bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surface Functionalization of Three Dimensional-Printed Polycaprolactone-Bioactive Glass Scaffolds by Grafting GelMA Under UV Irradiation
Authors: Ghorbani Farnaz , Sahranavard Melika , Mousavi Nejad Zohre , Li Dejian , Zamanian Ali , Yu Baoqing 
Published: December 2020

In this study, bioactive glass nanoparticles (BGNPs) with an average diameter of less than 10 nm were synthesized using a sol-gel method and then characterized by transmission electron microscopy (TEM), differential scanning calorimetric (DSC), Fourier transforms infrared spectroscopy (FTIR), and x-ray spectroscopy (XRD). Afterward, three dimensional (3D)-printed polycaprolactone (PCL) scaffolds along with fused deposition modeling (FDM) were incorporated with BGNPs, and the surface of the composite constructs was then functionalized by coating with the gelatin methacryloyl (GelMA) under UV irradiation. Field emission scanning electron microscopy micrographs demonstrated the interconnected porous microstructure with an average pore diameter of 260 µm and homogeneous distribution of BGNPs. Therefore, no noticeable shrinkage was observed in 3D-printed scaffolds compared with the computer-designed file. Besides, the surface was uniformly covered by GelMA, and no effect of surface modification was observed on the microstructure while surface roughness increased. The addition of the BGNPs the to PCL scaffolds showed a slight change in pore size and porosity; however, it increased surface roughness. According to mechanical analysis, the compression strength of the scaffolds was increased by the BGNPs addition and surface modification. Also, a reduction was observed in the absorption capacity and biodegradation of scaffolds in phosphate-buffered saline media after the incorporation of BGNPs, while the presence of the GelMA layer increased the swelling potential and stability of the composite matrixes. Moreover, the capability of inducing bio-mineralization of hydroxyapatite-like layers, as a function of BGNPs content, was proven by FE-SEM micrographs, EDX spectra, and x-ray diffraction spectra (XRD) after soaking the obtained samples in concentrated simulated body fluid. A higher potential of the modified constructs to interact with the aqueous media led to better precipitation of minerals. According to in-vitro assays, the modified scaffolds can provide a suitable surface for the attachment and spreading of the bone marrow mesenchymal stem cells (BMSCs). Furthermore, the number of the proliferated cells confirms the biocompatibility of the scaffolds, especially after a modification process. Cell differentiation was verified by alkaline phosphatase activity as well as the expression of osteogenic genes such as osteocalcin and osteopontin. Accordingly, the scaffolds showed an initial potential for reconstruction of the injured bone.
Prevalence and Risk Factors for COPD at High Altitude: A Large Cross-Sectional Survey of Subjects Living Between 2,100–4,700 m Above Sea Level
Authors: Guo Yanfei , Xing Zhenzhen , Shan Guangliang , Janssens Jean-Paul , Sun Tieying , Chai Di , Liu Weiming , Wang Yuxia , Ma Yali , Tong Yaqi , Huang Yilin , Cao Yang , Wang Chen 
Published: December 2020

Aim of Study: Four hundred million people live at high altitude worldwide. Prevalence and risk factors for COPD in these populations are poorly documented. We examined the prevalence and risk factors for COPD in residents living at an altitude of 2,100–4,700 m.Methods: We performed a cross-sectional survey in Xinjiang and Tibet autonomous region. A multistage stratified sampling procedure was used to select a representative population aged 15 years or older from eight high altitude regions. All participants underwent pre- and post-bronchodilator measurement of forced expiratory volumes. COPD was diagnosed according to 2019 Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria.Results: Between June, 2015 and August 2016, 4,967 subjects were included. Median age was 38.0 years (range: 15–91 years; inter-quartile range: 28–49 years); 51.4% participants were female. Overall prevalence of spirometry-defined COPD was 8.2% (95% CI 7.4–8.9%): 9.3% in male (95% CI 8.2–10.4%), and 7.1% in female (95% CI 6.1–8.2%). By multivariable logistic regression analysis, COPD was significantly associated with being aged ≥40 years (odds ratio: 2.25 [95% CI 1.72–2.95], P &lt; 0.0001), exposure to household air pollution (OR: 1.34 [95% CI 1.01–1.79], P = 0.043), and a history of tuberculosis (OR: 1.79 [95% CI 1.23–2.61], P = 0.030), while living at a higher altitude (OR: 0.45 [95% CI 0.33–0.61], P &lt; 0.0001) and having a higher educational level (OR: 0.64 [95% CI 0.43–0.95], P = 0.025) were associated with a lower prevalence of COPD.Conclusions: Our results show that the spirometry-defined COPD is a considerable health problem for residents living at high altitudes and COPD prevalence was inversely correlated with altitude. Preventing exposure to household air pollution and reducing the incidence of tuberculosis should be public health priorities for high altitude residents.
Correlational Analysis of ALS Progression and Serum NfL Measured by Simoa Assay in Chinese Patients
Authors: Sugimoto Kazuo , Han Yi , Song Yuebo , Gao Ying 
Published: December 2020

