bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extension of the TASTE toolset to support publisher-subscriber communication
Authors: Valente Hugo , A de Miguel Miguel , Pérez Ángel G , Alonso Alejandro , Zamorano Juan , A de la Puente uan 
Published: December 2024

New Space has been revolutionizing how space software is developed. While in the past the development of systems lasted years to minimize errors, nowadays, with the reduction in manufacturing costs of micro and nanosatellites, companies are capitalizing by focusing on launching frequently, focusing on rapid iterations and innovations. As a result, software development of space systems is also adapting to meet the demands from platform specific code to code that can be reused across different platforms. As a result, there has been a shift from developing tightly coupled client-server systems to loosely coupled publisher subscriber systems.
In this article, we propose a solution focused on integrating cFS, a Publisher Subscriber runtime made by NASA, inside TASTE, a model-based toolset developed by ESA, to build space systems focusing on a publishersubscriber methodology, allowing the user to develop platform agnostic components, allowing for faster iterations, reducing the development time and increasing portability and reusability.
Antifatigue Effects of Deer‐Hide Gelatin on Mice by Regulating Nrf2/Keap1 and AMPK/PGC1α Signaling Pathways and Intestinal Flora
Authors: Chang Yuan , Zhang Lulu , Nie Zixuan , Miao Yixiang , Jia Tianzhu , Shi Ji , Liu Pengpeng 
Published: December 2024

Objective: This study investigated the antifatigue effects of deer‐hide gelatin (DHG) and its mechanism in mice through a weight‐loaded swimming experiment.Methods: The subjects were assigned to the blank group (BC), positive group (PC), model group (MC), and high, medium, and low doses of DHG groups (HP, MP, and LP). After 4 weeks of treatment, the subjects were sacrificed to detect fatigue‐related biochemical indicators and the protein and mRNA expressions of Nrf2/Keap1 and AMPK/PGC1α pathways. The morphological changes of skeletal muscle were detected. High‐throughput sequencing technology was used to detect the changes in the relative abundance of intestinal flora and the content of short‐chain fatty acids (SCFAs) in tired subjects.Results: Compared with MC, DHG could prolong the exhaustion time of weight‐loaded swimming mice; reduce the CK, BUN, lactic acid, MDA, 5‐HT, and GABA levels; and increase the LDH, SOD, CAT, Glycogen, MG, BG, ACH, and Glu levels. Moreover, DHG increased the protein and mRNA expression of Nrf2, HO‐1, AMPK, PGC1α, and P‐AMPK and reduced the protein and mRNA expression of Keap1. The 16S rDNA sequencing analysis also showed that DHG regulated the abundance of intestinal microbiota and the content of SCFAs and increased the growth of beneficial bacteria.Conclusions: DHG exhibited antifatigue effects on mice by activating Nrf2/Keap1 and AMPK/PGC1α pathways, reducing oxidative stress damage, and enhancing mitochondrial energy supply. The study’s findings confirmed the considerable antioxidant and antifatigue activities of DHG, providing a preliminary foundation and practical theory for the further development of DHG as a nutritional supplement.
Paralog Co-Targeting Identifies Selective Genetic Redundancies across Cancer Types
Authors: Gauthier-Coles Gregory , Sheltzer Jason M. 
Published: December 2024

Summary:In this issue, Klingbeil and colleagues deploy a paralog co-targeting strategy to reveal microtubule affinity–regulating kinases 2 and 3 as redundant negative regulators of the Hippo pathway and potentially actionable targets in YAP/TAZ-addicted tumors.See related article by Klingbeil et.al., p. 2471
Targeting RNA and Protein Turnover in Aneuploid Cancers
Authors: Bakhoum Samuel F. 
Published: December 2024

Summary:Aneuploidy, an imbalance in chromosome number, is a hallmark of human cancers with chromosomal instability, and it remains a major therapeutic challenge. In this issue, Ippolito and colleagues identify RNA and protein turnover as targetable therapeutic vulnerabilities in aneuploid cancers.See related article by Ippolito et al., p. 2532
Characterization of Persister Cells Provides Insights into Mechanisms of Therapy Resistance in Neuroblastoma
Authors: Wolf Amber B. , Reynolds C. Patrick , Barbieri Eveline 
Published: December 2024

