bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum metabolite markers of early Mycoplasma hyopneumoniae infection in pigs
Authors: Surendran Nair Meera , Yao Dan , Chen Chi , Pieters Maria 
Published: November 2019

AbstractMycoplasma hyopneumoniae, the primary pathogenic bacterium causing enzootic pneumonia, significantly affects worldwide swine production. The infection is usually persistent and bacterial identification and isolation of M. hyopneumoniae in clinical samples are challenging due to the fastidious requirements for its growth. Hence, new practical surveillance tools that improve or complement existing diagnostics on M. hyopneumoniae are desirable, especially in early infection. The objective of this study was to identify potential metabolite markers of early M. hyopneumoniae infection in pigs through metabolomics analysis. Samples obtained from pigs in a previous M. hyopneumoniae experimental infection were used in this study. Briefly, two pigs served as mock inoculated controls and ten pigs were intra-tracheally inoculated with M. hyopneumoniae. Sera, laryngeal swabs (LS), and tracheo-bronchial lavage fluid (TBLF) were collected from all pigs at 0, 2, 5, 9, 14, 21 and 28 days post-inoculation (dpi). Bronchial swabs (BS) were collected post-mortem at 28 dpi. Mycoplasma hyopneumoniae infection was confirmed by PCR in LS, TBLF and BS. Serum metabolites were profiled using high-resolution liquid chromatography–mass spectrometry (LC–MS) analysis. Metabolite markers were identified by structural analysis following multivariate analysis of LC–MS data. The results showed that M. hyopneumoniae infection time-dependently altered the serum levels of selective amino acids and fatty acids. α-Aminobutyric acid and long-chain fatty acids were markedly increased at 14 and 21 dpi in inoculated pigs (p < 0.05). These results indicated that M. hyopneumoniae infection caused systemic changes in host metabolism, warranting further studies to determine underlying biochemical and physiological mechanisms responsible for the observed changes.
Limit theorems for ratios of order statistics from uniform distributions
Authors: Xu Shoufang , Mei Changlin , Miao Yu 
Published: November 2019

AbstractLet $\{X_{ni}, 1 \leq i \leq m_{n}, n\geq 1\}${Xni,1≤i≤mn,n≥1} be an array of independent random variables with uniform distribution on $[0, \theta _{n}]$[0,θn], and $\{X_{n(k)}, k=1, 2, \ldots , m_{n}\}${Xn(k),k=1,2,…,mn} be the kth order statistics of the random variables $\{X_{ni}, 1 \leq i \leq m_{n}\}${Xni,1≤i≤mn}. We study the limit properties of ratios $\{R_{nij}=X_{n(j)}/X_{n(i)}, 1\leq i < j \leq m_{n}\}${Rnij=Xn(j)/Xn(i),1≤i<j≤mn} for fixed sample size $m_{n}=m$mn=m based on their moment conditions. For $1=i < j \leq m$1=i<j≤m, we establish the weighted law of large numbers, the complete convergence, and the large deviation principle, and for $2=i < j \leq m$2=i<j≤m, we obtain some classical limit theorems and self-normalized limit theorems.
Effects of dietary tributyrin on intestinal mucosa development, mitochondrial function and AMPK-mTOR pathway in weaned pigs
Authors: Wang Chunchun , Cao Shuting , Shen Zhuojun , Hong Qihua , Feng Jie , Peng Yan , Hu Caihong 
Published: November 2019

Abstract
Background
The objective of this experiment was to investigate the influence of dietary tributyrin on intestinal mucosa development, oxidative stress, mitochondrial function and AMPK-mTOR signaling pathway.

Methods
Seventy-two pigs were divided into two treatments and received either a basal diet or the same diet supplemented with 750 mg/kg tributyrin. Each treatment has six replicates of six pigs. After 14 days, 6 pigs from each treatment were selected and the jejunal samples were collected.