Background: Neurofilament light chain (NFL) was believed to be a promising biomarker for the diagnosis of Amyotrophic lateral sclerosis (ALS) and disease burden evaluation.Objective: To determine the serum NFL level and its clinical relevance, including its association with disease severity [evaluated by the ALS Functional Rating Scale–revised (ALSFRS-r) score and King's College staging system] and progression (evaluated by the disease progression rate (DPR) and diagnostic delay), in ALS patients in China.Method: Serum NFL levels were detected using the Single Molecule Array (Simoa) technology in 30 ALS patients and 20 healthy controls (HCs).Results: There were significantly elevated levels of serum NFL in patients with ALS than in the HCs (P &lt; 0.001). The serum NFL levels were significantly higher in rapidly progressive ALS and patients in Stage 3 than in slowly progressive ALS and patients in Stage 2 (PDPR &lt; 0.001, PDiagnosticdelay = 0.019; Pstage= 0.033). Furthermore, the serum NFL levels negatively correlated with the diagnostic delay (R2 = 0.23, P = 0.016), the ALSFRS-r score (R2 = 0.15, P = 0.047) and disease duration (R2 = 0.15, P = 0.034), and positively correlated with the DPR (R2 = 0.42, P &lt; 0.001).Conclusions: The present study preliminarily investigated the diagnostic value of serum NFL and its clinical relevance in the Chinese ALS population using the ultrasensitive Simoa technology. The results demonstrated that the level of serum NFL may become a potential biomarker for ALS diagnosis and indicate disease severity and progression.
Imaging Neurochemistry and Brain Structure Tracks Clinical Decline and Mechanisms of ALS in Patients
Authors: Andronesi Ovidiu C. , Nicholson Katharine , Jafari-Khouzani Kourosh , Bogner Wolfgang , Wang Jing , Chan James , Macklin Eric A. , Levine-Weinberg Mark , Breen Christopher , Schwarzschild Michael A. , Cudkowicz Merit , Rosen Bruce R. , Paganoni Sabrina , Ratai Eva-Maria 
Published: December 2020

Background: Oxidative stress and protein aggregation are key mechanisms in amyotrophic lateral sclerosis (ALS) disease. Reduced glutathione (GSH) is the most important intracellular antioxidant that protects neurons from reactive oxygen species. We hypothesized that levels of GSH measured by MR spectroscopic imaging (MRSI) in the motor cortex and corticospinal tract are linked to clinical trajectory of ALS patients.Objectives: Investigate the value of GSH imaging to probe clinical decline of ALS patients in combination with other neurochemical and structural parameters.Methods: Twenty-four ALS patients were imaged at 3 T with an advanced MR protocol. Mapping GSH levels in the brain is challenging, and for this purpose, we used an optimized spectral-edited 3D MRSI sequence with real-time motion and field correction to image glutathione and other brain metabolites. In addition, our imaging protocol included (i) an adiabatic T1ρ sequence to image macromolecular fraction of brain parenchyma, (ii) diffusion tensor imaging (DTI) for white matter tractography, and (iii) high-resolution anatomical imaging.Results: We found GSH in motor cortex (r = −0.431, p = 0.04) and corticospinal tract (r = −0.497, p = 0.016) inversely correlated with time between diagnosis and imaging. N-Acetyl-aspartate (NAA) in motor cortex inversely correlated (r = −0.416, p = 0.049), while mean water diffusivity (r = 0.437, p = 0.033) and T1ρ (r = 0.482, p = 0.019) positively correlated with disease progression measured by imputed change in revised ALS Functional Rating Scale. There is more decrease in the motor cortex than in the white matter for GSH compared to NAA, glutamate, and glutamine.Conclusions: Our study suggests that a panel of biochemical and structural imaging biomarkers defines a brain endophenotype, which can be used to time biological events and clinical progression in ALS patients. Such a quantitative brain endophenotype may stratify ALS patients into more homogeneous groups for therapeutic interventions compared to clinical criteria.
Dopaminergic System Alteration in Anxiety and Compulsive Disorders: A Systematic Review of Neuroimaging Studies
Authors: Dong Mei-Xue , Chen Guang-Hui , Hu Ling 
Published: December 2020

