bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overlap time is an independent risk factor of radiation pneumonitis for patients treated with simultaneous EGFR-TKI and thoracic radiotherapy
Authors: Jia Wenxiao , Gao Qianqian , Wang Min , Li Ji , Jing Wang , Yu Jinming , Zhu Hui 
Published: February 2021

Abstract
Background
The exact rate and relevant risk factors of radiation pneumonitis (RP) for non-small-cell cancer (NSCLC) patients treated with the combination of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and thoracic radiotherapy have not been reported. Thus, this study aimed to investigate the rate and risk factors of RP for EGFR-positive NSCLC patients simultaneously treated with first-generation EGFR-TKI and TRT.

Patients and methods
We retrospectively evaluated NSCLC patients simultaneously treated with first-generation EGFR-TKI and thoracic radiotherapy between January 2012 and December 2019 at Shandong Cancer Hospital and Institute, Shandong, China. RP was diagnosed via computed tomography and was classified according to the Common Terminology Criteria for Adverse Events v5.0. The risk factors of RP were identified using uni- and multivariate analyses.

Results
Of the 67 patients included, 44.78% (30/67) developed grade ≥ 2 RP. Grade ≥ 2 RP occurred within a median of 3.48 (range 1.07–13.6) months. The EGFR-TKI icotinib, ipsilateral lung V30 > 34%, and overlap time of > 20 days between EGFR-TKI and thoracic radiotherapy were identified to be independent predictive factors of grade ≥ 2 RP.

Conclusions
Grade ≥ 2 RP is highly frequent in NSCLC patients simultaneous treated with first-generation EGFR-TKI and thoracic radiotherapy. Icotinib, ipsilateral lung V30 ≤ 34%, and overlap time of ≤ 20 days for EGFR-TKI and thoracic radiotherapy will be helpful to lower the risk of RP in these patients. The addition of thoracic radiotherapy should be cautious, and the treatment strategies can be optimized to reduce the rate of RP for patients treat with simultaneous EGFR-TKI and thoracic radiotherapy.
Protocol for the development of a repository of individual participant data from randomised controlled trials conducted in adult care homes (the Virtual International Care Homes Trials Archive (VICHTA))
Authors: Irvine Lisa , Burton Jennifer Kirsty , Ali Myzoon , Quinn Terence J. , Goodman Claire 
Published: February 2021

Abstract
Background
Approximately 418,000 people live in care homes in the UK, yet accessible, robust data on care home populations and organisation are lacking. This hampers our ability to plan, allocate resources or prevent risk. Large randomised controlled trials (RCTs) conducted in care homes offer a potential solution. The value of detailed data on residents’ demographics, outcomes and contextual information captured in RCTs has yet to be fully realised. Irrespective of the intervention tested, much of the trial data collected overlaps in terms of structured assessments and descriptive information. Given the time and costs required to prospectively collect data in these populations, pooling anonymised RCT data into a structured repository offers benefit; secondary analyses of pooled RCT data can improve understanding of this under-researched population and enhance the future trial design. This protocol describes the creation of a project-specific repository of individual participant data (IPD) from trials conducted in care homes and subsequent expansion into a legacy dataset for wider use, to address the need for accurate, high-quality IPD on this vulnerable population.

Methods
Informed by scoping of relevant literature, the principal investigators of RCTs conducted in adult care homes in the UK since 2010 will be invited to contribute trial IPD. Contributing trialists will form a Steering Committee who will oversee data sharing and remain gatekeepers of their own trial’s data. IPD will be cleaned and standardised in consultation with the Steering Committee for accuracy. Planned analyses include a comparison of pooled IPD with point estimates from administrative sources, to assess generalisability of RCT data to the wider care home population. We will also identify key resident characteristics and outcomes from within the trial repository, which will inform the development of a national minimum dataset for care homes. Following project completion, management will migrate to the Virtual Trials Archives, forming a legacy dataset which will be expanded to include international RCTs, and will be accessible to the wider research community for analyses.

