bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quantitative performance of humanized serum and epithelial lining fluid exposures of tigecycline and levofloxacin against a challenge set of Klebsiella pneumoniae and Pseudomonas aeruginosa in a standardized neutropenic murine pneumonia model
Authors: Fratoni Andrew J , Padgett Alissa M , Duffy Erin M , Nicolau David P 
Published: September 2024

Abstract

Background
Lack of uniformity in infection models complicates preclinical development. The COMBINE protocol has standardized the murine neutropenic pneumonia model. Herein we provide benchmark efficacy data of humanized exposures of tigecycline and levofloxacin in plasma and epithelial lining fluid (ELF) against a collection of Klebsiella pneumoniae and Pseudomonas aeruginosa.

Methods
Following the COMBINE protocol, plasma and ELF human-simulated regimens (HSRs) of tigecycline 100 mg followed by 50 mg q12h and levofloxacin 750 mg once daily were developed and confirmed in the murine neutropenic pneumonia model. Tigecycline HSRs were tested against seven K. pneumoniae isolates. Levofloxacin HSRs were assessed against 10 K. pneumoniae and 9 P. aeruginosa. The change in cfu/lung over 24 h for each treatment was calculated. Each isolate was tested in duplicate against both the plasma and ELF HSRs on separate experiment days.

Results
Tigecycline 1.8 and 3 mg/kg q12h achieved humanized exposures of serum and ELF, respectively. Levofloxacin 120 and 90 mg/kg q8h led to fAUC exposures in plasma and ELF similar to in humans. Both tigecycline regimens were ineffective across the MIC range. Levofloxacin regimens achieved multilog kill against susceptible isolates, and no appreciable cfu/lung reductions in isolates with an MIC of ≥32 mg/L. Differences in cfu/lung were evident between the levofloxacin plasma and ELF HSRs against isolates with MICs of 4 and 8 mg/L.

Conclusions
Administering HSRs of tigecycline and levofloxacin based on both serum/plasma and ELF in the COMBINE pneumonia model resulted in cfu/lung values reasonably aligned with MIC. These data serve as translational benchmarks for future investigations with novel compounds.
Multi-omics analysis reveals associations between host gene expression, gut microbiota, and metabolites in chickens
Authors: Shi Kai , Liu Xiangping , Duan Ying , Ding Jiqiang , Jia Yimin , Jiang Ziqin , Feng Chungang 
Published: September 2024

Abstract
Egg-laying is an important trait in chickens, and it is affected by many factors, such as hormones regulated by the hypothalamic-pituitary axis and precursors synthesized by the liver. Recent studies showed that gut microbiota was associated with egg-laying, however, its underlying mechanism remains unclear. We comprehensively analyzed the host transcriptome, gut microbiota, and metabolome in broiler breeder hens during the pre-laying, peak-laying, and late-laying periods. The transcriptome analysis of the tissues related to the hypothalamic-pituitary-liver (HPL) axis revealed dynamic gene expression during egg-laying periods. Differentially expressed genes (DEGs) (i.e., PENK, NPY, AVP, PRL, RLN3, and FST) from the hypothalamus and pituitary gland were involved in female gonadal development, hormone secretion, response to endogenous stimulus, liver development, and amide metabolism. In liver, DEGs (i.e., FABP3, VTG1, LPL, APOA5, APOV1, and RBP5) were enriched in efferocytosis, sphingolipid metabolism, amide, and peptide biosynthesis. Alpha and beta diversity changed significantly in cecum microbiota during different laying periods. The abundance of Firmicutes was decreased and the abundance of Bacteroidota was increased during the peak-laying period. Functional analysis showed that the biosynthesis of secondary metabolites, amino acids, purine, and steroid hormones was altered during laying. The metabolome analysis from cecal contents showed that amino acid metabolism and steroid hormone biosynthesis changed during laying. Integrated analysis of the cecal microbiota and metabolites showed the genus Megasphaera was involved in amino acid metabolism, which included 3-phenyllatic acid, quinic acid, caffeic acid, and folic acid, and the genus Hungatella participated in steroid hormone biosynthesis through its strong correlation with estradiol. These results explored the dynamic changes in tissues related to the HPL axis and cecal microbiota and provided new insights into the interaction between the host and microbiota during egg-laying in chickens.
The only terrestrial lineage in the Branchiopoda redefined: a new species of Bryospilus Frey, 1980 (Cladocera: Anomopoda) from India and adaptations of waterfleas to life on land
Authors: Van Damme Kay , Padhye Sameer M 
Published: September 2024