Objective: The dopaminergic system is involved in many psychiatric disorders as a GABAergic, serotonergic, and glutamatergic system. A systematic review and meta-analysis was performed to elucidate the alteration of the dopaminergic system in anxiety and compulsive disorders.Methods: The databases of Pubmed, Embase, and ScienceDirect were searched and articles reporting the involvement of the dopaminergic system in patients with anxiety disorder and obsessive compulsive disorder (OCD) were recognized. The key research data were extracted from the included articles and standardized mean differences were calculated using meta-analyses if there were more than two studies with obtainable data. Sensitivity analyses were further performed to detect the stability of results, and the qualities of all the included studies were assessed using the Newcastle Ottawa scale.Results: Finally, we identified 8 and 11 studies associated with anxiety disorder and OCD for further analysis, respectively. Most consistently, the striatal dopamine D2 receptor (D2R) of OCD patients had decreased while no significant correlation was found between striatal D2R and disease severity. The striatal dopamine transporter (DAT) had not been significantly altered in both the anxiety disorder and OCD patients. The heterogeneity values from the meta-analyses were extremely high while those results remained stable after sensitivity analyses. Inconsistent data were found in the striatal D2R of patients with anxiety disorder. Limited data had suggested that dopamine synthesis increased in most regions of the cerebral cortex and cerebellum in OCD patients.Conclusions: The most convincing finding was that the D2 receptor decreased in patients with obsessive compulsive disorder. The dopamine transporter may have no relationship with anxiety and compulsive disorder.
Tracing of Human Tumor Cell Lineages by Mitochondrial Mutations
Authors: Refinetti Paulo , Morgenthaler Stephan , Thilly William G. , Arstad Christian , Ekstrøm Per O. 
Published: December 2020

BackgroundPrevious studies have shown the value in studying lineage tracing in slices of human tumors. However, a tumor is not a two-dimensional structure and to better understand how a tumor, and its corresponding metastasis grow, a three-dimensional (3-D) view is necessary.ResultsUsing somatic mitochondrial mutations as a marker for lineage tracing, it is possible to identify and follow tumor specific cell lineages. Using cycling temperature capillary electrophoresis (CTCE) a total of 8 tissues from 5 patients (4 primary tumors and 4 metastasis) containing clear mitochondrial markers of tumor lineages were selected. From these 8 tissues over 9,500 laser capture microdisection (LCM) samples were taken and analyzed, in a way that allows 3-D rendering of the observations.ConclusionUsing CTCE combined with LCM makes it possible to study the 3-D patterns formed by tumors and metastasis as they grow. These results clearly show that the majority of the volume occupied by a tumor is not composed of tumor derived cells. These cells are most likely recruited from the neighboring tissue.
Ubiquitin-Like Modifier Activating Enzyme 1 as a Novel Diagnostic and Prognostic Indicator That Correlates With Ferroptosis and the Malignant Phenotypes of Liver Cancer Cells
Authors: Shan Yiru , Yang Guang , Huang Haixia , Zhou Yehan , Hu Xiangyu , Lu Qiuhong , Guo Peng , Hou Jun , Cao Li , Tian Fuhua , Pan Qi 
Published: December 2020

PurposeFerroptosis is a type of cell death that is iron dependent, a characteristic that distinguishes it from necrosis, apoptosis, and autophagy. However, the ferroptotic mechanisms for hepatitis B virus-associated hepatocellular carcinoma (HCC) remain incompletely described.MethodsTwo hepatitis B virus-associated HCC public datasets, GSE22058 (n=192) and GSE54238 (n=23), were obtained from the NCBI Gene Expression Omnibus (GEO) database. Bioinformatics methods, including weighted gene coexpression network analysis (WGCNA), Cox regression, and LASSO analysis, were used to identify signature markers for diagnosis and prognosis. CCK8, wound healing, Transwell migration/invasion, and ferroptosis assays were employed to explore the biological function of novel candidate markers weight gene coexpression network analysis.ResultsIn total, 926 differentially expressed genes (DEGs) were common between the GSE22058 and GSE54238 datasets. Following WGCNA, 515 DEGs derived from the MEturquoise gene module were employed to establish diagnosis and prognosis models in The Cancer Genome Atlas (TCGA) HCC RNA-Seq cohort (n=423). The score of the diagnostic model was strikingly upregulated in the TCGA HCC group (p&lt;2.2e-16). The prognostic model exhibited high specificity and sensitivity in both training and validation (AUC=0.835 and 0.626, respectively), and the high-risk group showed dismal prognostic outcomes compared with the low-risk group (training: p=1.416e-10; validation: p=4.495e-02). Ubiquitin-like modifier activating enzyme 1 (UBA1) was identified among both diagnosis and prognosis signature genes, and its overexpression was associated with poor survival. We validated the expression level of UBA1 in eight pairs of HCC patient tissues and liver cancer cell lines. UBA1 silencing decreased proliferation, migration, and invasion in Huh7 cells while elevating the Fe2+ and malondialdehyde (MDA) levels. Additionally, these biological effects were recovered by oltipraz (an Nrf2 activator). Furthermore, blocking UBA1 strikingly repressed the protein expression levels of Nrf2, HO-1, NQO1, and FTH1 in the Nrf2 signal transduction pathway.ConclusionOur findings demonstrated that UBA1 participates in the development of HCC by modulating Huh7 phenotypes and ferroptosis via the Nrf2 signal transduction pathway and might be a promising diagnostic and prognostic indicator for HCC.
Summary of the Key Concepts on How to Develop a Perinatal Palliative Care Program
Authors: Lago Paola , Cavicchiolo Maria Elena , Rusalen Francesca , Benini Franca 
Published: December 2020

