bluuebunny/crossref_metadata_2025_split huggingface dataset:
LPS-inducible circAtp9b is highly expressed in osteoporosis and promotes the apoptosis of osteoblasts by reducing the formation of mature miR-17-92a
Authors: Feng Yinan , Ding Li , Li Longguang 
Published: March 2022

Abstract
Background
Circular RNA circAtp9b is an enhancer of LPS-induced inflammation, which promotes osteoporosis (OS). This study explored the role of circAtp9b in OS.

Methods
RT-qPCR was performed to detect the expression of circAtp9b and microRNA (miR)-17-92a (both mature and premature) in OS and healthy controls. The subcellular location of circAtp9b was assessed by nuclear fractionation assay. The direct interaction between circAtp9b and premature miR-17-92a was detected by RNA pull-down assay. The role of circAtp9b in regulating the maturation of miR-17-92a in osteoblasts was explored by overexpression assay and RT-qPCR. Cell apoptosis was analyzed by cell apoptosis assay.

Results
OS patients exhibited upregulation of circAtp9b and premature miR-17-92a, but downregulation of mature miR-17-92a. In osteoblasts, circAtp9b suppressed the maturation of miR-17-92a. LPS upregulated circAtp9b and premature miR-17-92a, and downregulated mature miR-17-92a in osteoblasts. CircAtp9b was detected in both nucleus and cytoplasm, and it directly interacted with premature miR-17-92a. Overexpression of circAtp9b reduced the effects of miR-17-92a on the apoptosis of osteoblasts induced by LPS.

Conclusion
CircAtp9b is LPS-inducible and upregulation of circAtp9b in OS promotes the apoptosis of osteoblasts by reducing the formation of mature miR-17-92a.
Long non-coding RNA SNHG5 promotes the osteogenic differentiation of bone marrow mesenchymal stem cells via the miR-212-3p/GDF5/SMAD pathway
Authors: Han Yineng , Yang Qiaolin , Huang Yiping , Jia Lingfei , Zheng Yunfei , Li Weiran 
Published: March 2022

Abstract
Background
The treatment of bone loss has posed a challenge to clinicians for decades. Thus, it is of great significance to identify more effective methods for bone regeneration. However, the role and mechanisms of long non-coding RNA small nucleolar RNA host gene 5 (SNHG5) during osteogenic differentiation remain unclear.

Methods
We investigated the function of SNHG5, Yin Yang 1 (YY1), miR-212-3p and growth differentiation factor 5 (GDF5) in osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro and in vivo. Molecular mechanisms were clarified by chromatin immunoprecipitation assay and dual luciferase reporter assay.

Results
We found SNHG5 expression was upregulated during osteogenesis of hBMSCs. Knockdown of SNHG5 in hBMSCs inhibited osteogenic differentiation while overexpression of SNHG5 promoted osteogenesis. Moreover, YY1 transcription factor directly bound to the promoter region of SNHG5 and regulated SNHG5 expression to promote osteogenesis. Dual luciferase reporter assay confirmed that SNHG5 acted as a miR-212-3p sponge and miR-212-3p directly targeted GDF5 and further activated Smad1/5/8 phosphorylation. miR-212-3p inhibited osteogenic differentiation, while GDF5 promoted osteogenic differentiation of hBMSCs. In addition, calvarial defect experiments showed knockdown of SNHG5 and GDF5 inhibited new bone formation in vivo.

Conclusion
Our results demonstrated that the novel pathway YY1/SNHG5/miR-212-3p/GDF5/Smad regulates osteogenic differentiation of hBMSCs and may serve as a potential target for the treatment of bone loss.
Impact of resettlement on livestock production and performance among the Maasai pastoralists of RAPland village, Olkaria Kenya
Authors: Gai Abraham Biar , Wahome Raphael Githaiga , Bett Rawlynce Cheruiyot 
Published: March 2022

