bluuebunny/crossref_metadata_2025_split huggingface dataset:
The application of spatial measures to analyse health service accessibility in Australia: a systematic review and recommendations for future practice
Authors: Wood Sarah M. , Alston Laura , Beks Hannah , Mc Namara Kevin , Coffee Neil T. , Clark Robyn A. , Wong Shee Anna , Versace Vincent L. 
Published: April 2023

Abstract
Background
Australia's inequitable distribution of health services is well documented. Spatial access relates to the geographic limitations affecting the availability and accessibility of healthcare practitioners and services. Issues associated with spatial access are often influenced by Australia's vast landmass, challenging environments, uneven population concentration, and sparsely distributed populations in rural and remote areas. Measuring access contributes to a broader understanding of the performance of health systems, particularly in rural/remote areas. This systematic review synthesises the evidence identifying what spatial measures and geographic classifications are used and how they are applied in the Australian peer-reviewed literature.

Methods
A systematic search of peer-reviewed literature published between 2002 and 2022 was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Search terms were derived from three major topics, including: [1] Australian population; [2] spatial analysis of health service accessibility; and [3] objective physical access measures.

Results
Database searches retrieved 1,381 unique records. Records were screened for eligibility, resulting in 82 articles for inclusion. Most articles analysed access to primary health services (n = 50; 61%), followed by specialist care (n = 17; 21%), hospital services (n = 12; 15%), and health promotion and prevention (n = 3; 4%). The geographic scope of the 82 articles included national (n = 33; 40%), state (n = 27; 33%), metropolitan (n = 18; 22%), and specified regional / rural /remote area (n = 4; 5%). Most articles used distance-based physical access measures, including travel time (n = 30; 37%) and travel distance along a road network (n = 21; 26%), and Euclidean distance (n = 24; 29%).

Conclusion
This review is the first comprehensive systematic review to synthesise the evidence on how spatial measures have been applied to measure health service accessibility in the Australian context over the past two decades. Objective and transparent access measures that are fit for purpose are imperative to address persistent health inequities and inform equitable resource distribution and evidence-based policymaking.
Effect of improvement measures in reducing interruptions in a Japanese hospital pharmacy using a synthetic approach based on resilience engineering and systems thinking
Authors: Kojima Takahiro , Kinoshita Noriyasu , Kitamura Harumi , Tanaka Koji , Tokunaga Ayumi , Nakagawa Satoshi , Abe Takeru , Nakajima Kazue 
Published: April 2023

Abstract
Background
Workflow interruptions in pharmacies contribute to dispensing errors, a high-priority issue in patient safety, but have rarely been studied from a systemic perspective partly because of the limitations of the conventional reductionistic approach. This study aims to identify a mechanism for the occurrence of interruptions in a hospital pharmacy and find interventional points using a synthetic approach based on resilience engineering and systems thinking, and assess implemented measures for reducing them.

Methods
At a Japanese university hospital, we gathered information about performance adjustments of pharmacists in the inpatient medication dispensing unit for oral and topical medicines (IMDU-OT) and nurses in the inpatient wards (IPWs) in the medication dispensing and delivery process. Data about the workload and workforce of pharmacists were collected from hospital information systems. Telephone inquiries and counter services in the IMDU-OT, the primary sources of interruptions to pharmacists' work, were documented. The feedback structure between the IMDU-OT and the IPWs was analyzed using a causal loop diagram to identify interventional points. The numbers of telephone calls and counter services were measured cross-sectionally before (February 2017) and four months after implementing measures (July 2020).

Results
This study found that interruptions are a systemic problem emerging from the adaptive behavior of pharmacists and nurses to their work constraints, such as short staffing of pharmacists, which limited the frequency of medication deliveries to IPWs, and lack of information about the medication dispensing status for nurses. Measures for mitigating cross-system performance adjustments—a medication dispensing tracking system for nurses, request-based extra medication delivery, and pass boxes for earlier pick-up of medicines—were introduced. Following their implementation, the daily median number of telephone calls and counter services was significantly reduced (43 to 18 and 55 to 15, respectively), resulting in a 60% reduction in the total number of interruptions.

