bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of intraoral scans in the mixed dentition: a prospective non-randomized comparative clinical trial
Authors: Liczmanski Konrad , Stamm Thomas , Sauerland Cristina , Blanck-Lubarsch Moritz 
Published: May 2020

Abstract
Objective
In-vivo accuracy of intraoral scans of complete mixed dentitions of patients in active treatment have not yet been investigated. The aim was to test the hypothesis that dimensional differences between intraoral scans and conventional alginate impressions in the mixed dentition are clinically irrelevant.

Methods
Trial design: Prospective non-randomized comparative clinical trial. Based on sample size calculation 44 evaluable mixed dentition jaws of patients in active orthodontic treatment were included. Each patient received an alginate impression following an intraoral scan (TRIOS® Ortho). Plaster cast was fabricated and scanned with an external scanner (ATOS-SO®). Both STL datasets were analyzed with the 3D inspection and mesh processing software GOM Inspect®. Statistical analysis comprised sample size calculation, t-test as well as nonparametric tests.

Results
The absolute mean difference between digital plaster casts and intraoral scans is 0.022 mm ± 0.027 mm (median 0.015 mm). The obtained measurements are in the range of comparable studies on full arch permanent dentitions. Gender, the size of the jaw represented by the dentition stage and upper respectively lower jaw, as well the malocclusion have no effect on the total deviations between digital plaster casts and intraoral scans. Detectable impression errors were bubbles in fissures and marginal ridges as well as incomplete alginate flow and detachment from the tray. Detectable scanning errors were incomplete distal surface of the most distal molar.

Conclusion
Dimensional differences between intraoral scans and conventional alginate impressions in the mixed dentition are clinically irrelevant for orthodontic purposes. In all clinical situations of active treatment in the mixed dentition, the intraoral scans are more detailed and less error-prone.
Systematic analysis and identification of the absorption and metabolic components of Zengye decoction in type 2 diabetic rats by HPLC-ESI-Q-TOF–MS/MS
Authors: Chang Shanquan , Wang Mei , Tian Yushan , Qi Jin , Qiu Zhixia 
Published: May 2020

Abstract
Background
Zengye decoction (ZYD) has been widely used in the treatment of type 2 diabetes mellitus (T2DM). Exploring the fate of various components of ZYD in vivo is of considerable significance for pharmacological research and molecular mechanism elaboration. However, the systematic analysis on the metabolic behavior of chemical components of ZYD in T2DM rats has not been reported.

Methods
To screen and characterize the complex chemical compositions of ZYD, and metabolism fate in plasma, urine, bile, and feces of T2DM rats, the model of T2DM rats was prepared. A rapid procedure using high-performance liquid chromatography coupled with electrospray ionization quadrupole time of flight tandem mass spectrometry (HPLC-ESI-Q-TOF–MS/MS) was established. Data were acquired and analyzed by Agilent MassHunter Workstation Qualitative Analysis software version B.07.00 and PCDL manager B.07.00.

Results
A total of 80 compounds were identified or tentatively characterized in ZYD, 31 more than previously detected. Besides, 36 prototype components and 49 metabolites of ZYD were found and characterized in T2DM rats, and the proposed fragmentation pathways and possible metabolic behaviors of the main types of compounds were described.

Conclusions
This study developed the understanding of the composition of ZYD as well as the cleavage rules and metabolic pathways of the prototype compounds. Besides, this study provided abundant data for further research and for study of the metabolism of traditional Chinese medicine prescriptions.
ERα-36 regulates progesterone receptor activity in breast cancer
Authors: Konan Henri-Philippe , Kassem Loay , Omarjee Soleilmane , Surmieliova-Garnès Ausra , Jacquemetton Julien , Cascales Elodie , Rezza Amélie , Trédan Olivier , Treilleux Isabelle , Poulard Coralie , Le Romancer Muriel 
Published: May 2020

Abstract
Background
Alterations in estrogen and progesterone signaling, via their respective receptors, estrogen receptor alpha (ERα) and progesterone receptor (PR), respectively, are largely involved in the development of breast cancer (BC). The recent identification of ERα-36, a splice variant of ERα, has uncovered a new facet of this pathology. Although ERα-36 expression is associated with poor prognosis, metastasis development, and resistance to treatment, its predictive value has so far not been associated with a BC subtype and its mechanisms of action remain understudied.

