bluuebunny/crossref_metadata_2025_split huggingface dataset:
LASSO type Penalized Spline Regression for Binary Data
Authors: Mullah Muhammad , Hanley James , Benedetti Andrea 
Published: October 2020

Abstract
Background: Generalized linear mixed models (GLMMs), typically used for analyzing correlated data, can also be used for smoothing by considering the knot coefficients from a regression spline as random effects. The resulting models are called semiparametric mixed models (SPMMs). Allowing the random knot coefficients to follow a normal distribution with mean zero and a constant variance is equivalent to using a penalized spline with a ridge regression type penalty. We introduce the least absolute shrinkage and selection operator (LASSO) type penalty in the SPMM setting by considering the coefficients at the knots to follow a Laplace double exponential distribution with mean zero. Methods: We adopt a Bayesian approach and use the Markov Chain Monte Carlo (MCMC) algorithm for model fitting. Through simulations, we compare the performance of curve fitting in a SPMM using a LASSO type penalty to that of using ridge penalty for binary data. We apply the proposed method to obtain smooth curves from data on the relationship between the amount of pack years of smoking and the risk of developing chronic obstructive pulmonary disease (COPD). Results: The LASSO penalty performs as well as ridge penalty for simple shapes of association and outperforms the ridge penalty when the shape of association is complex or linear. Conclusion: We demonstrated that LASSO penalty captured complex dose-response association better than the Ridge penalty in a SPMM.
PET/MR Imaging for the Evaluation of Cervical Cancer During Pregnancy
Authors: Ishiguro Tatsuya , Nishikawa Nobumichi , Ishii Shiro , Yoshihara Kosuke , Haino Kazufumi , Yamaguchi Masayuki , Adachi Sosuke , Watanabe Takafumi , Soeda Shu , Enomoto Takayuki 
Published: October 2020

Abstract
Background: To assess the diagnostic value of positron emission tomography/magnetic resonance imaging (PET/MRI) for cervical cancer propagation before surgery, especially in pregnant women.Methods: 18F Fluorodeoxyglucose (FDG)-PET/MRI was performed in seven pregnant cervical cancer patients (28 - 34 years old) at 9-18 gestational weeks. In case #5, a second PET/MRI was performed at 24 gestational weeks. Results: Of seven FDG-PET/MRI examination series in six cases (cases #1-#6), FDG-PET/MR imaging could detect cervical tumors with abnormal FDG accumulation; these tumors were confirmed with a standardized uptake value max (SUV max) titer of 4.5 - 16. A second PET/MRI examination in case #5 revealed the same SUV max titer as the first examination. In these six imaging series (cases #1-#5), there were no signs of cancer metastasis to the parametrium and lymph nodes. However, in case #6, abnormal FDG accumulation in the left parametrial lymph nodes was also detectable. Pathological examination showed lymph node metastasis in case #6. In case #7, PET/MRI could not detect any abnormal FDG accumulation in the cervix and other sites. Cone biopsy demonstrated only micro-invasive squamous cell carcinoma. After treatment for cervical cancer, all seven patients have had no recurrence of disease within the follow-up period (2.4 – 5.2 years), and their children have developed appropriately.Conclusion: PET/MRI is an effective and relatively safe imaging tool to evaluate cervical cancer progression in pregnancy.
Clinical effects of probiotic or azithromycin as an adjunct to scaling and root planing in the treatment of periodontitis stage III: A pilot randomized controlled clinical trial
Authors: Morales Alicia , Contador Rafael , Bravo Joel , Carvajal Paola , Silva Nora , Strauss Franz Josef , Gamonal Jorge 
Published: October 2020

