bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing the equity gap in child health care and health system reforms in Latin America
Authors: Maceira Daniel , Brumana Luisa , Aleman Joaquín González 
Published: February 2022

Abstract
Background
During the first decade of the current century, Latin American countries have shown high and consistent economic growth rates, increasing per capita GDP and reducing poverty. Social indicators improved in even the poorest and least equitable countries in the region. In terms of health care results, marked advances were made in infant mortality rates.

Objective
The aim of this paper is to identify if decreasing poverty rates in Latin America and the Caribbean during the first decade of the century have had an effect on health inequality, specifically by reducing the health care equity gap and, if so, whether that trend and its effects were distributed evenly at the sub-national level.

Methods
Basic statistical tools were applied to national and sub-national administrative data for eleven Latin American countries (Argentina, Belize, Bolivia, Brazil, Colombia, Dominican Republic, El Salvador, Mexico, Nicaragua, Peru, and Uruguay) to compare the evolution of a set of social determinants with a classic health care outcome, such infant mortality) during the period 1995–2012. This document proposes a set of indicators to analyze relative evolution of results and convergence to equity, and to discuss general trends in health care reforms across the region.

Results
The document shows a correspondence between poverty reduction, and improvement of health care indicators at a regional level, though national differences persist. In some cases, like Brazil and Peru, the reduction in infant mortality rates is coupled with significant movements towards health equity. This trend is different in Bolivia, where the drop in poverty is not followed by better outcomes in poor departments. At the same, results are not necessarily linked to health systems organization and/or specific reforms. For instance, both Brazil and Peru pursue in applying decentralized solutions, although the incentive mechanisms are quite different: the former has a supply side structure at the public provision level while the latter has implemented mixed payment systems.

Conclusion
While some of the same instruments and measures of effectiveness in health care reforms appear across the region, specific impact evaluations should be performed. To reduce the equity gap in Latin America requires not only major improvements in social determinants but also the design and implementation of sound institutional policy and more robust regulatory frameworks (institutional determinants) so that more resources yield better practices.
The impact of body mass index (BMI) on MRI diagnostic performance and surgical management for axillary lymph node in breast cancer
Authors: Chen Shu-Tian , Lai Hung-Wen , Wu Wen-Pei , Chen Shou-Tung , Liao Chiung-Ying , Wu Hwa-Koon , Chen Dar-Ren , Mok Chi Wei 
Published: February 2022

Abstract
Background
We hypothesized that different BMI might have different impact on pre-operative MRI axillary lymph node (ALN) prediction accuracy and thereby subsequent surgical lymph node management. The aim of this study is to evaluate the effect of BMI on presentation, surgical treatment, and MRI performance characteristics of breast cancer with the main focus on ALN metastasis evaluation.

Methods
The medical records of patients with primary invasive breast cancer who had pre-operative breast MRI and underwent surgical resection were retrospectively reviewed. They were categorized into 3 groups in this study: underweight (BMI < 18.5), normal (BMI of 18.5 to 24), and overweight (BMI > 24). Patients’ characteristics, surgical management, and MRI performance for axillary evaluation between the 3 groups were compared.

Results
A total of 2084 invasive breast cancer patients with a mean age of 53.4 ± 11.2 years were included. Overweight women had a higher rate of breast conserving surgery (56.7% vs. 54.5% and 52.1%) and initial axillary lymph node dissection (15.9% vs. 12.2% and 8.5%) if compared to normal and underweight women. Although the post-operative ALN positive rates were similar between the 3 groups, overweight women were significantly found to have more axillary metastasis on MRI compared with normal and underweight women (50.2% vs 37.7% and 18.3%). There was lower accuracy in terms of MRI prediction in overweight women (65.1%) than in normal and underweight women (67.8% and 76.1%).

Conclusion
Our findings suggest that BMI may influence the diagnostic performance on MRI on ALN involvement and the surgical management of the axilla in overweight to obese women with breast cancer.
Proton magnetic resonance spectroscopy detects cerebral metabolic derangement in a mouse model of brain coenzyme a deficiency
Authors: Li Yanan , Steinberg Jeffrey , Coleman Zane , Wang Shubo , Subramanian Chitra , Li Yimei , Patay Zoltan , Akers Walter , Rock Charles O. , Jackowski Suzanne , Bagga Puneet 
Published: February 2022

Abstract
Background
Pantothenate kinase (PANK) is the first and rate-controlling enzymatic step in the only pathway for cellular coenzyme A (CoA) biosynthesis. PANK-associated neurodegeneration (PKAN), formerly known as Hallervorden–Spatz disease, is a rare, life-threatening neurologic disorder that affects the CNS and arises from mutations in the human PANK2 gene. Pantazines, a class of small molecules containing the pantazine moiety, yield promising therapeutic effects in an animal model of brain CoA deficiency. A reliable technique to identify the neurometabolic effects of PANK dysfunction and to monitor therapeutic responses is needed.