Results
Results showed that supplemental tributyrin increased (P < 0.05) villus height and villus height: crypt depth of weaned pigs. Pigs fed tributyrin had greater (P < 0.05) RNA/DNA and protein/DNA ratios than pigs on the control group. The mRNA levels of sodium glucose transport protein-1 and glucose transporter-2 in the jejunum were upregulated (P < 0.05) in pigs fed the tributyrin diet. Dietary tributyrin supplementation lowered (P < 0.05) the malondialdehyde and hydrogen peroxide (H2O2) content in jejunum, enhanced (P < 0.05) the mitochondrial function, as demonstrated by decreased (P < 0.05) reactive oxygen species level and increased (P < 0.05) mitochondrial membrane potential. Furthermore, tributyrin increased (P < 0.05) mitochondrial DNA content and the mRNA abundance of genes related to mitochondrial functions, including peroxisomal proliferator-activated receptor-γ coactivator-1α, mitochondrial transcription factor A, nuclear respiratory factor-1 in the jejunum. Supplementation with tributyrin elevated (P < 0.05) the phosphorylation level of AMPK and inhibited (P < 0.05) the phosphorylation level of mTOR in jejunum compared with the control group.

Conclusions
These findings suggest that dietary supplementation with tributyrin promotes intestinal mucosa growth, extenuates oxidative stress, improves mitochondrial function and modulates the AMPK-mTOR signal pathway of weaned pigs.
Man-made blue and purple barium copper silicate pigments and the pabstite (BaSnSi3O9) mystery of ancient Chinese wall paintings from Luoyang
Authors: Zhang Zhiguo , Ma Qinglin , Berke Heinz 
Published: November 2019

Abstract
Man-made ancient Chinese barium copper silicate pigments: Chinese (Han) Purple, BaCuSi2O6; Chinese (Han) Blue, BaCuSi4O10; Chinese Dark Blue, BaCu2Si2O7 (in summary called Chinese blues), and platelet-like crystals of BaSnSi3O9 were detected on mural paintings of a tomb in Luoyang City, Henan Province, China, dated to Western Han Dynasty (206 BC–8 AD). The pigments of the LY01 and LY02 samples were analyzed by archaeometrical methods: powder X-ray diffractometry (XRD), scanning electron microscopy (SEM–EDX) and micro-Raman spectroscopy. While the artificial nature of the ancient barium copper silicates was undoubted, the synthetic or mineral origin of BaSnSi3O9 of these murals had to be clarified. Involvement of the rare mineral pabstite Ba(Sn,Ti,Zr)Si3O9 from the Tian Shan mountains could be ruled out due to absence of Ti and Zr in the elemental composition. Tin compounds as admixtures to the lead minerals—the latter required as flux additive for the preparation of the Chinese blues—or tin admixtures to pristine barium starting minerals could be excluded, as well as the use of tin containing mineral mushistonite (CuSn(OH)6), primarily intended to be applied as copper source. Related to the findings for the production of Egyptian Blue (CaCuSi4O10), bronze or bronze scrap including also corroded material was used intending copper recycling. For the synthesis of the Luoyang Chinese blues only low amounts of bronze or bronze scrap were required providing the additional advantage to form in presence of air a tin/lead oxide flux with lowered vitrification temperatures and viscosities. This marked the advent of an ‘innovative production technology’ avoiding addition of large amounts of lead minerals as an effective lead-only flux. Despite of the chemical similarity to production of Egyptian Blue, the tin/lead based developments for the Chinese blues were anticipated to be independent excluding technology transfer from ancient Egypt. For further substantiation of the appearance of pabstite in the Luoyang Chinese blues a contemporary independent synthesis was sought, carried out under conditions similar to those of the barium copper silicate syntheses (1000 °C, but absence of a flux) starting from cassiterite (SnO2), quartz (SiO2) and witherite (BaCO3).
Assessing the feasibility and acceptability of Changing Health for the management of prediabetes: protocol for a pilot study of a digital behavioural intervention
Authors: Cassidy Sophie , Okwose Nduka , Scragg Jadine , Houghton David , Ashley Kirsten , Trenell Michael I. , Jakovljevic Djordje G. , Hallsworth Kate , Avery Leah 
Published: November 2019

Abstract
Background
The prevalence of prediabetes is rapidly rising in the UK, largely associated with an increase in obesity. Lifestyle programmes that provide support to make and sustain dietary and physical activity behavioural changes are necessary to initiate and maintain weight loss. However, these programmes are often intensive and time consuming. Given the magnitude of the problem, there is a need for behavioural interventions that can be delivered at scale. Digital interventions can address some of the aforementioned issues. The primary aim of the present study is to assess the feasibility and acceptability of a digital intervention called Changing Health that provides structured education and lifestyle behaviour change support to adults with prediabetes.