Summary:The study by Grossmann and colleagues uses single-nucleus RNA sequencing in a cohort of matched high-risk neuroblastoma primary tumor samples, obtained from the same patient at diagnosis and definitive surgery, to identify persister cells that survive induction chemotherapy. These persister cells utilize mechanisms of chemoresistance that are both tumor-intrinsic and tumor-extrinsic, are highly dependent on the original genetic profile of the tumor, and represent novel, patient-specific targets to precisely inhibit chemoresistance and disease recurrence.See related article by Grossmann et.al., p. 2387
Precision Oncology: 2024 in Review
Authors: Repetto Matteo , Fernandez Nicole , Drilon Alexander , Chakravarty Debyani 
Published: December 2024

Summary:
This article discusses the specific advances made in precision oncology in 2024. We comment on the evolving nature of predictive molecular events used to select patients who will most benefit clinically from treatment. We also discuss advances in the development of strategic treatment regimens for combination therapies, rational drug design of small-molecule inhibitors, and structurally informed drug repurposing.
Battra: The Traditional Knowledge Holder on Medicinal Plant among People of East Lampung, Indonesia
Authors: Yudiyanto Yudiyanto , Wakhidah Anisatu Z. , Abdullah Irwan , Indiyanto Agus 
Published: December 2024

Local knowledge continues to experience two fundamental problems that cause its existence to be marginalized and cannot be widely passed on. Externally, local knowledge has always been questioned for its relevance to the times. Internally, it has become elitist, making it difficult for other groups to access it. Gradually, local knowledge is alienated in people's lives. To date, ethnobotany studies have focused on identifying plants and their properties for policy and business purposes. This study was carried out in four old villages near the Way Kambas National Park, East Lampung, which were selected using the purposive sampling method. The key respondents were selected using the snowball sampling method, while data were collected from respondents through semi-structured interviews. Selected medicinal plants were observed, and the data were analyzed qualitatively and descriptively. Interviews with parties interested in medicinal plant knowledge show the monopolistic mastery of knowledge by all parties and their interests. The study shows a great need for synergy between parties for the preservation of medicinal plant knowledge, starting with the opening of access to knowledge for all. The openness of the battras (traditional healers) to share sources of knowledge, the dedication of researchers/scientists in transforming knowledge into the public domain, the willingness of the private sector to share the value of medicinal plants benefits, and a pro-people policy framework will be key to the sustainability of medicinal plant knowledge for the development of fair and dignified public health.
Cancer-associated fibroblasts derived-exosomal circ_0076535 promotes esophageal squamous cell carcinoma progression
Authors: Kang Ningning , Ge Wei , Hu Jinxiu , Zhao Yuan , Zheng Hao , Lu Xuan 
Published: December 2024

Background Esophageal cancer (EC) is a common malignant tumor of the digestive tract and an important health-related problem in many developing countries. Esophageal squamous cell carcinoma (ESCC) is the most common subtype of EC. The cancer-associated fibroblasts (CAFs) are the major stromal cells in ESCC microenvironment. They play important role in ESCC proliferation, metastasis, angiogenesis and chemotherapy resistance through paracrine processes. However, the roles of circRNAs enriched in CAF-derived exosmes have not been reported. Objective To explore the mechanisms of how CAF affects ESCC proliferation and metastasis through paracrine processes and to investigate the role of circRNAs enriched in CAF-derived exosomes. Methods Exosomes were isolated from the conditional medium of CAF using differential ultracentrifugation, and then validated by Nanosight analysis. Exosome secretion inhibitor-GW4869 validates the pro-carcinogenic role of exosomes. The qRT-PCR showed the highest expression of circ_0076535 in the exosomal CircRNA, and knockdown of it confirmed its function. Online bioinformatics tool was utilized to predict the potential target gene of circ_0076535, and captured miR-145-5p as the target gene with high predictive value. The targeting association between miR-145-5p and circ_0076535 is further confirmed by the dual luciferase reporter experiment. The stimulation of tumour development and EMT by the CAF-derived exosome circ_0076535 is further validated in vivo. Results In our research, we found that CAF-derived exosomes increased proliferation, migration, invasion and EMT in ESCC cells. Circ_0076535 was highly enriched in CAF-exosomes and transferred into ESCC cells directly depend on internalization of exosomes. CAF-exosomal circ_0076535 increased the level of circ_0076535 in ESCC cells and induced EMT. Mechanistic experiments revealed circ_0076535 acted as a sponge to absorb miR-145-5p and activated NF-κB signaling pathway. Conclusions Conclusively, CAF-exosomal circ_0076535 promoted the ESCC progression via miR-145-5p/NF-κB axis and expected to be a potential biomarker for early diagnosis and treatment of ESCC.
A digital version of the nine-hole peg test: Speed may be a more reliable measure of upper-limb disability than completion time in patients with multiple sclerosis
Authors: Jiang Xiaotong , McGinley Marisa , Johnston Joshua , Alberts Jay , Bermel Robert , Ontaneda Daniel , Naismith Robert T , Hyde Robert , Levitt Nick , van Beek Johan , Sun Zhaonan , Campbell Nolan , Barro Christian 
Published: December 2024