Abstract
Only a small proportion of the world’s crustacean taxa is adapted to limno-terrestrial microhabitats that are disconnected from conventional surface waterbodies. In rare occasions, water films on terrestrial tropical and subtropical vegetation may also harbour specialised cladocerans. Bryospilus Frey, 1980 (Chydoridae) is the only genus within the class Branchiopoda that is specialised to living almost exclusively in water-saturated terrestrial moss patches, leaf litter, and phytotelms. The remarkable waterflea lineage, which has a suite of highly unusual characters within the family, has been found in terrestrial habitats in rainforests of West Africa, South and Central America, and New Zealand. We discovered a new moss-inhabiting chydorid from western India, Bryospilus (Indobryospilus) bharaticus n. sp., the first representative of the genus from the Oriental Region. Its morphology and behaviour are highly unusual for a species of Bryospilus. In comparison to its congeners, the new species can swim and it has significantly less oligomerisation, with three terminal setae on the antennal endopod instead of two and seven exopod setae on the third limb instead of six, among other features. We define a new subgenus Indobryospilus nov. and we amend the genus Bryospilus. The new species is a living evolutionary connection, characterised by a phenotype which provides us with new clues about evolutionary transitions in the only terrestrial branchiopod genus. Our results are informative beyond Cladocera, as the morphology of this species provides insights about the evolution and parallelisms of aquatic crustaceans that have specialised in limno-terrestrial habitats. We revisit the morphology of the genus, the disjunct biogeographical pattern with a potential ancient signature, and discuss the functional adaptations of these cladocerans to life on land, as well as convergences with subterranean lineages. A new key to the world species of Bryospilus species is included.
Fitness implications of low-temperature storage for Eocanthecona furcellata (Hemiptera: Pentatomidae)
Authors: Pan Chun-Ni , Zhou Wei , Lu Chang-Hao , Pan Ying-Na , Liu Ling-Yi , Chen Wen-Long 
Published: September 2024

Abstract
Exploring the impact of low-temperature storage on the fitness of natural enemy insects is crucial for practical field applications because this parameter directly influences their potential for population growth and effective pest control. Eocanthecona furcellata (Wolff) (Hemiptera: Pentatomidae) is widely used in biological pest control. This study aimed to identify optimal storage stages, temperatures, and durations for E. furcellata to produce high-quality individuals for practical use. The quality of E. furcellata after storage was evaluated by assessing parameters such as predatory capacity and fecundity, along with age-stage, two-sex life table. The findings revealed that the adult stage was the optimal storage form for E. furcellata, and the most favorable temperature for storage was 12 °C. Adult females had the highest predatory ability after 15 days of storage at 12 °C. Although survival rates declined with prolonged storage, they remained above 50% after 30 days, and longevity, fecundity, and predatory capacity of surviving individuals remained comparable to those of individuals in the control group (rearing at a constant temperature of 26 °C without low-temperature storage). The effects of low-temperature storage extended to the F1 generation of E. furcellata, which exhibited maximum mean longevity, fecundity, net reproductive rate, and mean generation time as well as fastest population growth after 30 days of storage at 12 °C. These results can be used to achieve optimal low-temperature storage conditions for E. furcellata production, particularly for extending its shelf life.
Victims’ Perspectives on Participation in the Ongwen Case
Authors: Massidda Paolina , Akwenyu Joseph , Moffett Luke 
Published: September 2024

Abstract
The Ongwen case has so far involved one of the largest number of victims represented before the International Criminal Court, both in terms of participation in trial proceedings (4,095) and potential beneficiaries for reparations (49,772). This piece offers some new insights following the trial from victims represented by both victim legal teams that are not captured in victims’ statements or submissions before the Court. It draws on additional interviews with victims after the completion of the trial and sentencing, but before the reparation order issued in the case. It focuses on three elements — victims’ role in proceedings; how victims felt they were represented before the Court; and victims’ satisfaction with the outcome of the proceedings.
Explanatory frameworks in complex change and resilience system modelling
Authors: Addis Mark , Eckert Claudia 
Published: September 2024

