bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of personal factors, unmet need and service obstacles on the relationship between health service use and outcome after brain injury
Authors: Borg David N. , Fleming Jennifer , Bon Joshua J. , Foster Michele M. , Kendall Elizabeth , Geraghty Timothy 
Published: April 2022

Abstract
Background
This exploratory study aimed to: (i) examine the relationship between health service use and quality of life, psychological wellbeing, global function and participation after discharge from brain injury inpatient rehabilitation, and (ii) determine the influence of personal factors, unmet need for services and service obstacles on the relationship between service use and these outcomes.

Methods
Using a prospective cohort design, 41 adults with acquired brain injury (median age = 46 years; 71% male; 61% severe traumatic injury) were followed for 6-months after discharge from specialist brain injury inpatient rehabilitation. Service use was continuously recorded and obtained through data linkage methods, focusing on the use of: outpatient medical services, outpatient nursing, outpatient allied health; medical acute services; incidents of re-hospitalization; and transitional rehabilitation service use. Outcome questionnaire measures were completed via telephone, at 6-months after discharge, and included: the EuroQol-5D; Depression Anxiety and Stress Scale, Mayo-Portland Adaptability Inventory and Sydney Psychosocial Reintegration Scale. Data were analyzed in a heterogeneous treatment effects framework, using Bayesian Additive Regression Trees.

Results
There was weak evidence that transitional rehabilitation service use was associated with better psychological wellbeing scores. The posterior probability of lower depression, anxiety and stress scores was .87, .81 and .86, respectively (average treatment effect). There was also weak evidence that re-hospitalization was associated with worse independent living skills scores. The posterior probability of worse scores was .87. However, most re-hospitalizations were due to unavoidable medical complications. We did not find that place of residence at discharge, marital status, unmet need, or service obstacles affected the relationship between service use and the studied outcomes.

Conclusions
This study may highlight the importance of participation in transitional rehabilitation, in the 6-months after discharge from brain injury rehabilitation. Replication in a larger sample size is required to confirm these findings.
Air pollution and hospitalization of patients with idiopathic pulmonary fibrosis in Beijing: a time-series study
Authors: Liang Lirong , Cai Yutong , Lyu Baolei , Zhang Di , Chu Shuilian , Jing Hang , Rahimi Kazem , Tong Zhaohui 
Published: April 2022

Abstract
Background
A small number of studies suggested that air pollution was associated with idiopathic pulmonary fibrosis (IPF) exacerbation, incidence and mortality. However, no studies to date were conducted in regions where air pollution is substantial. We aimed to investigate whether there are associations between acute increases in air pollution and hospitalization of patients with a confirmed primary diagnosis of IPF in Beijing.

Methods
Daily count of IPF hospitalizations (International Classification of Disease-10th Revision, J84.1) was obtained from an administrative database for 2013–2017 while daily city-wide average concentrations of PM10, PM2.5, NO2, Ozone, SO2 were obtained from 35 municipal monitoring stations for the same period. The association between daily IPF hospitalization and average concentration of each pollutant was analyzed with a generalized additive model estimating Poisson distribution.

Results
Daily 24-h mean PM2.5 concentration during 2013–2017 was 76.7 μg/m3. The relative risk (RR) of IPF hospitalization per interquartile range (IQR) higher (72 μg/m3) in PM2.5 was 1.049 (95% CI 1.024–1.074) and 1.031 (95% CI 1.007–1.056) for lag0 and moving averages 0–1 days respectively. No significant associations were observed for other lags. Statistically significant positive associations were also observed at lag0 with SO2, Ozone and NO2 (in men only). Positive associations were seen at moving averages 0–30 days for PM10 (RR per 86 μg/m3: 1.021, 95% CI 0.994–1.049), NO2 (RR per 30 μg/m3: 1.029, 95% CI 0.999–1.060), and SO2 (RR per 15 μg/m3: 1.060 (95% CI 1.025–1.097), but not with PM2.5 or Ozone.

Conclusions
Despite improvement in air quality since the implementation of clean air policy in 2013, acute exposure to higher levels of air pollution is significantly associated with IPF hospitalization in Beijing. Air quality policy should be continuously enforced to protect vulnerable IPF populations as well as the general public.
The association between exacerbation of chronic obstructive pulmonary disease and timing of paracetamol use: a cohort study in elderly Australians
Authors: Kelly Thu-Lan , Ward Michael , Pratt Nicole L. , Ramsay Emmae , Gillam Marianne , Roughead Elizabeth E. 
Published: April 2022

Abstract
Background
In elderly populations, paracetamol may be used regularly for conditions such as osteoarthritis. Paracetamol has been associated with respiratory disease through a proposed mechanism of glutathione depletion and oxidative stress. Given that chronic obstructive pulmonary disease (COPD) is frequently co-morbid with osteoarthritis, this study investigated whether the dose and timing of paracetamol exposure may induce COPD exacerbations.

