bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical rehabilitation financing in Iran: a policy analysis using Kingdon’s multiple streams
Authors: Shahabi Saeed , Mojgani Parviz , Shabaninejad Hosein , Teymourlouy Ahmad Ahmadi , Behzadifar Masoud , Lankarani Kamran Bagheri 
Published: May 2021

AbstractBackgroundAdequate financing is a crucial function, securing that physical rehabilitation services (i.e., physiotherapy, occupational therapy, prosthetics and orthotics) are available with no financial hardship. Like many other countries, despite the adoption of various policies and strategies in recent decades, Iran enjoys no desirable physical rehabilitation financing (PRF). Accordingly, this qualitative study aimed to explore the PRF-related strategies and issues as well as their impacts on relevant policies in Iran.MethodsAn analysis of PRF-related policies was conducted in Iran using semi-structured interviews and policy documents review. Purposive and snowball sampling techniques were employed to select key informants, including health-policy makers, civil society, rehabilitation-policy makers, university professors, and practitioners. Thematic analysis was used to analyze the collected data. The analysis was framed within Kingdon’s multiple streams.ResultsThe hindering factors for desirable financing were weak insurance coverage, lack of sustainable financial resources, fragmented financing, lack of split between provider and financer, high-cost of physical rehabilitation services, low engagement of relevant experts in policy-making processes, and corrupt activities. In the policy stream, the following factors were highlighted: involvement of sustainable financial resources, the use of external revenue sources, allocated resources’ earmarking, the integration of the current funds to have better pooling, the use of incentive and timely payment mechanisms, the implementation of strategic purchasing principals, and the employment of effective rationing strategies. Moreover, parliament support, changes in administrations, international effects, pressures from interest campaigns and NGOs, and international sanctions were found as factors affecting the politics stream.ConclusionThe study findings revealed that a variety of national and international factors affect PRF-related issues in Iran. The recently enacted laws indicate that the PRF policies have already been on the national health political agenda. The study reflected the multifaceted nature of barriers to optimal PRF in Iran.
Downregulation of GeBP-like α factor by MiR827 suggests their involvement in senescence and phosphate homeostasis
Authors: Ma Chao , Chen Qiuju , Wang Shiping , Lers Amnon 
Published: May 2021

Abstract
Background
Leaf senescence is a genetically controlled degenerative process intimately linked to phosphate homeostasis during plant development and responses to environmental conditions. Senescence is accelerated by phosphate deficiency, with recycling and mobilization of phosphate from senescing leaves serving as a major phosphate source for sink tissues. Previously, miR827 was shown to play a significant role in regulating phosphate homeostasis, and induction of its expression was also observed during Arabidopsis leaf senescence. However, whether shared mechanisms underlie potentially common regulatory roles of miR827 in both processes is not understood. Here, we dissect the regulatory machinery downstream of miR827.

Results
Overexpression or inhibited expression of miR827 led to an acceleration or delay in the progress of senescence, respectively. The transcriptional regulator GLABRA1 enhancer-binding protein (GeBP)-like (GPLα) gene was identified as a possible target of miR827. GPLα expression was elevated in miR827-suppressed lines and reduced in miR827-overexpressing lines. Furthermore, heterologous co-expression of pre-miR827 in tobacco leaves reduced GPLα transcript levels, but this effect was eliminated when pre-miR827 recognition sites in GPLα were mutated. GPLα expression is induced during senescence and its inhibition or overexpression resulted in senescence acceleration and inhibition, accordingly. Furthermore, GPLα expression was induced by phosphate deficiency, and overexpression of GPLα led to reduced expression of phosphate transporter 1 genes, lower leaf phosphate content, and related root morphology. The encoded GPLα protein was localized to the nucleus.

Conclusions
We suggest that MiR827 and the transcription factor GPLα may be functionally involved in senescence and phosphate homeostasis, revealing a potential new role for miR827 and the function of the previously unstudied GPLα. The close interactions between senescence and phosphate homeostasis are further emphasized by the functional involvement of the two regulatory components, miR827 and GPLα, in both processes and the interactions between them.
Viscoelasticity measured by shear wave elastography in a rat model of nonalcoholic fatty liver disease: comparison with dynamic mechanical analysis
Authors: Pi Zhaoke , Wang Mengke , Lin Haoming , Guo Yanrong , Chen Siping , Diao Xianfen , Xia Hui , Liu Guoqiang , Zeng Jie , Zhang Xinyu , Chen Xin 
Published: May 2021

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is rapidly becoming one of the most common liver diseases. Ultrasound elastography has been used for the diagnosis of NAFLD. However, clinical research on steatosis by elastography technology has mainly focused on steatosis with fibrosis or non-alcoholic steatohepatitis (NASH), while steatosis without fibrosis has been poorly studied. Moreover, the relationship between liver viscoelasticity and steatosis grade is not clear. In this study, we evaluated the degree of liver steatosis in a simple steatosis rat model using shear wave elastography (SWE).