Methods
We applied 1H magnetic resonance spectroscopy as a noninvasive technique to evaluate the therapeutic effects of the newly developed Pantazine BBP-671.

Results
1H MRS reliably quantified changes in cerebral metabolites, including glutamate/glutamine, lactate, and N-acetyl aspartate in a neuronal Pank1 and Pank2 double-knockout (SynCre+Pank1,2 dKO) mouse model of brain CoA deficiency. The neuronal SynCre+Pank1,2 dKO mice had distinct decreases in Glx/tCr, NAA/tCr, and lactate/tCr ratios compared to the wildtype matched control mice that increased in response to BBP-671 treatment.

Conclusions
BBP-671 treatment completely restored glutamate/glutamine levels in the brains of the mouse model, suggesting that these metabolites are promising clinically translatable biomarkers for future therapeutic trials.
Modulation of the tumor microenvironment by armed vesicular stomatitis virus in a syngeneic pancreatic cancer model
Authors: Tang Sijia , Shi Lei , Luker Breona T. , Mickler Channen , Suresh Bhavana , Lesinski Gregory B. , Fan Daping , Liu Yuan , Luo Ming 
Published: February 2022

Abstract
Background
The immunosuppressive microenvironment in pancreatic ductal adenocarcinoma is a major factor that limits the benefits of immunotherapy, especially immune checkpoint blockade. One viable strategy for reverting the immunosuppressive conditions is the use of an oncolytic virus (OV) in combination with other immunotherapy approaches. Infection of PDAC cells with a robust OV can change the tumor microenvironment and increase tumor antigen release by its lytic activities. These changes in the tumor may improve responses to immunotherapy, including immune checkpoint blockade. However, a more potent OV may be required for efficiently infecting pancreatic tumors that may be resistant to OV.

Methods
Vesicular stomatitis virus, a rapid replicating OV, was armed to express the Smac protein during virus infection (VSV-S). Adaptation by limited dilution largely increased the selective infection of pancreatic cancer cells by VSV-S. The engineered OV was propagated to a large quantity and evaluated for their antitumor activities in an animal model.

Results
In a syngeneic KPC model, intratumoral injection of VSV-S inhibited tumor growth, and induced increasing tumor infiltration of neutrophils and elimination of myeloid derived suppressor cells and macrophages in the tumor. More importantly, M2-like macrophages were eliminated preferentially over those with an M1 phenotype. Reduced levels of arginase 1, TGF-β and IL-10 in the tumor also provided evidence for reversion of the immunosuppressive conditions by VSV-S infection. In several cases, tumors were completely cleared by VSV-S treatment, especially when combined with anti-PD-1 therapy. A long-term survival of 44% was achieved.

Conclusions
The improved OV, VSV-S, was shown to drastically alter the immune suppressive tumor microenvironment when intratumorally injected. Our results suggest that the combination of potent OV treatment with immune checkpoint blockade may be a promising strategy to treat pancreatic cancer more effectively.
Identification of immune-infiltrated hub genes as potential biomarkers of Moyamoya disease by bioinformatics analysis
Authors: Jin Fa , Duan Chuanzhi 
Published: February 2022

Abstract
Background
Moyamoya disease (MMD) is a rare chronic progressive cerebrovascular disease. Recent studies have shown that autoimmune inflammation may also be an important pathology in MMD but the molecular mechanisms of inflammation in this disease are still large unknown. This study was designed to identify key biomarkers and the immune infiltration in vessel tissue of MMD using bioinformatics analysis.

Methods
Raw gene expression profiles (GSE157628, GSE141024) were downloaded from the Gene Expression Omnibus (GEO) database, identified differentially expressed genes (DEGs) and performed functional enrichment analysis. The CIBERSORT deconvolution algorithm was used to analyze the proportion of immune cells between MMD and an MMD-negative control group. We screened for neutrophil-associated DEGs, constructed a protein–protein interaction network (PPI) using STRING, and clarified the gene cluster using the Cytoscape plugin MCODE analysis. The receiver operating characteristic (ROC) curve was applied to test and filter the best gene signature.