Methods
The study population was 3523 Australian Government Department of Veterans’ Affairs full entitlement holders who had existing COPD on 1 January 2011, who were dispensed at least one prescription of paracetamol between 1 January 2011 and 30 September 2015, and had no paracetamol dispensed in the 6 months prior to 1 January 2011. The outcome was time to first hospitalisation for COPD exacerbation after initiation of paracetamol. A weighted cumulative exposure approach was used.

Results
The association between paracetamol exposure and COPD exacerbation was protective or harmful depending on the dose, duration, and recency of exposure. Compared to non-use, current use at the maximum dose of 4 g daily for 7 days was associated with a lower risk (HR = 0.78, 95% CI = 0.67–0.92) and a higher risk after 30 days (HR = 1.27, 95% CI = 1.06–1.52). Risk declined to baseline after 2 months. For past use, there was a short-term increase in risk on discontinuation depending of dose, duration and time since stopping.

Conclusions
Patients and doctors should be aware of the possible risk of COPD exacerbation with higher dose paracetamol 1 to 6 weeks after initiation or discontinuation, but no increased risk after 2 months.
School-related sedentary behaviours and indicators of health and well-being among children and youth: a systematic review
Authors: Kuzik Nicholas , da Costa Bruno G. G. , Hwang Yeongho , Verswijveren Simone J. J. M. , Rollo Scott , Tremblay Mark S. , Bélanger Stacey , Carson Valerie , Davis Melanie , Hornby Susan , Huang Wendy Yajun , Law Barbi , Salmon Jo , Tomasone Jennifer R. , Wachira Lucy-Joy , Wijndaele Katrien , Saunders Travis J. 
Published: April 2022

Abstract
Background
The purpose of this systematic review was to examine the associations between school-related sedentary behaviours and indicators of health and well-being in children and youth (~ 5–18 years) attending school.

Methods
This review was conducted to inform the development of School-Related Sedentary Behaviour Recommendations. Peer-reviewed, published, or in-press articles in English were included. Reviews, meta-analyses, and case studies were excluded; all other study designs were eligible. Further, articles had to meet the a priori study criteria for population, intervention, comparator (PROSPERO ID: CRD42021227600). Embase, MEDLINE® ALL, and PsycINFO were searched. Risk of bias was assessed for individual experimental studies using the Cochrane risk of bias assessment tool, and in observational studies based on the GRADE framework and in line with previous systematic reviews examining sedentary behaviours in children. Overall quality of evidence was assessed using the GRADE framework for each outcome category and study design. Results were synthesized narratively, grouped by study design and outcome category. Further, several high-level summaries were conducted to help interpret results.

Results
Evidence was synthesized from 116 reports, including 1,385,038 participants and 1173 extracted associations. More school-related sedentary behaviour was favourably associated with nearly one-third of extracted associations for cognitive (33%) and social-emotional (32%) indicators (e.g., less anxiety), but unfavourably associated with other movement behaviours (e.g., less physical activity) (35%). Active lessons were favourable (72%), compared to more school-related sedentary behaviours, when examining associations for all health and well-being indicators. More homework was favourable across all health and well-being indicators in 4% of extracted associations for primary school children, and 25% of extracted associations for secondary school children. However, ≥2 h/day of homework appeared to be unfavourable for health and well-being. Limitations for synthesized studies included generally low quality of evidence and a lack of studies in South American, African, or low-middle income countries.

Conclusions
Findings can help inform policy makers, schools, and teachers, regarding the amount of homework assigned and the introduction of active lessons into the classroom to enhance health and well-being of children. More research is needed examining school-related sedentary behaviours and indicators of health and well-being in low- and middle-income countries.
Roles and clinical application of exosomal circRNAs in the diagnosis and treatment of malignant tumors
Authors: Ye Dong , Gong Mengdan , Deng Yongqin , Fang Shuai , Cao Yujie , Xiang Yizhen , Shen Zhisen 
Published: April 2022