AbstractDisplacements from developmental-related projects such as dams, conservancies, and geothermals displace 15–20 million people annually, necessitating the relocation of project-affected persons (PAPs). Most resettlement action plans (RAPs) fail in resettling the PAPs fully, causing loss of livelihoods and impoverishment. In 2014, Kenya Electricity Generating Company Limited (KenGen) displaced 155 Maasai pastoral households to create space for the expansion of existing geothermal electricity generation plants at Olkaria. The PAPs were relocated into a newly created area called RAPland village. The study aimed at answering the question: how did displacement and relocation affect livestock production and performance of the resettled pastoralists. Data on livestock population structures and cattle herd structures and performance (age at first calving, calving interval, lactation length, and milk yields) before and after the relocation were collected by a survey of 105 household heads of the intended census of 155. Data collected were summarised using Excel and analysed with Statistical Package for Social Sciences (SPSS). Results showed that daily milk yield per cow decreased from a mean of 3.8 ± 0.19 to 2.38 ± 0.19 l, while total livestock populations reduced from 8383 to 3124 tropical livestock units (TLU) after the relocation. The mean livestock holding per household (TLU) before the relocation was 75.7 ± 8.83, 15.5 ± 1.78, 5.83 ± 0.67, 1.46 ± 0.22, and 0.14 ± 0.02; this decreased after the relocation to 26.4 ± 8.3, 4.62 ± 1.7, 2.5 ± 0.63, 0.34 ± 0.21, and 0.3 ± 0.02 for cattle, sheep, goats, donkeys, and poultry, respectively. Young cattle proportions reduced from 27.6 to 20%, while that of cows increased from 51.7 to 60% after resettlement. Relocation affected livestock production and performances through reduced daily milk yield and livestock populations, thus reducing pastoralists’ resilience for food, nutritional security, and coping with catastrophes. As such, future displacement and resettlement programmes involving pastoral communities should address grazing needs and pastoral resilience to avoid impoverishment.
MIR210HG promotes breast cancer progression by IGF2BP1 mediated m6A modification
Authors: Shi Wenjing , Tang Yongzhe , Lu Jing , Zhuang Yihui , Wang Jie 
Published: March 2022

Abstract
Background
Breast cancer is the most common cancer in women around the world, and the molecular mechanisms of breast cancer progression and metastasis are still unclear. This study aims to clarify the function and N6,2′-O-dimethyladenosine (m6A) regulation of lncRNA MIR210HG in breast cancer.

Results
High expression of MIR210HG was confirmed in breast cancer. MIR210HG promoted breast cancer progression, which was mediated by its encoded miR-210. MIR210HG was regulated by IGF2BP1 mediated m6A modification. IGF2BP1 was confirmed highly expressed in breast cancer and induced both MIR210HG and miR-210 expression, which contributed to breast cancer progression. In addition, MIR210HG transcript was stabilized by IGF2BP1 and co-factor ELAVL1. IGF2BP1 was a direct target of MYCN via E-box binding motif. MYCN induced IGF2BP1 expression in breast cancer cells. MIR210HG and miR-210 expressions were also increased by MYCN.

Conclusions
In breast cancer, MIR210HG functions as an oncogenic lncRNA, which is also mediated by its encoded miR-210. In addition, both IGF2BP1 and ELAVL1 enhance the stability of MIR210HG, which contributes to the progression of breast cancer. Interestingly, IGF2BP1 is directly activated by MYCN, which explains the oncogenic role of MYCN. These findings clarify the m6A regulation related molecular mechanism of breast cancer progression. The MYCN/IGF2BP1/MIR210HG axis may serve as an alternative molecular mechanism of breast cancer progression.
Results of the national biomonitoring program show persistent iodine deficiency in Israel
Authors: Barnett-Itzhaki Zohar , Ehrlich Daniel , Troen Aron M. , Rorman Efrat , Groismann Luda , Blaychfeld-Magnazi Moran , Endevelt Ronit , Berman Tamar 
Published: March 2022

Abstract
Background
Adequate iodine intake is essential for human health, for normal thyroid function, and for attainment of full intellectual potential in children. In light of Israel's lack of a mandatory salt fortification policy, heavy reliance on desalination and low iodine intake from dairy products and seafood, there is concern in Israel that the population is iodine deficient. Indeed, the first Israeli National Iodine Survey in 2016 found a median urinary iodine concentration (UIC) of 83 µg/L among school age children, falling below the WHO’s adequacy range of 100–299 µg/L for children.

