bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Accumulation of Wealth in Marriage: Over-Time Change and Within-Couple Inequalities
Authors: Kapelle Nicole , Lersch Philipp M 
Published: January 2020

AbstractThis study examines the accumulation of personal wealth of husbands and wives and investigates the development of within-couple wealth inequalities over time in marriage. Going beyond previous research that mostly studied the marriage wealth premium using household-level wealth data and that conceptualized marriage as an instantaneous transition with uniform consequences over time, we argue that entry into marriage is a gendered life-course event that dynamically shapes husbands’ and wives’ wealth accumulation. Using high-quality data from the German Socio-Economic Panel Study (2002, 2007, 2012, and 2017), we apply fixed-effects regression models to describe wealth accumulation within marriage. We find evidence that wealth premiums are lower during early years of marriage, but increase steadily thereafter. The premium is mostly concentrated in housing wealth. Results from supplementary analyses with limited data, however, suggest that the premium may not be causal for men. Regarding within-couple wealth inequalities, we find a pronounced within-couple wealth gap prior to marriage during pre-marital cohabitation. This gap remains stable over time in marriage. In contrast to findings regarding income, our study indicates that the institution of marriage may not amplify within-couple wealth inequalities further.
Roles and recommendations from primary care physicians towards managing low-risk breast cancer survivors in a shared-care model with specialists in Singapore—a qualitative study
Authors: Fok Rose Wai-Yee , Low Lian Leng , Quah Hui Min Joanne , Vasanwala Farhad , Low Sher Guan , Soh Ling Ling , Mohamad Farid , Loh Kiley Wei-Jen , Soong Yoke Lim , Ke Yu , Chan Alexandre , Tan Ngiap-Chuan 
Published: January 2020

Abstract

Background
Breast cancer is prevalent and has high cure rates. The resultant increase in numbers of breast cancer survivors (BCS) may overwhelm the current oncology workforce in years to come. We postulate that primary care physicians (PCPs) could play an expanded role in comanaging survivors, provided they are given the appropriate tools and training to do so.

Objective
To explore the perspectives of PCPs towards managing BCS in a community-based shared-care programme with oncologists.

Methods
Eleven focus groups and six in-depth interviews were conducted with seventy PCPs recruited by purposive sampling. All sessions were audio-recorded, transcribed verbatim and coded by three independent investigators. Thematic data analysis was performed and the coding process facilitated by NVivo 12.

Results
Majority of PCPs reported currently limited roles in managing acute and non-cancer issues, optimizing comorbidities and preventive care. PCPs aspired to expand their role to include cancer surveillance, risk assessment and addressing unmet psychosocial needs. PCPs preferred to harmonize cancer survivorship management of their primary care patients who are also BCS, with defined role distinct from oncologists. Training to understand the care protocol, enhancement of communication skills, confidence and trust were deemed necessary. PCPs proposed selection criteria of BCS and adequacy of their medical information; increased consultation time; contact details and timely access to oncologists (if needed) in the shared-care programme.

Conclusions
PCPs were willing to share the care of BCS with oncologists but recommended role definition, training, clinical protocol, resources and access to oncologist’s consultation to optimize the programme implementation.
Telescope: an interactive tool for managing large-scale analysis from mobile devices
Authors: Brito Jaqueline J , Mosqueiro Thiago , Rotman Jeremy , Xue Victor , Chapski Douglas J , la Hoz Juan De , Matias Paulo , Martin Lana S , Zelikovsky Alex , Pellegrini Matteo , Mangul Serghei 
Published: January 2020

Abstract

Background
In today's world of big data, computational analysis has become a key driver of biomedical research. High-performance computational facilities are capable of processing considerable volumes of data, yet often lack an easy-to-use interface to guide the user in supervising and adjusting bioinformatics analysis via a tablet or smartphone.

Results
To address this gap we proposed Telescope, a novel tool that interfaces with high-performance computational clusters to deliver an intuitive user interface for controlling and monitoring bioinformatics analyses in real-time. By leveraging last generation technology now ubiquitous to most researchers (such as smartphones), Telescope delivers a friendly user experience and manages conectivity and encryption under the hood.

