bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does a GP service package matter in addressing the absence of health management by the occupational population? A modelling study
Authors: Guo Jing , Qian Ying , Chen Chen , Liang Hong , Huang Jiaoling 
Published: May 2024

Abstract
Objective
To assess the influence of supply and demand factors on the contract behavior of occupational populations with general practitioner (GP) teams.

Methods
We employed a system dynamics approach to assess and predict the effect of the general practitioner service package (GPSP) and complementary incentive policies on the contract rate for 2015–2030. First, the GPSP is designed to address the unique needs of occupational populations, enhancing the attractiveness of GP contracting services, including three personalized service contents tailored to demand-side considerations: work-related disease prevention (WDP), health education & counseling (HEC), and health-care service (HCS). Second, the complementary incentive policies on the supply-side included income incentives (II), job title promotion (JTP), and education & training (ET). Considering the team collaboration, the income distribution ratio (IDR) was also incorporated into supply-side factors.

Findings
The contract rate is predicted to increase to 57.8% by 2030 after the GPSP intervention, representing a 15.4% increase on the non-intervention scenario. WDP and HEC have a slightly higher (by 2%) impact on the contract rate than that from HCS. Regarding the supply-side policies, II have a more significant impact on the contract rate than JTP and ET by 3–5%. The maximum predicted contract rate of 75.2% is expected by 2030 when the IDR is 0.5, i.e., the GP receives 50% of the contract income and other members share 50%.

Conclusion
The GP service package favorably increased the contract rate among occupational population, particularly after integrating the incentive policies. Specifically, for a given demand level, the targeted content of the package enhanced the attractiveness of contract services. On the supply side, the incentive policies boost GPs’ motivation, and the income distribution motivated other team members.
Key issues in Japan’s public health centers to prepare for future pandemics: a text mining study using a topic model
Authors: Sakai Kosuke , Igarashi Yu , Tounai Shuji , Shirai Chika , Tsurugi Yoko , Kakuno Fumihiko , Komasa Yukako , Fujimura Maya , Uruha Mika , Mori Koji , Tateishi Seiichiro 
Published: May 2024

Abstract
Background
In Japan, over 450 public health centers played a central role in the operation of the local public health system in response to the COVID-19 pandemic. This study aimed to identify key issues for improving the system for public health centers for future pandemics.

Methods
We conducted a cross-sectional study using an online questionnaire. The respondents were first line workers in public health centers or local governments during the pandemic. We solicited open-ended responses concerning improvements needed for future pandemics. Issues were identified from these descriptions using morphological analysis and a topic model with KHcoder3.0. The number of topics was estimated using Perplexity as a measure, and Latent Dirichlet Allocation for meaning identification.

Results
We received open-ended responses from 784 (48.6%) of the 1,612 survey respondents, which included 111 physicians, 330 nurses, and 172 administrative staff. Morphological analysis processed these descriptions into 36,632 words. The topic model summarized them into eight issues: 1) establishment of a crisis management system, 2) division of functions among public health centers, prefectures, and medical institutions, 3) clear role distribution in public health center staff, 4) training of specialists, 5) information sharing system (information about infectious diseases and government policies), 6) response to excessive workload (support from other local governments, cooperation within public health centers, and outsourcing), 7) streamlining operations, and 8) balance with regular duties.

Conclusions
This study identified key issues that need to be addressed to prepare Japan’s public health centers for future pandemics. These findings are vital for discussions aimed at strengthening the public health system based on experiences from the COVID-19 pandemic.
Metabolic profile and gene expression pattern of cytokines and antioxidants markers during different physiological stages in Barki ewes
Authors: El-Sayed Ahmed Adel , Sallam Ahmed M. , Abou-Soliman Ibrahim 
Published: May 2024

Abstract
Background
In livestock, identifying the physiological and reproductive stages is valuable in guiding management decisions related to nutrition, veterinary procedures, and breeding programs. To achieve this goal, a cohort of Barki ewes in this research underwent observation across three pivotal physiological conditions: pre-pregnancy, late pregnancy, and early lactation. Blood samples were collected to investigate the changes in serum metabolic profile as well as gene expression pattern of cytokines and antioxidants markers during these stages.