Abstract
Background: The aim of this triple- blind placebo- controlled parallel- arm randomized clinical trial was to evaluate the clinical effects of Lactobacillus rhamnosus SP1 or azithromycin as an adjunct to scaling and root planing (SRP) in patients with stage III periodontitis.Methods: Forty-seven systemically healthy participants with stage III periodontitis were recruited. Following SRP, the participants were randomly assigned to one of three treatment modalities; 1) placebo (n=15), 2) probiotics (n=16) and 3) antibiotics-azithromycin (n=16). The participants were monitored at baseline, 3, 6, 9 and 12 months after therapy. Probing pocket depth (PPD), bleeding on probing (BOP), clinical attachment loss (CAL) and plaque accumulation (PI) were evaluated. Results: All 47 participants completed the study. At 12 months, all groups showed significant improvements of PPD and PI (p<0.012) irrespective of the treatment modality and without significant differences between the groups. Probiotics and azithromycin showed no added benefit in terms of CAL. While the placebo (p=0.002) and the antibiotic-azithromycin (p=0.002) group showed a significant reduction of BOP, only the placebo group revealed a significant reduction of CAL at 12 months follow-up (p=0.003). The number of sites and teeth with PPD ≥5, ≥6 and ≥7mm were significantly reduced in all groups at 12 months follow-up (p<0.025) irrespective of the treatment regime and without significant differences between the groups. Conclusion: The use of probiotics or azithromycin as an adjunct to SRP failed to provide additional benefits in the treatment of stage III periodontitis. The benefits of these two treatment regimes as an adjunct to SRP remain unclear.
Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorate Airway Inflammation in a Rat Model of chronic obstructive pulmonary disease (COPD)
Authors: Ridzuan Noridzzaida , Zakaria Norashikin , Widera Darius , Sheard Jonathan , Morimoto Mitsuru , Kiyokawa Hirofumi , Isa Seoparjoo Azmel Mohd , Singh Gurjeet Kaur Chatar , Then Kong-Yong , Ooi Ghee-Chien , Yahaya Badrul Hisham 
Published: October 2020

Abstract
Background: Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin. Methods: In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSCs) derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSCs-derived EVs. Lung tissue was subjected to histological analysis using hematoxylin and eosin staining, alcian blue-periodic acid Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t-test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median±standard deviation (SD). Results: Both, transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, as well as a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions: In conclusion, we show that hUC-MSCs-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free based therapy for the treatment of COPD.
Feeding malic acid to chickens at slaughter age benefits poultry production and microbial safety in regard to Campylobacter
Authors: Ren Fangzhe , Yang Wenbin , Hu Juanjuan , Huang Pinyu , Jiao Xin-an , huang jinlin 
Published: October 2020

Abstract
Background

Chicken meat has become popular for consumption worldwide. However, chicken flocks suffer the Campylobacter infection during the rearing period, which allows chicken meat products act as a vehicle for transmitting this pathogen through the food chain and bring great health and economic burden to the public. Malic acid is a dicarboxylic organic acid with antimicrobial activity, the application of malic acid during food animal rearing period also found could improve the performance of animals and the quality of their products. This study applied malic acid to chicken flocks and evaluated its potential benefits on the poultry production and microbial safety.
Results

In Experiment 1, AA broilers and partridge chicken were provided with the malic acid-supplemented drinking water for three weeks, although the Campylobacter carriages were found decreased by 0.91–0.98 log after the first week of use (P < 0.05). However, this effect was not consistent, significant decontamination could not be found in the second and the third week of application. Thus, in Experiment 2, the malic acid-supplemented drinking water was used for five days to flocks at slaughter age, the Campylobacter carriage was found decreased by 1.05–1.55 log (P < 0.05), suggesting an effective reduction effect exist. Malic acid has no adverse effects on chicken performance, including body weight, intestinal indices and microflora. However, the meat quality of AA broilers was found to be promoted, the moisture increased by 5.12% − 5.92% (P < 0.05), and the fat decreased by 1.60% (P < 0.05). In Experiment 3, the malic acid-supplemented drinking water was provided to AA broilers which were suffering from respiratory disease. The results showed that the mortality rate of malic acid treated group was consistently lower than that of the control group during the experimental period, and the total mortality was decreased from 52% in the control group, to 32% in malic acid treated group.
Conclusions

Our results suggest that feeding malic acid to flocks could decrease the contamination of Campylobacter while also benefit chicken farming, and is worthy of application to promote safe development of the poultry production and its products.
Integrative MicroRNAome Analysis of Skeletal Muscle of Colossoma Macropomum (Tambaqui), Piaractus Mesopotamicus (Pacu), and the Hybrid Tambacu, based on Next-generation Sequencing Data.
Authors: Fantinatti Bruno EA , Perez Erika S , Zanella Bruna TT , Valente Jéssica S , de Paula Tassiana G , Mareco Edson A , Carvalho Robson F , Piazza Silvano , Denti Michela A , Pai Maeli Dal 
Published: October 2020

