bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effects of Foods on Blood Lipids in Non-alcoholic Fatty Liver Disease (NAFLD)—A Systematic Review and Meta-Analysis
Authors: Rosqvist Fredrik , Rydell Andreas , Iggman David 
Published: January 2021

Background: Non-alcoholic fatty liver disease (NAFLD) is associated with dyslipidemia and increased cardiovascular disease risk. Dietary choices may produce profound effects on blood lipids. Thus, the purpose of this study was to investigate which foods modify blood lipids in NAFLD.Methods: Systematic review of published systematic reviews and randomized controlled trials (RCTs). Searches were performed in PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, from inception through March 2020. Studies in populations with NAFLD, which provided data on foods or dietary patterns and blood lipids were included, but not weight loss diets, supplements, nor individual nutrients. The strength of evidence was evaluated using The Grading of Recommendations Assessment, Development, and Evaluation (GRADE).Results: No relevant systematic reviews were identified. Eleven RCTs were included in the qualitative synthesis. Two RCTs were included in meta-analyses, regarding the comparison between Mediterranean and Low-fat diets, in which there were no clear effects on either high-density lipoprotein cholesterol or triglycerides, with Low evidence. From single RCTs, there was Moderate evidence for reduced triglycerides by a healthy dietary pattern, compared with usual care; and for reduced total cholesterol by a probiotic yogurt, enriched with Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12, compared with conventional yogurt. For all other comparisons, the evidence was considered as Low or Very low.Conclusion: Few studies were identified which reported effects of foods on blood lipids in subjects with NAFLD. The possible beneficial effect of probiotics warrants further study. PROSPERO identifier: CRD42020178927.
Genotyping Squamous Cell Lung Carcinoma in Colombia (Geno1.1-CLICaP)
Authors: Cardona Andrés F. , Ruiz-Patiño Alejandro , Arrieta Oscar , Ricaurte Luisa , Zatarain-Barrón Zyanya Lucia , Rodriguez July , Avila Jenny , Rojas Leonardo , Recondo Gonzalo , Barron Feliciano , Archila Pilar , Sotelo Carolina , Bravo Melissa , Zamudio Nataly , Corrales Luis , Martín Claudio , Rolfo Christian , Viola Lucia , Carranza Hernán , Vargas Carlos , Otero Jorge , Bermudez Maritza , Gamez Tatiana , Pino Luis Eduardo , Rosell Rafael 
Published: January 2021

BackgroundLung cancer is a public health problem, and squamous cell carcinoma (SCC) is the second most prevalent subtype of this neoplasm. Compared to other subtypes, including adenocarcinoma, SCC is less well understood in terms of molecular pathogenesis, limiting therapeutic options among targeted agents approved for other disease subgroups. In this study, we sought to characterize the SCC genomic profile using a validated Next Generation Sequencing (NGS) platform.MethodsThe comprehensive NGS assay (TruSight Tumor 170) was used in order to target the full coding regions of 170 cancer-related genes on SCC samples. PD-L1 expression in tumor cells (TCs) was assessed using clone 22C3 (Dako). Clinical outcomes were correlated with molecular profile, including progression free survival (PFS), overall response rate (ORR), and overall survival (OS).ResultsA total of 26 samples were included, median age was 67 years (r, 33–83) and 53.8% were men. Tobacco consumption was identified in all subjects (mean 34-year package). For first-line treatment 80.8% of patients received cisplatin or carboplatin plus gemcitabine. In terms of molecular profile, we identified a high prevalence of inactivating mutations in TP53 (61.5%), PIK3CA (34.6%), MLL2 (34.6%), KEAP1 (38.4%), and NOTCH1 (26.9%). PD-L1 expression ranged from negative, 1, 2–49, and ≥50% in 23.1, 38.5, 26.9, and 11.5%, respectively. Interestingly, the genetic alterations did not have an effect in PFS, OS or ORR in this study. However, PDL1 expression was higher among those who had mutations in TP53 (p = 0.037) and greater expression of PDL1 was related to PIK3CA alterations (p = 0.05).ConclusionsThe genomic profile of SCC encompasses important genes including TP53, PIK3CA and KEAP1. TP53 mutations could be associated with PDL1 expression, generating hypothesis regarding specific treatment options.
Pentoxifylline Sensitizes Cisplatin-Resistant Human Cervical Cancer Cells to Cisplatin Treatment: Involvement of Mitochondrial and NF-Kappa B Pathways
Authors: Bravo-Cuellar Alejandro , Ortiz-Lazareno Pablo Cesar , Sierra-Díaz Erick , Solorzano-Ibarra Fabiola , Méndez-Clemente Anibal Samael , Aguilar-Lemarroy Adriana , Jave-Suárez Luis Felipe , Ruiz Velazco-Niño Édgar , Hernández-Flores Georgina 
Published: January 2021