Results
The viscoelasticity values of 69 rats with hepatic steatosis were measured quantitatively by SWE in vivo and validated by a dynamic mechanical analysis (DMA) test. Pathological sections were used to determine the steatosis grade for each rat. The results showed that the elasticity values µ obtained by the two methods followed the same trend, and µ is significantly correlated with liver steatosis. The Pearson’s correlation coefficients indicate that $$\mu$$
μ
obtained by SWE is positively linear correlated with DMA (r = 0.628, p = 7.85 × 10–9). However, the viscosity values $$\eta$$
η
obtained by SWE were relatively independent of those obtained by DMA with a correlation coefficient of − 0.01. The combined Voigt elasticity measurements have high validity in the prediction of steatosis (S0 vs. S1–S4), with an AUROC of 0.755 (95% CI 0.6175–0.8925, p < 0.01) and the optimal cutoff value was 2.08 kPa with a sensitivity of 78% and specificity of 63%.

Conclusion
SWE might have the feasibility to be introduced as an auxiliary technique for NAFLD patients in clinical settings. However, the viscosity results measured by SWE and DMA are significantly different, because the two methods work in different frequency bands.
High-resolution age-specific mapping of the two-week illness prevalence rate based on the National Health Services Survey and geostatistical analysis: a case study in Guangdong province, China
Authors: Wen Chuchun , Huang Xiaoliang , Feng Lifen , Chen Long , Hu Wei , Lai Yingsi , Hao Yuantao 
Published: May 2021

Abstract
Background
The two-week illness prevalence rate is an important and comparable indicator of health service needs. High-spatial-resolution, age-specific risk mapping of this indicator can provide valuable information for health resource allocation. The age-prevalence relationships may be different among areas of the study region, but previous geostatistical models usually ignored the spatial-age interaction.

Methods
We took Guangdong province, the province with the largest population and economy in China, as a study case. We collected two-week illness data and other potential influencing predictors from the fifth National Health Services Survey in 2013 and other open-access databases. Bayesian geostatistical binary regression models were developed with spatial-age structured random effect, based on which, high-resolution, age-specific two-week illness prevalence rates, as well as number of people reporting two-week illness, were estimated. The equality of health resource distribution was further evaluated based on the two-week illness mapping results and the health supply data.

Results
The map across all age groups revealed that the highest risk was concentrated in the central (i.e., Pearl River Delta) and northern regions of the province. These areas had a two-week illness prevalence > 25.0%, compared with 10.0–20.0% in other areas. Age-specific maps revealed significant differences in prevalence between age groups, and the age-prevalence relationships also differed across locations. In most areas, the prevalence rates decrease from age 0 to age 20, and then increase gradually. Overall, the estimated age- and population-adjusted prevalence was 16.5% [95% Bayesian credible interval (BCI): 14.5–18.6%], and the estimated total number of people reporting illness within the two-week period was 17.5 million (95% BCI: 15.5–19.8 million) in Guangdong Province. The Lorenz curve and the Gini coefficient (resulted in 0.3526) showed a moderate level of inequality in health resource distribution.

Conclusions
We developed a Bayesian geostatistical modeling framework with spatial-age structured effect to produce age-specific, high-resolution maps of the two-week illness prevalence rate and the numbers of people reporting two-week illness in Guangdong province. The methodology developed in this study can be generalized to other global regions with available relevant survey data. The mapping results will support plans for health resource allocation.
Unclassified mesenchymal sarcoma with NTRK1-KHDRBS1 gene fusion: a case report of long-term tumor-free survival with crizotinib treatment
Authors: Chen Weijie , Wang Huimei , Jiang Dongxian , Luan Lijuan , Zhou Yuhong , Hou Yingyong 
Published: May 2021

Abstract
Background
Mesenchymal sarcomas are tumors that originate from mesenchymal tissue. Most mesenchymal sarcomas can be accurately classified, but some are unclassifiable in clinical practice. Molecular detection methods enable patients to benefit from molecular-targeted therapies for many cancers, including lung, breast, and bowel cancers. Further, even unclassified tumors can have therapeutic targets. NTRK gene fusions are sporadic genetic alterations that occur across tumor entities. If NTRK gene fusions are detected, TRK inhibitors can be used regardless of the tumor entity.