Methods
To study ERα-36 expression in BC specimens, we performed immunochemical experiments. Next, the role of ERα-36 in progesterone signaling was investigated by generating KO clones using the CRISPR/CAS9 technology. PR signaling was also assessed by proximity ligation assay, Western blotting, RT-QPCR, and ChIP experiments. Finally, proliferation assays were performed with the IncuCyte technology and migration experiments using scratch assays.

Results
Here, we demonstrate that ERα-36 expression at the plasma membrane is correlated with a reduced disease-free survival in a cohort of 160 BC patients, particularly in PR-positive tumors, suggesting a crosstalk between ERα-36 and PR. Indeed, we show that ERα-36 interacts constitutively with PR in the nucleus of tumor cells. Moreover, it regulates PR expression and phosphorylation on key residues, impacting the biological effects of progesterone.

Conclusions
ERα-36 is thus a regulator of PR signaling, interfering with its transcriptional activity and progesterone-induced anti-proliferative effects as well as migratory capacity. Hence, ERα-36 may constitute a new prognostic marker as well as a potential target in PR-positive BC.
Evaluation of resistance to pyrethroid and organophosphate adulticides and kdr genotyping in Aedes aegypti populations from Roraima, the northernmost Brazilian State
Authors: Hayd Ramão Luciano Nogueira , Carrara Luana , de Melo Lima Joel , de Almeida Nathalia Coelho Vargas , Lima José Bento Pereira , Martins Ademir Jesus 
Published: May 2020

Abstract
Background
Roraima, the northernmost State in Brazil, borders Venezuela and Guyana. Although mostly covered by the tropical forests, the urban centers of this state are highly infested with Ae. aegypti and are endemic for dengue, Zika and chikungunya. We accessed the insecticide resistance status of Ae. aegypti populations from the capital Boa Vista, two cities on international borders (Pacaraima and Bonfim) and Rorainópolis bordering Amazonas State, in order to evaluate the chemical control efficacy in these localities.

Methods
Tests with World Health Organization (WHO)-like tubes impregnated with the pyrethroid deltamethrin (0.05% and 0.12%) and the organophosphate malathion (0.7%) were conducted with Ae. aegypti from Boa Vista, Pacaraima, Bonfim and Rorainópolis, collected in 2016 and 2018. Genotyping of kdr mutations, related to resistance to pyrethroids, was performed for the SNP variations at sites 1016 and 1534 of the voltage gated sodium channel gene (NaV) with a TaqMan qPCR approach.

Results
Aedes albopictus was absent in our collections, and therefore only Ae. aegypti was tested. All Ae. aegypti populations were susceptible to 0.7% malathion in 2016; however, mortality dropped to under 90% in Bonfim and Pacaraima populations in 2018. All populations were resistant to 0.05% deltamethrin in both years. The time that 50% of females suffered knockdown (KdT50) under exposure to 0.05% deltamethrin was 3.3–5.9-fold longer in mosquitoes from the natural populations compared to the susceptible Rockefeller strain. Only the Pacaraima population (2018) remained resistant to 0.12% deltamethrin. Kdr genotyping revealed the absence of the wild-type NaVS haplotype (1016Val + 1534Phe) in the populations from Roraima, indicating that all tested insects had a genetic background for pyrethroid resistance. The double kdr NaVR2 haplotype (1016Ile + 15434Cys) was present in higher frequencies in all populations except for Rorainópolis, where this haplotype seems to have arrived recently.