Purpose of review:The aim of this study is to assess the most significant Perinatal Palliative Care (PnPC) development projects in the literature and summarize the shared key principles.Recent findings:PnPC is a new concept in neonatal intensive care approach. Advancements in perinatal diagnostics and medical technology have changed the landscape of the perinatal world. The threshold of viability continues to decrease, and diagnostic information is available earlier in pregnancy and more rapidly at the bedside; overall outcomes continue to improve. This rapid technological improvement brings ethical debates on the quality of life of patients with life-limiting and life-threatening conditions and the need to involve the family in the decision-making process, according to their wishes and cultural beliefs. Although the Perinatal Hospice concept was developed in the 1980s in the US, the first recommendations on how to develop a PnPC pathway were published in the early 2000s. We considered the most relevant position statements or guidelines on PnPC published in the last two decades. Some of them were more pertinent to pediatrics but still useful for the fundamental concepts and PnPC project's development.Summary:Health care providers and institutions are encouraged to develop PnPC programs, which have the goal of maximizing the quality of life of infants with non-curable conditions. These may generally include the following: a formal prenatal consultation; development of a coordinated birth plan between obstetrician, newborn care, and family; access to other neonatal and pediatric specialties, as needed; comfort palliative care during the prenatal, birth, and postnatal periods; and psychosocial and spiritual support for families, siblings, and staff.
Efficacy and Safety of CAR-Modified T Cell Therapy in Patients with Relapsed or Refractory Multiple Myeloma: A Meta-Analysis of Prospective Clinical Trials
Authors: Xiang Xinrong , He Qiao , Ou Yang , Wang Wen , Wu Yu 
Published: December 2020

Background: In recent years, chimeric antigen receptor-modified T (CAR-T) cell therapy for B-cell leukemia and lymphoma has shown high clinical efficacy. Similar CAR-T clinical trials have also been carried out in patients with refractory/relapsed multiple myeloma (RRMM). However, no systematic review has evaluated the efficacy and safety of CAR-T cell therapy in RRMM. The purpose of this study was to fill this literature gap.Methods: Eligible studies were searched in PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), CNKI, and WanFang from data inception to December 2019. For efficacy assessment, the overall response rate (ORR), minimal residual disease (MRD) negativity rate, strict complete response (sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) were calculated. The incidence of any grade cytokine release syndrome (CRS) and grade ≥3 adverse events (AEs) were calculated for safety analysis. The effect estimates were then pooled using an inverse variance method.Results: Overall, 27 studies involving 497 patients were included in this meta-analysis. The pooled ORR and MRD negativity rate were 89% (95% Cl: 83–94%) and 81% (95% Cl: 67–91%), respectively. The pooled sCR, CR, VGPR, and PR were 14% (95% Cl: 5–27%), 13% (95% Cl: 4–26%), 23% (95% Cl: 14–33%), and 15% (95% Cl: 10–21%), respectively. Subgroup analyses of ORR by age, proportion of previous autologous stem cell transplantation (ASCT), and target selection of CAR-T cells revealed that age ≤ 55 years (≤55 years vs. &gt; 55 years, p = 0.0081), prior ASCT ≤70% (≤70% vs. &gt; 70%, p = 0.035), and bispecific CAR-T cells (dual B-cell maturation antigen (BCMA)/BCMA + CD19 vs specific BCMA, p = 0.0329) associated with higher ORR in patients. Subgroup analyses of remission depth by target selection suggested that more patients achieved a better response than VGPR with dual BCMA/BCMA + CD19 CAR-T cells compared to specific BCMA targeting (p = 0.0061). In terms of safety, the pooled incidence of any grade and grade ≥ 3 CRS was 76% (95% CL: 63–87%) and 11% (95% CL: 6–17%). The most common grade ≥ 3 AEs were hematologic toxic effects.Conclusion: In heavily treated patients, CAR-T therapy associates with promising responses and tolerable AEs, as well as CRS in RRMM. However, additional information regarding the durability of CAR-T cell therapy, as well as further randomized controlled trials, is needed.
Effect of Glycosaminoglycan Replacement on Markers of Interstitial Cystitis In Vitro
Authors: Rooney Peadar , Ryan Christina , McDermott Barry J. , Dev Kapil , Pandit Abhay , Quinlan Leo R. 
Published: December 2020

