bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urban forest soils harbour distinct and more diverse communities of bacteria and fungi compared to less disturbed forest soils
Authors: Scholier Tiffany , Lavrinienko Anton , Brila Ilze , Tukalenko Eugene , Hindström Rasmus , Vasylenko Andrii , Cayol Claire , Ecke Frauke , Singh Navinder J. , Forsman Jukka T. , Tolvanen Anne , Matala Juho , Huitu Otso , Kallio Eva R. , Koskela Esa , Mappes Tapio , Watts Phillip C. 
Published: November 2022

AbstractAnthropogenic changes to land use drive concomitant changes in biodiversity, including that of the soil microbiota. However, it is not clear how increasing intensity of human disturbance is reflected in the soil microbial communities. To address this issue, we used amplicon sequencing to quantify the microbiota (bacteria and fungi) in the soil of forests (n = 312) experiencing four different land uses, national parks (set aside for nature conservation), managed (for forestry purposes), suburban (on the border of an urban area) and urban (fully within a town or city), which broadly represent a gradient of anthropogenic disturbance. Alpha diversity of bacteria and fungi increased with increasing levels of anthropogenic disturbance, and was thus highest in urban forest soils and lowest in the national parks. The forest soil microbial communities were structured according to the level of anthropogenic disturbance, with a clear urban signature evident in both bacteria and fungi. Despite notable differences in community composition, there was little change in the predicted functional traits of urban bacteria. By contrast, urban soils exhibited a marked loss of ectomycorrhizal fungi. Soil pH was positively correlated with the level of disturbance, and thus was the strongest predictor of variation in alpha and beta diversity of forest soil communities, indicating a role of soil alkalinity in structuring urban soil microbial communities. Hence, our study shows how the properties of urban forest soils promote an increase in microbial diversity and a change in forest soil microbiota composition.
Weekly line planning to improve the match between rail supply and passenger demand
Authors: Nie Bowen , Nie Lei , Fu Huiling , Wu Xin 
Published: November 2022

AbstractTraditional railway line planning approaches are used to determine the best train lines during specified periods (e.g., 1 day, 1 h, or several hours). However, mismatches occur relative to the spatiotemporal changes in travel demands over longer time periods (e.g., 1 week). To more effectively match rail supply with passenger demand, a weekly line planning (WLP) model considering both peak and nonpeak passenger demand over an entire week and during all periods of each day is proposed. This model maximizes the defined supply–demand matching utility and minimizes train operational cost. Important constraints to ensure proper daily and hourly train repetition over multiple days are included. A customized genetic algorithm (GA) is developed, which outperforms the CPLEX solver in real‐world cases of high‐speed railways in China. Compared with practical and single‐day planning, WLP shows clear improvement in terms of operational cost, passenger travel speed, and supply–demand matching.
Modeling adult COX‐2 cerebrospinal fluid pharmacokinetics to inform pediatric investigation
Authors: Hannam Jacqueline A. , Murto Kimmo T. , Anderson Brian J. , Dembo Gregory , Kharasch Evan D. 
Published: November 2022

