bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of the workforce allocation on the technical performance of mental health services: the collective case of Helsinki-Uusimaa (Finland)
Authors: Diaz-Milanes Diego , Almeda Nerea , Gutierrez-Colosia Mencia R. , Garcia-Alonso Carlos R. , Sadeniemi Minna , Salvador-Carulla Luis 
Published: October 2023

Abstract
Background
Long-term mental health (MH) policies in Finland aimed at investing in community care and promoting reforms have led to a reduction in the number of psychiatric hospital beds. However, most resources are still allocated to hospital and community residential services due to various social, economic and political factors. Despite previous research focussing on the number and cost of these services, no study has evaluated the emerging patterns of use, their technical performance and the relationship with the workforce structure.

Objective
The purpose of this study was to observe the patterns of use and their technical performance (efficiency) of the main types of care of MH services in the Helsinki-Uusimaa region (Finland), and to analyse the potential relationship between technical performance and the corresponding workforce structure.

Methods
The sample included acute hospital residential care, non-hospital residential care and outpatient care services. The analysis was conducted using regression analysis, Monte Carlo simulation, fuzzy inference and data envelopment analysis.

Results
The analysis showed a statistically significant linear relationship between the number of service users and the length of stay, number of beds in non-hospital residential care and number of contacts in outpatient care services. The three service types displayed a similar pattern of technical performance, with high relative technical efficiency on average and a low probability of being efficient. The most efficient acute hospital and outpatient care services integrated multidisciplinary teams, while psychiatrists and nurses characterized non-hospital residential care.

Conclusions
The results indicated that the number of resources and utilization variables were linearly related to the number of users and that the relative technical efficiency of the services was similar across all types. This suggests homogenous MH management with small variations based on workforce allocation. Therefore, the distribution of workforce capacity should be considered in the development of effective policies and interventions in the southern Finnish MH system.
Circulating miR-133a-3p defines a low-risk subphenotype in patients with heart failure and central sleep apnea: a decision tree machine learning approach
Authors: de Gonzalo-Calvo David , Martinez-Camblor Pablo , Belmonte Thalia , Barbé Ferran , Duarte Kevin , Cowie Martin R. , Angermann Christiane E. , Korte Andrea , Riedel Isabelle , Labus Josephine , Koenig Wolfgang , Zannad Faiez , Thum Thomas , Bär Christian 
Published: October 2023

Abstract
Background
Patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnea (CSA) are at a very high risk of fatal outcomes.

Objective
To test whether the circulating miRNome provides additional information for risk stratification on top of clinical predictors in patients with HFrEF and CSA.

Methods
The study included patients with HFrEF and CSA from the SERVE-HF trial. A three-step protocol was applied: microRNA (miRNA) screening (n = 20), technical validation (n = 60), and biological validation (n = 587). The primary outcome was either death from any cause, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening of heart failure, whatever occurred first. MiRNA quantification was performed in plasma samples using miRNA sequencing and RT-qPCR.

Results
Circulating miR-133a-3p levels were inversely associated with the primary study outcome. Nonetheless, miR-133a-3p did not improve a previously established clinical prognostic model in terms of discrimination or reclassification. A customized regression tree model constructed using the Classification and Regression Tree (CART) algorithm identified eight patient subphenotypes with specific risk patterns based on clinical and molecular characteristics. MiR-133a-3p entered the regression tree defining the group at the lowest risk; patients with log(NT-proBNP) ≤ 6 pg/mL (miR-133a-3p levels above 1.5 arbitrary units). The overall predictive capacity of suffering the event was highly stable over the follow-up (from 0.735 to 0.767).

Conclusions
The combination of clinical information, circulating miRNAs, and decision tree learning allows the identification of specific risk subphenotypes in patients with HFrEF and CSA.
Potential regulatory role of the Nrf2/HMGB1/TLR4/NF-κB signaling pathway in lupus nephritis
Authors: Li Shi-jie , Ruan Dan-dan , Wu Wei-zhen , Wu Min , Wu Qiu-yan , Wang Han-lu , Ji Yuan-yuan , Zhang Yan-ping , Lin Xin-fu , Fang Zhu-ting , Liao Li-sheng , Luo Jie-wei , Gao Mei-zhu , Wu Jia-bin 
Published: October 2023