Methods
In the framework of the National Human Biomonitoring Program in Israel, spot urine samples and questionnaire data were collected from 166 healthy children aged 4–12 years in 2020–2021. Urinary iodine concentrations were measured at the Ministry of Health National Biomonitoring Laboratory, using mass spectrometry. An international comparison of median urinary iodine concentrations (UIC) was performed taking into consideration the levels of desalinated water per capita, and fortification policies.

Results
The overall median (interquartile range [IQR]) UIC was 80.1 µg/L (44.7–130.8 µg/L) indicating that the population’s iodine status has not improved in the five years that have passed since inadequacy was first identified. When comparing 13 countries with population size above 150,000, whose desalinated water per capita was at least 1 m3, Israel and Lebanon were the only countries with median UIC below the WHO adequacy range.

Conclusions
There is an urgent need for mandatory salt fortification in Israel. Based on our international comparison, we conclude that the potential impact of desalination on iodine intake can be compensated for using the implementation of salt fortification policy. This study highlights the critical need for public health surveillance of nutritional and environmental exposures using human biomonitoring, with emphasis on vulnerable populations such as pregnant women and children.
Metadta: a Stata command for meta-analysis and meta-regression of diagnostic test accuracy data – a tutorial
Authors: Nyaga Victoria Nyawira , Arbyn Marc 
Published: March 2022

AbstractBackgroundAlthough statistical procedures for pooling of several epidemiological metrics are generally available in statistical packages, those for meta-analysis of diagnostic test accuracy studies including options for multivariate regression are lacking. Fitting regression models and the processing of the estimates often entails lengthy and tedious calculations. Therefore, packaging appropriate statistical procedures in a robust and user-friendly program is of great interest to the scientific community.Methodsmetadtais a statistical program for pooling of diagnostic accuracy test data in Stata. It implements both the bivariate random-effects and the fixed-effects model, allows for meta-regression, and presents the results in tables, a forest plot and/or summary receiver operating characteristic (SROC) plot. For a model without covariates, it quantifies the unexplained heterogeneity due to between-study variation using an I2statistic that accounts for the mean-variance relationship and the correlation between sensitivity and specificity. To demonstratemetadta,we applied the program on two published meta-analyses on: 1) the sensitivity and specificity of cytology and other markers including telomerase for primary diagnosis of bladder cancer, and 2) the accuracy of human papillomavirus (HPV) testing on self-collected versus clinician-collected samples to detect cervical precancer.ResultsWithout requiring a continuity correction, the pooled sensitivity and specificity generated bymetadtaof telomerase for the diagnosis of primary bladder cancer was 0.77 [95% CI, 0.70, 0.82] and 0.91 [95% CI, 0.75, 0.97] respectively.Metadtaalso allowed to assess the relative accuracy of HPV testing on self- versus clinician-taken specimens using data from comparative studies conducted in different clinical settings. The analysis showed that HPV testing with target-amplification assays on self-samples was as sensitive as on clinician-samples in detecting cervical pre-cancer irrespective of the clinical setting.ConclusionThemetadtaprogram implements state of art statistical procedures in an attempt to close the gap between methodological statisticians and systematic reviewers. We expect the program to popularize the use of appropriate statistical methods for diagnostic meta-analysis further.
AQP4 labels a subpopulation of white matter-dependent glial radial cells affected by pediatric hydrocephalus, and its expression increased in glial microvesicles released to the cerebrospinal fluid in obstructive hydrocephalus
Authors: Castañeyra-Ruiz Leandro , González-Marrero Ibrahim , Hernández-Abad Luis G. , Carmona-Calero Emilia M. , Pardo Marta R. , Baz-Davila Rebeca , Lee Seunghyun , Muhonen Michael , Borges Ricardo , Castañeyra-Perdomo Agustín 
Published: March 2022