AbstractAimHysteresis is reported between plasma concentration and analgesic effect from nonsteroidal anti‐inflammatory drugs. It is possible that the temporal delay between plasma and CSF nonsteroidal anti‐inflammatory drugs mirrors this hysteresis. The temporal relationship between plasma and CSF concentrations of COX‐inhibitors (celecoxib, rofecoxib, valdecoxib) has been described. The purpose of this secondary data analysis was to develop a compartmental model for plasma and CSF disposition of these COX‐2 inhibitors.MethodsPlasma and CSF concentration‐time profiles and protein binding data in 10 adult volunteers given oral celecoxib 200 mg, valdecoxib 40 mg and rofecoxib 50 mg were available for study. Nonlinear mixed effects models with a single plasma compartment were used to link a single CSF compartment with a transfer factor and an equilibration rate constant (Keq). To enable predictive modeling in pediatrics, celecoxib pharmacokinetics were standardized using allometry.ResultsMovement of all three unbound plasma COX‐2 drugs into CSF was characterized by a common equilibration half‐time (T1/2keq) of 0.84 h. Influx was faster than efflux and a transfer scaling factor of 2.01 was required to describe conditions at steady‐state. Estimated celecoxib clearance was 49 (95% CI 34–80) L/h/70 kg and the volume of distribution was 346 (95% CI 237–468) L/70 kg. The celecoxib absorption half‐time was 0.35 h with a lag time of 0.62 h. Simulations predicted a 70‐kg adult given oral celecoxib 200 mg with maintenance 100 mg twice daily would have a mean steady‐state total (bound and unbound) plasma concentration of 174 μg L−1 and CSF concentration of 1.1 μg L−1. A child (e.g., 25 kg, typically 7 years) given oral celecoxib 6 mg kg−1 with maintenance of 3 mg kg−1 twice daily would have 282 and 1.7 μg L−1 mean plasma and CSF concentrations, respectively.ConclusionsTransfer of unbound COX‐2 inhibitors from plasma to CSF compartment can be described with a delayed effect model using an equilibration rate constant to collapse observed hysteresis. An additional transfer factor was required to account for passage across the blood–brain barrier. Use of a target concentration strategy for dose and consequent plasma (total and unbound) and CSF concentration prediction could be used to inform pediatric clinical studies.
Who are pure exporters?
Authors: Mahakitsiri Doungdao , Suwanprasert Wisarut 
Published: November 2022

AbstractThe existing literature establishes the pattern that exporters in developed countries sell most of their output in their own domestic markets; however, recent evidence suggests that the export intensity distributions of 47 countries exhibit peaks at each end. In this study, we study the characteristics of pure exporters, namely exporters at the right‐hand peak of the distribution. We use Thailand's firm‐level panel data covering the period from 2007 through 2017 to estimate factors that explain the likelihood that a firm self‐selects to be a pure exporter. We do not find evidence that firm‐level productivity can explain the decision to become a pure exporter. Rather, the main factors that determine the decision are the capital–labour ratio, the amount of labour, foreign ownership, investment promotion and firm age.
Emission reduction and value‐added export nexus at firm level
Authors: Deng Yuping , Wu Yanrui , Xu Helian 
Published: November 2022

AbstractThis paper aims to investigate the effects of the share of domestic value added in exports on firm‐level emission intensity in China. It shows that the ratio of domestic value added in exports is negatively associated with firms' emission discharges. This relation is more profound for firms in ordinary trade than those in processing trade. Further analysis illustrates that the observed relationship is especially prevalent in eastern regions, technology‐intensive industries and non‐state‐owned firms.
Barriers and facilitators to HIV and syphilis rapid diagnostic testing in antenatal care settings in low-income and middle-income countries: a systematic review
Authors: Zhang Ye , Guy Rebecca , Camara Hawa , Applegate Tanya L , Wiseman Virginia , Treloar Carla , Lafferty Lise 
Published: November 2022

BackgroundTesting and treatment during pregnancy is a well-established and cost-effective prevention strategy, which relies largely on use of rapid diagnostic tests (RDTs). Yet, in many low-income and-middle-income countries, the uptake of RDTs is suboptimal. A qualitative meta-synthesis was conducted to identify the barriers and enablers to use of HIV and syphilis RDTs among pregnant women in low-income and middle-income countries.MethodsThis review was conducted using PRISMA guidelines. Eligible studies included peer-reviewed publications, which used qualitative methods to explore HIV and syphilis RDT in antenatal care clinics in low-income and middle-income countries. Studies focusing on perspectives of pregnant women, healthcare workers and/or stakeholders were included. We used an inductive approach informed by a modified socioecological model to synthesise the data.Results62 manuscripts met the eligibility criteria. For pregnant women, initial acceptance of the RDT and continuation in antenatal care depends on the perception that engaging in testing will be a beneficial experience for their baby and themselves, often influenced by the provision of services that are gender-sensitive, confidential, respectful, flexible and considers their well-being into the future. Local sociocultural beliefs about pregnancy and diseases, awareness of diseases and gender roles in society also influenced RDT acceptability among pregnant women. For healthcare workers, the ability to provide high-quality RDT care required ongoing training, accurate and easy to use tests, support from supervisors and communities, sufficient resources and staffing to provide services, and reliable salary. At the stakeholder level, well-developed guidelines and health system infrastructures were imperative to the delivery of RDT in antenatal clinics.ConclusionOur findings highlight clear gaps to the provision of sustainable and culturally acceptable maternal HIV and/or syphilis screening using RDTs. In addition, greater attention needs to be paid to community stakeholders in promoting the uptake of RDT in antenatal clinics.PROSPERO registration numberCRD42018112190.
School readiness among children born to women living with HIV in Dar es Salaam, Tanzania: a cohort study protocol
Authors: Perumal Nandita , Saleh Arvin , Muhihi Alfa , McCoy Dana , Seiden Jonathan , Bakari Mohamed , Ndesangia Veneranda , Ulenga Nzovu , Sudfeld Christopher R , Manji Karim P 
Published: November 2022