BackgroundCervical cancer continues to be a major public health problem worldwide, and Cisplatin is used as first-line chemotherapy for this cancer; however, malignant cells exposed to CISplatin (CIS) become insensitive to the effects of this drug. PenToXifylline (PTX) is a xanthine that sensitizes several types of tumor cells to apoptosis induced by antitumor drugs, such as Adriamycin, Carboplatin, and CIS. The effects of PTX on tumor cells have been related to the disruption of the NF-κB pathway, thus preventing the activation of cell survival mechanisms such as the expression of anti-apoptotic genes, the secretion of proinflammatory interleukins, and growth factors.ObjectiveIn this work, we studied the antitumor proprieties of PTX in human SiHa cervical carcinoma cells resistant to CIS.Materials and MethodsSiHa and HeLa cervical cancer cells and their CIS-resistant derived cell lines (SiHaCIS-R and HeLaCIS-R, respectively) were used as in-vitro models. We studied the effects of PTX alone or in combination with CIS on cell viability, apoptosis, caspase-3, caspase-8, and caspase-9 activity, cleaved PARP-1, anti-apoptotic protein (Bcl-2 and Bcl-xL) levels, p65 phosphorylation, cadmium chloride (CdCl2) sensitivity, Platinum (Pt) accumulation, and glutathione (GSH) levels, as well as on the gene expression of GSH and drug transporters (influx and efflux).ResultsPTX sensitized SiHaCIS-R cells to the effects of CIS by inducing apoptosis, caspase activation, and PARP-1 cleavage. PTX treatment also decreased p65 phosphorylation, increased Pt levels, depleted GSH, and downregulated the expression of the ATP7A, ATP7B, GSR, and MGST1 genes.ConclusionPTX reverses the acquired phenotype of CIS resistance close to the sensitivity of parental SiHa cells.
Cowpea Mosaic Virus Nanoparticle Enhancement of Hypofractionated Radiation in a B16 Murine Melanoma Model
Authors: Duval Kayla E. A. , Wagner Robert J. , Beiss Veronique , Fiering Steven N. , Steinmetz Nicole F. , Hoopes P. Jack 
Published: January 2021

IntroductionVirus and virus-like nanoparticles (VNPs) have been used for a variety of preclinical treatments, including in situ anti-cancer vaccination. The Cowpea mosaic virus (CPMV) is a VNP that has shown the ability to stimulate an anti-cancer immune response. The hypothesis of this study is two-fold: that intratumoral CPMV enhances the immunogenetic and cytotoxic response of hypofractionated radiation (15 Gy or 3 x 8 Gy), and that the effect differs between fraction regimens in the murine B16 flank melanoma model.MethodsCPMV nanoparticles were delivered intratumorally, 100 μg/tumor to B16 murine melanoma flank tumors alone, and in combination with either 15 Gy or 3 x 8 Gy (3 consecutive days). Tumors were assessed for immune and cytotoxic gene and protein expression, and cytotoxic T cell infiltration 4 days post treatment. Treatment based tumor control was assessed by a 3-fold tumor growth assay.ResultsBoth CPMV and radiation alone demonstrated the activation of a number of important immune and cytotoxic genes including natural killer cell and T cell mediated cytotoxicity pathways. However, the combination treatment activated greater expression than either treatment alone. CPMV combined with a single dose of 15 Gy demonstrated greater immune and cytotoxic gene expression, protein expression, CD8+ T cell infiltration activity, and greater tumor growth delay compared to 3 x 8 Gy with CPMV.ConclusionCPMV presents a unique and promising hypofractionated radiation adjuvant that leads to increased anti-tumor cytotoxic and immune signaling, especially with respect to the immune mediated cytotoxicity, immune signaling, and toll-like receptor signaling pathways. This improvement was greater with a single dose than with a fractionated dose.
Value of N1 Lymph Node Examination in the Prognosis of Patients With pT1-3N0M0 Non-Small Cell Lung Cancer
Authors: Wang Gaoxiang , Wu Xianning , Sun Xiaohui , Li Tian , Xu Meiqing , Xu Liangdong , Xie Mingran 
Published: January 2021