AbstractHydrocephalus is a distension of the ventricular system associated with ventricular zone disruption, reactive astrogliosis, periventricular white matter ischemia, axonal impairment, and corpus callosum alterations. The condition's etiology is typically attributed to a malfunction in classical cerebrospinal fluid (CSF) bulk flow; however, this approach does not consider the unique physiology of CSF in fetal and perinatal patients. The parenchymal fluid contributes to the glymphatic system, and plays a fundamental role in pediatric hydrocephalus, with aquaporin 4 (AQP4) as the primary facilitator of these fluid movements. Despite the importance of AQP4 in the pathophysiology of hydrocephalus, it’s expression in human fetal life is not well-studied. This manuscript systematically defines the brain expression of AQP4 in human brain development under control (n = 13) and hydrocephalic conditions (n = 3). Brains from 8 postconceptional weeks (PCW) onward and perinatal CSF from control (n = 2), obstructive (n = 6) and communicating (n = 6) hydrocephalic samples were analyzed through immunohistochemistry, immunofluorescence, western blot, and flow cytometry. Our results indicate that AQP4 expression is observed first in the archicortex, followed by the ganglionic eminences and then the neocortex. In the neocortex, it is initially at the perisylvian regions, and lastly at the occipital and prefrontal zones. Characteristic astrocyte end-feet labeling surrounding the vascular system was not established until 25 PCW. We also found AQP4 expression in a subpopulation of glial radial cells with processes that do not progress radially but, rather, curve following white matter tracts (corpus callosum and fornix), which were considered as glial stem cells (GSC). Under hydrocephalic conditions, GSC adjacent to characteristic ventricular zone disruption showed signs of early differentiation into astrocytes which may affect normal gliogenesis and contribute to the white matter dysgenesis. Finally, we found that AQP4 is expressed in the microvesicle fraction (p < 0.01) of CSF from patients with obstructive hydrocephalus. These findings suggest the potential use of AQP4 as a diagnostic and prognostic marker of pediatric hydrocephalus and as gliogenesis biomarker.
Integrative Proposals of Sports Monitoring: Subjective Outperforms Objective Monitoring
Authors: Montull Lluc , Slapšinskaitė-Dackevičienė Agne , Kiely John , Hristovski Robert , Balagué Natàlia 
Published: March 2022

AbstractCurrent trends in sports monitoring are characterized by the massive collection of tech-based biomechanical, physiological and performance data, integrated through mathematical algorithms. However, the application of algorithms, predicated on mechanistic assumptions of how athletes operate, cannot capture, assess and adequately promote athletes’ health and performance. The objective of this paper is to reorient the current integrative proposals of sports monitoring by re-conceptualizing athletes as complex adaptive systems (CAS). CAS contain higher-order perceptual units that provide continuous and multilevel integrated information about performer–environment interactions. Such integrative properties offer exceptional possibilities of subjective monitoring for outperforming any objective monitoring system. Future research should investigate how to enhance this human potential to contribute further to athletes’ health and performance. This line of argument is not intended to advocate for the elimination of objective assessments, but to highlight the integrative possibilities of subjective monitoring.
Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients (REFACED Sepsis)—protocol for a multicenter, randomized, clinical, proof-of-concept trial
Authors: Jessen Marie Kristine , Andersen Lars Wiuff , Thomsen Marie-Louise Holm , Kristensen Peter , Hayeri Wazhma , Hassel Ranva Espegård , Perner Anders , Petersen Jens Aage Kølsen , Kirkegaard Hans 
Published: March 2022

Abstract
Background
Intravenous fluids are often used in the treatment of sepsis. The better strategy regarding fluid volume is debated, but preliminary data in patients with septic shock or sepsis-related hypotension favor restrictive fluid administration. We describe the protocol and statistical analysis plan for the Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients (REFACED Sepsis)—a multicenter, randomized clinical proof-of-concept trial. The aim of the REFACED Sepsis trial is to test if a restrictive intravenous fluid protocol in emergency department patients with sepsis without shock is feasible and decreases the intravenous fluid volume administered in comparison to standard care.

Methods
This is an investigator-initiated, multicenter, randomized, parallel-group, open-labeled, feasibility trial investigating volumes of crystalloid fluid within 24 h in 124 patients with sepsis without shock enrolled at three emergency departments in the Central Denmark Region. Patients are allocated to two different intravenous fluid regimens: a restrictive approach using four trigger criteria for fluid administration vs. standard care.
The primary, feasibility outcome is total intravenous, crystalloid fluid volume within 24 h, and key secondary outcomes include protocol violations, total fluids (intravenous and oral) within 24 h, and serious adverse reactions and suspected unexpected serious adverse reactions.
Status: The trial started in November 2021, and the last patient is anticipated to be included in January 2022.