Case presentation
This report describes a case with an unclassifiable mesenchymal sarcoma carrying a neurotrophic tyrosine receptor kinase NTRK1-KHDRBS1 gene fusion that was diagnosed and treated at multiple hospitals. Diagnostic work-up included pathological and immunohistochemical analysis, which excluded angiosarcoma, dendritic cell sarcoma, and pseudomyogenic hemangioendothelioma. The patient achieved a long-term survival without tumor relapse after treatment with crizotinib.

Conclusions
This case will be of significant interest to pathologists because, despite the tumor being unclassified, a molecular target was identified. Although the FDA does not currently approve crizotinib for treatment of patients harboring NTRK gene fusions, this case provides new insights for diagnosis and treatment of mesenchymal sarcomas with NTRK1 gene translocations. Similar to ALKomas, which can be successfully treated using NTRK molecular-targeted therapy, tumors with NTRK gene translocations can be classified as NTRKomas, even when they occur at different organ sites, and with varying histological morphologies, and immunophenotypes.
Risk factors for central lymph node metastasis in the cervical region in papillary thyroid carcinoma: a retrospective study
Authors: Li Xiang , Zhang Hanwen , Zhou Yu , Cheng Ruochuan 
Published: May 2021

Abstract
Background
To investigate the influence of different risk factors on central lymph node metastasis (CLNM) in the cervical region in patients with papillary thyroid carcinoma (PTC).

Methods
This retrospective study included 2586 PTC patients. Potential risk factors were identified by univariate analysis, and the relationships between these factors and CLNM were ascertained by multivariable analysis. A scoring system was constructed, and the optimal cut-off value was determined.

Results
On univariate analysis, sex, age, tumor diameter, multifocality, capsule invasion, vascular invasion, total number of lymph nodes in the central region, and serum thyroid peroxidase antibody (TPOAb) concentration were identified as potential risk factors for CLNM in the cervical region, whereas nerve invasion, thyroid-stimulating hormone concentration, and thyroglobulin antibody (TgAb) concentration were not. Multivariable analysis indicated that male sex, young age, large tumor diameter, multifocality, vascular invasion, a large number of central lymph nodes, and a low TPOAb concentration were significant risk factors. From these factors, a preoperative CLNM risk assessment scale was constructed for predicting CLNM in the cervical region for PTC patients.

Conclusion
Male sex, young age, large tumor diameter, multifocality, vascular invasion, a large number of central lymph nodes, and a low TPOAb concentration were positively correlated with CLNM in the cervical region in PTC patients. The preoperative CLNM risk assessment scale based on these risk factors is expected to offer accurate preoperative assessment of central lymph node status in PTC patients.
Assessing preparation for care transition among adolescents with rheumatologic disease: a single-center assessment with patient survey
Authors: Roberts Jordan E. , Halyabar Olha , Petty Carter R. , Son Mary Beth 
Published: May 2021

Abstract
Background
Despite the risk for poor outcomes and gaps in care in the transfer from pediatric to adult care, most pediatric rheumatology centers lack formal transition pathways. As a first step in designing a pathway, we evaluated preparation for transition in a single-center cohort of adolescents and young adults (AYA) with rheumatologic conditions using the ADolescent Assessment of Preparation for Transition (ADAPT) survey.

Findings
AYA most frequently endorsed receiving counseling on taking charge of their health and remembering to take medications. Less than half reported receiving specific counseling about transferring to an adult provider.
AYA with lower education attainment compared with those who had attended some college or higher had lower scores in self-management (1.51 vs 2.52, p = 0.0002), prescription medication counseling (1.96 vs 2.41, p = 0.029), and transfer planning (0.27 vs 1.62, p < 0.001). AYA with a diagnosis of MCTD, Sjögren’s or SLE had higher self-management scores than those with other diagnoses (2.6 vs 1.9; p = 0.048). Non-white youth indicated receiving more thorough medication counseling than white youth (2.71 vs 2.07, p = 0.027).
When adjusting for age, educational attainment remained an independent predictor of transfer planning (p = 0.037). AYA with longer duration of seeing their physician had higher transition preparation scores (p = 0.021).