Abstract
Background: Colossoma macropomum (tambaqui) and Piaractus mesopotamicus (pacu) are good fish species for aquaculture. The tambacu, individuals originating from the induced hybridization of the female tambaqui with the male pacu, present rapid growth and robustness, characteristics which have made the tambacu a good choice for Brazilian fish farms. Here, we used small RNA sequencing to examine global miRNA expression in the genotypes pacu (PC), tambaqui (TQ), and hybrid tambacu (TC), (Juveniles, n=5 per genotype), in order to better understand the relationship between tambacu and its parental species, and also to clarify the mechanisms involved in tambacu muscle growth and maintenance based on miRNAs expression. Results: Regarding differentially expressed (DE) miRNAs between the three genotypes, we observed 8 upregulated and 7 downregulated miRNAs considering TC vs. PC; 14 miRNAs were upregulated and 10 were downregulated considering TC vs. TQ, and 15 miRNAs upregulated and 9 were downregulated considering PC vs. TQ. The majority of the miRNAs showed specific regulation for each genotype pair, and no miRNA were shared between the 3 genotype pairs, in both up- and down-regulated miRNAs. Considering only the miRNAs with validated target genes, we observed the miRNAs miR-144-3p, miR-138-5p, miR-206-3p, and miR-499-5p. GO enrichment analysis showed that the main target genes for these miRNAs were grouped in pathways related to oxygen homeostasis, blood vessel modulation, and oxidative metabolism.Conclusions: Our global miRNA analysis provided interesting DE miRNAs in the skeletal muscle of pacu, tambaqui, and the hybrid tambacu. In addition, in the hybrid tambacu, we identified some miRNAs controlling important molecular muscle markers that could be relevant for the farming maximization.
Heparinized chitosan/hydroxyapatite scaffolds stimulate angiogenesis
Authors: Nájera-Romero Griselda V , Yar Muhammad , Rehman Ihtesham Ur 
Published: October 2020

Abstract
Formation of blood vessels during bone regeneration represents a major challenge for tissue engineered constructs. Poor revascularization can lead to scaffold failure and consequently, leads to non-healing fracture. Heparin is known to bind with angiogenic growth factors influencing the process of new blood vessels formation. There are several problems associated with the use of growth factors in clinic such as low stability, controlled delivery to the site, and price. The aim of the present study was to explore the potential of heparin to produce pro-angiogenic bone regeneration materials. Chitosan/hydroxyapatite freeze-gelled scaffolds were prepared and loaded with heparin. Different concentrations of heparin were successfully loaded onto the scaffolds, its release from the scaffold was analysed by toluidine blue assay and their angiogenic effect was evaluated by chorioallantoic membrane (CAM) assay to determine the optimal concentration of heparin to induce a proangiogenic effect. It was noted that low heparin concentrations exhibited a positive effect, with approximately 28μg per scaffold indicating a significant increment in blood vessels. The synthesized materials showed no cytotoxic effects when evaluated by using U2OS cell line.
Significantly Reducing Blood Loss Using Intra-muscular Injection of Tranexamic Acid during Total Knee Arthroplasty
Authors: Lin Yu-Kuan , Tsai Shang-Wen , Wu Po-Kuei , Chen Chao-Ming , Yang Jesse Chieh-Szu , Chen Cheng Fong , Chen Wei-Ming 
Published: October 2020