IntroductionChildren who are born to women living with HIV are at a greater risk of suboptimal neurodevelopment; however, evidence from sub-Saharan Africa is limited and functional developmental outcomes are rarely assessed in this vulnerable population. The School Readiness among HIV-Exposed Children (SRHEC) cohort study aims to assess the school readiness of preschool aged children born to women living with HIV and to identify the biological, environmental and social factors that contribute to school readiness in this population.Methods and analysisThe SRHEC cohort is an observational follow-up study of children born to HIV-infected pregnant women who were previously enrolled in a maternal vitamin D supplementation randomised, placebo-controlled trial in Dar es Salaam, Tanzania. This parent trial enrolled 2300 pregnant women and followed mothers and infants up to 1-year postpartum. Mother/caregiver and child pairs will be eligible for the SRHEC follow-up study if the child is between 3 and 6.5 years of age at assessment, and the mother/caregiver provides informed consent. The International Development and Early Learning Assessment tool will be used to assess children’s school readiness, including their early literacy, early numeracy, motor, socialemotional, and executive function skills. Data on maternal and child health and nutritional status (eg, anthropometry, blood pressure and diet) will be collected using standardised instruments and survey-based questionnaires. Data on maternal/caregiver depression and anxiety, maternal exposure to intimate partner violence, and HIV-related stigma will also be collected. Generalised linear and logistic regressions will be used to assess the relationship between child school readiness and biological, social, environmental factors.Ethics and disseminationThis study received ethical clearance from the Tanzanian National Institute of Medical Research, the Muhimbili University of Health and Allied Sciences, and the Harvard T.H. Chan School of Public Health. We will disseminate our results in the form of scientific conference presentations and peer-reviewed publications.
ATF3 Reprograms the Bone Marrow Niche in Response to Early Breast Cancer Transformation
Authors: Perrone Milena , Chiodoni Claudia , Lecchi Mara , Botti Laura , Bassani Barbara , Piva Annamaria , Jachetti Elena , Milani Matteo , Lecis Daniele , Tagliabue Elda , Verderio Paolo , Sangaletti Sabina , Colombo Mario P. 
Published: November 2022

Abstract
Cancer is a systemic disease able to reprogram the bone marrow (BM) niche towards a protumorigenic state. The impact of cancer on specific BM subpopulations can qualitatively differ according to the signals released by the tumor, which can vary on the basis of the tissue of origin. Using a spontaneous model of mammary carcinoma, we identified BM mesenchymal stem cells (MSC) as the first sensors of distal cancer cells and key mediators of BM reprogramming. Through the release of IL1B, BM MSCs induced transcriptional upregulation and nuclear translocation of the activating transcription factor 3 (ATF3) in hematopoietic stem cells. ATF3 in turn promoted the formation of myeloid progenitor clusters and sustained myeloid cell differentiation. Deletion of Atf3 specifically in the myeloid compartment reduced circulating monocytes and blocked their differentiation into tumor-associated macrophages. In the peripheral blood, the association of ATF3 expression in CD14+ mononuclear cells with the expansion CD11b+ population was able to discriminate between women with malignant or benign conditions at early diagnosis. Overall, this study identifies the IL1B/ATF3 signaling pathway in the BM as a functional step toward the establishment of a tumor-promoting emergency myelopoiesis, suggesting that ATF3 could be tested in a clinical setting as a circulating marker of early transformation and offering the rationale for testing the therapeutic benefits of IL1B inhibition in patients with breast cancer.
Significance: Bone marrow mesenchymal stem cells respond to early breast tumorigenesis by upregulating IL1B to promote ATF3 expression in hematopoietic stem cells and to induce myeloid cell differentiation that supports tumor development.
Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma
Authors: Jiang Haowen , Greathouse Rachel L. , Tiche Sarah Jane , Zhao Man , He Bo , Li Yang , Li Albert M. , Forgo Balint , Yip Michaela , Li Allison , Shih Moriah , Banuelos Selene , Zhou Meng-Ning , Gruber Joshua J. , Rankin Erinn B. , Hu Zhen , Shimada Hiroyuki , Chiu Bill , Ye Jiangbin 
Published: November 2022