Conclusions
Telescope helps to mitigate the digital divide between wet and computational laboratories in contemporary biology. By delivering convenience and ease of use through a user experience not relying on expertise with computational clusters, Telescope can help researchers close the feedback loop between bioinformatics and experimental work with minimal impact on the performance of computational tools. Telescope is freely available at https://github.com/Mangul-Lab-USC/telescope.
A new method to estimate ocean-bottom-seismometer orientation using teleseismic receiver functions
Authors: Zheng Hong , Fan Jianke , Zhao Dapeng , Li Cuilin , Dong Dongdong , Zhang Guangxu , Wang Xiujuan 
Published: January 2020

SUMMARYThe orientation of an ocean-bottom-seismometer (OBS) is a critical parameter for analysing three-component seismograms, but it is difficult to estimate because of the uncontrollable OBS posture after its deployment. In this study, we develop a new and effective method to estimate the OBS orientation by fitting the amplitude of direct P wave of teleseismic receiver functions. The reliability of this method is verified using synthetic data and observed waveforms recorded at land seismic stations in Shandong Province, China. Our extensive synthetic tests show that our new method is little affected by a thin sedimentary layer that has a low S-wave velocity. The orientations of OBS stations that we deployed in the Yap subduction zone in the Western Pacific Ocean are estimated and corrected using our new method. After the correction, the direct P waves of teleseismic receiver functions show very good consistency. The effects of white and coloured noise in different levels, epicentral distance and backazimuth are also investigated, and the results show that these factors have small effects on the new method. We also examine the effect of sensor tilting on estimation of the OBS orientation, and find that a tilting correction should be made before the misorientation correction. We compare the OBS orientations determined with the new method and other methods and find that they are generally consistent with each other. We also discuss advantages and shortcomings of various methods, and think that our new method is more robust than the existing methods.
‘Real Toryism’ or Christian democracy? The political thought of Douglas Jerrold and Charles Petrie at the New English Review, 1945–50*
Authors: Love Gary 
Published: January 2020

Abstract
This article uses the periodical press, memoirs and archival sources to examine the Conservative thought of Douglas Jerrold and Charles Petrie at the New English Review between 1945 and 1950. It seeks to argue that while there was more continuity than rupture in their political thought, they were able to make a transition from interwar authoritarianism and ‘fascism’ to postwar anti-communism and democracy. There were similarities between their political Catholicism and Christian democracy, but ultimately their ‘real Toryism’ and continued sympathy for Franco prevented them from fully aligning themselves with British and west European Christian democrats.
17 AZD4205, A SELECTIVE, GI TRACT-ENRICHED SELECTIVE JAK1 INHIBITOR FOR CROHN’S DISEASE: PRECLINICAL EVIDENCE AND PHASE I DATA
Authors: Wang Mei , Zhang Lin , Han Sufang , Xu Yanping , Li Jingrun , Chen Kan , Li Li , Yang Zhenfan , Liang Jie , Wu Kaichun , Rubin David 
Published: January 2020

Abstract

Background
AZD4205 is an oral, ATP-competitive, JAK1 selective inhibitor. Nonclinical data showed its higher drug concentration within the gastrointestinal (GI) tract relative to plasma in the rodents, suggesting its potential as an effective and safe treatment option for patients with Crohn’s disease (CD). AZD4205 also has been evaluated in a phase I study in healthy volunteers (HVs). Here we report AZD4205 preclinical data in cells and animal models, and phase I data from HVs.

Method
Enzymatic activity of AZD4205 was assessed in in vitro biochemical assay with human isolated JAK kinase domains. The cellular activity of AZD4205 was evaluated in human peripheral blood mononuclear cells (PBMCs) by assessing cytokine induced phosphorylated-STATs (pSTATs). The in vivo efficacy of AZD4205 was assessed in a murine CD model induced by subcutaneous injection of 10 mg/kg indomethacin, and AZD4205 was orally administered at different doses for 5 consecutive days. The ileum and bone marrow tissues were collected post AZD4205 treatment to measure pSTAT3 expression using immunohistochemistry. The drug concentration of AZD4205 in ileum and plasma were measured by HPLC.
Phase I study of HVs (Clinicaltrial.gov Identifier: NCT03728023) comprised of single ascending dose (SAD) of 5 to 150 mg, food effect (FE) with 50 mg single dosing with or without food, and multiple ascending dose (MAD) of 25 to 100 mg once daily for 14 days. Safety monitoring was conducted, and blood samples were collected to assess PK of AZD4205.