Results
Our results showed that during late pregnancy, there was a significant (P < 0.05) increase in red blood cells (11.9 ± 0.5 1012/L), hemoglobin (10.8 ± 0.4 g/dl) and neutrophils count (7 ± 0.1 109/L) with significant decrease (P < 0.05) of total white blood cell count (9.1 ± 0.05 109/L). The packed cell volume (%) and monocyte count showed a significant (P < 0.05) decrease during both late pregnancy and early lactation stages. The serum concentrations of glucose, cholesterol, GSH, GPx, SOD and catalase displayed significant (P < 0.05) decrease during late pregnancy and early-lactation. Notably, during late pregnancy, there was a significant (P < 0.05) increase in the serum concentrations of albumin, globulin, urea, IGF-1, and malondialdehyde with significant decrease (P < 0.05) of total protein (4.9 ± 0.08 g/dl). Additionally, during early lactation, there was a significant (P < 0.05) increase in the serum levels of non-esterified fatty acids, triiodothyronine (T3), and thyroxin (T4). The gene expression profiles of cytokines (IL-4, IL-6, IL-8, and NFKB) were decreased in the ewes during late pregnancy compared to pre-pregnant and early lactation stages. In addition, the expression profile of antioxidant genes (SOD, CAT, GPX, and Nrf2) was significantly upsurged in the non-pregnant ewes compared to late pregnancy and early lactation ones.

Conclusions
The results concluded that different physiological status significantly affects the blood metabolic profile and gene expression pattern in Barki sheep. Our findings can be helpful in monitoring animal health and applying in breeding programs of Barki sheep under harsh environmental conditions.
Biosynthesis of photostable CdS quantum dots by UV-resistant psychrotolerant bacteria isolated from Union Glacier, Antarctica
Authors: Vargas-Reyes Matías , Bruna Nicolás , Ramos-Zúñiga Javiera , Valenzuela-Ibaceta Felipe , Rivas-Álvarez Paula , Navarro Claudio A. , Pérez-Donoso José M. 
Published: May 2024

Abstract
Background
Quantum Dots (QDs) are fluorescent nanoparticles with exceptional optical and optoelectronic properties, finding widespread utility in diverse industrial applications. Presently, chemically synthesized QDs are employed in solar cells, bioimaging, and various technological domains. However, many applications demand QDs with prolonged lifespans under conditions of high-energy radiation. Over the past decade, microbial biosynthesis of nanomaterials has emerged as a sustainable and cost-effective process. In this context, the utilization of extremophile microorganisms for synthesizing QDs with unique properties has recently been reported.

Results
In this study, UV-resistant bacteria were isolated from one of the most extreme environments in Antarctica, Union Glacier at the Ellsworth Mountains. Bacterial isolates, identified through 16 S sequencing, belong to the genera Rhodococcus, Pseudarthrobacter, and Arthrobacter. Notably, Rhodococcus sp. (EXRC-4 A-4), Pseudarthrobacter sp. (RC-2-3), and Arthrobacter sp. (EH-1B-1) tolerate UV-C radiation doses ≥ 120 J/m². Isolated UV-resistant bacteria biosynthesized CdS QDs with fluorescence intensities 4 to 8 times higher than those biosynthesized by E. coli, a mesophilic organism tolerating low doses of UV radiation. Transmission electron microscopy (TEM) analysis determined QD sizes ranging from 6 to 23 nm, and Fourier-transform infrared (FTIR) analysis demonstrated the presence of biomolecules. QDs produced by UV-resistant Antarctic bacteria exhibit high photostability after exposure to UV-B radiation, particularly in comparison to those biosynthesized by E. coli. Interestingly, red fluorescence-emitting QDs biosynthesized by Rhodococcus sp. (EXRC-4 A-4) and Arthrobacter sp. (EH-1B-1) increased their fluorescence emission after irradiation. Analysis of methylene blue degradation after exposure to irradiated QDs biosynthesized by UV-resistant bacteria, indicates that the QDs transfer their electrons to O2 for the formation of reactive oxygen species (ROS) at different levels.