AbstractObjectivesSystemic lupus erythematosus is an autoimmune disease that involves multiple organ systems. One of its major complications, lupus nephritis (LN), is associated with a high mortality rate, and children-onset LN have a more severe course and worse prognosis than adults. Oxidative stress and inflammatory responses are involved in LN development and pathogenesis. Thus, this study aimed to explore the role of signaling regulation of the Nrf2/HMGB1/TLR/NF-κB pathway in LN pathogenesis and unravel the expression of TLR4+CXCR4+plasma cells subset (PCs) in LN.MethodsC57BL/6 and MRL/lpr mice were divided into four groups: control, model, vector control, and Nrf2 overexpression groups. The vector control and Nrf2 overexpression groups were injected with adenoviral vectors into the kidney in situ. Pathological changes in kidney tissues were observed by hematoxylin–eosin staining. The expression of Nrf2, HMGB1, TLR4, NF-κB, and downstream inflammatory factors in kidney samples was analyzed by quantitative polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. The ratios of TLR4+CXCR4+PC subsets in the blood and kidneys of mice were determined by flow cytometry.ResultsIn MRL/lpr mice, Nrf2 was downregulated while HMGB1/TLR4/NF-κB pathway proteins were upregulated. Nrf2 overexpression decreased the expression of HMGB1, TLR4, NF-κB, and its downstream inflammatory cytokines (IL-1β and TNFα). These cytokines were negatively correlated with an increase in Nrf2 content. PC and TLR4 + CXCR4 + PCs in the blood and kidney samples were significantly increased in MRL/lpr mice; however, they were decreased upon Nrf2 overexpression.ConclusionThis study showed severe kidney injury in an LN mouse model and an increased ratio of TLR4 + CXCR4 + PCs. Furthermore, we observed that Nrf2 regulates LN immune response through the Nrf2/HMGB1/TLR4/NF-κB pathway, which can be considered an important target for LN treatment. The clinical value of the findings of our study requires further investigation.
Bifidobacterium bifidum and Lactobacillus paracasei alleviate sarcopenia and cognitive impairment in aged mice by regulating gut microbiota-mediated AKT, NF-κB, and FOXO3a signaling pathways
Authors: Baek Ji-Su , Shin Yoon-Jung , Ma Xiaoyang , Park Hee-Seo , Hwang Yun-Ha , Kim Dong-Hyun 
Published: October 2023

AbstractSarcopenia is closely associated with gut dysbiosis. Probiotics alleviate gut dysbiosis. Therefore, we selected probiotics Lactobacillus paracasei P62 (Lp) and Bifidobacterium bifidum P61 (Bb), which suppressed muscle RING-finger protein-1 (MuRF1) expression and NF-κB activation in C2C12 cells, and examined their effects on muscle mass loss and dysfunction in aged mice. Oral administration of Lp, Bb, or their mix (LB) increased grip strength and treadmill running distance and time. They significantly increased muscle weight in aged mice. They also increased AKT activation, PGC1α, SIRT1, and myosin heavy chain (MyHC) expression, MyHC-positive cell population, and cell size in the gastrocnemius (GA) muscle, while FOXO3a and NF-κB activation, MuRF1, muscle atrophy F-box, and p16 expression, and NF-κB+CD11c+ cell population decreased. Furthermore, they reduced cognitive impairment-like behavior, IL-6 expression, FOXO3a activation, and NF-κB-positive cell population in the hippocampus, GA, and colon, while hippocampal brain-derived neurotropic factor expression increased. They shifted gut microbiota composition in aged mice: they increased Akkermansiaceae and Bacteroidaceae populations, which were positively correlated with total muscle weight and MyHC expression, and decreased Odoribacteraceae and Deferribacteriaceae populations, which were positively correlated with MuRF1 and IL-6 expression. LB alleviated sarcopenia- and cognitive impairment-like symptoms more potently than Lp or Bb alone. Based on these findings, probiotics, particularly Lp, Bb, and LB, can alleviate aging-dependent sarcopenia and cognitive impairment by regulating gut microbiota-mediated AKT, NF-κB, and/or FOXO3a signaling pathways.
Eight characteristics of rigorous multilevel implementation research: a step-by-step guide
Authors: Lengnick-Hall Rebecca , Williams Nathaniel J. , Ehrhart Mark G. , Willging Cathleen E. , Bunger Alicia C. , Beidas Rinad S. , Aarons Gregory A. 
Published: October 2023

Abstract
Background
Although healthcare is delivered in inherently multilevel contexts, implementation science has no widely endorsed methodological standards defining the characteristics of rigorous, multilevel implementation research. We identify and describe eight characteristics of high-quality, multilevel implementation research to encourage discussion, spur debate, and guide decision-making around study design and methodological issues.

