With a median follow-up of 15.8 months, the median overall survival was 28.4 months (95% confidence interval, 15.3–31.0). In a multivariate Cox regression analysis, age, body mass index, disease status, EGFR mutational status and first-line epidermal growth factor receptor tyrosine kinase inhibitor were identified as significant prognostic factors after adjusting for background factors including study period, hospital volume and hospital type. The estimated 2-year overall survival rates for gefitinib, erlotinib, afatinib and osimertinib were 70.1% (95% confidence interval 59.7–82.4), 67.8% (95% confidence interval 55.3–83.2), 75.5% (95% confidence interval 64.7–88.0) and 90.8% (95% confidence interval 84.8–97.3), respectively. The median time to treatment failure of gefitinib, erlotinib, afatinib and osimertinib were 12.8, 8.8, 12.0 and 16.9 months or more, respectively.

Conclusions
Our real-world data revealed that the swift and widespread utilization of newer-generation EGFR-TKIs in patients with EGFR mutation-positive non-small-cell lung cancer, and that these newer-generation EGFR-TKIs can prolong overall survival regardless of hospital volume or type. Therefore, osimertinib could be a reasonable first choice treatment for these patients across various clinical practice settings.