Result
In enzymatic assay, AZD4205 exhibits greater than 200-400-fold selectivity over other JAK family kinases. AZD4205 inhibits pSTAT1, pSTAT3, and pSTAT5 in human PBMCs with IC50 of 50, 308, and 90 nM, respectively.
The drug concentration of AZD4205 in murine ileum was around 100-fold higher than that in plasma. In murine CD model, the pSTAT3 was inhibited by 93% in ileum but only 43% in bone marrow at 4 hr post AZD4205 treatment. AZD4205 exhibited a dose-dependent effect on improving body weight loss and decreasing colon density in this model.
In the NCT03728023 study, 66HVs were dosed with AZD4205 or matched placebo, SAD (n=20 in AZD4205, n=10 in placebo), FE (n=12 in AZD4205) and MAD (n=18 in AZD4205, n=6 in placebo). AZD4205 was well-tolerated, and no ≥ G3 drug related AE was observed. A dose-proportional increase of AZD4205 plasma concentrations was detected in HVs. The T1/2 was close to 48 hr and hence accumulation of about 3-fold in Cmax and AUC was observed after multiple once daily dosing. No relevant food effect was observed to significantly impact AZD4205 PK.

Conclusion
Based on preclinical murine data, AZD4205 has unique GI-tract enriched PK properties, as a promising agent for CD. Clinical data in HVs demonstrated its favorable safety and PK profiles. A phase II study in moderate to severe CD is planned.
16 CCL11 EXACERBATES COLITIS VIA MODULATION OF EPITHELIAL WOUND REPAIR
Authors: Polosukhina Dina , Singh Kshipra , Barry Daniel , Allaman Margaret , Piazuelo Maria , Washington Mary , Wilson Keith , Coburn Lori 
Published: January 2020

Abstract

Background
We have shown that CCL11 (eotaxin-1), an eosinophil chemoattractant, is significantly increased in the serum of ulcerative colitis and Crohn’s disease patients vs controls and is also increased in dextran sulfate sodium (DSS)-induced murine colitis. In response to azoxymethane (AOM)-DSS, Ccl11–/– mice have significantly decreased colonic tumor number and burden, histologic injury, and colonic eosinophil infiltration vs wild-type (WT) mice. Ccl11 is expressed by isolated colonic epithelial and lamina propria immune cells. Studies in bone marrow chimera mice revealed that both hematopoietic- and epithelial-cell derived CCL11 were important for protection in the AOM-DSS model. Our aim was to assess the role of CCL11 in an injury and recovery colitis model and in an epithelial wound restitution model.

Methods
C57BL/6 WT and Ccl11–/– mice were exposed to 4% DSS in the drinking water for 5 days followed by 5 days of water for an injury and recovery model. Body weights were assessed daily. Histologic injury was assessed by a validated scoring system including depth and percent involvement of inflammation and crypt damage. Colonic eosinophil and neutrophil infiltration was determined by immunohistochemistry for major basic protein (MBP) and myeloperoxidase (MPO), respectively. The number of MBP- and MPO-positive cells per high-powered field (HPF) were quantified in a blinded manner. Young Adult Mouse Colon (YAMC) epithelial cells were stained with antibodies to the CCL11 receptors CCR2, CCR3, and CCR5 for assessment by flow cytometry. YAMC cell monolayers were wounded and followed for 24 h in normal media or with the addition of 100ng/mL recombinant CCL11 (rCCL11). The wound area was measured at 0 and 24 h to determine percent restitution. RNA was isolated and assessed for Ccl11 mRNA expression.

Results
In the injury and recovery model, Ccl11–/– mice exhibited decreased body weight loss (p&lt;0.05), histologic injury (20.6 ± 1.5 vs 12.4 ± 1.6, p&lt;0.001), and fewer MBP-positive cells/HPF (23.5 ± 1.4 vs 2.4 ± 0.2, p&lt;0.001) vs WT mice. While colonic MPO-positive cells were increased with DSS exposure, there was no difference in Ccl11–/– mice. Naïve/unstimulated YAMC cells expressed both CCR3 and CCR5. Wounding the YAMC monolayer alone did not lead to increased Ccl11 mRNA expression. However, in the presence of rCCL11, there was a decrease in wound restitution at 24 h (48.0% ± 1.7 vs 31.3% ± 2.1, p&lt;0.001).