Abstract

The Warburg effect is the major metabolic hallmark of cancer. According to Warburg himself, the consequence of the Warburg effect is cell dedifferentiation. Therefore, reversing the Warburg effect might be an approach to restore cell differentiation in cancer. In this study, we used a mitochondrial uncoupler, niclosamide ethanolamine (NEN), to activate mitochondrial respiration, which induced neural differentiation in neuroblastoma cells. NEN treatment increased the NAD+/NADH and pyruvate/lactate ratios and also the α-ketoglutarate/2-hydroxyglutarate (2-HG) ratio. Consequently, NEN treatment induced promoter CpG island demethylation and epigenetic landscape remodeling, activating the neural differentiation program. In addition, NEN treatment upregulated p53 but downregulated N-Myc and β-catenin signaling in neuroblastoma cells. Importantly, even under hypoxia, NEN treatment remained effective in inhibiting 2-HG generation, promoting DNA demethylation, and suppressing hypoxia-inducible factor signaling. Dietary NEN intervention reduced tumor growth rate, 2-HG levels, and expression of N-Myc and β-catenin in tumors in an orthotopic neuroblastoma mouse model. Integrative analysis indicated that NEN treatment upregulated favorable prognosis genes and downregulated unfavorable prognosis genes, which were defined using multiple neuroblastoma patient datasets. Altogether, these results suggest that mitochondrial uncoupling is an effective metabolic and epigenetic therapy for reversing the Warburg effect and inducing differentiation in neuroblastoma.

Significance:
Targeting cancer metabolism using the mitochondrial uncoupler niclosamide ethanolamine leads to methylome reprogramming and differentiation in neuroblastoma, providing a therapeutic opportunity to reverse the Warburg effect and suppress tumor growth.
See related commentary by Byrne and Bell, p.167
DOT1 L Regulates Ovarian Cancer Stem Cells by Activating β-catenin Signaling
Authors: Zhang Yaqi , Wang Yinu , Valdivia Andres , Huang Hao , Matei Daniela 
Published: November 2022

Abstract

Cancer stem cells (CSC) represent a population of cancer cells responsible for tumor initiation, chemoresistance, and metastasis. Here, we identified the H3K79 methyltransferase disruptor of telomeric silencing-1–like (DOT1L) as a critical regulator of self-renewal and tumor initiation in ovarian CSCs. DOT1 L was upregulated in ovarian CSCs versus non-CSCs. shRNA-mediated DOT1 L knockdown decreased the aldehyde dehydrogenase (ALDH)+ cell population, impaired the tumor initiation capacity (TIC) of ovarian CSCs, and blocked the expression of stemness-associated genes. Inhibition of DOT1L's methyltransferase activity by the small-molecule inhibitor (DOT1Li) EPZ-5676 also effectively targeted ovarian CSCs. Integrated RNA-sequencing analyses of ovarian cancer cells in which DOT1 L was knocked down versus control cells and of ovarian CSCs versus non-CSCs, identified Wnt signaling as a shared pathway deregulated in both CSCs and in DOT1L-deficient ovarian cancer cells. β-catenin, a key transcription factor regulated by Wnt, was downregulated in ovarian cancer cells in which DOT1 L was knocked down and upregulated in DOT1 L overexpressing ovarian cancer cells. Chromatin immunoprecipitation (ChIP) revealed enrichment of the H3K79Me3 mark at the β-catenin promoter, suggesting that its transcription is regulated by DOT1L. Our results suggest that DOT1 L is critical for the self-renewal and TIC of ovarian CSCs by regulating β-catenin signaling. Targeting DOT1 L in ovarian cancer could be a new strategy to eliminate CSCs.