Conclusions
UV-resistant Antarctic bacteria represent a novel alternative for the sustainable generation of nanostructures with increased radiation tolerance—two characteristics favoring their potential application in technologies requiring continuous exposure to high-energy radiation.

Graphical abstract
Low expression of ELOVL6 may be involved in fat loss in white adipose tissue of cancer-associated cachexia
Authors: Jin Chenyang , Wang Shuangjie , Sui Xiangyu , Meng Qingyang , Wu Guohao 
Published: May 2024

Abstract
Background
Cancer-associated cachexia (CAC) arises from malignant tumors and leads to a debilitating wasting syndrome. In the pathophysiology of CAC, the depletion of fat plays an important role. The mechanisms of CAC-induced fat loss include the enhancement of lipolysis, inhibition of lipogenesis, and browning of white adipose tissue (WAT). However, few lipid-metabolic enzymes have been reported to be involved in CAC. This study hypothesized that ELOVL6, a critical enzyme for the elongation of fatty acids, may be involved in fat loss in CAC.

Methods
Transcriptome sequencing technology was used to identify CAC-related genes in the WAT of a CAC rodent model. Then, the expression level of ELOVL6 and the fatty acid composition were analyzed in a large clinical sample. Elovl6 was knocked down by siRNA in 3T3-L1 mouse preadipocytes to compare with wild-type 3T3-L1 cells treated with tumor cell conditioned medium.

Results
In the WAT of patients with CAC, a significant decrease in the expression of ELOVL6 was found, which was linearly correlated with the extent of body mass reduction. Gas chromatographic analysis revealed an increase in palmitic acid (C16:0) and a decrease in linoleic acid (C18:2n-6) in these tissue samples. After treatment with tumor cell-conditioned medium, 3T3-L1 mouse preadipocytes showed a decrease in Elovl6 expression, and Elovl6-knockdown cells exhibited a reduction in preadipocyte differentiation and lipogenesis. Similarly, the knockdown of Elovl6 in 3T3-L1 cells resulted in a significant increase in palmitic acid (C16:0) and a marked decrease in oleic acid (C18:1n-9) content.

Conclusion
Overall, the expression of ELOVL6 was decreased in the WAT of CAC patients. Decreased expression of ELOVL6 might induce fat loss in CAC patients by potentially altering the fatty acid composition of adipocytes. These findings suggest that ELOVL6 may be used as a valuable biomarker for the early diagnosis of CAC and may hold promise as a target for future therapies.
Brain-targeted drug delivery - nanovesicles directed to specific brain cells by brain-targeting ligands
Authors: Moreira Ricardo , Nóbrega Clévio , de Almeida Luís Pereira , Mendonça Liliana 
Published: May 2024

AbstractNeurodegenerative diseases are characterized by extensive loss of function or death of brain cells, hampering the life quality of patients. Brain-targeted drug delivery is challenging, with a low success rate this far. Therefore, the application of targeting ligands in drug vehicles, such as lipid-based and polymeric nanoparticles, holds the promise to overcome the blood-brain barrier (BBB) and direct therapies to the brain, in addition to protect their cargo from degradation and metabolization. In this review, we discuss the barriers to brain delivery and the different types of brain-targeting ligands currently in use in brain-targeted nanoparticles, such as peptides, proteins, aptamers, small molecules, and antibodies. Moreover, we present a detailed review of the different targeting ligands used to direct nanoparticles to specific brain cells, like neurons (C4-3 aptamer, neurotensin, Tet-1, RVG, and IKRG peptides), astrocytes (Aquaporin-4, D4, and Bradykinin B2 antibodies), oligodendrocytes (NG-2 antibody and the biotinylated DNA aptamer conjugated to a streptavidin core Myaptavin-3064), microglia (CD11b antibody), neural stem cells (QTRFLLH, VPTQSSG, and NFL-TBS.40–63 peptides), and to endothelial cells of the BBB (transferrin and insulin proteins, and choline). Reports demonstrated enhanced brain-targeted delivery with improved transport to the specific cell type targeted with the conjugation of these ligands to nanoparticles. Hence, this strategy allows the implementation of high-precision medicine, with reduced side effects or unwanted therapy clearance from the body. Nevertheless, the accumulation of some of these nanoparticles in peripheral organs has been reported indicating that there are still factors to be improved to achieve higher levels of brain targeting. This review is a collection of studies exploring targeting ligands for the delivery of nanoparticles to the brain and we highlight the advantages and limitations of this type of approach in precision therapies.
High-density lipoprotein mimetic nano-therapeutics targeting monocytes and macrophages for improved cardiovascular care: a comprehensive review
Authors: Zhen Juan , Li Xiangjun , Yu Haitao , Du Bing 
Published: May 2024