Recommendations
Implementation researchers who conduct rigorous multilevel implementation research demonstrate the following eight characteristics. First, they map and operationalize the specific multilevel context for defined populations and settings. Second, they define and state the level of each construct under study. Third, they describe how constructs relate to each other within and across levels. Fourth, they specify the temporal scope of each phenomenon at each relevant level. Fifth, they align measurement choices and construction of analytic variables with the levels of theories selected (and hypotheses generated, if applicable). Sixth, they use a sampling strategy consistent with the selected theories or research objectives and sufficiently large and variable to examine relationships at requisite levels. Seventh, they align analytic approaches with the chosen theories (and hypotheses, if applicable), ensuring that they account for measurement dependencies and nested data structures. Eighth, they ensure inferences are made at the appropriate level. To guide implementation researchers and encourage debate, we present the rationale for each characteristic, actionable recommendations for operationalizing the characteristics in implementation research, a range of examples, and references to make the characteristics more usable. Our recommendations apply to all types of multilevel implementation study designs and approaches, including randomized trials, quantitative and qualitative observational studies, and mixed methods.

Conclusion
These eight characteristics provide benchmarks for evaluating the quality and replicability of multilevel implementation research and promote a common language and reference points. This, in turn, facilitates knowledge generation across diverse multilevel settings and ensures that implementation research is consistent with (and appropriately leverages) what has already been learned in allied multilevel sciences. When a shared and integrated description of what constitutes rigor is defined and broadly communicated, implementation science is better positioned to innovate both methodologically and theoretically.
Oxidative stress and inflammatory markers in ovarian follicular fluid of women with diminished ovarian reserve during in vitro fertilization
Authors: Huang Yan , Cheng Yi , Zhang Min , Xia Yan , Chen Xiaoyan , Xian Yexing , Lin Dewei , Xie Suyan , Guo Xinyu 
Published: October 2023

Abstract
Background
Follicular microenvironment has been proposed as an important factor for oocyte grown and maturation. We sought to evaluate the oxidative stress and inflammatory levels in follicular fluid (FF) and association with embryo quality in patients with diminished ovarian reserve (DOR).

Methods
The current research included 46 DOR cases and 56 normal ovarian reserve (NOR) cases. Twelve representative oxidative stress markers and eight representative inflammatory factors were measured in the FF.

Results
Oxidative stress markers total GSH (T-GSH) was decreased in the FF from women with DOR compared with that in NOR group (P = 0.041). More modest differences were observed for reduced GSH (rGSH) and rGSH/GSSG. Women with DOR compared to controls had higher level of TNF-α (P = 0.000) and lower level of IL-18 (P = 0.013). Correlation analysis revealed that GSSG was negatively correlated with normal fertilization rate in NOR group (r = -0.358, P = 0.008), and reduced GSH was negatively correlated with normal fertilization rate in DOR group (r = -0.299, P = 0.049). Moreover, as the regression analysis data showed, the GSSG level was significantly associated with embryo quality indicator.

Conclusions
The FF in DOR patients was accompanied by increased oxidative stress and inflammatory levels. Follicular development of women with DOR might be influenced by unusual IL-18 and TNF-α levels in FF. And oxidative stress marker GSSG in NOR group was a negative predictor for embryo quality.
aMeta: an accurate and memory-efficient ancient metagenomic profiling workflow
Authors: Pochon Zoé , Bergfeldt Nora , Kırdök Emrah , Vicente Mário , Naidoo Thijessen , van der Valk Tom , Altınışık N. Ezgi , Krzewińska Maja , Dalén Love , Götherström Anders , Mirabello Claudio , Unneberg Per , Oskolkov Nikolay 
Published: October 2023