ObjectiveThis study aimed to analyze the relationship between the number of examined lymph nodes (ELNs) at the N1 station and the postoperative clinicopathological features and prognosis of patients with pT1-3N0M0 non-small cell lung cancer (NSCLC).MethodsThe cut-off value of the number of ELNs at the N1 station was obtained using X-tile software analysis. Kaplan-Meier survival curve analysis and the Cox proportional hazard model were used to study the impact of the number of ELNs at the N1 station on the prognosis of postoperative patients with pT1-3N0M0 NSCLC.ResultsThe median survival time and 1-, 3- and 5-year survival rates of 0 ELNs at the N1 station were 28.0 months and 74.8%, 45.4%, and 21.2%, respectively. The median survival time and 1-, 3-, and 5-year survival rates of 1–4 ELNs at the N1 station were 45.0 months and 85.5%, 55.4%, and 39.1%, respectively. In the group with ≥ 5 ELNs at the N1 station, the median survival time and the 1-, 3- and 5-year survival rates were 59.0 months and 94.0%, 62.7%, and 48.2%, respectively. Both univariate and multivariate Cox regression analyses showed that the number of ELNs at the N1 station, T stage and operation type were independent factors affecting the prognosis of patients with pT1-3N0M0 NSCLC.ConclusionIncreasing the number of ELNs at the N1 station is positively correlated with the long-term survival rate of patients with T1-3N0M0 NSCLC. At least 5 LNs at the N1 station should be examined in pathological examination.
Microsatellite Status Affects Tumor Response and Survival in Patients Undergoing Neoadjuvant Chemotherapy for Clinical Stage III Gastric Cancer
Authors: Cai Zhenghao , Rui Weiwei , Li Shuchun , Fingerhut Abraham , Sun Jing , Ma Junjun , Zang Lu , Zhu Zhenggang , Zheng Minhua 
Published: January 2021

BackgroundWe assessed the association between microsatellite instability-high (MSI-H) and tumor response to neoadjuvant chemotherapy (NAC) as well as its prognostic relevance in patients with clinical stage III gastric cancer (cStage III GC).Materials and MethodsThe NAC + surgery and the control cohorts consisted of 177 and 513 cStage III GC patients, respectively. The clinical and pathological features were compared between patients with MSI-H [n=57 (8.3%)] and microsatellite stability or microsatellite instability-low (MSS/MSI-L) [n=633 (91.7%)]. Radiological and histological response to NAC were evaluated based on response evaluation criteria in solid tumors (RECIST) and tumor regression grade (TRG) systems, respectively. The log-rank test and Cox analysis were used to determine the survival associated with MSI status as well as tumor regression between the two groups in both NAC + surgery and the control cohorts.ResultsA statistically significant association was found between MSI-H and poor histological response to NAC (p=0.038). Significant survival priority of responders over poor-responders could only be observed in MSS/MSI-L but not in MSI-H tumors. However, patients with MSI-H had statistically significantly better survival compared to patients with MSS/MSI-L in both the NAC + surgery (hazard ratio=0.125, 95% CI, 0.017–0.897, p=0.037 ) and the control cohort (hazard ratio=0.479, 95% CI, 0.268–0.856, p=0.013).ConclusionMSI-H was associated with poorer regression and better survival after NAC for cStage III GC. TRG evaluation had prognostic significance in MSS/MSI-L but not in MSI-H. Further studies are needed to assess the value of NAC for cStage III GC patients with MSI-H phenotype.
Long Non-Coding RNA 554 Promotes Cardiac Fibrosis via TGF-β1 Pathway in Mice Following Myocardial Infarction
Authors: Luo Bihui , He Zhiyu , Huang Shijun , Wang Jinping , Han Dunzheng , Xue Hao , Liu Peiying , Zeng Xiaojun , Lu Dongfeng 
Published: January 2021