Discussion
Analysis of pooled IPD has the potential to inform and direct future practice, research and policy at low cost, enhancing the value of existing data and reducing research waste. We aim to create a permanent archive for care home trial data and welcome the contribution of emerging trial datasets.
Extraction socket grafting using recombinant human bone morphogenetic protein-2-clinical implications and histological observations
Authors: Durge Khushboo Jeevan , Baliga Vidya Sudhindra , Sridhar Shilpa Bangalore , Dhadse Prasad Vijayrao , Ragit Gayatri Chandrakant 
Published: February 2021

AbstractObjectivesRehabilitation of edentulous ridges to promote the insertion of dental implants has been the key indicator for retaining osseous structures since tooth extraction. Recombinant Bone Morphogenetic Protein-2(rhBMP-2) is exploited for bone augmentation due to its osteoinductive capacity. The objective of the study to determine the effectiveness of bone induction for implant placement by rhBMP-2 delivered on beta-tricalcium phosphate graft (β-TCP) and PRF following tooth extraction.ResultsMinimal changes in the width of the crestal bone relative to baseline values were found three months after socket grafting. A bone loss in the mesiodistal and buccolingual aspects of 0.6 ± 0.13 mm and 0.5 ± 0.13 mm was found, respectively. While drilling before the implant placement, the bone's clinical hardness evaluated through tactile was analogous to drilling into spruce or white pine wood. Total radiographic bone filling was seen in 3 months and no additional augmentation was needed during implant placement. Besides, histology shows no residual graft of bone particles. Therefore, the data from this study demonstrated that the novel combination of rhBMP-2 + β-TCP mixed with PRF has an effect on de novo bone formation and can be recommended for socket grafting before implant placement.
Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms
Authors: Kato Yasuhiko , Kuwabara Hitoshi , Okada Takashi , Munesue Toshio , Benner Seico , Kuroda Miho , Kojima Masaki , Yassin Walid , Eriguchi Yosuke , Kameno Yosuke , Murayama Chihiro , Nishimura Tomoko , Tsuchiya Kenji , Kasai Kiyoto , Ozaki Norio , Kosaka Hirotaka , Yamasue Hidenori 
Published: February 2021

Abstract
Background
Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown.

Methods
The current study explored metabolites representing the molecular mechanisms of oxytocin’s efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N = 106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial.

Results
Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P = 0.043, d = 0.74, N = 83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR = 0.004, d = 1.13, N = 60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR = 0.006, r = − 0.485, N = 43) and deteriorations between 2 and 4 weeks (PFDR = 0.032, r = 0.415, N = 37).

Limitations
The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes.

Conclusion
Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin’s efficacy.
Trial registration: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703) (UMIN000015264).
Hybrid semantic recommender system for chemical compounds in large-scale datasets
Authors: Barros Marcia , Moitinho Andre , Couto Francisco M. 
Published: February 2021

AbstractThe large, and increasing, number of chemical compounds poses challenges to the exploration of such datasets. In this work, we propose the usage of recommender systems to identify compounds of interest to scientific researchers. Our approach consists of a hybrid recommender model suitable for implicit feedback datasets and focused on retrieving a ranked list according to the relevance of the items. The model integrates collaborative-filtering algorithms for implicit feedback (Alternating Least Squares and Bayesian Personalized Ranking) and a new content-based algorithm, using the semantic similarity between the chemical compounds in the ChEBI ontology. The algorithms were assessed on an implicit dataset of chemical compounds, CheRM-20, with more than 16.000 items (chemical compounds). The hybrid model was able to improve the results of the collaborative-filtering algorithms, by more than ten percentage points in most of the assessed evaluation metrics.
Dietary purslane (Portulaca oleracea L.) promotes the growth performance of broilers by modulation of gut microbiota
Authors: Wang Cong , Liu Qing , Ye Fengchun , Tang Hongbo , Xiong Yanpeng , Wu Yongfei , Wang Luping , Feng Xuanbiao , Zhang Shuiyin , Wan Yongmei , Huang Jianhua 
Published: February 2021