Conclusions
These results are important for the knowledge about insecticide resistance status of Ae. aegypti populations from Roraima and will help improve vector control strategies that may be applied to diverse localities under similar geographical and urban conditions.
Changes of circulating neuregulin 4 and its relationship with 25-hydroxy vitamin D and other diabetic vascular complications in patients with diabetic peripheral neuropathy
Authors: Yan Pijun , Zhang Zhihong , Miao Ying , Xu Yong , Zhu Jianhua , Wan Qin 
Published: May 2020

Abstract
Background
Neuregulin 4 (Nrg4) is a novel neurotrophic adipokine associated with the development of diabetic peripheral neuropathy (DPN), however, the pathological mechanism remains poorly understood. The purpose of our study was to investigate the association of circulating Nrg4 with DPN and 25-hydroxy vitamin D [25(OH)D], a multifunctional secosteroid hormone that regulates other neurotrophic factors and adipokines gene expression, and other diabetic vascular complications.

Methods
Circulating Nrg4 levels were measured with an ELISA kit in 164 newly diagnosed type 2 diabetes mellitus (nT2DM) patients. The relationship between circulating Nrg4 and DPN and other parameters was analyzed.

Results
Circulating Nrg4 levels were significantly lower in nT2DM patients with DPN than those without, and subjects in the highest quartile of circulating Nrg4 had significantly lower vibration perception threshold (VPT), the prevalence of DPN, the proportion of persons with VPT > 25 V, and significantly higher circulating 25(OH)D (all P < 0.01). Moreover, circulating Nrg4 was positively and independently associated with 25(OH)D, and was negatively with VPT (P < 0.01 or P < 0.05), but showed no associations with the prevalence of peripheral arterial disease, diabetic nephropathy, and diabetic retinopathy (all P > 0.05). Additionally,the prevalence of DPN and risk of DPN development were progressively decreased with increasing circulating Nrg4 quartiles, independently of potential confounding factors.

Conclusions
These data demonstrate that decreased levels of circulating Nrg4 might lead to the development of DPN through its close interaction with circulating 25(OH)D not with other diabetic vascular complications. Further prospective studies are needed to identify our findings in these populations.
Co-culture of hWJMSCs and pACs in double biomimetic ACECM oriented scaffold enhances mechanical properties and accelerates articular cartilage regeneration in a caprine model
Authors: Zhang Yu , Hao Chunxiang , Guo Weimin , Peng Xiaoyu , Wang Mingjie , Yang Zhen , Li Xu , Zhang Xueliang , Chen Mingxue , Sui Xiang , Peng Jiang , Lu Shibi , Liu Shuyun , Guo Quanyi , Jiang Qing 
Published: May 2020

AbstractBackgroundThe dedifferentiation of chondrocytes and the unstable chondrogenic differentiation status of pluripotent mesenchymal stem cells (MSCs) are immense issues in cell-based articular cartilage repair and regenerative strategies. Here, to improve the cartilage characteristics of seed cells, a double biomimetic acellular cartilage extracellular matrix (ACECM)-oriented scaffold was used to mimic the cartilage microenvironment for human umbilical cord Wharton’s jelly-derived MSCs (hWJMSCs) and primary cartilage cells (pACs) to regenerate hyaline cartilage.MethodsA double biomimetic ACECM-oriented scaffold was created from the cartilage extracellular matrix of pig articular cartilage using pulverization decellularization freeze-drying procedures. hWJMSCs and pACs were co-cultured at ratios of 50:50 (co-culture group, ACCC), 0:100 (ACAC group) and 100:0 (ACWJ group) in the ACECM-oriented scaffold, and the co-culture system was implanted in a caprine model for 6 months or 9 months to repair full-thickness articular cartilage defects. The control groups, which had no cells, comprised the blank control (BC) group and the ACECM-oriented scaffold (AC) group. Gross morphology and magnetic resonance imaging (MRI) as well as histological and biomechanical evaluations were used to characterize the cartilage of the repair area.ResultsRelative to the control groups, both the gross morphology and histological staining results demonstrated that the neotissue of the ACCC group was more similar to native cartilage and better integrated with the surrounding tissue. Measurements of glycosaminoglycan content and Young’s modulus showed that the repair areas had more abundant cartilage-specific content and significantly higher mechanical strength in the ACCC group than in the control groups, especially at 9 months. On MRI, the T2-weighted signal of the repair area was homogeneous, and the oedema signal disappeared almost completely in the ACCC group at 9 months. HLA-ABC immunofluorescence staining demonstrated that hWJMSCs participated in the repair and regeneration of articular cartilage and escaped surveillance and clearance by the caprine immune system.ConclusionThe structure and components of double biomimetic ACECM-oriented scaffolds provided a cartilage-like microenvironment for co-cultured seed cells and enhanced the biomechanics and compositions of neotissue. This co-culture system has the potential to overcome the dedifferentiation of passage chondrocytes and the unstable chondrogenic differentiation status of MSCs.
Inhibition of LSD1 promotes the differentiation of human induced pluripotent stem cells into insulin-producing cells
Authors: Yang Xiao-Fei , Zhou Shu-Yan , Wang Ce , Huang Wei , Li Ning , He Fei , Li Fu-Rong 
Published: May 2020