Abstract
Background
Administration of an intra-muscular injection (IMI) of tranexamic acid (TXA) had been demonstrated to be effective in reducing both blood loss and the transfusion rate during total knee arthroplasty (TKA). However, few studies have reported on the efficiency of IMI of TXA. We studied the efficiency of IMI of TXA to reduce blood loss during TKA.
Methods
In this prospective study, 50 patients undergoing primary simultaneous bilateral TKA were enrolled. The right knee received a IMI of 1 g of TXA (Group I), and the left knee received an intra-articular injection (IAI) of 1 g of TXA (Group II). The clinical outcome measures were a change in hemoglobin levels, blood loss from Hemovac, and number of allogeneic blood units.
Results
Compared with Group II, the decrease in blood loss from Hemovac was significantly less for Group I (460.1 ± 36.79 vs. 576.0 ± 34.01, P < 0.001), and no significant difference in surgical times was observed.
Conclusions
IMI of TXA can significantly reduce blood loss than IAI of TXA during TKA without increased complications such as surgical site infection, poor wound healing, skin necrosis, pulmonary embolism, and deep vein thrombosis.
Transcriptome Analysis Reveals that Long Noncoding RNAs Contribute to Development Differences of Medium-sized Ovarian Follicle between Meishan and Duroc Sows
Authors: Li Mengxun , Liu Yi , Ma Lipeng , Zhao Zhichao , Xie Su , Gong Hongbin , Sun Yishan , Huang Tao 
Published: October 2020

Abstract
Background: Ovulation rate is an extremely important factor of litter size in sows. It differs greatly among pig breeds of different genetic backgrounds. Long non-coding RNAs (lncRNAs) can regulate follicle development, granulosa cell(GC) growth and hormone secretion, which in turn affects sow litter size.Results: In our research, we identified 3554 lncRNAs and 25491 mRNAs in M2 follicle from Meishan and Duroc pigs. lncRNAs sequence and open reading frame(ORF) length is shorter than mRNAs, and it has fewer exons, lower abundance and conserved than protein-coding RNAs. Furthermore, 201 lncRNAs were differentially expressed in breeds, and quantitative trait loci (QTL) analysis of differential expression (DE) lncRNAs were performed. 127 DE lncRNAs are located in 119 reproduction trait-related loci. In addition, the lncRNAs potential target genes (PTGs) in cis or trans were predicted. Gene ontology(GO) and KEGG pathway analysis revealed that some PTGs were include some follicular development and hormone secretion-related biological processes or pathways, such as regulation of progesterone biosynthetic process, oestrogen metabolic process and ovarian steroidogenesis and PI3K-Akt signalling pathway. Furthermore，We also screened 19 differentially expressed lncRNAs of PI3K-Akt signalling pathway as candidates. Conclusions: This study provided a new significance on the roles of lncRNAs in follicular growth and development and porcine reproduction.
Prevention Services via Public Long-term Care Insurance can be Effective Among a Specific Group of Older Adults: A City Claim Data Analysis
Authors: Ito Tomoko , Mori Takahiro , Shimafuji Natsumi , Iijima Katsuya , Yoshie Satoru , Tamiya Nanako 
Published: October 2020

Abstract
BackgroundTo evaluate the effects of prevention services provided by long-term care insurance (LTCI) for older adults who require support from LTCI in Kashiwa City, Japan MethodsWe conducted an analysis using the following population-based longitudinal data in Kashiwa City between April 2012 and March 2015: Data of National Health Insurance and LTCI claims, the survey for certification of LTCI, the register, and premium tier classification. All data was linked using the pre-assigned anonymous identifying numbers. We analyzed the Cox regression model using the time for the deteriorations of long-term care levels as an outcome and the use of preventive care services as the primary exposure among participants aged 75 years or older, who had either support levels 1 or 2 at the beginning of this analysis. The study was further stratified by both age and initial support level. ResultsThe final analysis included 1,289 participants. The primary result showed, among all participants, that preventive service was not effective (hazard ratio 0.96, 95% confidence interval 0.78-1.19). In our sub-analysis, the preventive service was effective in avoiding deteriorations only among those aged 85 and older with support level 1 (HR 0.65, 95% CI 0.43-0.97) out of four groups.ConclusionsThe preventive services of LTCI in Kashiwa City showed a significant effect on the deterioration among subjects aged 85 or older, whose disabled level were low (support level 1). Our results suggest that the prevention services provided by LTCI may not be effective for all older individuals; to provide these services efficiently, local governments, as insurers of LTCI, will need to identify the specified groups that may benefit from the preventive services.
Serum Uric Acid Showed U-shaped Relationship with All-Cause Mortality and Cardiovascular Mortality in High Atherosclerosis Risk Patients: ASSURE Study
Authors: Cang Yan , Xu Shaojie , Zhang Jinying , Chen Zijun , Wang Keke , Ju Jingyi , Li Jue , Xu Yawei 
Published: October 2020