Methods
A single-group pilot study will be undertaken. We aim to recruit 40 participants with prediabetes defined by HbA1c or fasting plasma glucose (FPG), aged between 18 and 75 years with a BMI ≥ 25. Participants will receive the digital intervention (a mobile phone app incorporating structured education and behavioural tools to support lifestyle behaviour change) with the aim of losing and maintaining 5–6% of their baseline body weight. Each participant will receive 100 min of lifestyle coaching over the 9-month intervention period and will have continued access to the digital intervention. Clinical outcome measures will be collected during four visits to our clinical research facility: two visits at baseline, one visit at month 3, and one visit at month 9. These secondary outcome measures will include diet, physical activity, sleep, metabolic control, body composition, cardiorespiratory fitness, and cardiovascular function. To measure primary outcomes, an embedded qualitative study will be conducted to obtain data on feasibility and acceptability of the intervention.

Discussion
This pilot study will establish whether Changing Health is feasible and acceptable to adults with prediabetes. Clinical outcome measures will provide estimates of variability to inform sample size calculations, and qualitative data generated will inform any necessary refinements to the intervention. This will provide a platform for a larger evaluation to assess the effectiveness of Changing Health for changing diet and physical activity to initiate and maintain weight loss in adults with prediabetes.

Trial registration
ISRCTN Registry: ISRCTN69270299.
A combinatorial immunotherapy for malignant brain tumors: D2C7 immunotoxin and immune checkpoint inhibitors.
Authors: Bao Xuhui , Keir Stephen T. , Nair Smita K , Pastan Ira , Bigner Darell D. , Chandramohan Vidyalakshmi 
Published: November 2019

102 Background: Immunotoxins can induce direct and rapid cytotoxicity by targeting specific tumor antigens. D2C7 is a unique recombinant immunotoxin targeting EGFRwt/EGFRvIII, two frequently overexpressed proteins on gliomas, and is currently being tested in a phase I/II clinical trial (NCT02303678) for recurrent malignant gliomas. Immunotoxins have also been shown to induce a secondary antitumor immune response via stimulation of cytotoxic T lymphocytes (CTLs). Immune checkpoint inhibitors, which have successfully treated several advanced tumors by promoting the antitumor function of CTLs, may further enhance this immunotoxin-induced antitumor response. Thus, we hypothesize that combining D2C7 with immune checkpoint inhibitors will promote long-term tumor regression due to primary cytotoxicity and enhanced anti-tumor immunity. Methods: We developed a CT2A-mD2C7 mouse glioma cell line with robust in vitro cytotoxicity of D2C7 (IC50= 0.47 ng/mL). In vivo anti-tumor efficacy was evaluated by intratumoral injection of D2C7 combined with intraperitoneal injection of anti-CTLA4 or anti-PD1 antibodies in single-side and bilateral subcutaneous (SC) CT2A-mD2C7 glioma models in C57BL/6 immunocompetent mice. Results: In the single-side model, D2C7 monotherapy and combinatorial therapy showed a significant tumor growth delay (P < 0.01). Complete regression ( ≥ 40%) was only observed in combinatorial therapy groups. All cured mice rejected the rechallenging of CT2A parental cells in the contralateral flank and the subsequent rechallenging of CT2A-mD2C7 cells in the brain. In the bilateral model, the larger right tumors were treated with D2C7/anti-CTLA4/anti-PD1 monotherapy or D2C7+anti-CTLA4/PD1 combinatorial therapy, while the left tumors were untreated by D2C7. In the groups where the right tumors were treated with monotherapy or combinatorial therapy, the left untreated tumors also grew much slower. Furthermore, the combinatorial therapy led to the most significantly delayed growth of the left untreated tumors (P < 0.05). Conclusions: Immune checkpoint inhibitors can enhance D2C7-induced anti-tumor immunity to achieve a synergistic long-term tumor regression.
Hypoxia-inducible factor 1α in regulation of programmed death: Ligand 1 in glioma under hypoxia microenvironment.
Authors: Hu Man , Xue Song , Yu Jinming , Fan Bingjie , Ma Ji , Xie Li 
Published: November 2019