AbstractThe prevalence of cardiovascular diseases continues to be a challenge for global health, necessitating innovative solutions. The potential of high-density lipoprotein (HDL) mimetic nanotherapeutics in the context of cardiovascular disease and the intricate mechanisms underlying the interactions between monocyte-derived cells and HDL mimetic showing their impact on inflammation, cellular lipid metabolism, and the progression of atherosclerotic plaque. Preclinical studies have demonstrated that HDL mimetic nanotherapeutics can regulate monocyte recruitment and macrophage polarization towards an anti-inflammatory phenotype, suggesting their potential to impede the progression of atherosclerosis. The challenges and opportunities associated with the clinical application of HDL mimetic nanotherapeutics, emphasize the need for additional research to gain a better understanding of the precise molecular pathways and long-term effects of these nanotherapeutics on monocytes and macrophages to maximize their therapeutic efficacy. Furthermore, the use of nanotechnology in the treatment of cardiovascular diseases highlights the potential of nanoparticles for targeted treatments. Moreover, the concept of theranostics combines therapy and diagnosis to create a selective platform for the conversion of traditional therapeutic medications into specialized and customized treatments. The multifaceted contributions of HDL to cardiovascular and metabolic health via highlight its potential to improve plaque stability and avert atherosclerosis-related problems. There is a need for further research to maximize the therapeutic efficacy of HDL mimetic nanotherapeutics and to develop targeted treatment approaches to prevent atherosclerosis. This review provides a comprehensive overview of the potential of nanotherapeutics in the treatment of cardiovascular diseases, emphasizing the need for innovative solutions to address the challenges posed by cardiovascular diseases.
Toxicological inhalation studies in rats to substantiate grouping of zinc oxide nanoforms
Authors: Thoma Tizia , Ma-Hock Lan , Schneider Steffen , Honarvar Naveed , Treumann Silke , Groeters Sibylle , Strauss Volker , Marxfeld Heike , Funk-Weyer Dorothee , Seiffert Svenja , Wohlleben Wendel , Dammann Martina , Wiench Karin , Lombaert Noömi , Spirlet Christine , Vasquez Marie , Dewhurst Nicole , Landsiedel Robert 
Published: May 2024

Abstract
Background
Significant variations exist in the forms of ZnO, making it impossible to test all forms in in vivo inhalation studies. Hence, grouping and read-across is a common approach under REACH to evaluate the toxicological profile of familiar substances. The objective of this paper is to investigate the potential role of dissolution, size, or coating in grouping ZnO (nano)forms for the purpose of hazard assessment. We performed a 90-day inhalation study (OECD test guideline no. (TG) 413) in rats combined with a reproduction/developmental (neuro)toxicity screening test (TG 421/424/426) with coated and uncoated ZnO nanoforms in comparison with microscale ZnO particles and soluble zinc sulfate. In addition, genotoxicity in the nasal cavity, lungs, liver, and bone marrow was examined via comet assay (TG 489) after 14-day inhalation exposure.

Results
ZnO nanoparticles caused local toxicity in the respiratory tract. Systemic effects that were not related to the local irritation were not observed. There was no indication of impaired fertility, developmental toxicity, or developmental neurotoxicity. No indication for genotoxicity of any of the test substances was observed. Local effects were similar across the different ZnO test substances and were reversible after the end of the exposure.