Abstract
Heterogenous flows across system boundaries continue to pose significant problems for efficient resource allocation especially with respect to long term strategic planning and immediate problems about allocation to address particular resource shortages. The approach taken here to modelling such flows is an engineering change prediction one. This enables margin modelling by producing system models in dependency matrices with different linkage types. Change prediction approaches from engineering design can analyse where these bottlenecks in integrated systems would be so that resources can be deployed flexibility to avoid them and address them when they occur. Current state of the art of margin research can be furthered by identifying margins on multiple levels of system composition. It can usefully be complemented by a category theory based approach which allows representation of variable and constant properties of models under changing conditions, and the identification of flows within models. Category theory is useful for formalising such explanatory frameworks as it can both structure systems and permit analysis of their applications in a complementary way.
Microservices architecture to enable an open platform for realizing zero defects in cyber-physical manufacturing
Authors: Pedro Lopes Rui , Ibrahim Ahmed , Barbosa José , Leitao Paulo 
Published: September 2024

Abstract
The market’s demand for high-quality products necessitates innovative manufacturing approaches that emphasize flexibility, adaptability, and the reduction of defects. Traditional systems are currently evolving towards embracing I4.0 technologies, including data collection, processing, analytics and digital twin, aiming for zero-defect manufacturing quality. This paper introduces an open platform, compliant with RAMI4.0 standards, designed to improve manufacturing quality. The platform integrates data using Asset Administration Shells with microservices adaptation for data ingestion and advanced analytics. Additionally, it incorporates Non-Destructive Inspection tools, demonstrating a seamless integration of measurement and quality assurance. This study details the architectural specification and validation of the openZDM platform, employing microservices to ensure flexibility, modularity and scalability, aligning with the RAMI4.0 model. The platform was validated through deployment in an automotive assembly line, highlighting its effectiveness in integrating inspection scenarios and early defect detection tools. The architecture employs a choreographed approach to manage loosely coupled microservices, enabling efficient data lifecycle management from collection through analytics to visualization.
Sparganothis sulfureana (Lepidoptera: Tortricidae) egg surface characteristics stimulate parasitism by Ascogaster mimetica (Hymenoptera: Braconidae)
Authors: Ben-Zvi Yahel , Rodriguez-Saona Cesar 
Published: September 2024

Abstract
Ascogaster mimetica Viereck is an egg-larval parasitoid that targets Sparganothis sulfureana Clemens, a major cranberry pest in North America. While previous studies have shown that other Ascogaster species respond to cues from their hosts’ eggs, it remains unknown whether A. mimetica utilizes these cues to recognize S. sulfureana. We hypothesized that female A. mimetica recognizes S. sulfureana from another cranberry pest, Choristoneura parallela Robinson, based on the presence of surface cues on eggs. To test this, we observed female A. mimetica behavior when exposed to eggs from its host, S. sulfureana; a nonhost, C. parallela; and eggs of S. sulfureana that were washed clean with hexane. Additionally, we tracked parasitism rates in each group. Our results revealed that A. mimetica spent 9.5 times longer walking when exposed to C. parallela eggs and 6 times longer when exposed to hexane-washed S. sulfureana eggs compared to unwashed S. sulfureana eggs. Also, A. mimetica spent 3 times longer grooming when exposed to hexane-washed than unwashed S. sulfureana eggs. In contrast, females spent 6 and 18 times longer drumming and probing/ovipositing on unwashed S. sulfureana eggs than on C. parallela eggs and 5 times longer probing/ovipositing on unwashed S. sulfureana eggs than on hexane-washed S. sulfureana eggs. Higher parasitism rates were observed from unwashed S. sulfureana eggs compared to those from C. parallela eggs and hexane-washed S. sulfureana eggs. Our findings suggest that the presence of egg surface cues, like scales, of S. sulfureana likely plays a crucial role in host acceptance and parasitism success for A. mimetica.
Glia maturation factor-γ regulates amyloid-β42 phagocytosis through scavenger receptor class A type I in murine macrophages
Authors: Aerbajinai Wulin , Zhu Jianqiong , Chin Kyung , Rodgers Griffin P 
Published: September 2024