AbstractAnalysis of microbial data from archaeological samples is a growing field with great potential for understanding ancient environments, lifestyles, and diseases. However, high error rates have been a challenge in ancient metagenomics, and the availability of computational frameworks that meet the demands of the field is limited. Here, we propose aMeta, an accurate metagenomic profiling workflow for ancient DNA designed to minimize the amount of false discoveries and computer memory requirements. Using simulated data, we benchmark aMeta against a current state-of-the-art workflow and demonstrate its superiority in microbial detection and authentication, as well as substantially lower usage of computer memory.
Utilizing AAV-mediated LEAPER 2.0 for programmable RNA editing in non-human primates and nonsense mutation correction in humanized Hurler syndrome mice
Authors: Yi Zongyi , Zhao Yanxia , Yi Zexuan , Zhang Yongjian , Tang Gangbin , Zhang Xiaoxue , Tang Huixian , Zhang Wei , Zhao Ying , Xu Huayuan , Nie Yuyang , Sun Xueqing , Xing Lijun , Dai Lian , Yuan Pengfei , Wei Wensheng 
Published: October 2023

Abstract
Background
The endogenous adenosine deaminases acting on RNA (ADAR) have been harnessed to facilitate precise adenosine-to-inosine editing on RNAs. However, the practicability of this approach for therapeutic purposes is still ambiguous due to the variable expression of intrinsic ADAR across various tissues and species, as well as the absence of all-encompassing confirmation for delivery methods.

Results
In this study, we demonstrate that AAV-mediated delivery of circular ADAR-recruiting RNAs (arRNAs) achieves effective RNA editing in non-human primates at dosages suitable for therapy. Within a time frame of 4 to 13 weeks following infection, the editing efficiency in AAV-infected cells can reach approximately 80%, with no discernible toxicity, even at elevated dosages. In addition, when AAV-delivered circular arRNAs are systematically administered to a humanized mouse model of Hurler syndrome, it rectifies the premature stop codon precisely and restores the functionality of IDUA enzyme encoded by the Hurler causative gene in multiple organs.

Conclusions
These discoveries considerably bolster the prospects of employing AAV-borne circular arRNAs for therapeutic applications and exploratory translational research.
Beyond gene-disease validity: capturing structured data on inheritance, allelic requirement, disease-relevant variant classes, and disease mechanism for inherited cardiac conditions
Authors: Josephs Katherine S. , Roberts Angharad M. , Theotokis Pantazis , Walsh Roddy , Ostrowski Philip J. , Edwards Matthew , Fleming Andrew , Thaxton Courtney , Roberts Jason D. , Care Melanie , Zareba Wojciech , Adler Arnon , Sturm Amy C. , Tadros Rafik , Novelli Valeria , Owens Emma , Bronicki Lucas , Jarinova Olga , Callewaert Bert , Peters Stacey , Lumbers Tom , Jordan Elizabeth , Asatryan Babken , Krishnan Neesha , Hershberger Ray E. , Chahal C. Anwar A. , Landstrom Andrew P. , James Cynthia , McNally Elizabeth M. , Judge Daniel P. , van Tintelen Peter , Wilde Arthur , Gollob Michael , Ingles Jodie , Ware James S. 
Published: October 2023

Abstract
Background
As the availability of genomic testing grows, variant interpretation will increasingly be performed by genomic generalists, rather than domain-specific experts. Demand is rising for laboratories to accurately classify variants in inherited cardiac condition (ICC) genes, including secondary findings.

Methods
We analyse evidence for inheritance patterns, allelic requirement, disease mechanism and disease-relevant variant classes for 65 ClinGen-curated ICC gene-disease pairs. We present this information for the first time in a structured dataset, CardiacG2P, and assess application in genomic variant filtering.

Results
For 36/65 gene-disease pairs, loss of function is not an established disease mechanism, and protein truncating variants are not known to be pathogenic. Using the CardiacG2P dataset as an initial variant filter allows for efficient variant prioritisation whilst maintaining a high sensitivity for retaining pathogenic variants compared with two other variant filtering approaches.

Conclusions
Access to evidence-based structured data representing disease mechanism and allelic requirement aids variant filtering and analysis and is a pre-requisite for scalable genomic testing.
Systemic sclerosis and risk of bronchiectasis: a nationwide longitudinal cohort study
Authors: Yang Bumhee , Kim Bo-Guen , Han Kyungdo , Jung Jin-Hyung , Kim Ji Hyoun , Park Dong Won , Kim Sang-Heon , Kim Eung-Gook , Sohn Jang Won , Yoon Ho Joo , Choi Hayoung , Lee Hyun 
Published: October 2023

Abstract
Background
The association between systemic sclerosis and the development of bronchiectasis is unclear. This study aimed to compare the risk of bronchiectasis between individuals with systemic sclerosis and those without using a nationwide longitudinal dataset.

