bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of TMAO-producer phenotype and host–diet–gut dysbiosis by carnitine challenge test in human and germ-free mice
Authors: Wu Wei-Kai , Chen Chieh-Chang , Liu Po-Yu , Panyod Suraphan , Liao Ben-Yang , Chen Pei-Chen , Kao Hsien-Li , Kuo Han-Chun , Kuo Ching-Hua , Chiu Tina H T , Chen Rou-An , Chuang Hsiao-Li , Huang Yen-Te , Zou Hsin-Bai , Hsu Cheng-Chih , Chang Ting-Yan , Lin Chin-Lon , Ho Chi-Tang , Yu Hon-Tsen , Sheen Lee-Yan , Wu Ming-Shiang 
Published: October 2018

ObjectiveThe gut microbiota-derived metabolite, trimethylamine N-oxide (TMAO) plays an important role in cardiovascular disease (CVD). The fasting plasma TMAO was shown as a prognostic indicator of CVD incident in patients and raised the interest of intervention targeting gut microbiota. Here we develop a clinically applicable method called oral carnitine challenge test (OCCT) for TMAO-related therapeutic drug efforts assessment and personalising dietary guidance.DesignA pharmacokinetic study was performed to verify the design of OCCT protocol. The OCCT was conducted in 23 vegetarians and 34 omnivores to validate gut microbiota TMAO production capacity. The OCCT survey was integrated with gut microbiome, host genotypes, dietary records and serum biochemistry. A humanised gnotobiotic mice study was performed for translational validation.ResultsThe OCCT showed better efficacy than fasting plasma TMAO to identify TMAO producer phenotype. The omnivores exhibited a 10-fold higher OR to be high TMAO producer than vegetarians. The TMAO-associated taxa found by OCCT in this study were consistent with previous animal studies. The TMAO producer phenotypes were also reproduced in humanised gnotobiotic mice model. Besides, we found the faecalCntAgene was not associated with TMAO production; therefore, other key relevant microbial genes might be involved. Finally, we demonstrated the urine TMAO exhibited a strong positive correlation with plasma TMAO (r=0.92, p<0.0001) and improved the feasibility of OCCT.ConclusionThe OCCT can be used to identify TMAO-producer phenotype of gut microbiota and may serve as a personal guidance in CVD prevention and treatment.Trial registration numberNCT02838732; Results.
Changes in health status predict changes in alcohol consumption in older adults: the Seniors-ENRICA cohort
Authors: Ortolá Rosario , García-Esquinas Esther , Soler-Vila Hosanna , Ordovas Jose M , López-García Esther , Rodríguez-Artalejo Fernando 
Published: October 2018

BackgroundSome of the previously reported health benefits of low-to-moderate alcohol consumption may derive from health status influencing alcohol consumption rather than the opposite. We examined whether health status changes influence changes in alcohol consumption, cessation included.MethodsData came from 571 current drinkers aged ≥60 years participating in the Seniors-ENRICA cohort in Spain. Participants were recruited in 2008–2010 and followed-up for 8.2 years, with four waves of data collection. We assessed health status using a 52-item deficit accumulation (DA) index with four domains: functional, self-rated health and vitality, mental health, and morbidity and health services use. To minimise reverse causation, we examined how changes in health status over a 3-year period (wave 0–wave 1) influenced changes in alcohol consumption over the subsequent 5 years (waves 1–3) using linear/logistic regression, as appropriate.ResultsCompared with participants in the lowest tertile of DA change (mean absolute 4.3% health improvement), those in the highest tertile (7.8% worsening) showed a reduction in alcohol intake (β: –4.32 g/day; 95% CI –7.00 to –1.62; p trend=0.002) and were more likely to quit alcohol (OR: 2.80; 95% CI 1.54 to 5.08; p trend=0.001). The main contributors to decreasing drinking were increased functional impairment and poorer self-rated health, whereas worsening self-rated health, onset of diabetes or stroke and increased prevalence of hospitalisation influenced cessation.ConclusionsHealth deterioration is related to a subsequent reduction and cessation of alcohol consumption contributing to the growing evidence challenging the protective health effect previously attributed to low-to-moderate alcohol consumption.
Tuberculosis and diabetes: bidirectional association in a UK primary care data set
Authors: Pearson Fiona , Huangfu Peijue , McNally Richard , Pearce Mark , Unwin Nigel , Critchley Julia A 
Published: October 2018