Abstract
Dysfunctional phagocytic clearance of β-amyloid (Aβ) in microglia and peripheral macrophages/monocytes has been implicated in Alzheimer's disease, but the mechanisms underlying this dysfunction are not yet well understood. In this study, we examined the role of glia maturation factor-γ (GMFG), an actin-disassembly protein, i.e. highly expressed in immune cells, in macrophage Aβ phagocytosis and in regulating type I class A scavenger receptor, a cell-surface receptor that has previously been implicated in Aβ clearance. GMFG knockdown–increased phagocytosis of Aβ42 in bone marrow-derived macrophages and RAW264.7 murine macrophages, while GMFG overexpression reduced Aβ42 uptake in these cells. Blocking with anti-type I class A scavenger receptor antibodies inhibited Aβ42 uptake in GMFG-knockdown cells, establishing a role for type I class A scavenger receptor in Aβ42 phagocytosis. GMFG knockdown–increased type I class A scavenger receptor protein expression under both basal conditions and in response to Aβ42 treatment via both the transcriptional and posttranscriptional levels in RAW264.7 macrophages. GMFG knockdown modulated Aβ42-induced K48-linked and K63-polyubiquitination of type I class A scavenger receptor, the phosphorylation of type I class A scavenger receptor and c-Jun N-Terminal kinase (JNK), suggesting that GMFG plays a role for intracellular signaling in the type I class A scavenger receptor-–mediated uptake of Aβ. Further, GMFG-knockdown cells displayed increased levels of the transcriptional factor MafB, and silencing of MafB in these cells reduced their type I class A scavenger receptor expression. Finally, GMFG was found to interact with the nuclear pore complex component RanBP2, and silencing of RanBP2 in GMFG-knockdown cells reduced their type I class A scavenger receptor expression. Collectively, these data support the role of GMFG as a novel regulator of type I class A scavenger receptor in macrophage Aβ phagocytosis and may provide insight into therapeutic approaches to potentially slow or prevent the progression of Alzheimer’s disease.
Impact of the serrated pathway on the simulated comparative effectiveness of colorectal cancer screening tests
Authors: Meester Reinier G S , Ladabaum Uri 
Published: September 2024

Abstract

Background
Colorectal cancers (CRCs) arise from adenomas, which can produce fecal occult blood and can be detected endoscopically, or sessile serrated lesions (SSLs), which rarely bleed and may be more challenging to detect. Models informing CRC screening policy should reflect both pathways, accounting for uncertainty.

Methods
Novel decision-analytic model of the adenoma and serrated pathways for CRC (ANSER) to compare current and emerging screening strategies, accounting for differential test sensitivities for adenomas and SSLs, and uncertainty. Strategies included colonoscopy every 10 years, stool-DNA/FIT (sDNA-FIT) every 1-3 years, or fecal immunochemical testing (FIT) every year from age 45 to 75 years. Outcomes included CRC cases and deaths, cost-effectiveness (cost/quality-adjusted life-year [QALY] gained), and burden–benefit (colonoscopies/life-year gained), with 95% uncertainty intervals (UIs).

Results
ANSER predicted 62.5 (95% UI = 58.8-66.3) lifetime CRC cases and 24.1 (95% UI = 22.5-25.7) CRC deaths/1000 45-year-olds without screening, and 78%-87% CRC mortality reductions with screening. The tests’ outcome distributions overlapped for QALYs gained but separated for required colonoscopies and costs. All strategies cost less than $100 000/QALY gained vs no screening. Colonoscopy was the most effective and cost-effective, costing $9300/life-year gained (95% UI = $500-$21 900) vs FIT. sDNA-FIT cost more than $500 000/QALY gained vs FIT. As more CRCs arose from SSLs, colonoscopy remained preferred based on clinical benefit and cost-effectiveness, but cost-effectiveness improved for a next-generation sDNA-FIT.