Results
A total of 570 DEGs were detected, including 212 downregulated and 358 up-regulated genes. Reactome and KEGG enrichment revealed that DEGs were involved in the cell cycle, molecular transport, and metabolic pathways. The immune infiltration profile demonstrated that MMD cerebrovascular tissues contained a higher proportion of neutrophils, monocytes, and natural killer cells in MMD than in controls. The PPI network and MCODE cluster identified nine DEGs (UNC13D, AZU1, PYCARD, ELANE, SDCBP, CCL11, CCL15, CCL20, and CXCL5) associated with neutrophil infiltration. ROC results showed that UNC13D has good specificity and sensitivity (AUC = 0.7846).

Conclusions
The characteristics of immune infiltration in the cerebrovascular tissues of MMD patients and abnormal expression of hub genes provide new insights for understanding MMD progression. UNC13D is shows promise as a candidate molecule to determine neutrophil infiltration characteristics in MMD.
Concordance between the schedule for the evaluation of individual quality of life-direct weighting (SEIQoL-DW) and the EuroQoL-5D (EQ-5D) measures of quality of life outcomes in adults with X-linked hypophosphatemia
Authors: Jandhyala Ravi 
Published: February 2022

Abstract
Background
Accurate measurement of any constructs in clinical studies is of critical importance, especially if the adoption of an intervention relies on detecting a significant treatment effect where one exists. Under Neutral theory, the amount of relevant and irrelevant indicators selected to operationalise the construct contribute equally to the accuracy of the observation. The Neutral or accurate observation is achieved by observing all relevant indicators only. Generic QoL instruments such as EQ-5D are increasingly being accepted as imprecise, especially in rare diseases, based on the relevance of their indicators. QoL is a construct that embodies a patient's subjectivity, individuality, and local circumstances at measurement. SEIQoL-DW is an instrument designed to respect these characteristics of QoL through eliciting indicators or cues directly from the subject along with the proportion of the overall QoL they contribute. EQ-5D and SEIQoL can therefore be considered as being at opposing ends of accuracy in QoL measurement. XLH is a hereditary, progressive, rare disease characterised by phosphate wasting, affecting both children and adults and impacting their QoL. The purpose of this study was to observe if any change in QoL of adult XLH patients were detectable using EQ-5D, SEIQoL eliciting new cues at each visit, and SEIQoL administering baseline cues overall visits (thereby silencing its time-dependency) versus baseline over 12 months. In addition, any association between the three sets of observations was explored.

Results
All quality of life scores were observed to decrease from baseline by 13.36%, 7.32% and 2.7% based on SEIQoLvisit_cues, SEIQoLbaseline_cues, and EQ-5D assessments, respectively. The decrease in the quality of life scores was only statistically significant (p = 0.037) for SEIQoLvisit_cues. Beyond the baseline visit, the only highly positive and statistically significant pairwise association was between SEIQoLvisit_cues and SEIQoLbaseline_cues at M6 (ρ = 0.782, P value < 0.05) and M9 (ρ = 0.879, P value < 0.05).

Conclusions
EQ-5D and SEIQoLbaseline_cues failed to detect the same statistically significant decrease in QoL observed by SEIQoLvisit_cues. Both sets of SEIQoL observations were more closely associated with each other than with EQ-5D. Observing constructs such as QoL in rare diseases benefit from a Neutrality in indicator selection and respecting variation in dominance of various indicators over time.
Construction and immune effect of an HPV16/18/58 trivalent therapeutic adenovirus vector vaccine
Authors: Wan Bing , Qin Lu , Ma Weihong , Wang He 
Published: February 2022

Abstract
Objective
This study aims to prepare candidate vaccines for cervical cancer immunotherapy by inserting the fused genes of human papillomavirus (HPV)16/18/58 mE6E7 lacking transforming activity into an adenovirus vector and to verify its efficiency in model mice with tumor expressing the associated HPV genes.

Methods
The E6/E7 genes of HPV16/18/58 were point-mutated to abolish their transforming activity, and adenovirus (AD)-HPV16/18/58 mE6E7 adenovirus vaccine was constructed. The immune effect of the adenovirus vaccine against HPV16/18/58-type tumors was analyzed by tumor morphology, enzyme linked immunosorbent assay, enzyme-linked immunospot and specific cytotoxic T lymphocyte (CTL) and T lymphocyte subsets.