Conclusion
This study found interruptions in the hospital pharmacy as a systemic problem that can be reduced by mitigating difficulties being compensated for by clinicians' cross-system performance adjustments. Our findings suggest that a synthetic approach can be effective for solving complex problems and have implications for methodological guidance for Safety-II in practice.
Plasmodium falciparum gametocytes display global chromatin remodelling during sexual differentiation
Authors: Jeninga Myriam D. , Tang Jingyi , Selvarajah Shamista A. , Maier Alexander G. , Duffy Michael F. , Petter Michaela 
Published: April 2023

Abstract
Background
The protozoan malaria parasite Plasmodium falciparum has a complex life cycle during which it needs to differentiate into multiple morphologically distinct life forms. A key process for transmission of the disease is the development of male and female gametocytes in the human blood, yet the mechanisms determining sexual dimorphism in these haploid, genetically identical sexual precursor cells remain largely unknown. To understand the epigenetic program underlying the differentiation of male and female gametocytes, we separated the two sexual forms by flow cytometry and performed RNAseq as well as comprehensive ChIPseq profiling of several histone variants and modifications.

Results
We show that in female gametocytes the chromatin landscape is globally remodelled with respect to genome-wide patterns and combinatorial usage of histone variants and histone modifications. We identified sex specific differences in heterochromatin distribution, implicating exported proteins and ncRNAs in sex determination. Specifically in female gametocytes, the histone variants H2A.Z/H2B.Z were highly enriched in H3K9me3-associated heterochromatin. H3K27ac occupancy correlated with stage-specific gene expression, but in contrast to asexual parasites this was unlinked to H3K4me3 co-occupancy at promoters in female gametocytes.

Conclusions
Collectively, we defined novel combinatorial chromatin states differentially organising the genome in gametocytes and asexual parasites and unravelled fundamental, sex-specific differences in the epigenetic code. Our chromatin maps represent an important resource for future understanding of the mechanisms driving sexual differentiation in P. falciparum.
Stress decreases spermatozoa quality and induces molecular alterations in zebrafish progeny
Authors: Valcarce David G. , Riesco Marta F. , Cuesta-Martín Leyre , Esteve-Codina Anna , Martínez-Vázquez Juan Manuel , Robles Vanesa 
Published: April 2023

Abstract
Background
Chronic stress can produce a severe negative impact on health not only in the exposed individuals but also in their offspring. Indeed, chronic stress may be contributing to the current worldwide scenario of increasing infertility and decreasing gamete quality in human populations. Here, we evaluate the effect of chronic stress on behavior and male reproductive parameters in zebrafish. Our goal is to provide information on the impact that chronic stress has at molecular, histological, and physiological level in a vertebrate model species.

Results
We evaluated the effects of a 21-day chronic stress protocol covering around three full waves of spermatogenesis in Danio rerio adult males. The induction of chronic stress produced anxiety-like behavior in stressed males as assessed by a novel tank test. At a molecular level, the induction of chronic stress consistently resulted in the overexpression of two genes related to endoplasmic reticulum (ER) stress in the brain. Gene set enrichment analysis (GSEA) of testes suggested a dysregulation of the nonsense-mediated decay (NMD) pathway, which was also confirmed on qPCR analysis. Histological analysis of the testicle did not show significant differences in terms of the relative proportions of each germ-cell type; however, the quality of sperm from stressed males was compromised in terms of motility. RNA-seq analysis in stress-derived larval progenies revealed molecular alterations, including those predicted to affect translation initiation, DNA repair, cell cycle control, and response to stress.

Conclusions
Induction of chronic stress during a few cycles of spermatogenesis in the vertebrate zebrafish model affects behavior, gonadal gene expression, final gamete quality, and progeny. The NMD surveillance pathway (a key cellular mechanism that regulates the stability of both normal and mutant transcripts) is severely affected in the testes by chronic stress and therefore the control and regulation of RNAs during spermatogenesis may be affected altering the molecular status in the progeny.