Aims:To examine the effect of three commercial intravesical formulations of glycosaminoglycan onin vitroinflammatory models of IC/BPS to better understand there effect on specific markers of disease.Methods:Human urothelial cells (HTB-4) were cultured under four conditions in the presence or absence of commercial GAG formulations. Cells were cultured under a basal condition or pre-treated with protamine sulfate (100 ng/ml) (damages the endogenous glycosaminoglycan layer), hydrogen peroxide (1%) (a metabolic stressor) or TNFα (10 ng/ml) (creating an inflammatory environment). Each of these four culture conditions was then treated with one of three GAG formulations, CystistatⓇ, iAluRilⓇ and HyacystⓇ. Assays were then performed to examine the effect of the exogenous GAGs on cell viability, cell migration, sGAG production, cytokine and gene expression.Results:All GAG formulations were well tolerated by the HTB-4 cells and supported cell growth and migration. iAluRilⓇ was most effective at stimulating endogenous sGAG production under all conditions, increasing sGAGs by up to 15-fold. All GAG formulations significantly reduced the production of the pro-inflammatory cytokine IL-8 under basal conditions, while no GAG treatment suppressed cytokine production under any other condition. Only CystistatⓇhad a significant effect on HA receptor expression, significantly increasing ICAM-1 expression at 3 h that returned to basal levels at 24 h. No GAG treatment significantly changed the expression of GAG synthesis enzymes (CSGALNACT1, CSGALNACT2) or markers of tissue remodeling (MMP2, TIMP1) and pain (COX-1/PTGS-1, NGF).Conclusions:The data presented in this study reveal that commercial intravesical formulation support cell viability and migration. In addition, the commercial GAG formulations have a mild anti-inflammatory effect in thein vitromodel of interstitial cystitis/bladder pain syndrome.
Antioxidant, Anti-Inflammatory and Anti-Angiogenic Properties of Citrus lumia Juice
Authors: Smeriglio Antonella , Denaro Marcella , D’Angelo Valeria , Germanò Maria Paola , Trombetta Domenico 
Published: December 2020

Citrus juices are a rich source of bioactive compounds with various and well-known health benefits. The aim of this study was to investigate the polyphenols and ascorbic acid content as well as to investigate the antioxidant, anti-inflammatory and anti-angiogenic properties of the juice of an ancient Mediterranean species, Citrus lumia Risso (CLJ). The antioxidant and anti-inflammatory activities were evaluated by several in vitro cell-free and cell-based assays, whereas two different in vivo models, the chick chorioallantoic membrane (CAM) and the zebrafish embryos, were used to characterize the anti-angiogenic properties. Twenty-eight polyphenols were identified by RP-LC-DAD-ESI-MS analysis (flavonoids 68.82% and phenolic acids 31.18%) with 1-caffeoyl-5-feruloylquinic acid and kaempferol 3′-rhamnoside, which represent the most abundant compounds (25.70 and 23.12%, respectively). HPLC-DAD analysis showed a high ascorbic acid content (352 mg/kg of CLJ), which contributes with polyphenols to the marked and dose-dependent antioxidant and anti-inflammatory properties observed. CLJ showed strong and dose-dependent anti-angiogenic activity as highlighted by the inhibition of blood vessel formation on CAMs and the decrease of endogenous alkaline phosphatase on zebrafish embryos. Moreover, within the concentration range tested, no dead or malformed embryos were recorded. Certainly, further studies are needed to investigate the molecular mechanisms underlying these promising biological effects, but considering the evidence of the present study, the use of CLJ as a ready-to drink safe prevention strategy for inflammatory-based diseases correlated to angiogenesis could be justified.