Methods
Using the Korean National Health Insurance Service dataset between 2010 and 2017, we identified 4845 individuals aged ≥ 20 years with systemic sclerosis and 24,225 without systemic sclerosis who were matched 1:5 by age and sex. They were followed up until the date of a bronchiectasis diagnosis, death, or December 31, 2019, whichever came first.

Results
During a median follow-up period of 6.0 (interquartile range, 3.2–8.7) years, 5.3% of the systemic sclerosis cohort and 1.9% of the matched cohort developed bronchiectasis, with incidence rates of 9.99 and 3.23 per 1000 person-years, respectively. Even after adjusting for potential confounders, the risk of incident bronchiectasis was significantly higher in the systemic sclerosis cohort than in the matched cohort (adjusted hazard ratio 2.63, 95% confidence interval 2.22–3.12). A subgroup analysis of individuals with systemic sclerosis revealed that the risk of incident bronchiectasis was notably higher in younger individuals aged 20–39 years (P for interaction = 0.048) and in those without other coexisting connective tissue diseases (P for interaction = 0.006) than in their counterparts.

Conclusions
The risk of incident bronchiectasis is higher in individuals with systemic sclerosis than those without. Bronchiectasis should be considered one of the pulmonary manifestations related to systemic sclerosis.
Potential alternatives for Norway spruce wood: a selection based on defect-free wood properties
Authors: Huber Christian , Langmaier Magdalena , Stadlmann Alexander , Hochbichler Eduard , Grabner Maximilian , Teischinger Alfred , Konnerth Johannes , Grabner Michael , Müller Ulrich , Pramreiter Maximilian 
Published: October 2023

Abstract
Key message
The application of material selection principles uncovered eight possible alternative tree species (two deciduous and six coniferous species) to substitute Norway spruce (Picea abies (L.) H. Karst.) and potentially prevent economic loss in European forest.

Context
Climate change is a major challenge for the Central European forest and timber industry. Increasing biotic (e.g. beetle damage) and abiotic (e.g. drought) calamities have led to major losses in forest value, especially on Norway spruce (Picea abies (L.) H. Karst.) stands. Therefore, a transition to climate change adapted forest management is necessary. Concurrently, neophytes (e.g. tree of heaven (Ailanthus altissima (Mill.) Swingle), Douglas fir (Pseudotsuga menziesii (Mirbel) Franco), grand fir (Abies grandis (Douglas ex D. Don) Lindl.) and Paulownia (Paulownia tomentosa (Thunb.) Steud.)) are increasing their dominance in forest communities and causing additional adaption of the forest ecosystem. Both factors will lead to significant changes in wood species distributions in Central European forests, mainly at the expanse of Norway spruce, over the next decades.

Aims
Choosing the “right” tree species for afforestation will become ever more complex and will require a holistic approach that combines forestry and technological aspects alike. Therefore, this review presents a selection approach based on available wood material data from literature and the material selection principles proposed by M. Ashby with the aim to identify suitable alternatives for Norway spruce (Picea abies (L.) H. Karst.) and further concisely assess their silvicultural relevance.

Methods
For this wood species comparison and selection process, dry and raw density, bending strength and modulus of elasticity were chosen as key properties. Beam- and plate-like components subjected to a bending load were chosen as representative use cases.

Results
European birch (Betula spp.), grand fir (Abies grandis (Douglas ex D. Don) Lindl.) and silver fir (Abies alba Mill.) were identified as suitable alternatives for Norway spruce (Picea abies (L.) H. Karst.) from a technological as well as silvicultural point of view. In addition, Paulownia (Paulownia tomentosa (Thunb.) Steud.), Sitka spruce (Picea sitchensis (Bong.) Carrière), yellow pine (Pinus strobus L.), western red cedar (Thuja plicata Donn ex D. Don in Lambert) and loblolly pine (Pinus taeda L.) offer a technological advantage but currently lack relevance in the forest sector.

Conclusion
The proposed selection process offers an evaluation of technical performance, and in combination with an assessment of the silvicultural relevance, it will be possible to optimize the wood-supply chain and prevent future economic loss of Central European forests.