Rationale: Cardiac fibrosis is observed in nearly every form of myocardial disease. Long non-coding RNAs (lncRNAs) have been shown to play an important role in cardiac fibrosis, but the detailed molecular mechanism remains unknown.Object: We aimed at characterizing lncRNA 554 expression in murine cardiac fibroblasts (CFs) after myocardial infarction (MI) to identify CF-enriched lncRNA and investigate its function and contribution to cardiac fibrosis and function.Methods and Results: In this study, we identified lncRNA NONMMUT022554 (lncRNA 554) as a regulator of MI-induced cardiac fibrosis. We found that lncRNA 554 was significantly up-regulated in the mouse hearts following MI. Further study showed that lncRNA 554 was predominantly expressed in cardiac fibroblasts, indicating a potential role of lncRNA 554 in cardiac fibrosis. In vitro knockdown of lncRNA 554 by siRNA suppressed fibroblasts migration and expression of extracellular matrix (ECM); while overexpression of lncRNA 554 promoted expression of ECM genes. Consistently, lentivirus mediated in vivo knockdown of lncRNA 554 could inhibit cardiac fibrosis and improve cardiac function in mouse model of MI. More importantly, TGF-β1 inhibitor (TEW-7197) could reverse the pro-fibrotic function of lncRNA 554 in CFs. This suggests that the effects of lncRNA 554 on cardiac fibrosis is TGF-β1 dependent.Conclusion: Collectively, our study illustrated the role of lncRNA 554 in cardiac fibrosis, suggested that lncRNA 554 might be a novel target for cardiac fibrosis.
Subacute Toxicity Study of Nicotinamide Mononucleotide via Oral Administration
Authors: You Yingnan , Gao Yang , Wang Han , Li Jingshu , Zhang Xiang , Zhu Zhengjiang , Liu Nan 
Published: January 2021

Nicotinamide mononucleotide (NMN), a key precursory metabolite of NAD+, has been shown to elevate the cellular level of NAD+ and ameliorate various age-related diseases. Despite these progresses, systemic evaluation pertaining to the subacute toxicity of NMN remains to be determined. Here, we examine the subacute toxicity of NMN in mice and beagle dogs. Mice were gavaged with a saturated concentration of NMN solution at the maximum intragastric dose once or twice per day for 7 days. Dogs were gavaged twice per day for 14 days. In mice, NMN administrated once per day for 7 days is well tolerated with minimal deleterious effects. Upon higher dosage, we observe slightly increased level of alamine aminotransferase, while other biomarkers remain unchanged. Consistently, administration of NMN in beagle dogs only results in mild increases in creatinine and uric acid. Together, our study highlights the safety of NMN, providing a possible safe dose range for oral administration of NMN.
Neuropsychiatric Outcome of Children Born to Women With Systemic Lupus Erythematosus and Exposed in Utero to Azathioprine: A Case-Control Study
Authors: Lazzaroni Maria-Grazia , Andreoli Laura , Crisafulli Francesca , Tamborini Francesco , Debeni Irene , Binda Valentina , Nalli Cecilia , Galli Jessica , Fazzi Elisa , Moroni Gabriella , Franceschini Franco , Tincani Angela 
Published: January 2021

Objective: The long-term outcome of children born to SLE mothers still represents a controversial topic in literature, with some studies reporting a possible increased prevalence of different neurologic and psychiatric diseases (NPD), including neurodevelopmental disorders (ND), and in particular learning disorders (LD). Different risk factors have been advocated, such as the in utero exposure to auto-antibodies and drugs, particularly Azathioprine (AZA).Methods: A case-control study was designed to compare pregnancies treated with AZA (cases) with those not treated with AZA (controls). All the pregnancies had been prospectively followed in two Italian centers. The match was based upon renal involvement, antiphospholipid (aPL) status, maternal age at pregnancy (±5 years) and child’s age at the time of the study (±2 years). SLE mothers were interviewed by a telephone survey, particularly focused on the presence of a certified NPD in their children ≥6 years of age.Results: Twenty-seven cases and 65 controls were similar in terms of demographic, immunological and clinical features, except for a higher rate of SLE flares during pregnancy in cases (22.2% vs. 10.8%, p:0.191). The 92 children had a mean age of 14.0 years at the time of the survey; 11 had at least one NPD (12.0%). The frequency of each single NPD was similar to that of the general pediatric population and no association was found with either the in utero exposure to AZA, or other specific factors (auto-antibodies, disease activity, obstetric complications, prematurity).Conclusion: The long-term neuropsychiatric outcome of the children born to SLE mothers did not show neither an increased frequency of NPD as compared to the general pediatric population nor a specific pattern of NPD. The in utero exposure to AZA was not associated with the development of NPD in this case-control study of prospectively-followed pregnancies. NPD are complex conditions and large prospective studies are needed to capture the wide range of variables that may contribute to their development in the offspring of SLE women.
art.pics Database: An Open Access Database for Art Stimuli for Experimental Research
Authors: Thieleking Ronja , Medawar Evelyn , Disch Leonie , Witte A. Veronica 
Published: January 2021