Abstract
Background: Previous studys have demonstrated association between hyperuricemia and cardiovascular disease (CVD), and Framingham study has confirmed patients with high atherosclerotic risk (HAR) had worse prognosis. But after controlling other traditional atherosclerotic risks, the association between serum uric acid (SUA) and all-cause mortality, cardiovascular mortality remains controversial, especially in HAR patients.Objective: The aim of study was to reveal the relationship with SUA and all-cause mortality, cardiovascular mortality in HAR patients.﻿Methods: The multi-center cohort study comprised 3,640 participants (1927male, 1713 female),whose mean age was 60.2±10.4 years andmean follow-uptimewere 68.85±11.37 months. Factors related to cardiovascular mortality and all-cause mortality, major adverse cardiac events in-hospital during follow-up were tested by multivariate Cox regression analysis and log-rank test. Restricted cubic splines with knots were used to explore theshape of dose-response relationship with SUA levels and Hazard risk (HR) of all-cause and CVD mortality.Results：The study showed SUA presented U-shaped relationship with all-cause and cardiovascular mortality. HR of all-cause mortality with hyperuricemia and hypouricemia was 2.11, 95% CI(1.61-3.07), and 2.05, 95% CI(1.35-2.90), respectively. HR of Cardiovascular mortality was 2.42, 95% CI (1.61-3.12), and 1.95, 95% CI(1.29-2.90), respectively. Conclusion：Abnormal SUA levels maybe significant and independent risk factors for all-cause and cardiovascular mortality. Routine SUA evaluation and intensive management are pressing needed, especially in HAR patients.
Therapeutic potential of human induced pluripotent stem cells and renal progenitor cells in experimental chronic kidney disease&nbsp;
Authors: Ribeiro Patrícia de Carvalho , Lojudice Fernando Henrique , Fernandes-Charpiot Ida Maria Maximina , Baptista Maria Alice Sperto Ferreira , Araújo Stanley de Almeida , Mendes Gloria Elisa Florido , Sogayar Mari Cleide , Abbud-Filho Mario , Caldas Heloisa Cristina 
Published: October 2020

Abstract
BackgroundChronic Kidney Disease (CKD) is a global public health problem. Cell therapy using pluripotent stem cells represents an attractive therapeutic approach for the treatment of CKD.MethodsWe transplanted Mitomycin C (MMC)-treated human induced pluripotent stem cells (hiPSCs) and renal progenitor cells (RPCs) into a CKD rat model system. The RPCs and hiPSCs cells were characterized by immunofluorescence and qRT-PCR. Untreated 5/6 nephrectomized rats were compared to CKD animals receiving the same amount of MMC-treated hiPSCs or RPCs. Renal function, histology and immunohistochemistry were evaluated 45 days post-surgery. ResultsWe successfully generated hiPSCs from peripheral blood and differentiated them into RPCs expressing renal progenitor genes (PAX2, WT1, SIX2, and SALL1) and podocyte-related genes (SYNPO, NPHS1). RPCs also exhibited reduced OCT4 expression, confirming the loss of pluripotency. After cell transplantation into CKD rats, the body weight change was significantly increased in both hiPSC and RPC groups, in comparison with the control group. Creatinine clearance (CCr) was preserved only in the hiPSC group. Similarly, the number of macrophages in the kidneys of the hiPSC group reached a statistically significant reduction, when compared to control rats. Both treatments reduced positive staining for the marker α-smooth muscle actin. Histological features showed decreased tubulointerstitial damage (interstitial fibrosis and tubular atrophy) as well as a reduction in glomerulosclerosis in both iPSC and RPC groups.ConclusionsIn conclusion, we describe that both MMC-treated hiPSCs and RPCs exert beneficial effects in attenuating CKD progression. Both cell types were equally efficient to reduce histological damage and weight loss caused by CKD. hiPSCs seems to be more efficient than RPCs, possibly due to a paracrine effect triggered by hiPSCs. These results demonstrate that the use of MMC-treated hiPSCs and RPCs improve clinical and histological CKD parameters, avoided tumor formation, and therefore may be a promising cell therapy strategy for CKD.