Background: A digital adaptation of the nine-hole peg test (9HPT) was developed with the potential to provide novel disability features for patients with multiple sclerosis (PwMS). Objectives: The objectives were to evaluate the 9HPT features based on reliability, prognosis, and discrimination between treatment groups. Methods: The MS partners Advancing Technology and Health Solutions (MS PATHS) cohort data were used to derive new features including completion time and speed. Association and reliability between features and clinical outcomes were tested by intraclass correlation coefficients (ICCs) with repeated measures. The added prognostic value of the features for a clinically meaningful decline was assessed by time-to-event analyses with likelihood ratio tests. The estimated effect size between treatment efficacy groups was acquired from linear mixed-effects models. Sample size was calculated for a hypothetical randomized clinical trial. Results: For the 10,843 PwMS, speed and completion time were associated with MS disability. Compared with time, speed showed higher reliability (ICC = 0.78 vs 0.74), added benefits in predicting disability worsening ( p < 0.001), better discrimination between high- and low-efficacy groups (effect size: 0.035 vs 0.015), and an 18% reduction in required sample size for a 1-year clinical trial. Conclusion: Integrating horizontal hand distances traveled over the 9HPT pegboard can be a more reliable measure of hand function.
Characteristics of gut microbiota of premature infants in the early postnatal period and their relationship with intraventricular hemorrhage
Authors: Zhao Yunlong , Li Shan , Zhang Rui , Zhang Xin , Shen Qiuyue , Zhang Xingyun , Tian Tian , Hou Xinlin 
Published: December 2024

Abstract
Background
Studies have shown correlations between gut microbiota and neurocognitive function, but little was known about the early postnatal gut microbiota and intraventricular hemorrhage (IVH). We aimed to explore the characteristics of gut microbiota in premature infants and their relationship with IVH, further exploring potential therapeutic targets.

Methods
Premature infants delivered at Peking University First Hospital from February 2023 to August 2023 were recruited as a cohort. Feces samples were collected on postnatal days 1, 3, and 5. Premature infants were divided into normal, mild IVH, and severe IVH groups based on cranial ultrasound. 16S rRNA amplicon sequencing technology was used to determine the fecal microbiota, and the results were analyzed.

Results
Thirty-eight premature infants were enrolled. There was a significant difference in alpha and beta diversity among the three groups. The relative abundance of E. coli and A. muciniphila was different among the three groups. Further random forest analysis indicated that S. lutetiensis, L. mirabilis, and N. macacae can effectively distinguish premature infants with IVH. Finally, the phylogenetic investigation of communities by reconstruction of unobserved states2 (PICRUSt2) functional gene analysis predicted significant differences in energy metabolism, carbohydrate metabolism, metabolism of cofactors and vitamins, and membrane transport between normal and severe IVH groups.

Conclusions
The gut microbiota in the early postnatal period of premature infants is closely associated with the IVH status. As age increases, the differences in gut microbiota of premature infants with different degrees of IVH continue to increase, and the trend of changes with severity of IVH becomes more and more obvious. E. coli, A. muciniphila, S. lutetiensis, L. mirabilis, N. macacae, G. haemolysans, and S. oralis can effectively distinguish between IVH infants and normal premature infants. The results indicate that gut microbiota is expected to provide effective therapeutic targets for the diagnosis and treatment of IVH.
The impact of the Dementia Care in Hospitals Program on hospital acquired complications – a non-randomised stepped wedge hybrid effectiveness-implementation study
Authors: Yates Mark W. , Bail Kasia , MacDermott Sean , Skvarc David , Theobald Meredith , Morvell Michelle , Jebramek Jessica C. , Tebbut Ian , Draper Brian , Brodaty Henry 
Published: December 2024

Abstract
Background
Hospitalized older patients with cognitive impairment (CI) experience poor outcomes and high rates of hospital acquired complications (HACs). This study investigated the effectiveness of a multimodal hospital CI identification and education program.