Graphical Abstract
Guanine crystal formation by bacteria
Authors: Pavan María Elisa , Movilla Federico , Pavan Esteban E. , Di Salvo Florencia , López Nancy I. , Pettinari M. Julia 
Published: April 2023

Abstract
Background
Guanine crystals are organic biogenic crystals found in many organisms. Due to their exceptionally high refractive index, they contribute to structural color and are responsible for the reflective effect in the skin and visual organs in animals such as fish, reptiles, and spiders. Occurrence of these crystals in animals has been known for many years, and they have also been observed in eukaryotic microorganisms, but not in prokaryotes.

Results
In this work, we report the discovery of extracellular crystals formed by bacteria and reveal that they are composed of guanine monohydrate. This composition differs from that of biogenic guanine crystals found in other organisms, mostly composed of β anhydrous guanine. We demonstrate the formation of these crystals by Aeromonas and other bacteria and investigate the metabolic traits related to their synthesis. In all cases studied, the presence of the bacterial guanine crystals correlates with the absence of guanine deaminase, which could lead to guanine accumulation providing the substrate for crystal formation.

Conclusions
Our finding of the hitherto unknown guanine crystal occurrence in prokaryotes extends the range of organisms that produce these crystals to a new domain of life. Bacteria constitute a novel and more accessible model to study the process of guanine crystal formation and assembly. This discovery opens countless chemical and biological questions, including those about the functional and adaptive significance of their production in these microorganisms. It also paves the road for the development of simple and convenient processes to obtain biogenic guanine crystals for diverse applications.
Identifying the causal effects of long-term exposure to PM2.5 and ground surface ozone on individual medical costs in China—evidence from a representative longitudinal nationwide cohort
Authors: Ju Ke , Lu Liyong , Yang Jingguo , Chen Ting , Lan Tianjiao , Duan Zhongxin , Xu Zongyou , Zhang En , Wang Wen , Pan Jay 
Published: April 2023

Abstract
Background
There is little evidence on whether PM2.5 and ground surface ozone have consistent effects on increased individual medical costs, and there is a lack of evidence on causality in developing countries.

Methods
This study utilized balanced panel data from 2014, 2016, and 2018 waves of the Chinese Family Panel Study. The Tobit model was developed within a counterfactual causal inference framework, combined with a correlated random effects and control function approach (Tobit-CRE-CF), to explore the causal relationship between long-term exposure to air pollution and medical costs. We also explored whether different air pollutants exhibit comparable effects.

Results
This study encompassed 8928 participants and assessed various benchmark models, highlighting the potential biases from failing to account for air pollution endogeneity or overlooking respondents without medical costs. Using the Tobit-CRE-CF model, significant effects of air pollutants on increased individual medical costs were identified. Specifically, margin effects for PM2.5 and ground-level ozone signifying that a unit increase in PM2.5 and ground-level ozone results in increased total medical costs of 199.144 and 75.145 RMB for individuals who incurred fees in the previous year, respectively.

Conclusions
The results imply that long-term exposure to air pollutants contributes to increased medical costs for individuals, offering valuable insights for policymakers aiming to mitigate air pollution’s consequences.
Xp22.31 copy number variations in 87 fetuses: refined genotype–phenotype correlations by prenatal and postnatal follow-up
Authors: Hu Huamei , Huang Yulin , Hou Renke , Xu Huanhuan , Liu Yalan , Liao Xueqian , Xu Juchun , Jiang Lupin , Wang Dan 
Published: April 2023

Abstract
Background
Xp22.31 deletion and duplication have been described in various studies, but different laboratories interpret pathogenicity differently.

Objectives
Our study aimed to refine the genotype–phenotype associations between Xp22.31 copy number variants in fetuses, with the aim of providing data support to genetic counseling.

Methods
We retrospectively analyzed karyotyping and single nucleotide polymorphism array results from 87 fetuses and their family members. Phenotypic data were obtained through follow-up visits.