While art is omnipresent in human history, the neural mechanisms of how we perceive, value and differentiate art has only begun to be explored. Functional magnetic resonance imaging (fMRI) studies suggested that art acts as secondary reward, involving brain activity in the ventral striatum and prefrontal cortices similar to primary rewards such as food. However, potential similarities or unique characteristics of art-related neuroscience (or neuroesthetics) remain elusive, also because of a lack of adequate experimental tools: the available collections of art stimuli often lack standard image definitions and normative ratings. Therefore, we here provide a large set of well-characterized, novel art images for use as visual stimuli in psychological and neuroimaging research. The stimuli were created using a deep learning algorithm that applied different styles of popular paintings (based on artists such as Klimt or Hundertwasser) on ordinary animal, plant and object images which were drawn from established visual stimuli databases. The novel stimuli represent mundane items with artistic properties with proposed reduced dimensionality and complexity compared to paintings. In total, 2,332 novel stimuli are available open access as “art.pics” database at https://osf.io/BTWNQ/ with standard image characteristics that are comparable to other common visual stimuli material in terms of size, variable color distribution, complexity, intensity and valence, measured by image software analysis and by ratings derived from a human experimental validation study [n = 1,296 (684f), age 30.2 ± 8.8 y.o.]. The experimental validation study further showed that the art.pics elicit a broad and significantly different variation in subjective value ratings (i.e., liking and wanting) as well as in recognizability, arousal and valence across different art styles and categories. Researchers are encouraged to study the perception, processing and valuation of art images based on the art.pics database which also enables real reward remuneration of the rated stimuli (as art prints) and a direct comparison to other rewards from e.g., food or money.Key Messages: We provide an open access, validated and large set of novel stimuli (n = 2,332) of standardized art images including normative rating data to be used for experimental research. Reward remuneration in experimental settings can be easily implemented for the art.pics by e.g., handing out the stimuli to the participants (as print on premium paper or in a digital format), as done in the presented validation task. Experimental validation showed that the art.pics’ images elicit a broad and significantly different variation in subjective value ratings (i.e., liking, wanting) across different art styles and categories, while size, color and complexity characteristics remained comparable to other visual stimuli databases.
An Investigation of the Effectiveness of Arts Therapies Interventions on Measures of Quality of Life and Wellbeing: A Pilot Randomized Controlled Study in Primary Schools
Authors: Moula Zoe , Powell Joanne , Karkou Vicky 
Published: January 2021

BackgroundOver the last decades there has been a change in the way schooling is perceived recognizing that children’s learning is closely linked to children’s health. Children spend most of their time at school, which is often the place where problems are identified and interventions are offered, not only for treatment but also prevention. Embedding arts therapies into the educational system may help address children’s emerging needs and have a positive impact on their wellbeing.MethodsA pilot cross-over randomized controlled design was employed to investigate the effectiveness of an arts therapies intervention on a series of child- and teacher-reported outcome measures, specifically, health related quality of life (assessed using a HRQOL scale; EQ-5D-Y), wellbeing and life functioning (assessed using the child outcome rating scale; CORS), emotional and behavioral difficulties (assessed using the strengths and difficulties questionnaire; SDQ), as well as duration of sleep (assessed using Fitbits). Sample size calculations for future large-scale studies were also performed, and the sustained impact of the intervention was evaluated at 3, 6, and 12 months follow-up. The pluralistic theoretical and therapeutic framework of this intervention was informed by a systematic review on school-based arts therapies interventions and is presented in detail in the study protocol. Participants were 62 children with mild emotional and behavioral difficulties.ResultsImprovements in HRQOL and CORS were greater in those engaged in the arts therapies intervention than the control groups and were maintained at the follow-up stages. Significant improvements were only found for duration of sleep (P = 0.002) and SDQ (P = 0.008). Minimal clinically important differences (MCIDs) as defined in the published protocol were found for CORS, SDQ and duration of sleep, but not HRQOL.DiscussionFindings indicate that the arts therapies interventions were having a clinically significant effect on life functioning, duration of sleep, emotional and behavioral difficulties. Findings also indicate a small effect size for health related quality of life, suggesting the intervention was having a small positive effect on this outcome measure. The study indicates that all outcome measures assessed here would be suitable for inclusion in a larger randomized controlled study utilizing these arts therapies interventions, and that a sample size of 225 participants would be required if these outcome measures were used.