Results
The HPV16/18/58 mE6E7 plasmid containing point mutations was verified by quantitative real-time polymerase chain reaction (qRT-PCR), enzyme digestion and electrophoresis, and gene sequencing. qRT-PCR and Western blots verified that AD-HPV16/18/58 mE6E7 could express the HPV16 mE6E7, HPV18 mE6E7 and HPV58 mE6E7 fusion genes and proteins in cells. The results of animal experiments were as follows: In the vaccine group, the tumors formed later, the incubation period was longer, the growth was slower, growth was inhibited, and the survival period was significantly prolonged. The immunological results all showed that the vaccine could induce effective humoral and cellular immunity in mice with three types of tumors, compared with the phosphate buffered saline (PBS) group and the adenovirus-negative control (AD-NC) group, the differences were statistically significant (P < 0.05).

Conclusion
We successfully constructed the HPV16/18/58 trivalent therapeutic adenovirus vaccine AD-HPV16/18/58 mE6E7. The AD-HPV16/18/58 mE6E7 adenovirus vaccine can protect immunized mice to a certain extent from TC-1, U14/LV-HPV18 E6E7 and U14/LV-HPV58 E6E7 cells, which contain HPV16, 18 and 58 E6 and/or E7 genes, respectively.
SARS-CoV-2 infection as possible downstream disease precipitator in autoantibody-positive insulin-dependent diabetes mellitus: a case report
Authors: Schiaffini Riccardo , Campana Andrea , Deodati Annalisa , Peschiaroli Emanuela , Lanzillotta Maria Francesca , Fierabracci Alessandra 
Published: February 2022

Abstract
Background
SARS-CoV-2 causes lesions, in addition to lung, in endocrine organs such as the pancreas through ACE2 receptor. Recently the relationship between SARS-CoV-2 exposition and the incidence or evolution of clinical autoimmune diabetes has attracted the attention of diabetologists.

Case presentation
We report the analysis of the clinical history of a child diagnosed for insulin-dependent diabetes mellitus (Type 1 diabetes) at the time a paucisymptomatic COVID-19 infection occurred, followed by well-controlled metabolic status. As opposite to previous findings SARS-CoV2 did not cause ketosis and ketoacidosis. Polydipsia was reported a few months and weight loss 4 weeks before SARS- CoV-2 infection suggesting that SARS-CoV-2 could not be the trigger of Type 1 diabetes in this patient.

Conclusions
SARS-CoV-2 in this patient was an unexpected event in the course of disease. We advance the hypothesis that the SARS-CoV-2 infection, even if paucisymptomatic could have acted in the present case report as a hypothetical downstream precipitating factor; whilst the inciting triggering event of the autoimmune disease, as confirmed by the presence of circulating autoantibodies, could have occurred even before, as generally assumed for this category of disorders. The precipitating mechanism could have been the acute interaction between virus and the ACE receptor on the beta cells, at the time that hyperglycemia and glycosuria were ascertained, and HbA1c levels confirmed a metabolic dysregulation over the previous 3 months in absence of ketoacidosis.
A novel apolipoprotein E mutation, ApoE Ganzhou (Arg43Cys), in a Chinese son and his father with lipoprotein glomerulopathy: two case reports
Authors: Wang Runxiu , Zhao Chengbo , Chen Wen , Liu Zhiping , Xie Fuhua 
Published: February 2022

Abstract
Background
Lipoprotein glomerulopathy is a rare and newly recognized glomerular disease that can lead to kidney failure. Its pathological features include the presence of lipoprotein embolus in the loop cavity of glomerular capillaries. It is believed that apolipoprotein E gene mutation is the initiator of the disease. Since the discovery of lipoprotein glomerulopathy, 16 different apolipoprotein E mutations have been reported worldwide, but most of these cases are sporadic. Here we report two cases of lipoprotein glomerulopathy, a Chinese son and his father, with a novel apolipoprotein E mutation, ApoE Ganzhou (Arg43Cys).