Abstract
Background
Human induced pluripotent stem cells (hiPSCs) represent a potentially unlimited source of pancreatic endocrine lineage cells. Although insulin-producing β cells derived from hiPSCs have been successfully induced, much work remains to be done to achieve mature β cells. Lysine-specific demethylase 1 (LSD1) plays an important role in the regulation of hiPSC self-renewal and differentiation. We propose a new strategy to acquire insulin-producing cells (IPCs) from hiPSCs by knocking down LSD1.

Methods
Knockdown of LSD1 in hiPSCs with five shRNA. Assessment of the effects of shRNA on hiPSC proliferation, cell cycle, and apoptosis. Using knockdown hiPSCs with 31.33% LSD1 activity, we achieved a four-step differentiation into IPCs and test its differentiation efficiency, morphology, and marker genes and proteins. We implanted the IPCs into the renal subcapsular of SCID-Beige diabetic mice to evaluate the hypoglycemic effect in vivo. We tested LSD1 and HDAC1 whether they are present in the CoREST complex through IP-WB, and analyzed LSD1, CoREST, HDAC1, H3K4me2/me3, and H3K27me3 protein expression before and after knockdown of LSD1.

Results
Differentiated hiPSCs were 38.32% ± 3.54% insulin-positive cells and released insulin/C-peptide in response to glucose stimulus in a manner comparable to adult human islets. Most of the IPCs co-expressed mature β cell-specific markers. When transplanted under the left renal capsule of SCID-Beige diabetic mice, these IPCs reversed hyperglycemia, leading to a significant increase in the definitive endoderm cells. IP-WB results showed that LSD1, HDAC1, and CoREST formed a complex in hiPSCs. Chip-PCR results showed that LSD1, HDAC1, and CoREST were enriched in the same district during the SOX17 and FOXA2 promoter region. Inhibition of LSD1 would not affect the level of CoREST but decreased the HDAC1 expressions. The H3K4me2/me3 and H3K9act level of SOX17 and FOXA2 promoter region increased after inhibited of LSD1, and promoted transcriptional activation. The H3K4me2/me3 and H3K9act level of OCT4 and SOX2 promoter region decreased with the transcriptional repressed.

Conclusions
LSD1 regulated histone methylation and acetylation in promoter regions of pluripotent or endodermal genes. Our results suggest a highly efficient approach to producing IPCs from hiPSCs.
Shadow and extended shadow cost sharing associated to informal long-term care: the case of Spain
Authors: Del Pozo-Rubio Raúl , Moya-Martínez Pablo , Ortega-Ortega Marta , Oliva-Moreno Juan 
Published: May 2020

Abstract
Background
A large part of the long-term care is provided by non-professional caregivers, generally without any monetary payment but a value economic of time invested. The economic relevance of informal caregivers has been recognized in Spain; however, public provision may still be scarce. The objective of this paper is to estimate the economic burden associated with informal long-term care that should assume the families through a new concept of cost sharing that consider opportunity costs of time provided by informal caregivers.

Methods
The study sample includes all dependent adults in Spain. Socioeconomic information and the number of hours of informal care was collected through the Spanish Disability and Dependency Survey. The terms of shadow and extended shadow cost sharing were defined as the difference between the maximum potential amount of money that families could receive for the provision of informal care and the amount that actually they received and the value of informal care time with respect to the amount received, respectively.