AbstractPurslane is a widespread wild vegetable with both medicinal and edible properties. It is highly appreciated for its high nutritional value and is also considered as a high-quality feed resource for livestock and poultry. In this study, Sanhuang broilers were used to investigate the effect of feeding purslane diets on the growth performance in broilers and their gut microbiota. A total of 48 birds with good growth and uniform weight were selected and randomly allocated to four treatment groups A (control), B, C and D. Dietary treatments were fed with basal diet without purslane and diets containing 1%, 2% and 3% purslane. The 16S rDNA was amplified by PCR and sequenced using the Illumina HiSeq platform to analyze the composition and diversity of gut microbiota in the four sets of samples. The results showed that dietary inclusion of 2% and 3% purslane could significantly improve the growth performance and reduce the feed conversion ratio. Microbial diversity analysis indicated that the composition of gut microbiota of Sanhuang broilers mainly included Gallibacterium, Bacteroides and Escherichia-Shigella, etc. As the content of purslane was increased, the abundance of Lactobacillus increased significantly, and Escherichia-Shigella decreased. LEfSe analysis revealed that Bacteroides_caecigallinarum, Lachnospiraceae, Lactobacillales and Firmicutes had significant differences compared with the control group. PICRUSt analysis revealed bacteria mainly enriched in carbohydrate metabolism pathway due to the additon of purslane in the diet. These results suggest that the addition of purslane to feed could increase the abundance of Lactobacillus in intestine, modulate the environment of gut microbiota and promote the metabolism of carbohydrates to improve its growth performance. This study indicates that the effect of purslane on the growth-promoting performance of broilers might depend on its modulation on gut microbiota, so as to provide a certain scientific basis for the application of purslane in the feed industry.
A critical role of AREG for bleomycin-induced skin fibrosis
Authors: Zhang Mary Yinghua , Fang Shuyi , Gao Hongyu , Zhang Xiaoli , Gu Dongsheng , Liu Yunlong , Wan Jun , Xie Jingwu 
Published: February 2021

AbstractWe report our discovery of an important player in the development of skin fibrosis, a hallmark of scleroderma. Scleroderma is a fibrotic disease, affecting 70,000 to 150,000 Americans. Fibrosis is a pathological wound healing process that produces an excessive extracellular matrix to interfere with normal organ function. Fibrosis contributes to nearly half of human mortality. Scleroderma has heterogeneous phenotypes, unpredictable outcomes, no validated biomarkers, and no effective treatment. Thus, strategies to slow down scleroderma progression represent an urgent medical need. While a pathological wound healing process like fibrosis leaves scars and weakens organ function, oral mucosa wound healing is a scarless process. After re-analyses of gene expression datasets from oral mucosa wound healing and skin fibrosis, we discovered that several pathways constitutively activated in skin fibrosis are transiently induced during oral mucosa wound healing process, particularly the amphiregulin (Areg) gene. Areg expression is upregulated ~ 10 folds 24hrs after oral mucosa wound but reduced to the basal level 3 days later. During bleomycin-induced skin fibrosis, a commonly used mouse model for skin fibrosis, Areg is up-regulated throughout the fibrogenesis and is associated with elevated cell proliferation in the dermis. To demonstrate the role of Areg for skin fibrosis, we used mice with Areg knockout, and found that Areg deficiency essentially prevents bleomycin-induced skin fibrosis. We further determined that bleomycin-induced cell proliferation in the dermis was not observed in the Areg null mice. Furthermore, we found that inhibiting MEK, a downstream signaling effector of Areg, by selumetinib also effectively blocked bleomycin-based skin fibrosis model. Based on these results, we concluded that the Areg-EGFR-MEK signaling axis is critical for skin fibrosis development. Blocking this signaling axis may be effective in treating scleroderma.
Shaping code in conjunction with DCT for PAPR reduction in multicarrier system
Authors: Aimer Younes , Bouazza Boubakar Seddik , Bachir Smail , Duvanaud Claude 
Published: February 2021