Conclusion
With exception of local toxicity, this study could not confirm the occasional findings in some of the previous studies regarding the above-mentioned toxicological endpoints. The two representative ZnO nanoforms and the microscale particles showed similar local effects. The ZnO nanoforms most likely exhibit their effects by zinc ions as no particles could be detected after the end of the exposure, and exposure to rapidly soluble zinc sulfate had similar effects. Obviously, material differences between the ZnO particles do not substantially alter their toxicokinetics and toxicodynamics. The grouping of ZnO nanoforms into a set of similar nanoforms is justified by these observations.
The isolation strategy and chemical analysis of oil cells from Asari Radix et Rhizoma
Authors: Hu Haibo , Liu Guangxue , Li Yaoli 
Published: May 2024

Abstract
Background
Single-cell analysis, a rapidly evolving field, encounters significant challenges in detecting individual cells within complex plant tissues, particularly oil cells (OCs). The intricate process of single-cell isolation, coupled with the inherent chemical volatility of oil cells, necessitates a comprehensive methodology.

Results
This study presents a method for obtaining intact OC from Asari Radix et Rhizoma (ARR), a traditional herbal medicine. The developed approach facilitates both qualitative and quantitative analysis of diverse OCs. To determine the most reliable approach, four practical methods—laser capture microdissection, micromanipulation capturing, micromanipulation piping, and cell picking—were systematically compared and evaluated, unequivocally establishing cell picking as the most effective method for OC isolation and chemical analysis. Microscopic observations showed that OCs predominantly distribute in the cortex of adventitious and fibrous roots, as well as the pith and cortex of the rhizome, with distinct morphologies—oblong in roots and circular in rhizomes. Sixty-three volatile constituents were identified in OCs, with eighteen compounds exhibiting significant differences. Safrole, methyleugenol, and asaricin emerged as the most abundant constituents in OCs. Notably, cis-4-thujanol and tetramethylpyrazine were exclusive to rhizome OCs, while isoeugenol methyl ether was specific to fibrous root OCs based on the detections. ARR roots and rhizomes displayed marked disparities in OC distribution, morphology, and constituents.

Conclusion
The study highlights the efficacy of cell picking coupled with HS–SPME–GC–MS as a flexible, reliable, and sensitive method for OC isolation and chemical analysis, providing a robust methodology for future endeavors in single-cell analyses.
A newborn Screening Programme for Inborn errors of metabolism in Galicia: 22 years of evaluation and follow-up
Authors: Couce María L. , Bóveda María-Dolores , Castiñeiras Daisy E. , Vázquez-Mosquera María-Eugenia , Barbosa-Gouveia Sofía , De Castro María-José , Iglesias-Rodríguez Agustin J. , Colón Cristóbal , Cocho José A. , Sánchez Paula 
Published: May 2024

Abstract
Background
There is a notable lack of harmonisation in newborn screening (NBS) programmes worldwide. The Galician programme for early detection of inborn errors of metabolism (IEM) was one of the first NBS programmes in Europe to incorporate mass spectrometry (July 2000). This programme currently screens for 26 IEMs in dried blood and urine samples collected 24–72 h after birth.

Results
In its 22-year history, this programme has analysed samples from 440,723 neonates and identified 326 cases of IEM with a prevalence of 1:1351. The most prevalent IEMs were hyperphenylalaninaemia (n = 118), followed by medium chain acyl-CoA dehydrogenase deficiency (MCADD, n = 26), galactosaemia (n = 20), and cystinurias (n = 43). Sixty-one false positives and 18 conditions related to maternal pathologies were detected. Urine samples have been identified as a useful secondary sample to reduce the rate of false positives and identify new defects. There were 5 false negatives. The overall positive value was 84.23%. The fatality rate over a median of 12.1 years of follow-up was 2.76%. The intelligence quotient of patients was normal in 95.7% of cases, and school performance was largely optimal, with pedagogic special needs assistance required in < 10% of cases. Clinical onset of disease preceded diagnosis in 4% of cases. The age at which first NBS report is performed was reduced by 4 days since 2021.

Conclusions
This study highlights the benefits of collecting urine samples, reduce NBS reporting time and expanding the number of IEMs included in NBS programmes.