BackgroundMany studies have found an increased risk of pulmonary tuberculosis (PTB) among those with diabetes mellitus (DM). However, evidence on whether the association is bidirectional remains sparse. This study investigates DM rates among those with and without prior tuberculosis (TB) disease as well as the reverse.MethodsData on a UK general practice population, between 2003 and 2009, were obtained from The Health Improvement Network database. A series of retrospective cohort studies were completed. Individuals were successively classified as ‘exposed’ or ‘unexposed’ to TB, PTB, extrapulmonary TB (EPTB) or DM. Multivariate negative binomial regression was used to calculate incidence rate ratios (IRR) among each exposure group for outcomes of interest (TB, PTB, EPTB or DM in turn) adjusting for plausible confounding variables (age, sex, region, Townsend quintile and smoking status). Potential confounding due to ethnicity was adjusted for using McNamee’s external method.ResultsDM risk was substantially raised among individuals with a history of TB disease (IRR 5.65 (95% CI 5.19 to 6.16)), PTB (IRR 5.74 (95% CI 5.08 to 6.50)) and EPTB (IRR 4.66 (95% CI 3.94 to 5.51)) compared with those without; results were attenuated after external adjustment for ethnicity (IRR 2.33 (95% CI 2.14 to 2.53)). TB risk was raised modestly among individuals with DM (IRR 1.50 (95% CI 1.27 to 1.76)) and was attenuated slightly after adjustment for ethnicity (IRR 1.26 (95% CI 1.07 to 1.48)).ConclusionDM risk was raised among those with previous TB disease; this finding has implications for follow-up and screening of patients with TB, who may be at high risk of developing DM or related complications.
Urinary 2,5-dicholorophenol and 2,4-dichlorophenol concentrations and prevalent disease among adults in the National Health and Nutrition Examination Survey (NHANES)
Authors: Rooney Mary R , Lutsey Pamela L , Bhatti Parveen , Prizment Anna 
Published: October 2018

ObjectiveTo test cross-sectional associations between urinary concentrations of 2,5-dichlorophenol (2,5-DCP) and 2,4-dichlorophenol (2,4-DCP) with the prevalence of cardiovascular disease (CVD), cancer, lung disease, thyroid problems and liver conditions.MethodsLogistic regression was used to evaluate associations of urinary concentrations of 2,5-DCP and 2,4-DCP with prevalence of various medical conditions among 3617 National Health and Nutrition Examination Survey participants from 2007–2008 and 2009–2010. ORs and 95% CIs for each disease were estimated. All regression models were adjusted for urinary creatinine.ResultsWe observed a monotonically increasing association between quartiles of 2,5-DCP and prevalence of CVD. After adjustment for sociodemographic and lifestyle characteristics, participants with the highest versus lowest quartile of urinary 2,5-DCP had an OR=1.84 (95% CI 1.26 to 2.70) (p linear trend=0.006). The association was similar with further adjustment for established clinical CVD risk factors. Higher 2,5-DCP was also associated with prevalence of all cancers combined (ORQ4 vs Q1=1.50 (95% CI 1.00 to 2.26); p trend=0.05) and, in exploratory analyses, with gynaecological cancers (ORQ4 vs Q1=4.15 (95% CI 1.51 to 11.40; p trend=0.01)). No associations were detected between 2,5-DCP and lung diseases, thyroid problems or liver conditions, nor between 2,4-DCP and prevalent disease.ConclusionIn this nationally representative study, higher urinary 2,5-DCP concentrations were associated with greater prevalence of CVD and all cancers combined. Further examination may be warranted to assess whether chronic exposure to 2,5-DCP is associated with incidence of adverse health outcomes.
Is blue the new green? Repackaging menthol cigarettes in response to a flavour ban in Ontario, Canada
Authors: Borland Tracey , D’Souza Sandra A , O’Connor Shawn , Chaiton Michael Oliver , Schwartz Robert 
Published: October 2018