AbstractExosomes are microvesicles secreted by cells. They contain a variety of bioactive substances with important roles in intercellular communication. Circular RNA (circRNA), a type of nucleic acid molecule found in exosomes, forms a covalently bonded closed loop without 5′ caps or 3′ poly(A) tails. It is structurally stable, widely distributed, and tissue specific. CircRNAs mainly act as microRNA sponges and have important regulatory roles in gene expression; they are superior to other non-coding RNAs as molecular diagnostic markers and drug treatment targets. Exosomal-derived circRNAs in the body fluids of tumor patients can modulate tumor proliferation, invasion, metastasis, and drug resistance. They can be used as effective biomarkers for early non-invasive diagnosis and prognostic evaluation of tumors, and also represent ideal targets for early precision therapeutic intervention. This review provides a theoretical basis for exploring the applications of exosomal circRNAs in malignant tumor diagnosis and treatment. We describe the biological functions of exosomal circRNAs in the occurrence and development of malignant tumors, their potential utility in diagnosis and treatment, and possible mechanisms.
Macrophage elastase (MMP12) critically contributes to the development of subretinal fibrosis
Authors: Yi Caijiao , Liu Jian , Deng Wen , Luo Chang , Qi Jinyan , Chen Mei , Xu Heping 
Published: April 2022

Abstract
Background
Macular subretinal fibrosis is the end-stage complication of neovascular age-related macular degeneration (nAMD). We previously developed a mouse model of two-stage laser-induced subretinal fibrosis that mimics closely the dynamic course of macular fibrosis in nAMD patients. This study was aimed to understand the molecular mechanism of subretinal fibrosis.

Methods
Subretinal fibrosis was induced in C57BL/6J mice using the two-stage laser-induced protocol. Twenty days later, eyes were collected and processed for RNA sequencing (RNA-seq) analysis. DESeq2 was used to determine the differentially expressed genes (DEGs). Gene Ontology (GO) and KEGG were used to analyze the enriched pathways. The expression of the selected DEGs including Mmp12 was verified by qPCR. The expression of MMP12 in subretinal fibrosis of mouse and nAMD donor eyes was examined by immunofluorescence and confocal microscopy. The expression of collagen 1, αSMA and fibronectin and cytokines in bone marrow-derived macrophages from control and subretinal fibrosis mice were examined by qPCR, immunocytochemistry and Luminex multiplex cytokine assay. The MMP12 specific inhibitor MMP408 was used to evaluate the effect of MMP12 on TGFβ-induced macrophage-to-myofibroblast transition (MMT) in vitro and its role in subretinal fibrosis in vivo.

Results
RNA-seq analysis of RPE-choroid from subretinal fibrosis eyes uncovered 139 DEGs (fold change log2(fc) ≥ 0.5, FDR < 0.05), including 104 up-regulated and 35 were down-regulated genes. The top 25 enrichment GO terms were related to inflammation, blood vessels/cardiovascular development and angiogenesis. One of the most significantly upregulated genes, Mmp12, contributed to 12 of the top 25 GO terms. Higher levels of MMP12 were detected in subretinal fibrotic lesions in nAMD patients and the mouse model, including in F4/80+ or Iba1+ macrophages. BMDMs from subretinal fibrosis mice expressed higher levels of MMP12, collagen-1, αSMA and fibronectin. MMP408 dose-dependently suppressed TGFβ-induced MMT in BMDMs. In vivo treatment with MMP408 (5 mg/kg) significantly reduced subretinal fibrosis accompanied by reduced F4/80+ macrophage infiltration.

Conclusions
MMP12 critically contributes to the development of subretinal fibrosis, partially through promoting MMT.
CSF sTREM2 in neurological diseases: a two-sample Mendelian randomization study
Authors: Dong Ming-Hao , Zhou Luo-Qi , Tang Yue , Chen Man , Xiao Jun , Shang Ke , Deng Gang , Qin Chuan , Tian Dai-Shi 
Published: April 2022

Abstract
Background
Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) has been described as a biomarker for microglial activation, which were observed increased in a variety of neurological disorders.

Objective
Our objective was to explore whether genetically determined CSF sTREM2 levels are causally associated with different neurological diseases by conducting a two-sample Mendelian randomization (MR) study.

Methods
Single nucleotide polymorphisms significantly associated with CSF sTREM2 levels were selected as instrumental variables to estimate the causal effects on clinically common neurological diseases, including stroke, Alzheimer’s diseases, Parkinson’s diseases, amyotrophic lateral sclerosis, multiple sclerosis, and epilepsy and their subtypes. Summary-level statistics of both exposure and outcomes were applied in an MR framework.