Conclusion
Few AYA endorsed receiving comprehensive transition counseling, including discussion of transfer planning. Those who were younger and with lower levels of education had lower preparation scores. A long-term relationship with providers was associated with higher scores. Further research, including longitudinal assessment of transition preparation, is needed to evaluate effective processes to assist vulnerable populations.
Factors associated with reduced infliximab exposure in the treatment of pediatric autoimmune disorders: a cross-sectional prospective convenience sampling study
Authors: Funk Ryan S. , Shakhnovich Valentina , Cho Yu Kyoung , Polireddy Kishore , Jausurawong Taina , Gress Kyle , Becker Mara L. 
Published: May 2021

Abstract
Background
Inadequate systemic exposure to infliximab (IFX) is associated with treatment failure. This work evaluated factors associated with reduced IFX exposure in children with autoimmune disorders requiring IFX therapy.

Methods
In this single-center cross-sectional prospective study IFX trough concentrations and anti-drug antibodies (ADAs) were measured in serum from children diagnosed with inflammatory bowel disease (IBD) (n = 73), juvenile idiopathic arthritis (JIA) (n = 16), or uveitis (n = 8) receiving maintenance IFX infusions at an outpatient infusion clinic in a tertiary academic pediatric hospital. IFX concentrations in combination with population pharmacokinetic modeling were used to estimate IFX clearance. Patient demographic and clinical data were collected by chart review and evaluated for their relationship with IFX clearance.

Results
IFX trough concentrations ranged from 0 to > 40 μg/mL and were 3-fold lower in children with IBD compared to children with JIA (p = 0.0002) or uveitis (p = 0.001). Children with IBD were found to receive lower IFX doses with longer dosing intervals, resulting in dose intensities (mg/kg/day) that were 2-fold lower compared to children with JIA (p = 0.0002) or uveitis (p = 0.02). Use of population pharmacokinetic analysis to normalize for variation in dosing practices demonstrated that increased IFX clearance was associated with ADA positivity (p = 0.004), male gender (p = 0.02), elevated erythrocyte sedimentation rate (ESR) (p = 0.02), elevated c-reactive protein (CRP) (p = 0.001), reduced serum albumin concentrations (p = 0.0005), and increased disease activity in JIA (p = 0.009) and IBD (p ≤ 0.08). No significant relationship between diagnosis and underlying differences in IFX clearance was observed. Multivariable analysis by covariate population pharmacokinetic modeling confirmed increased IFX clearance to be associated with anti-IFX antibody positivity, increased ESR, and reduced serum albumin concentrations.

Conclusions
Enhanced IFX clearance is associated with immunogenicity and inflammatory burden across autoimmune disorders. Higher systemic IFX exposures observed in children with rheumatologic disorders are driven primarily by provider drug dose and interval selection, rather than differences in IFX pharmacokinetics across diagnoses. Despite maintenance IFX dosing at or above the standard recommended range for IBD (i.e., 5 mg/kg every 8 weeks), the dosing intensity used in the treatment of IBD is notably lower than dosing intensities used to treat JIA and uveitis, and may place some children with IBD at risk for suboptimal maintenance IFX exposures necessary for treatment response.
Integrase inhibitors versus efavirenz combination antiretroviral therapies for TB/HIV coinfection: a meta-analysis of randomized controlled trials
Authors: Shu Yuanlu , Deng Ziwei , Wang Hongqiang , Chen Yi , Yuan Lijialong , Deng Ye , Tu Xiaojun , Zhao Xiang , Shi Zhihua , Huang Minjiang , Qiu Chengfeng 
Published: May 2021

Abstract
Background
Integrase inhibitors (INIs)-based antiretroviral therapies (ART) are more recommended than efavirenz (EFV)-based ART for people living with HIV/AIDS (PLWHA). Yet, the advantage of integrase inhibitors in treating TB/HIV coinfection is uncertain. Therefore, the objective of this systematic review is to evaluate the effects and safety of INIs- versus EFV-based ART in TB/HIV coinfection, and demonstrate the feasibility of the regimens.

Methods
Four electronic databases were systematically searched through September 2020. Fixed-effects models were used to calculate pooled effect size for all outcomes. The primary outcomes were virologic suppression and bacteriology suppression for INIs- versus EFV-based ART. Secondary outcomes included CD4+ cell counts change from baseline, adherence and safety.