BackgroundAs of 1 January 2017, the Canadian province of Ontario banned the distribution and sale of menthol tobacco products. There is limited knowledge about how tobacco companies will adapt their packaging in response to a menthol ban.MethodsWe conducted a content analysis of preban traditional menthol (no capsule) and menthol capsule cigarette packs and their postban replacements. Preban and postban packs were matched using tobacco company descriptions of replacement brands in business-to-business marketing materials, advertising on cigarette pack cellophane and a tobacco company website.ResultsA total of 63 menthol (n=30) and ‘non-menthol alternative’ (n=33) cigarette packs were included in the analysis. Approximately half of the preban packs were menthol capsule cigarettes and half traditional menthol cigarettes. While some postban brands continued to convey menthol-like qualities via the colour and/or brand descriptor ‘green’, ’blue' was the most common colour and brand descriptor postban. Packs shifted from using ‘menthol’ and/or ‘fresh’ as taste descriptor preban to using ‘smooth’ postban; some postban packs had ‘non-menthol alternative’ or ‘without menthol/capsules’ written on their cellophane. The presence of innovative filter technologies continued in the postban samples.ConclusionResults suggest that tobacco companies attempted to maintain menthol smokers in Ontario by aggressive preban promotion of menthol capsule cigarettes, continued promotion of innovative filter technologies and by directing smokers to non-menthol alternatives whose packaging both in text and in colour connoted menthol-like qualities (eg, green) and reduced harshness or harm (eg, blue, white, silver, smooth taste).
Prevalence and correlates of JUUL use among a national sample of youth and young adults
Authors: Vallone Donna M , Bennett Morgane , Xiao Haijun , Pitzer Lindsay , Hair Elizabeth C 
Published: October 2018

ObjectiveTo estimate the prevalence of JUUL use and identify demographic and psychosocial correlates of use among youth and young adults in the USA.MethodsA national, probability-based sample was recruited via address-based sampling, with subsamples recruited from an existing probability-based online panel. Participants (N=14 379) ages 15–34 were surveyed about JUUL use, tobacco use, electronic nicotine delivery system (ENDS) harm perceptions, sensation seeking and demographic characteristics. Data were collected February–May 2018. Χ2analyses assessed differences in JUUL use by demographic and psychosocial characteristics. Logistic regressions identified significant correlates of ever and current JUUL use.ResultsOverall, 6.0% reported ever JUUL use, and 3.3% reported past 30-day (ie, current) use. Rates were higher among participants aged 15–17 and 18–21 years, with 9.5% and 11.2% reporting ever use, and 6.1% and 7.7% reporting current use, respectively. Among current users aged 15–17 years, 55.8% reported use on 3 or more days in the past month, and over a quarter reported use on 10–30 days. Significant correlates of use included younger age, white race, greater financial comfort, perceptions of ENDS as less harmful than cigarettes, household ENDS use, high sensation seeking and current combustible tobacco use.ConclusionJUUL use was significantly higher among young people, with those under 21 having significantly higher odds of ever and current use. Frequency of use patterns suggest youth may not be experimenting with the device but using it regularly. Given the high nicotine content of JUUL, there is concern over the potential for addiction and other serious health consequences among young people. Findings suggest strong regulatory actions are needed to prevent youth and young adult uptake.
Characterization of Squamous Cell Lung Cancers from Appalachian Kentucky
Authors: Liu Jinpeng , Murali Thilakam , Yu Tianxin , Liu Chunming , Sivakumaran Theru A. , Moseley Hunter N.B. , Zhulin Igor B. , Weiss Heidi L. , Durbin Eric B. , Ellingson Sally R. , Liu Jinze , Huang Bin , Hallahan Brent J. , Horbinski Craig M. , Hodges Kurt , Napier Dana L. , Bocklage Thèrése , Mueller Joseph , Vanderford Nathan L. , Fardo David W. , Wang Chi , Arnold Susanne M. 
Published: October 2018

AbstractBackground:Lung cancer is the leading cause of cancer mortality in the United States (U.S.). Squamous cell carcinoma (SQCC) represents 22.6% of all lung cancers nationally, and 26.4% in Appalachian Kentucky (AppKY), where death from lung cancer is exceptionally high. The Cancer Genome Atlas (TCGA) characterized genetic alterations in lung SQCC, but this cohort did not focus on AppKY residents.Methods:Whole-exome sequencing was performed on tumor and normal DNA samples from 51 lung SQCC subjects from AppKY. Somatic genomic alterations were compared between the AppKY and TCGA SQCC cohorts.Results:From this AppKY cohort, we identified an average of 237 nonsilent mutations per patient and, in comparison with TCGA, we found that PCMTD1 (18%) and IDH1 (12%) were more commonly altered in AppKY versus TCGA. Using IDH1 as a starting point, we identified a mutually exclusive mutational pattern (IDH1, KDM6A, KDM4E, JMJD1C) involving functionally related genes. We also found actionable mutations (10%) and/or intermediate or high-tumor mutation burden (65%), indicating potential therapeutic targets in 65% of subjects.Conclusions:This study has identified an increased percentage of IDH1 and PCMTD1 mutations in SQCC arising in the AppKY residents versus TCGA, with population-specific implications for the personalized treatment of this disease.Impact:Our study is the first report to characterize genomic alterations in lung SQCC from AppKY. These findings suggest population differences in the genetics of lung SQCC between AppKY and U.S. populations, highlighting the importance of the relevant population when developing personalized treatment approaches for this disease.
Anti-Inflammatory Drug Use and Ovarian Cancer Risk by COX1/COX2 Expression and Infiltration of Tumor-Associated Macrophages
Authors: Barnard Mollie E. , Hecht Jonathan L. , Rice Megan S. , Gupta Mamta , Harris Holly R. , Eliassen A. Heather , Rosner Bernard A. , Terry Kathryn L. , Tworoger Shelley S. 
Published: October 2018