Case presentation
Case 1, a 33-year-old Chinese man, was hospitalized on 3 March 2014 owing to edema and weakness of facial and lower limbs for 1 month. Laboratory data showed urine protein 3+, hematuria 2+, serum creatinine 203 μmol/L, uric acid 670 μmol/L, total cholesterol 12.91 mmol/L, triglyceride 5.61 mmol/L, high-density lipoprotein 1.3 mmol/L, low-density lipoprotein 7.24 mmol/L, apolipoprotein B 2.48 g/L, and lipid protein (a) 571 mg/L. Renal tissue examined by immunofluorescence and electron microscopy indicated lipoprotein glomerulopathy. Case 2, 55-year-old father of case 1, was hospitalized on 12 January 2016 owing to edema of his lower extremities for 6 months. Laboratory data showed urine protein 2+, hematuria 2+, serum creatinine 95 μmol/L, uric acid 440 μmol/L, total cholesterol 4.97 mmol/L, triglyceride 1.91 mmol/L, high-density lipoprotein 1.18 mmol/L, low-density lipoprotein 3.12 mmol/L, apolipoprotein B 2.48 g/L, and lipid protein (a) 196 mg/L. Renal tissue examined by immunofluorescence and electron microscopy indicated lipoprotein glomerulopathy. Apolipoprotein E mutation test showed that they had the same gene mutation, a novel type of apolipoprotein E mutation.
Based on their clinical presentation and examination findings, they were diagnosed with lipoprotein glomerulopathy. Case 1 was treated with prednisone and dual plasma replacement, followed by simvastatin, nifedipine, triptolide, and angiotensin II receptor blocker drug therapy. After 1 month, the edema symptoms of the patient were alleviated, and urinary protein, serum creatinine, and uric acid were quantitatively reduced. Case 2 was treated with Tripterygium wilfordii and angiotensin II receptor blocker drugs for 3 weeks, and his edema symptoms were alleviated, and urinary protein, serum creatinine, and uric acid were quantitatively reduced.

Conclusions
The apolipoprotein E mutation in the two cases we reported was a familial aggregation phenomenon, and the mutation is a novel type, which we named ApoE Ganzhou (Arg43Cys). The location of the gene mutation is close to the most common mutation type of lipoprotein glomerulopathy, ApoE Kyoto (Arg25Cys), so we speculate that its pathogenic role might be the similar to that of ApoE Kyoto (Arg25Cys).
Note on difference equations with the right-hand side function nonincreasing in each variable
Authors: Stević Stevo , Iričanin Bratislav , Kosmala Witold , Šmarda Zdeněk 
Published: February 2022

AbstractWe present an example of a difference equation of arbitrary order, possessing the right-hand side function that is homogeneous to a certain degree and nonincreasing in each variable, which has a unique positive equilibrium, as well as solutions that do not converge to the equilibrium. The example shows that the main result in the paper: O. Moaaz, Dynamics of difference equation $x_{n+1}=f(x_{n-l}, x_{n-k})$

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Approximation by bivariate Chlodowsky type Szász–Durrmeyer operators and associated GBS operators on weighted spaces
Authors: Aslan Reşat , Mursaleen M. 
Published: February 2022

AbstractIn this article, we consider a bivariate Chlodowsky type Szász–Durrmeyer operators on weighted spaces. We obtain the rate of approximation in connection with the partial and complete modulus of continuity and also for the elements of the Lipschitz type class. Moreover, we examine the degree of convergence with regard to the weighted modulus of continuity and Peetre’sK-functional. Further, we construct the associated GBS type of these operators and estimate the degree of approximation using the mixed modulus of continuity and a class of the Lipschitz of Bögel type continuous functions. Finally, with the help of Maple software, we present the comparisons of the convergence of the bivariate Chlodowsky type Szász–Durrmeyer operators and associated GBS type operators to certain functions with some graphs and error estimation tables.
What drives internationalization of new ventures? Evidence from India
Authors: Arafat Mohd. Yasir , Khan Ahmed Musa , Ansari Mohd Shamim , Saleem Imran 
Published: February 2022

AbstractThe researchers have already recognized the importance of entrepreneurship, but the role of new venture internationalization is still a matter of research. This study is measuring the influence of education, age, technology, fear of failure, and competition on new venture internationalization. It based on the interviews of 3413 respondents from India done by the Global Entrepreneurship Monitor. The influence of various factors on new venture internationalization has been measured through logistic regression. The technology, fear of failure, and competition have a significantly positive influence on new venture internationalization. This is one of the inceptive studies to measure the impact of education, age, technology, fear of failure and competition on new venture internationalization.