103 Background: Glioma is a highly lethal tumor that is known for its immune inhibitory capabilities. Despite great progress in treatment modalities, the median survival time of high-grade gliomas patients is only about 11.1 months. Gliomas are aberrantly expressed programmed death–ligand 1 (PD-L1) which results in tumor-induced immune suppression. Hypoxia is well known to induce aggressiveness, promotes tumor progression and resistance to chemotherapy and radiotherapy. Recently, studies have indicated that hypoxia play a prominent role in tumor immune escape. The aim of the study was to explore the relationship between PD-L1 and hypoxia inducible factor 1α (HIF-1α) and the role in the progression of gliomas. Methods: We adopted immunohistochemistry methods to detect expressions of PD-L1 and HIF-1α in 64 surgical specimens (23 cases for low-grade and 41 cases for high-grade gliomas, respectively). Immunoreactivity was analyzed in association with patients’ clinical characteristics or survival time. Expression of the PD-L1 and HIF-1α was analyzed in three GBM cell lines, U343, U373, and U251, under in vitro hypoxia (12, 24 or 72 h at 0.1% O2). Reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out to detect the mRNA expression of PD-L1 and HIF-1α. Results: PD-L1 and HIF-1α protein expression was detected in 81.25% and 84.73% of glioma specimens, respectively. The expression of PD-L1 protein is positively correlated with HIF-1α (r = 0.52; p= 0.013). Kaplan–Meier analysis revealed a significant effect of PD-L1 grade on cumulative overall survival. Patients with negative PD-L1 expression survive longer than those with positive expression ( p= 0.007). PD-L1 and HIF-1α mRNA was most consistently upregulated in relation to duration of in-vitro hypoxia (72h, p= 0.007). There was a significant and positive relationship between the PD-L1 and HIF-1α mRNA expression (r = 0.45; p= 0.01). Conclusions: The present study showed a role for hypoxia/HIF-1α in driving immune escape and provided a potential novel cancer immunotherapy targeting hypoxia to block PD-L1 expression, which may boost the immune system in cancer patients.
Association of diversity and composition of the gut microbiome with differential responses to PD-1 based therapy in patients with metastatic melanoma.
Authors: Gopalakrishnan Vancheswaran , Spencer Christine , Reuben Alexandre , Karpinets Tatiana , Hutchinson Diane , Hoffman Kristi , Prieto Peter A. , Tetzlaff Michael T. , Lazar Alexander , Davies Michael A. , Gershenwald Jeffrey E. , Jenq Robert R. , Hwu Patrick , Sharma Padmanee , Allison James Patrick , Futreal Andrew , Ajami Nadim , Petrosino Joseph , Daniel-MacDougall Carrie , Wargo Jennifer A. 
Published: November 2019

2 Background: Tremendous advances have been made in cancer therapy through the use of immune checkpoint blockade, although responses are not always durable. There is a growing appreciation of the role of the microbiome in cancer-related outcomes and recent evidence in murine models suggests that modulation of the gut microbiome may enhance responses to immune checkpoint blockade in melanoma. However this has not been investigated in patients. Here, we demonstrate that differential bacterial “signatures” exist in the gut microbiome of responders (R) and non-responders (NR) to anti-PD1 therapy at baseline, and that insights gained could be used to derive actionable strategies to enhance responses. Methods: We collected oral (n = 222) and gut microbiome (n = 113) samples on a large cohort of patients with metastatic melanoma (n = 228), with a majority treated with anti-PD1 therapy (n = 110). Patients were classified as either R or NR based on RECIST criteria, and 16S rRNA gene sequencing was performed to characterize the diversity and composition of the microbiomes. Immune profiling (via 7-marker IHC panel of CD3, CD8, PD-1, PD-L1, Granzyme B, RORγT and FoxP3) was performed in available tumors at baseline. Results: In these studies, we observed significant differences in the diversity and composition of the gut microbiome in R versus NR to PD1 blockade at baseline, but no clear differences in oral microbiomes. Specifically, R had a significantly higher alpha diversity compared to NR (p = 0.017). Notable differences were also seen in the composition of the gut microbiome of R versus NR. Immune profiling demonstrated significantly increased immune infiltrates in baseline tumor samples of R, with a positive correlation between CD8, CD3, PD1 and FoxP3 T-cell density and abundance of specific bacteria enriched in R (e.g. Faecalibacterium). Conclusions: Differences exist in the diversity and composition of the gut microbiome in R vs NR to anti-PD1 therapy. These results have far-reaching implications and suggest that modifications to the gut microbiome could potentially enhance therapeutic responses to immune checkpoint blockade.
Association of tumor mutational burden with smoking and mutation status in non-small cell lung cancer (NSCLC).
Authors: Davis Andrew A. , Chae Young Kwang , Agte Sarita , Pan Alan , Mohindra Nisha Anjali , Villaflor Victoria Meucci , Giles Francis J. 
Published: November 2019