Method
A prospective stepped-wedge, cross-sectional, continuous-recruitment, hybrid effectiveness-Implementation study was conducted in acute hospitals in four Australian states/territories. The intervention, the Dementia Care in Hospitals Program (DHCP) provided: clinical/ non-clinical hospital staff CI awareness support and education; CI screening for older patients and a bedside alert—the Cognitive Impairment Identifier (CII). The primary outcome was change in the rate of the combined risk of four HACs (urinary tract infection, pneumonia, new onset delirium, pressure injury).

Results
Participants were patients aged 65 years and over admitted for 24 h or more over a 12-month period between 2015–2017 (n = 16,789). Of the 11,309 (67.4%) screened, 4,277 (37.8%) had CI. HACs occurred in 27.4% of all screened patients and were three times more likely in patients with CI after controlling for age and sex (RR = 3.03; 95%CI:2.74–3.27). There was no significant change in HAC rate for patients with CI (RR = 1.084; 95%CI: 0.93; 1.26). In the intervention period the raw HAC rate for all screened patients was 27.0%, which when adjusted for age and sex suggested a small reduction overall. However, when adjusted for hospital site, this reduction in HAC risk not statistically significant (RR = 0.968; 95%CI:0.865–1.083). There was considerable interhospital variation in intervention implementation and outcomes which explains the final non-significant effect.

Conclusion
For patient with CI the implementation of the DCHP did not result in a reduction in HAC rates. Education for hospital staff regarding cognitive impairment screening, care support, carer engagement and bedside alerts, using the DCHP, can be feasibly implemented in acute hospitals. Reducing high frequency HACs in older hospital patients with CI, warrants further research.
Trial Registration. The trial was registered retrospectively with the Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12615000905561 on 01/09/2015 with 92 patients (0.8% of total sample) recruited in the baseline and none in the intervention before registration submission.
Plasma ferritin, C-reactive protein, and adenosine deaminase levels in tuberculous lymphadenitis and pleuritis and their role in monitoring treatment response
Authors: Nisa Zaib un , Zeshan Basit , Ambreen Atiqa , Mustafa Tehmina 
Published: December 2024

Abstract
Background
We aimed to assess the plasma levels of ferritin, C-reactive protein (CRP), and adenosine deaminase (ADA) at baseline and their utility as biomarkers to monitor response to treatment in extrapulmonary tuberculosis (EPTB) patients.

Methods
Prospective measurements of ferritin, CRP, and ADA were done in unstimulated plasma samples of 92 EPTB (49 TB lymphadenitis and 43 TB pleuritis) patients registered for anti-TB treatment. Blood samples were taken at the start, 2, and 6 months of treatment, plasma levels of ferritin and CRP were measured by the enzyme-linked immunosorbent assay and ADA levels by kinetic chemistry method at each time point. Data was analyzed using SPSS version 22. Non-parametric tests were used for paired analysis and two groups’ comparison. Spearman’s rank test was used for correlation analysis. A Chi-square test was used for categorical variables. A p-value < 0.05 was considered statistically significant.

Results
Before the start of treatment, plasma levels of ferritin were raised in 13% and 45%, CRP in 21% and 64%, and ADA in 70% and 60% of TB lymphadenitis and pleuritis cases respectively. Levels of all three biomarkers with raised values at baseline decreased significantly with treatment at both 2 and 6 months in all patients. [Ferritin (2 months p = 0.001, 6 months p < 0.001), CRP (2 months p < 0.001, 6 months p < 0.001), ADA (2 months p = 0.039, 6 months p < 0.004)]. Plasma levels of ferritin (median 300 ng/ml range = 145–758 ng/ml) and CRP (median 11.73 mg/L, range = 10.45–17.84 mg/L) were significantly higher in TB pleuritis patients, while the levels of ADA were not significantly different among the two groups. Biosignatures generated by different combinations showed that a combination of all three biomarkers could predict treatment response in 83% and 100% of all patients at 2 and 6 months of treatment respectively.