Results
Three trials (including 672 TB/HIV patients) were eligible. ART combining INIs and EFV had similar effects for all outcomes, with none of the point estimates argued against the INIs-based ART on TB/HIV patients. Compared to EFV-based ART as the reference group, the RR was 0.94 (95% CI 0.85 to 1.05) for virologic suppression, 1.00 (95% CI 0.95 to 1.05) for bacteriology suppression, 0.98 (95% CI 0.95 to 1.01) for adherence. The mean difference in CD4+ cell counts increase between the two groups was 14.23 cells/μl (95% CI 0− 6.40 to 34.86). With regard to safety (adverse events, drug-related adverse events, discontinuation for drugs, grade 3–4 adverse events, IRIS (grade 3–4), and death), INIs-based regimen was broadly similar to EFV-based regimens. The analytical results in all sub-analyses of raltegravir- (RAL) and dolutegravir (DTG) -based ART were valid.

Conclusion
This meta-analysis demonstrates similar efficacy and safety of INIs-based ART compared with EFV-based ART. This finding supports INIs-based ART as a first-line treatment in TB/HIV patients. The conclusions presented here still await further validation owing to insufficient data.
The genetic variability, phylogeny and functional significance of E6, E7 and LCR in human papillomavirus type 52 isolates in Sichuan, China
Authors: Song Zhilin , Cui Yanru , Li Qiufu , Deng Junhang , Ding Xianping , He Jiaoyu , Liu Yiran , Ju Zhuang , Fang Liyuan 
Published: May 2021

Abstract
Background
Variations in human papillomavirus (HPV) E6 and E7 have been shown to be closely related to the persistence of the virus and the occurrence and development of cervical cancer. Long control region (LCR) of HPV has been shown multiple functions on regulating viral transcription. In recent years, there have been reports on E6/E7/LCR of HPV-16 and HPV-58, but there are few studies on HPV-52, especially for LCR. In this study, we focused on gene polymorphism of the HPV-52 E6/E7/LCR sequences, assessed the effects of variations on the immune recognition of viral E6 and E7 antigens, predicted the effect of LCR variations on transcription factor binding sites and provided more basic date for further study of E6/E7/LCR in Chengdu, China.

Methods
LCR/E6/E7 of the HPV-52 were amplified and sequenced to do polymorphic and phylogenetic analysis. Sequences were aligned with the reference sequence by MEGA 7.0 to identify SNP. A neighbor-joining phylogenetic tree was constructed by MEGA 7.0, followed by the secondary structure prediction of the related proteins using PSIPRED 4.0. The selection pressure of E6 and E7 coding regions were estimated by Bayes empirical Bayes analysis of PAML 4.9. The HLA class-I and II binding peptides were predicted by the Immune Epitope Database server. The B cell epitopes were predicted by ABCpred server. Transcription factor binding sites in LCR were predicted by JASPAR database.

Results
50 SNP sites (6 in E6, 10 in E7, 34 in LCR) were found. From the most variable to the least variable, the nucleotide variations were LCR > E7 > E6. Two deletions were found between the nucleotide sites 7387–7391 (TTATG) and 7698–7700 (CTT) in all samples. A deletion was found between the nucleotide sites 7287–7288 (TG) in 97.56% (40/41) of the samples. The combinations of all the SNP sites and deletions resulted in 12 unique sequences. As shown in the neighbor-joining phylogenetic tree, except for one belonging to sub-lineage C2, others sequences clustered into sub-lineage B2. No positive selection was observed in E6 and E7. 8 non-synonymous amino acid substitutions (including E3Q and K93R in the E6, and T37I, S52D, Y59D, H61Y, D64N and L99R in the E7) were potential affecting multiple putative epitopes for both CD4+ and CD8+ T-cells and B-cells. A7168G was the most variable site (100%) and the binding sites for transcription factor VAX1 in LCR. In addition, the prediction results showed that LCR had the high probability binding sites for transcription factors SOX9, FOS, RAX, HOXA5, VAX1 and SRY.

Conclusion
This study provides basic data for understanding the relation among E6/E7/LCR mutations, lineages and carcinogenesis. Furthermore, it provides an insight into the intrinsic geographical relatedness and biological differences of the HPV-52 variants, and contributes to further research on the HPV-52 therapeutic vaccine development.