Abstract

Background:
Nonsteroidal anti-inflammatory drug (NSAID) use may affect ovarian cancer risk via prostaglandin synthesis and tumor-associated macrophage (TAM) infiltration. We evaluated if associations between aspirin or non-aspirin NSAID use and ovarian cancer risk differed by tumor expression of prostaglandin-related (COX1, COX2) and TAM-related (CD68, CD163) markers.

Methods:
We evaluated cases and matched controls from the Nurses’ Health Study (NHS), NHSII, and New England Case-Control Study (NECC). Cases with IHC data on COX1 and COX2 (n = 532) or CD68 and CD163 (n = 530) were included. We used polytomous logistic regression, adjusted for ovarian cancer risk factors, to estimate OR for NSAID use and ovarian cancer risk by marker level.

Results:
Recent aspirin use had a nonsignificant inverse association and recent non-aspirin NSAID use had no association with ovarian cancer risk. NSAID use was not differentially associated with ovarian cancer by COX1 or COX2 expression. However, recent aspirin use was associated with lower ovarian cancer risk for high [OR 0.54; 95% confidence interval (CI), 0.37–0.78], but not low (OR 1.50; 95% CI, 0.97–2.31), CD163 density (Pheterogeneity &lt; 0.001). Similar results were observed for aspirin duration and tablets and for recent non-aspirin NSAID use. Results were not clearly different by macrophage density defined by the less specific macrophage marker, CD68.

Conclusions:
NSAID use was inversely associated with risk of ovarian cancer with high density CD163, a marker for M2-type, immunosuppressive macrophages. However, the relationship did not differ by prostaglandin synthesis markers.

Impact:
Future research should explore prostaglandin-independent mechanisms for the association between NSAID use and ovarian cancer risk, including immune mechanisms.
Circulating Plasma miRNAs as Potential Biomarkers of Non–Small Cell Lung Cancer Obtained by High-Throughput Real-Time PCR Profiling
Authors: Niu Yanqin , Su Mingyang , Wu Yike , Fu Liwu , Kang Kang , Li Qing , Li Li , Hui Gang , Li Furong , Gou Deming 
Published: October 2018

Abstract

Background:
Because of limited stability and sensitivity, circulating miRNAs as noninvasive biomarkers have not so far been used for early diagnosis and prognosis of non–small cell lung cancer (NSCLC) in clinic. Therefore, it is imperative to find more reliable biomarker(s).

Methods:
We performed one of most sensitive qRT-PCR assays, S-Poly(T) Plus, to select differently expressed miRNAs from genome-wide miRNA profiling. miRNA candidates were validated through a three-phase selection and two validation processes with 437 NSCLC cases and 415 controls.

Results:
A unique set of 7 and 9 miRNAs differed significantly in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) samples compared with those in controls, of which, there were 5 universal biomarkers for NSCLC (ADC or SCC). Ten of 11 miRNAs could discriminate early stage (stage I) of NSCLC from healthy individuals. Risk score was obtained from the validation set-1 and was tested using the ROC curves with a high area under ROC curve of 0.89 in ADC and 0.96 in SCC. Ultimately, potential biomarkers and the risk score were verified by the validation set-2 with a sensitivity of 94% and a specificity of 91.6% in ADC, and a sensitivity of 98.5% and a specificity of 51.5% in SCC, respectively.

Conclusions:
Taken together, 7 miRNAs and 9 miRNAs may provide noninvasive biomarkers for diagnosis and prognosis in ADC and SCC, respectively.