Results
Genetically predicted per 1 pg/dL increase of CSF sTREM2 levels was associated with higher risk of multiple sclerosis (OR = 1.038, 95%CI = 1.014–1.064, p = 0.002). Null association was found in risk of other included neurological disorders.

Conclusions
These findings provide support for a potential causal relationship between elevated CSF sTREM2 levels and higher risk of multiple sclerosis.
The effect of Ulinastatin on postoperative course in cardiopulmonary bypass patients in Asia: a meta-analysis of randomized controlled trials
Authors: Zhenyu Hu , Qiaoli Yuan , Guangxiang Chen , Maohua Wang 
Published: April 2022

AbstractObjectivesTo evaluate the effect of urinary trypsin inhibitor (UTI) or Ulinastatin on postoperative course and clinical outcomes in patients with cardiopulmonary bypass.MethodsWe searched PubMed, Embase, Web of Science, and Cochrane Library for the keywords UTI and Cardiopulmonary bypass (CPB). The primary outcome measure was the intensive care unit length of stay (ICU LOS), and results were stratified for relevant subgroups (dosage of UTI). The effects of UTI on mechanical ventilation duration (MVD), hospital LOS, renal failure incidence (RFI), and all-cause mortality were studied as secondary outcomes.ResultsTwelve randomized controlled trials (enrolling 1620 patients) were evaluated. Eleven studies pooled for subgroup analysis showed that using UTI persistently or with a considerable amount would lead to a shorter ICU LOS (95% CI, − 0.69 to − 0.06;P = 0.0001). Ten studies showed that UTI could shorten MVD in patients (95% CI, − 1.505 to − 0.473;P < 0.0001). RFI generally showed a more favourable outcome with UTI treatment (95%CI, 0.18–1.17;P = 0.10). And the current evidence was insufficient to prove that UTI could reduce the hospital LOS (95% CI, − 0.22 to 0.16;P = 0.75) and the all-cause mortality rate (95% CI, 0.24–2.30;P = 0.60).ConclusionsVarious subsets of UTI treatment suggested that UTI could shorten ICU LOS, and it is associated with the dosage of UTI. Considering the substantial heterogeneity and lack of criteria for UTI dosage, more evidence is needed to establish a standard dosing guideline.
PPFIA4 promotes castration-resistant prostate cancer by enhancing mitochondrial metabolism through MTHFD2
Authors: Zhao Ru , Feng Tingting , Gao Lin , Sun Feifei , Zhou Qianqian , Wang Xin , Liu Junmei , Zhang Wenbo , Wang Meng , Xiong Xueting , Jia Wenqiao , Chen Weiwen , Wang Lin , Han Bo 
Published: April 2022

Abstract
Background
The development of castration-resistant prostate cancer (CRPC) remains a major obstacle in the treatment of prostate cancer (PCa). Dysregulated mitochondrial function has been linked to the initiation and progression of diverse human cancers. Deciphering the novel molecular mechanisms underlying mitochondrial function may provide important insights for developing novel therapeutics for CRPC.

Methods
We investigate the expression of the protein tyrosine phosphatase receptor type F polypeptide interacting protein alpha 4 (PPFIA4) using public datasets and tumor specimens from PCa cases by immunohistochemistry. Gain- and loss-of-function studies are performed in PCa cell lines and mouse models of subcutaneous xenograft to characterize the role of PPFIA4 in CRPC. Gene expression regulation is evaluated by a series of molecular and biochemical experiments in PCa cell lines. The therapeutic effects of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) inhibitor combined enzalutamide are assessed using in vitro functional assays and in vivo mouse models.

Results
We show that the increase of PPFIA4 exacerbates aggressive phenotype resembling CRPC. A fraction of PPFIA4 localizes to mitochondria and interacts with MTHFD2, a key enzyme for one-carbon metabolism. Androgen deprivation increases the translocation of PPFIA4 into mitochondria and increases the interaction between PPFIA4 and MTHFD2, which result in the elevation of tyrosine phosphorylated MTHFD2. Consequently, the levels of NADPH synthesis increase, resulting in protection against androgen deprivation-induced mitochondrial dysfunction, as well as promotion of tumor growth. Clinically, PPFIA4 expression is significantly increased in CRPC tissues compared with localized PCa ones. Importantly, an MTHFD2 inhibitor, DS18561882, combined with enzalutamide can significantly inhibit CRPC cell proliferation in vitro and tumor growth in vivo.