Results
The percentage of fetuses carrying the Xp22.31 deletions (9 females, 12 males) was 24.1% (n = 21), while duplications (38 females, 28 males) accounted for 75.9% (n = 66). Here, we noted that the typical region (from 6.4 to 8.1 Mb, hg19) was detected in the highest ratio, either in the fetuses with deletions (76.2%, 16 of 21) or duplications (69.7%, 46 of 66). In female deletion carriers, termination of pregnancy was chosen for two fetuses, and the remaining seven were born without distinct phenotypic abnormalities. In male deletion carriers, termination of pregnancy was chosen for four fetuses, and the remaining eight of them displayed ichthyosis without neurodevelopmental anomalies. In two of these cases, the chromosomal imbalance was inherited from the maternal grandfathers, who also only had ichthyosis phenotypes. Among the 66 duplication carriers, two cases were lost at follow-up, and pregnancy was terminated for eight cases. There were no other clinical findings in the rest of the 56 fetuses, including two with Xp22.31 tetrasomy, for either male or female carriers.

Conclusion
Our observations provide support for genetic counseling in male and female carriers of Xp22.31 copy number variants. Most of them are asymptomatic in male deletion carriers, except for skin findings. Our study is consistent with the view that the Xp22.31 duplication may be a benign variant in both sexes.
Potential diagnostic value of N1LR and SNHG1 in acute myocardial infarction
Authors: Zhu Wei , Luo Li , Ye Guangning , Ou Jiaman 
Published: April 2023

Abstract
Introduction
Acute myocardial infarction (AMI) is a common cardiovascular disease that can lead to myocardial necrosis and a poor prognosis. Clinical practice requires an accurate and quick diagnosis of AMI due to the inherent limitations of current biomarkers. Therefore, research into novel biomarkers is necessary. We aimed to explore the diagnostic potency of the long non-coding RNA (lncRNA) N1LR and SNHG1 in patients diagnosed with AMI.

Method
We measured lncRNA levels in 148 AMI patients and 50 healthy volunteers with quantitative RT-PCR method. Receiver operating characteristic (ROC) analysis was administered to detect the diagnostic power of selected lncRNAs. Correlation analysis was performed to explore the relationship between N1LR as well as SNHG1 and the conventional myocardial biomarkers (LDH, CK, CKMB and cTnI).

Results
ROC analysis reveals the possibility of N1LR and SNHG1 as biomarkers in AMI diagnosis (AUC of N1LR: 0.873; AUC of SNHG1: 0.890). Correlation analysis revealed that N1LR was negatively correlated with the conventional biomarkers and SNHG1 was positively correlated with the conventional biomarkers.

Conclusion
For the first time, we investigated the potential predictive diagnostic value of N1LR and SNHG1 in AMI diagnosis and substantial outcomes were obtained. Also, they may be capable of reflecting the progress of the disease during clinical practice from the correlation analysis.
Phenotypic and genotypic characterization of linezolid resistance and the effect of antibiotic combinations on methicillin-resistant Staphylococcus aureus clinical isolates
Authors: AbdAlhafiz Asmaa I. , Elleboudy Nooran S. , Aboshanab Khaled M. , Aboulwafa Mohammad M. , Hassouna Nadia A. 
Published: April 2023

Abstract
Background
Methicillin-Resistant Staphylococcus aureus (MRSA) causes life-threatening infections, with narrow therapeutic options including: vancomycin and linezolid. Accordingly, this study aimed to characterize phenotypically and genotypically, the most relevant means of linezolid resistance among some MRSA clinical isolates.