Conclusion
When the serrated pathway is considered, modeling suggests that colonoscopy is cost-effective vs FIT. In contrast, modeling suggests that sDNA-FIT is not cost-effective vs FIT despite its greater sensitivity for SSLs, even if a substantial minority of CRCs arise from SSLs.
Cost-effectiveness analysis with surrogate endpoint: mobile targeted active case detection for early detection of tuberculosis
Authors: Liaw Yau-Chun , Ramdzan Abdul Rahman , Avoi Richard 
Published: September 2024

Abstract

Objective
This study aimed to determine cost-effectiveness analysis with the surrogate endpoint of mobile targeted active case detection (MTACD) programmes in the early detection of tuberculosis (TB) cases.

Methods
A cross-sectional study to determine the cost-effectiveness with the surrogate endpoint of MTACD as compared with passive case detection (PCD) from the provider’s perspective. Data were gathered on the costs and significant dates (TB screening date, first TB symptoms date, TB diagnosis date, and TB treatment starting date) for 904 patients from five Sabah districts in 2022. A combined step-down and activity-based costing method was used to estimate provider costs. The health outcome measures used were the time taken by the day to detect TB cases. Cost-effectiveness analysis with surrogate endpoint was assessed using cost per TB screening by MTACD and PCD, and the mean of the time taken by the day to detect TB cases.

Key findings
The total cost for a patient to be screened by MTACD was Malaysian Ringgit (MYR) 96.6 (MYR 1 = USD 0.22), while the cost by PCD was MYR 43.1. The MTACD generally costs MYR 1727.1 to detect a case of TB, compared with MYR 586.9 for PCD. However, MTACD used a shorter mean time to detect TB cases (52.7 days) than PCD (98.9 days).

Conclusions
Despite the higher costs per screening, MTACD may shorten the days of diagnosis from the onset of TB symptoms when compared with PCD. This study is beneficial when budgeting for TB programmes since MTACD can detect TB cases earlier and lead to early treatment.
Altered expression of a raspberry homologue of VRN1 is associated with disruption of dormancy induction and misregulation of subsets of dormancy-associated genes
Authors: Mateos Brezo , Preedy Katharine , Milne Linda , Morris Jenny , Hedley Pete E , Simpson Craig , Hancock Robert D , Graham Julie 
Published: September 2024

Abstract
Winter dormancy is a key process in the phenology of temperate perennials. Climate change is severely impacting its course leading to economic losses in agriculture. A better understanding of the underlying mechanisms, as well as the genetic basis of the different responses, is necessary for the development of climate-resilient cultivars. This study aims to provide an insight into winter dormancy in red raspberry (Rubus idaeus L). We report the transcriptomic profiles during dormancy in two raspberry cultivars with contrasting responses. The cultivar ‘Glen Ample’ showed a typical perennial phenology, whereas ‘Glen Dee’ registered consistent dormancy dysregulation, exhibiting active growth and flowering out of season. RNA-seq combined with weighted gene co-expression network analysis identified gene clusters in both genotypes that exhibited time-dependent expression profiles. Functional analysis of ‘Glen Ample’ gene clusters highlighted the significance of the cell and structural development prior to dormancy entry as well the role of genetic and epigenetic processes such as RNAi and DNA methylation in regulating gene expression. Dormancy release in ‘Glen Ample’ was associated with up-regulation of transcripts associated with the resumption of metabolism, nucleic acid biogenesis, and processing signal response pathways. Many of the processes occurring in ‘Glen Ample’ were dysregulated in ‘Glen Dee’ and 28 transcripts exhibiting time-dependent expression in ‘Glen Ample’ that also had an Arabidopsis homologue were not found in ‘Glen Dee’. These included a gene with homology to Arabidopsis VRN1 (RiVRN1.1) that exhibited a sharp decline in expression following dormancy induction in ‘Glen Ample’. Characterization of the gene region in the ‘Glen Dee’ genome revealed two large insertions upstream of the ATG start codon. We propose that expression below detection level of a specific VRN1 homologue in ‘Glen Dee’ causes dormancy misregulation as a result of inappropriate expression of a subset of genes that are directly or indirectly regulated by RiVRN1.1.