Conclusion
Overall, our findings reveal a PPFIA4-MTHFD2 complex in mitochondria that links androgen deprivation to mitochondrial metabolism and mitochondrial dysfunction, which suggest a potential strategy to inhibit CRPC progression.
Evaluation of the protective efficacy of a spatial repellent to reduce malaria incidence in children in western Kenya compared to placebo: study protocol for a cluster-randomized double-blinded control trial (the AEGIS program)
Authors: Ochomo Eric O. , Gimnig John E. , Bhattarai Achuyt , Samuels Aaron M. , Kariuki Simon , Okello George , Abong’o Bernard , Ouma Eunice A. , Kosgei Jackline , Munga Stephen , Njagi Kiambo , Odongo Wycliffe , Liu Fang , Grieco John P. , Achee Nicole L. 
Published: April 2022

AbstractBackgroundSpatial repellents are widely used for prevention of mosquito bites and evidence is building on their public health value, but their efficacy against malaria incidence has never been evaluated in Africa. To address this knowledge gap, a trial to evaluate the efficacy of Mosquito Shield™, a spatial repellent incorporating transfluthrin, was developed for implementation in Busia County, western Kenya where long-lasting insecticidal net coverage is high and baseline malaria transmission is moderate to high year-round.MethodsThis trial is designed as a cluster-randomized, placebo-controlled, double-blinded clinical trial. Sixty clusters will be randomly assigned in a 1:1 ratio to receive spatial repellent or placebo. A total of 6120 children aged ≥6 months to 10 years of age will be randomly selected from the study clusters, enrolled into an active cohort (baseline, cohort 1, and cohort 2), and sampled monthly to determine time to first infection by smear microscopy. Each cohort following the implementation of the intervention will be split into two groups, one to estimate direct effect of the spatial repellent and the other to estimate degree of diversion of mosquitoes and malaria transmission to unprotected persons. Malaria incidence in each cohort will be estimated and compared (primary indicator) to determine benefit of using a spatial repellent in a high, year-round malaria transmission setting. Mosquitoes will be collected monthly using CDC light traps to determine if there are entomological correlates of spatial repellent efficacy that may be useful for the evaluation of new spatial repellents. Quarterly human landing catches will assess behavioral effects of the intervention.DiscussionFindings will serve as the first cluster-randomized controlled trial powered to detect spatial repellent efficacy to reduce malaria in sub-Saharan Africa where transmission rates are high, insecticide-treated nets are widely deployed, and mosquitoes are resistant to insecticides. Results will be submitted to the World Health Organization Vector Control Advisory Group for assessment of public health value towards an endorsement to recommend inclusion of spatial repellents in malaria control programs.Trial registrationClinicalTrials.govNCT04766879. Registered February 23, 2021.
Introduction of a Zn-based metal–organic framework @ biomass porous activated carbon as a high-sensitive coating for a stainless steel SPME fiber: application to the simultaneous analysis of nonsteroidal anti-inflammatory drugs
Authors: Pasandideh Yalda , Razmi Habib 
Published: April 2022

AbstractThe present study introduces a high-efficiency nanocomposite material featuring a zinc-based metal–organic framework and a novel porous activated carbon derived from bread waste. The prepared nanocomposite, namely Zn-MOF-5@BHPAC, has been synthesized by a low-temperature hydrothermal process and coated onto the surface of a stainless steel wire with epoxy glue. The fabricated fiber has been employed as an SPME fiber applied in the extraction and pre-concentration of some nonsteroidal anti-inflammatory drugs (NSAIDs) before their high-performance liquid chromatography-ultraviolet (HPLC-UV) studies. The characterization studies were performed utilizing field emission scanning electron microscopy, elemental mapping, energy-dispersive X-ray spectroscopy, elemental analyzer, Fourier-transform infrared spectroscopy, and Brunauer–Emmett–Teller surface area analysis. Under the optimal conditions, the method demonstrated low detection limits (LODs, 0.06–0.15 µg L–1), wide linear ranges (LRs, 0.20–380 µg L–1) with good linearity (R2 > 0.991), good precisions (RSDs < 6.95%), and acceptable relative recoveries (RR > 85%). Using the green and affordable biomass of bread as a novel carbon-rich source is an innovative idea provided in this study. In addition, the hybridization of the obtained carbon-based material with the MOF compound to create a new high-capacity sorbent is another strength of the proposed method. Long service lifetime, economic efficiency, environmental friendliness, and high extraction capability were some of the other advantages of the suggested procedure. Therefore, the method can utilize successfully for the simultaneous determination of NSAIDs (as model analytes) in different matrixes.