24 Background: Reponses to immunotherapy have been observed in multiple solid tumors including non-small cell lung cancer (NSCLC). Identifying optimal biomarkers for response to anti-PD-1/PD-L1 therapies remains critical. Tumor mutational burden (TMB) may indicate genomic instability and potential neoantigen binding sites to activated effector T cells. Methods: We retrospectively examined tumor mutational burden (TMB) using next-generation sequencing (Foundation Medicine) for 83 patients with NSCLC in our institution. TMB included both coding and non-coding regions, but excluded potentially functional mutations. We correlated TMB (mutations per megabase) with smoking history, number of potentially functional mutations, variants of unknown significance, and the driver mutations EGFR, ALK, and KRAS. TMB high versus low was stratified based on 15 mutations per megabase pair. Results: Our findings demonstrated that TMB was significantly associated with current/former smoking status (p = 0.01, Table 1). TMB was also significantly associated with number of potentially functional mutations, number of variants of unknown significance (VUS), and total reported mutations (p < 0.01). The absence of mutations in EGFR, ALK, or KRAS tended to be associated with higher TMB as well (p = 0.07). Conclusions: TMB was associated with smoking status, as well as potentially functional mutations, VUS, and total number of reported mutations. Our results indicate that number of coding region mutations predict genomic instability in non-coding regions. Future studies are needed to correlate this measure with other immune biomarkers and patient outcome in NSCLC. [Table: see text]
Age-related differences in cannabis use by cancer patients referred for supportive care.
Authors: Portman Diane , Donovan Kristine A. 
Published: November 2019

104 Background: Increasingly, cancer patients are using cannabis in their efforts to manage symptoms. Studies of legal recreational cannabis suggest young adults (YA) may disproportionately account for increases in cannabis use. There are few studies of cannabis use in cancer patients and its effect on symptoms, however, and most have not stratified their results by age. To address this, we examined rates of cannabis use across three age groups: YA ages 18 to 39, adults 40 to 65, and adults older than 65 (OA). We also examined the effects of age and cannabis use on patients’ report of cancer-related symptoms. Methods: We conducted a retrospective review of 1223 cancer patients referred to outpatient supportive care for symptom management between 2014 and 2017. Patients underwent urine drug testing for tetrahydrocannabinol (THC) and completed the Edmonton Symptom Assessment Scale-Revised-CSS during their initial visit. Results: In Chi square analysis, age was significantly associated with cannabis use (p < .001): 30% of YA tested positive for THC compared to 21% of adults and 8% of OA. As a group, cannabis users reported significantly higher scores for pain, tiredness, nausea, lack of appetite, anxiety, depression, difficulty sleeping, and worse overall well-being (p values < .05). In MANOVA, there was a significant interaction effect between age and cannabis use for pain, lack of appetite, shortness of breath, anxiety, depression, difficulty sleeping, and overall well-being (p values < .05). While YA and adults who tested positive for THC reported higher symptom scores for each of these symptoms, OA patients who were THC positive reported lower scores for pain, anxiety, depression, and better overall well-being. Conclusions: Findings suggest that compared to adults and OA, more YA patients are using cannabis in attempts to control cancer-related symptoms. With the exception of OA, cannabis users rate their cancer-related symptoms as more severe than nonusers. Findings support the need for patient education about potential therapeutic benefits and adverse effects of cannabis use in cancer. Prospective, observational studies are needed to characterize patients’ use before and after a cancer diagnosis.