AbstractNonlinear behavior and power efficiency of the Power Amplifier (PA) contradictorily depend on the input signal amplitude distribution. The transmitted signal in multi-carrier modulation exhibits high Peak-to-Average Power Ratio (PAPR) and large bandwidths, leading to the degradation of the radio link and additional generation out-of-band interferences, which degrade the quality of the transmission. Practical solutions exist, like a power back-off, but with unacceptable efficiency performances of the transmitter. This paper deals with efficiency and linearity improvement using a new PAPR reduction method based on the combination of Discrete Cosine Transform and shaping technique. The main principle is to determine an optimal coding scheme according to a trade-off between coding complexity and performance benefits in the presence of PA nonlinearities. Simulation and experimental results in the context of OFDM signal and using a 20 W–3.7 GHz Radio-Frequency Power Amplifier show an improvement on PAPR reduction of about 3.25 dB. Also, the communication criteria like Bit Error Rate and Error Vector Magnitude are improved by about one decade and a half and $$8\%$$

8
%

, respectively.
Acquisition of oral microbiota is driven by environment, not host genetics
Authors: Mukherjee Chiranjit , Moyer Christina O. , Steinkamp Heidi M. , Hashmi Shahr B. , Beall Clifford J. , Guo Xiaohan , Ni Ai , Leys Eugene J. , Griffen Ann L. 
Published: February 2021

AbstractBackgroundThe oral microbiota is acquired very early, but the factors shaping its acquisition are not well understood. Previous studies comparing monozygotic (MZ) and dizygotic (DZ) twins have suggested that host genetics plays a role. However, all twins share an equal portion of their parent’s genome, so this model is not informative for studying parent-to-child transmission. We used a novel study design that allowed us to directly examine the genetics of transmission by comparing the oral microbiota of biological versus adoptive mother-child dyads.ResultsNo difference was observed in how closely oral bacterial community profiles matched for adoptive versus biological mother-child pairs, indicating little if any effect of host genetics on the fidelity of transmission. Both adopted and biologic children more closely resembled their own mother as compared to unrelated women, supporting the role of contact and environment. Mother-child strain similarity increased with the age of the child, ruling out early effects of host genetic influence that are lost over time. No effect on the fidelity of mother-child strain sharing from vaginal birth or breast feeding was seen. Analysis of extended families showed that fathers and mothers were equally similar to their children, and that cohabitating couples showed even greater strain similarity than mother-child pairs. These findings support the role of contact and shared environment, and age, but not genetics, as determinants of microbial transmission, and were consistent at both species and strain level resolutions, and across multiple oral habitats. In addition, analysis of individual species all showed similar results.ConclusionsThe host is clearly active in shaping the composition of the oral microbiome, since only a few of the many bacterial species in the larger environment are capable of colonizing the human oral cavity. Our findings suggest that these host mechanisms are universally shared among humans, since no effect of genetic relatedness on fidelity of microbial transmission could be detected. Instead our findings point towards contact and shared environment being the driving factors of microbial transmission, with a unique combination of these factors ultimately shaping the highly personalized human oral microbiome.
Toll-like receptor 5-mediated signaling enhances liver regeneration in mice
Authors: Zhang Wen , Wang Lei , Sun Xue-Hua , Liu Xian , Xiao Yang , Zhang Jie , Wang Ting , Chen Hui , Zhan Yi-Qun , Yu Miao , Ge Chang-Hui , Li Chang-Yan , Ren Guang-Ming , Yin Rong-Hua , Yang Xiao-Ming 
Published: February 2021

Abstract
Background
Toll-like receptor 5 (TLR5)-mediated pathways play critical roles in regulating the hepatic immune response and show hepatoprotective effects in mouse models of hepatic diseases. However, the role of TLR5 in experimental models of liver regeneration has not been reported. This study aimed to investigate the role of TLR5 in partial hepatectomy (PHx)-induced liver regeneration.