Conclusion
A combination of serum ferritin, CRP, and ADA shows a promising role in monitoring response to treatment in TB lymphadenitis and TB pleuritis patients. Similar studies in larger cohorts are needed to establish a definite role of these biomarkers in EPTB patients.
Reduced oxycodone brain delivery in rats due to lipopolysaccharide-induced inflammation: microdialysis insights into brain disposition and sex-specific pharmacokinetics
Authors: Bällgren Frida , Hammarlund-Udenaes Margareta , Loryan Irena 
Published: December 2024

Abstract
Background
Oxycodone, a widely used opioid analgesic, has an unbound brain-to-plasma concentration ratio (Kp,uu) greater than unity, indicating active uptake across brain barriers associated with the putative proton-coupled organic cation (H+/OC) antiporter system. With this study, we aimed to elucidate oxycodone's CNS disposition during lipopolysaccharide (LPS)-induced systemic inflammation in Sprague–Dawley rats.

Methods
Using brain microdialysis, we dynamically and simultaneously monitored unbound oxycodone concentrations in blood, striatum, lateral ventricle, and cisterna magna following intravenous administration of oxycodone post-LPS challenge.

Results
Our results indicated a reduced, sex-independent brain net uptake of oxycodone across the blood–brain barrier (BBB) measured in the striatum. Notably, the LPS challenge has significantly altered the systemic pharmacokinetics (PK) of oxycodone, in a sex-specific manner, leading to lower clearance and higher blood concentrations in females compared to LPS-treated males and healthy rats of both sexes. Proteomic analysis using Olink Target 96 Mouse Exploratory assay confirmed the induction of systemic inflammation and neuroinflammation. The inflammation led to an increased paracellular transport, measured using 4 kDa dextran, while preserving net active uptake of oxycodone across both BBB and the blood-cerebrospinal fluid barrier (BCSFB), with Kp,uu values of 2.7 and 2.5, respectively. The extent of uptake was 1.6-fold lower (p < 0.0001) at the BBB and unchanged at the BCSFB after the LPS challenge compared to that in healthy rats. However, the mean exposure of unbound oxycodone in the brain following LPS was similar to that in healthy rats, primarily due to the LPS-induced changes in systemic exposure.

Conclusions
These findings highlight the dissimilar responses at blood–brain interfaces during LPS-induced inflammation. Advancing the knowledge of neuropharmacokinetic mechanisms, specifically those involving the H+/OC antiporter system, will enable the development of more effective therapeutic strategies during inflammation conditions.

Graphical Abstract
Sexual dimorphism in the effects of maternal adipose tissue growth hormone receptor deficiency on offspring metabolic health
Authors: Ran Liyuan , Wang Xiaoshuang , Ma Rui , Wang Haoan , Wu Yingjie , Yu Zichao 
Published: December 2024

Abstract
Background
The global incidence of obesity continues to rise, which increases the prevalence of metabolic diseases. We previously demonstrated the beneficial effect of adipose-specific growth hormone receptor (Ghr) knockout (KO) on metabolic parameters in male mice exposed to high fat diet. Although the effect of the growth hormone (GH) axis on lipid metabolism has been well studied, sexual dimorphism has not been considered. Furthermore, the effects of the GH axis on intergenerational adipose development are understudied. The present study aimed to evaluate whether adipose-specific Ghr knockout is associated with sex-specific differences in metabolic health of female offspring.

Methods
Ghrflox/flox (LL) mice were crossed with Adipoq-Cre mice to generate adipose-specific Ghr knockout (KO) mice. Physiological phenotype and fertility of female LL and KO mice were measured. Body weight, organ weight, glucose homeostasis, liver and adipose histology, hepatic triglycerides (TG) content, serum TG and low-density lipoprotein cholesterol (LDL-C) levels of female offspring were detected.

Results
We found an increase in adipocyte size in female KO mice, but no change in glucose tolerance or insulin sensitivity. Adipose-specific Ghr deficiency impairs fertility in female KO mice. Maternal adipose-specific Ghr deficiency had a considerable beneficial effect on glucose metabolism in female offspring. The female offspring of the KO mice were protected against diet-induced obesity and the degree of hepatic steatosis and hyperlipidemia was reduced. The adipocyte size of the KO offspring did not change significantly despite the decrease in fat weight. Furthermore, the phenotypes of the offspring of LL mice fostered by the KO mothers differed from those of offspring remaining in the maternal nest.

Conclusions
The findings of our study suggest that adipose GH axis plays a complex and important role in the intergenerational effects of metabolic health and adipocytes on offspring in a sex-specific manner. Future studies are needed to reveal the mechanisms of these sexually dimorphic phenotypes and the feasibility of providing new interventions for improving offspring metabolic health.