Impact:
On the basis of our sensitive and accurate method, we hope that these candidate miRNAs may have strong impact on the early lung cancer diagnosis.
Right Time and Place for IL12: Targeted Delivery Stimulates Immune Therapy
Authors: Lyerly H. Kim , Osada Takuya , Hartman Zachary C. 
Published: October 2018

Abstract
Systemic IL12 therapy has potent antitumor effects, but clinical delivery of this potent cytokine has been complicated by systemic toxicity. A novel strategy to deliver IL12 to the tumor microenvironment appears promising in a first-in-human study, appearing to stimulate tumor-specific adaptive immune responses with minimal systemic toxicity.
See related article by Strauss et al., p. 99
‘Tot eeuwige memorie de druckerye-konste’
Authors: Dijkstra Trude 
Published: October 2018

Abstract
This article explores the ways in which early modern writers and readers related to and reflected on the Chinese invention of print by way of an examination of Simon de Vries’s Curieuse aenmerckingen der bysonderste Oost en West-Indische dingen of 1682. It will consider De Vries in his ternary role of author, compiler and reader, meaning that his account not only displays the economic rules of cultural consumption to which De Vries was bound as author and compiler, but also his own opinions and preferences as reader.
In the guise of writer, editor, and reader De Vries aims to present his potential readership with a thought-out consideration of the wide variety of European sources available on the subject of Chinese print, concentrating on those elements of contention that may speak for or against either Europe or China’s reputation as technological and cultural power. In the end, neither takes pride of place. By arguing for an independent invention of print, De Vries essentially put China on the same level as Europe.
Adapting Dynamically to Change in Diplomacy: A Comparative Look at Special Envoys in the International Arena
Authors: Morini Francesco 
Published: October 2018

Summary
This article provides a comparative overview of the main features of special envoys/representatives dispatched by major foreign-policy players. It underlines the relevance of this instrument within a fast-changing diplomatic environment, characterized by increasingly numerous actors, evolving practices and complex processes that require a flexible approach. The analysis draws on nearly 650 cases of special envoys appointed by national administrations and international organizations over the span of 25 years, exposing commonalities and differences in the use of a long-standing diplomatic tool. The article argues that the incremental employment of ad-hoc envoys, mandated to deal with issues of a geographical or thematic nature, signals the ambition of individual actors to achieve specific policy objectives on a crowded global stage. In this perspective, and in keeping with their role of precursors in diplomatic practice, special envoys constitute a versatile resource with boundless potential in terms of adaptation to an ever-expanding diplomatic agenda.
The Reconstruction of the Circulation of Muḥammad al-Hindī’s Ǧumal al-falsafa Using Manuscript Notes
Authors: Jabbour Jawdath 
Published: October 2018

AbstractMuḥammad al-Hindī’s Ǧumal al-falsafa is a philosophical summa from the 12th century CE. The text is preserved in two manuscripts: an autograph (Esad Efendi 1918) and a copy thereof. Various notes and annotations pervade MS Esad Efendi 1918’s fly-leaves and title-page. An examination of these, to date, understudied elements provides us with the only information that links this author to Yemen. It also reveals the steps taken on its journey, from 12th-century Yemen to Mamluk Egypt and Syria, and eventually Safavid Iran and Ottoman Istanbul.
Scattered Manuscripts
Authors: Khabibullaev Akram 
Published: October 2018

AbstractThis article examines notes left by readers, endowers, owners, or borrowers of manuscripts on their fly-leaves, title pages, colophons, etc. The notes under review were found on pages of different manuscripts belonging to the medieval library associated with the name of shaykh Khwājah Muḥammad Pārsā (d. 822/1420). The findings add to our knowledge of the intellectual history of medieval Bukhārā. They also shed some light on the history of Muḥammad Pārsā’s library and its physical location.
The Lives and Afterlives of the Library of the Maronite Physician Ḥannā al-Ṭabīb (c. 1702–1775) from Aleppo
Authors: Krimsti Feras 
Published: October 2018

AbstractIn eighteenth-century Aleppo, books acquired an unprecedented significance among Aleppo’s Christians, against the background of an expanding “culture of the book”. This paper attempts to reconstruct the library of the Maronite physician Ḥannā al-Ṭabīb (c. 1702–1775), based on ownership statements in manuscripts purchased by the German scholar and Oriental traveller Ulrich Jasper Seetzen (1767–1811) in Aleppo, presently preserved in Gotha’s Research Library. Proceeding from an assessment of the ownership statements and a thematic analysis of the library, the paper will address the implications for our understanding of book ownership in the social and intellectual milieu of the owner. It will be argued that owning books was a facet of an intensifying and active—not passive—preoccupation with literature among Christians.