Discussion
Sepsis is very common in emergency department patients and fluid administration is very frequently administered in these patients. However, the evidence to guide fluid administration is very sparse. This feasibility trial will be the foundation for a potential future large-scale trial investigating restrictive vs. standard fluid administration in patients with sepsis.

Trial registration
EudraCT number: 2021-000224-35 (date: 2021 May 03), ClinicalTrials.gov number: NCT05076435 (date: 2021 October 13), Committee on Health Research Ethics – Central Denmark Region: 1-10-72-163-21 (date: 2021 June 28).
Understanding the implication of Kawakita model parameters using in-die force-displacement curve analysis for compacted and non-compacted API powders
Authors: Rashid Iyad , Haddadin Rula Raji , Alkafaween Ashaar Abdulsalam , Alkaraki Rawan Nayef , Alkasasbeh Rehan Mohammad 
Published: March 2022

AbstractThe aim of this study was to investigate powder mechanics upon compression using data obtained from force-displacement (F-D) curves. The Kawakita model of powder compression analysis was adopted in order to compare the pressure-volume reduction relationship of the drug powders in relation to the F-D curves. Experiments were carried out on six model drugs (metronidazole, metformin, secnidazole, ciprofloxacin, norfloxacin, and mebeverine). The drugs were compressed at different pressures in the non-processed or processed (using a roller compactor) forms. Results indicate the similarity between the F-D curves and a rearranged form of the Kawakita model. The foregoing enables the calculation of two important powder parameters, “a” (maximum powder volume reduction) and “Pk” (pressure required to achieve half of the maximum volume reduction) from the F-D curves without the need, as in the case of the conventional Kawakita model, to compress powders into tablets at different compression forces.
Graphical abstract
A new concept for the production of 11C-labelled radiotracers
Authors: Wenz Jan , Arndt Felix , Samnick Samuel 
Published: March 2022

Abstract
Background
The GMP-compliant production of radiopharmaceuticals has been performed using disposable units (cassettes) with a dedicated synthesis module. To expand this “plug ‘n’ synthesize” principle to a broader scope of modules we developed a pressure controlled setup that offers an alternative to the usual stepper motor controlled rotary valves. The new concept was successfully applied to the synthesis of N-methyl-[11C]choline, L-S-methyl-[11C]methionine and [11C]acetate.

Results
The target gas purification of cyclotron produced [11C]CO2 and subsequent conversion to [11C]MeI was carried out on a TRACERlab Fx C Pro module. The labelling reactions were controlled with a TRACERlab Fx FE module. With the presented modular principle we were able to produce N-methyl-[11C]choline and L-S-methyl-[11C]methionine by loading a reaction loop with neat N,N'-dimethylaminoethanol (DMAE) or an ethanol/water mixture of NaOH and L-homocysteine (L-HC), respectively and a subsequent reaction with [11C]MeI. After 18 min N-methyl-[11C]choline was isolated with 52% decay corrected yield and a radiochemical purity of > 99%. For L-S-methyl-[11C]methionine the total reaction time was 19 min reaction, yielding 25% of pure product (> 97%). The reactor design was used as an exemplary model for the technically challenging [11C]acetate synthesis. The disposable unit was filled with 1 mL MeMgCl (0.75 M) in tetrahydrofuran (THF) bevore [11C]CO2 was passed through. After complete release of [11C]CO2 the reaction mixture was quenched with water and guided through a series of ion exchangers (H+, Ag+ and OH−). The product was retained on a strong anion exchanger, washed with water and finally extracted with saline. The product mixture was acidified and degassed to separate excess [11C]CO2 before dispensing. Under these conditions the total reaction time was 18 ± 2 min and pure [11C]acetate (n = 10) was isolated with a decay corrected yield of 51 ± 5%.

Conclusion
Herein, we described a novel single use unit for the synthesis of carbon-11 labelled tracers for preclinical and clinical applications of N-methyl-[11C]choline, L-S-methyl-[11C]methionine and [11C]acetate.