Methods
A total of 159 methicillin-resistant clinical isolates were collected, of which 146 were indentified microscopically and biochemically as MRSA. Both biofilm formation and efflux pump activity were assessed for linezolid-resistant MRSA (LR-MRSA) using the microtiter plate and carbonyl cyanide 3-chlorophenylhydrazone (CCCP) methods, respectively. Linezolid resistance was further characterized by polymerase chain reaction (PCR) amplification and sequencing of domain V of 23 S rRNA; rplC; rplD;and rplV genes. Meanwhile, some resistance genes were investigated: cfr; cfr(B); optrA; msrA;mecA; and vanA genes. To combat LR-MRSA, the effect of combining linezolid with each of 6 different antimicrobials was investigated using the checkerboard assay.

Results
Out of the collected MRSA isolates (n = 146), 5.48% (n = 8) were LR-MRSA and 18.49% (n = 27) were vancomycin-resistant (VRSA). It is worth noting that all LR-MRSA isolates were also vancomycin-resistant. All LR-MRSA isolates were biofilm producers (r = 0.915, p = 0.001), while efflux pumps upregulation showed no significant contribution to development of resistance (t = 1.374, p = 0.212). Both mecA and vanA genes were detected in 92.45% (n = 147) and 6.92% (n = 11) of methicillin-resistant isolates, respectively. In LR-MRSA isolates, some 23 S rRNA domain V mutations were observed: A2338T and C2610G (in 5 isolates); T2504C and G2528C (in 2 isolates); and G2576T (in 1 isolate). Amino acids substitutions were detected: in L3 protein (rplC gene) of (3 isolates) and in L4 protein (rplD gene) of (4 isolates). In addition, cfr(B) gene was detected (in 3 isolates). In 5 isolates, synergism was recorded when linezolid was combined with chloramphenicol, erythromycin, or ciprofloxacin. Reversal of linezolid resistance was observed in some LR-MRSA isolates when linezolid was combined with gentamicin or vancomycin.

Conclusions
LR-MRSA biofilm producers’ phenotypes evolved in the clinical settings in Egypt. Various antibiotic combinations with linezolid were evaluated in vitro and showed synergistic effects.
Green synthesis of glyco-CuInS2 QDs with visible/NIR dual emission for 3D multicellular tumor spheroid and in vivo imaging
Authors: Guan Xiaolin , Zhang Liyuan , Lai Shoujun , Zhang Jiaming , Wei Jingyu , Wang Kang , Zhang Wentao , Li Chenghao , Tong Jinhui , Lei Ziqiang 
Published: April 2023

AbstractGlyco-quantum dots (glyco-QDs) have attracted significant interest in bioimaging applications, notably in cancer imaging, because they effectively combine the glycocluster effect with the exceptional optical properties of QDs. The key challenge now lies in how to eliminate the high heavy metal toxicity originating from traditional toxic Cd-based QDs for in vivo bioimaging. Herein, we report an eco-friendly pathway to prepare nontoxic Cd-free glyco-QDs in water by the “direct” reaction of thiol-ending monosaccharides with metal salts precursors. The formation of glyco-CuInS2 QDs could be explained by a nucleation-growth mechanism following the LaMer model. As-prepared four glyco-CuInS2 QDs were water-soluble, monodispersed, spherical in shape and exhibited size range of 3.0–4.0 nm. They exhibited well-separated dual emission in the visible region (500–590 nm) and near-infrared range (~ 827 nm), which may be attributable to visible excitonic emission and near-infrared surface defect emission. Meanwhile, the cell imaging displayed the reversibly distinct dual-color (green and red) fluorescence in tumor cells (HeLa, A549, MKN-45) and excellent membrane-targeting properties of glyco-CuInS2 QDs based on their good biorecognition ability. Importantly, these QDs succeed in penetrating uniformly into the interior (the necrotic zone) of 3D multicellular tumor spheroids (MCTS) due to their high negative charge (zeta potential values ranging from − 23.9 to − 30.1 mV), which overcame the problem of poor penetration depth of existing QDs in in vitro spheroid models. So, confocal analysis confirmed their excellent ability to penetrate and label tumors. Thus, the successful application in in vivo bioimaging of these glyco-QDs verified that this design strategy is an effective, low cost and simple procedure for developing green nanoparticles as cheap and promising fluorescent bioprobes.