Methods
We performed 2/3 PHx in wild-type (WT) mice, TLR5 knockout mice, or TLR5 agonist CBLB502 treated mice, as a model of liver regeneration. Bacterial flagellin content was measured with ELISA, and hepatic TLR5 expression was determined with quantitative PCR analyses and flow cytometry. To study the effects of TLR5 on hepatocyte proliferation, we analyzed bromodeoxyuridine (BrdU) incorporation and proliferating cell nuclear antigen (PCNA) expression with immunohistochemistry (IHC) staining. The effects of TLR5 during the priming phase of liver regeneration were examined with quantitative PCR analyses of immediate early gene mRNA levels, and with Western blotting analysis of hepatic NF-κB and STAT3 activation. Cytokine and growth factor production after PHx were detected with real-time PCR and cytometric bead array (CBA) assays. Oil Red O staining and hepatic lipid concentrations were analyzed to examine the effect of TLR5 on hepatic lipid accumulation after PHx.

Results
The bacterial flagellin content in the serum and liver increased, and the hepatic TLR5 expression was significantly up-regulated in WT mice after PHx. TLR5-deficient mice exhibited diminished numbers of BrdU- and PCNA-positive cells, suppressed immediate early gene expression, and decreased cytokine and growth factor production. Moreover, PHx-induced hepatic NF-κB and STAT3 activation was inhibited in Tlr5−/− mice, as compared with WT mice. Consistently, the administration of CBLB502 significantly promoted PHx-mediated hepatocyte proliferation, which was correlated with enhanced production of proinflammatory cytokines and the recruitment of macrophages and neutrophils in the liver. Furthermore, Tlr5−/− mice displayed significantly lower hepatic lipid concentrations and smaller Oil Red O positive areas than those in control mice after PHx.

Conclusion
We reveal that TLR5 activation contributes to the initial events of liver regeneration after PHx. Our findings demonstrate that TLR5 signaling positively regulates liver regeneration and suggest the potential of TLR5 agonist to promote liver regeneration.
Cut wires: The Electrophysiology of Regenerated Tissue
Authors: Lowe Alexis L. , Thakor Nitish V. 
Published: February 2021

AbstractWhen nerves are damaged by trauma or disease, they are still capable of firing off electrical command signals that originate from the brain. Furthermore, those damaged nerves have an innate ability to partially regenerate, so they can heal from trauma and even reinnervate new muscle targets. For an amputee who has his/her damaged nerves surgically reconstructed, the electrical signals that are generated by the reinnervated muscle tissue can be sensed and interpreted with bioelectronics to control assistive devices or robotic prostheses. No two amputees will have identical physiologies because there are many surgical options for reconstructing residual limbs, which may in turn impact how well someone can interface with a robotic prosthesis later on. In this review, we aim to investigate what the literature has to say about different pathways for peripheral nerve regeneration and how each pathway can impact the neuromuscular tissue’s final electrophysiology. This information is important because it can guide us in planning the development of future bioelectronic devices, such as prosthetic limbs or neurostimulators. Future devices will primarily have to interface with tissue that has undergone some natural regeneration process, and so we have explored and reported here what is known about the bioelectrical features of neuromuscular tissue regeneration.
Changing the tune using bioelectronics
Authors: Chang Eric H. 
Published: February 2021

AbstractThe desire to harness electricity for improving human health dates back at least two millennia. As electrical signals form the basis of communication within our nervous system, the ability to monitor, control, and precisely deliver electricity within our bodies holds great promise for treating disease. The nascent field of bioelectronic medicine capitalizes on this approach to improve human health, however, challenges remain in relating electrical nerve activity to physiological function. To overcome these challenges, we need more long-term studies on neural circuits where the nerve activity and physiological output is well-established. In this Letter, I highlight a recent study that takes just such an approach.