Implications:
This study found that the histone methyltransferase DOT1 L regulates the self-renewal and tumor initiation capacity of ovarian CSCs and suggests DOT1 L as a new cancer target.
Muscle strength is associated with fracture risk obtained by fracture risk assessment tool (FRAX) in women with breast cancer
Authors: de Almeida Marques Bernabé Rayne , de Souza Vieira Mariana , Felício de Souza Vanusa , Gomes Fontana Luana , Albergaria Ben-Hur , Marques-Rocha José Luiz , Guandalini Valdete Regina 
Published: November 2022

Abstract
Background
Women with breast cancer are at risk for the development of sarcopenia and occurrence of fractures. The initial and periodic screening of these conditions can prevent the risks of disability, poor quality of life, and death. The present study investigated the association between sarcopenia phenotypes and fracture risk, assessed by the Fracture Risk Assessment Tool (FRAX) in women with breast cancer.

Methods
Cross-sectional study. It included women aged between 40 and 80 years, diagnosed with Luminal subtype breast cancer, with time of diagnosis ≤ 12 months, who had not started endocrine therapy, did not have metastasis, had not been treated for another malignancy, and had no recurrences. Sociodemographic, habits and lifestyle, clinical, anthropometric, and body composition variables were considered. Muscle strength, skeletal muscle mass, and physical performance were investigated using handgrip strength (HGS), appendicular skeletal muscle mass index (ASMI), and Timed Up and Go test (TUGT), respectively. Fracture risk was assessed using FRAX. Multiple linear regression models were conducted to verify the association between exposure variables and sarcopenia phenotypes. A significance level of p < 0.05 was adopted for all tests using the SPPS 25.0 program.

Results
Sixty-two women with a mean age of 58.1 ± 10.4 years were evaluated. Of these, 66.1% self-declared to be non-white, 41.9% and 71.0% did not consume alcohol or smoke, respectively, and 61.3% were insufficiently active. A total of 45.2% had clinical stage II carcinoma and 65.5% had the invasive breast carcinoma histological subtype. There was a predominance of adequacy of HGS (88.7%), ASMI (94.5%), and TUGT (96.8%), as well as low risk of hip fractures (85.5%) and major fractures (82.3%). HGS remained associated with FRAX hip fractures (p = 0.007) and FRAX major fractures (p = 0.007) in the adjusted models, while ASMI was associated with body mass (p < 0.001).

Conclusions
Low muscle strength was the sarcopenia phenotype that remained associated with fracture risk in women with breast cancer, independently of sociodemographic factors, level of physical activity, and clinical factors. In addition to the assessment of probable sarcopenia, this measurement may point out the risk of fractures.
Development of accreditation standards for midwifery clinical education in Iran
Authors: Abedian Sara , Javadnoori Mojgan , Montazeri Simin , Khosravi Shahla , Ebadi Abbas , Nikbakht Roshan 
Published: November 2022

Abstract
Background
Accreditation is one of the most important methods of quality assurance and improvement in medical education. In Iran, there are no specific midwifery education accreditation standards. This study was designed to develop accreditation standards for midwifery clinical education in Iran.

Methods
This study was performed in Iran in 2021. It consisted of two phases. In the first phase, accreditation standards for midwifery education in the United Kingdom, the United States, Australia and the International Confederation of Midwives were thoroughly examined through a narrative review. The domains obtained from this phase were used as a framework for coding in the second phase. In the second phase, a qualitative study was conducted with a directed content analysis approach to determine standards and criteria for clinical midwifery education accreditation in Iran. Participants were policymakers and senior managers of midwifery education, faculty members of midwifery departments with clinical teaching experience, and final year undergraduate midwifery students. The participants were selected by purposive sampling method, and data collection continued until data saturation.

Results
The standards and accreditation criteria of midwifery education from the review study were formed 6 domains: Mission and goals; Curricula; Clinical instructors; Students, Clinical setting; and Assessment. In the second phase, data analysis led to the extraction of 131 codes, which were divided into 35 sub-subcategories, 15 sub-categories, and 6 main categories.

Conclusion
Implementing the specific and localized standards of clinical midwifery education in Iran can lead to improved quality of clinical education programs.