Results
53.87% of dependent persons received an economic benefit associated to informal care. The average weekly hours of care were 71.59 (92.62 without time restrictions). Shadow cost sharing amounted to, on average, two thirds, whereas the State financed the remaining third. In terms of extended shadow cost sharing, the State financed between 3% and 10% of informal care provided by caregivers.

Conclusions
This study reveals the deficient support received for the provision of informal care in Spain. More than 90% of informal care time is not covered by the economic benefits that families receive from the State.
Early sepsis markers in patients admitted to intensive care unit with moderate-to-severe diabetic ketoacidosis
Authors: Blanchard Florian , Charbit Judith , Van der Meersch Guillaume , Popoff Benjamin , Picod Adrien , Cohen Regis , Chemouni Frank , Gaudry Stephane , Bihan Helene , Cohen Yves 
Published: May 2020

Abstract
Background
Bacterial infections are frequent triggers for diabetic ketoacidosis. In this context, delayed antibiotic treatment is associated with increased morbidity and mortality. Unnecessary administration of antimicrobial therapy might however, also negatively impact the prognosis. The usefulness of sepsis markers in diabetic ketoacidosis has not been assessed. Thus, we sought to investigate diagnostic performances of clinical and biological sepsis markers during diabetic ketoacidosis.

Methods
In this monocentric retrospective cohort study, all consecutive episodes of diabetic ketoacidosis (defined as pH ≤ 7.25, glycaemia > 300 mg/dL and presence of ketones) admitted in intensive care unit were included. A proven bacterial infection was defined as bacteriological documentation on any bacterial sample. Clinical (presence of fever: temperature > 38 °C and presence of hypothermia: temperature < 36 °C) and biological markers (whole blood count, neutrophils count, neutrophils-to-lymphocytes count ratio and procalcitonin), recorded at admission, were compared according to the presence or absence of a proven bacterial infection.

Results
Between 2011 and 2018, among 134 episodes of diabetic ketoacidosis, 102 were included (91 patients). Twenty out of 102 were infected. At admission, procalcitonin (median: 3.58 ng/mL vs 0.52 ng/mL, p < 0.001) and presence of fever (25% vs 4%, p = 0.007) were different between episodes with and without proven bacterial infection in both univariate and multivariate analysis. Whole blood count, neutrophils count, neutrophils-to-lymphocytes count ratio and presence of hypothermia were not different between both groups. The diagnostic performance analysis for procalcitonin revealed an area under the curve of 0.87 with an optimal cutoff of 1.44 ng/mL leading to a sensitivity of 0.90 and a specificity of 0.76. Combining procalcitonin and presence of fever allowed to distinguish proven bacterial infection episodes from those without proven bacterial infection. Indeed, all patients with procalcitonin level of more than 1.44 ng/mL and fever had proven bacterial infection episodes. The presence of one of these 2 markers was associated with 46% of proven bacterial infection episodes. No afebrile patient with procalcitonin level less than 1.44 ng/mL had a proven bacterial infection.

Conclusion
At admission, combining procalcitonin and presence of fever may be of value to distinguish ketoacidosis patients with and without proven bacterial infection, admitted in intensive care unit.
Fundamental limits of single anchor-based cooperative localization in millimeter wave systems
Authors: Zhao Feng , Huang Tiancheng , Wang Donglin 
Published: May 2020

AbstractThanks to massive antenna arrays in millimeter wave communications, a much higher resolution can be achieved for the estimation of angle of arrival. By taking full advantage of beamforming capability and high angular resolution in millimeter wave systems, a single anchor is sufficient to obtain a good position estimation for agents by combining angle of arrival and time of arrival. In this paper, a single-anchor based cooperative localization is proposed for millimeter wave systems. Fundamental limits of cooperative localization with a single anchor is investigated, where all nodes are equipped with massive antenna arrays. Bounds of time-based range and position estimation are derived by Crámer-Rao bound in general multipath channels. For the single-anchor based cooperative localization, the structure of the fisher information matrix is investigated and the relationship between ranging accuracy and positioning accuracy is theoretically clarified. Numerical results demonstrate a consistency with theory behind the proposed millimeter wave’s cooperative localization network.