Conclusions
Loss of CCL11 leads to clinical and histologic improvement in an injury and recovery colitis model. Colonic epithelial cells express both CCR3 and CCR5, and epithelial wound restitution is decreased in the presence of rCCL11. These data suggest that CCL11 has a deleterious effect on epithelial restitution leading to an exacerbation of colitis. Therefore, treatment with anti-CCL11 antibodies may be a therapeutic strategy in IBD patients.
P058 ISOLATED TERMINAL ILEITIS AT COLONOSCOPY – WHAT FACTORS PREDICT A NEW DIAGNOSIS OF CROHN’S DISEASE?
Authors: Patel Rajan , Ang Kar Mun , Moledina Saadiq , Musa Saif , Alisa Akeel , Tang Kwok 
Published: January 2020

Abstract

Background
Faecal calprotectin (FC) is a biomarker elevated in active inflammatory bowel disease (IBD). FC is more sensitive in colonic than small bowel IBD. Ileo-colonoscopy is usually performed to confirm a diagnosis of IBD. Isolated non-specific terminal ileitis is often inconclusive despite biopsy. We aimed to assess the factors that predict terminal ileal Crohn’s disease after ileitis is seen at colonoscopy.

Methods
A single centre retrospective study of all endoscopic cases of isolated terminal ileitis diagnosed at colonoscopy over a 4 year period (January 2015 – December 2018) was performed. Data was obtained from the Unisoft Endoscopy reporting software. Statistical analyses included chi-square, student t-test and binary logistic regression. Faecal calprotectin, CRP and histology were noted. &gt;150μg/mg was used as a cut off for elevated FC.

Results
139 cases were identified and exclusion criteria were applied (known Crohn’s disease, colonic disease). 74 cases were included for analysis. The mean age was 43.9. 44 (59.5%) of the cases were women. 38 (51.4%) had FC performed of which 27 (71.1%) had a FC &gt;150μg/mg.
60 (81.1%) cases had macroscopic terminal ileum ulcers, 9 (15%) of these had histological evidence of ulceration. Subsequent diagnoses of Crohn’s disease were made in 15 (20.3%) patients. Odds ratio of 1.28 (p = 0.016, Cl 0.45-0.047) in the TI ulcers + FC &gt;150μg/mg vs. no TI ulcers + FC &lt;150μg/mg.

Conclusion
1 in 5 patients with isolated terminal ileitis were subsequently diagnosed with Crohn’s disease. Almost 90% of these new cases had a faecal calprotectin &gt;150μg/mg. There is poor correlation between endoscopic and histological terminal ileum ulceration. We conclude that terminal ileal ulceration in combination with faecal calprotectin &gt;150μg/mg increases the likelihood of a new diagnosis of Crohn’s disease.
9 METABOLIC UTILIZATION OF PROPANEDIOL BY ADHERENT-INVASIVE E. COLI REGULATES INTESTINAL TISSUE IMMUNITY
Authors: Viladomiu Monica , Metz Maeva , Lima Svetlana , Guo Chun-Jun , Simpson Kenneth , Longman Randy 
Published: January 2020

Abstract
While the molecular mechanisms by which the microbiome modulates mucosal immunity in Crohn’s disease (CD) are still largely unknown, recent data highlight the involvement of specific diet- and bacterial-derived metabolites in the regulation of intestinal immune cell activation and differentiation. We have recently shown that Adherent-Invasive E.coli (AIEC), which are enriched in CD patients, are sufficient to induce intestinal Th17 cells. Although AIEC lack pathogenic factors including type III secretion systems, many CD-derived isolates express virulence-associated metabolic enzymes including propanediol dehydratase (PduC), which enables AIEC to use fucose-derived propanediol as an alternate carbon source in the gut. We found that pduC is enriched in the microbiome and among E. coli genomes in CD patients compared to healthy controls. With fucosylated oligosaccharides on the surface of intestinal epithelial cells, we hypothesized that this propanediol utilization pathway provides AIEC a competitive advantage for epithelial cell adherence and intestinal immune cell activation. To evaluate the physiologic contribution of pduC to mucosal Th17 induction, we generated a pduC-deficient (ΔpduC) mutant of a CD-derived, AIEC isolate. Deletion of pduC resulted in reduced inflammatory Th17 cells and attenuated weight loss following T cell transfer colitis. Using genetic mouse models, we found that CX3CR1+ mononuclear phagocytes are required for this AIEC-mediated Th17 induction and IL-10 is required to restrain pduC-dependent dextran sodium sulfate (DSS)-induced colitis. Using a catalytically-inactive mutant, we determined that PduC metabolic activity was required for this immune phenotype. Cell-free supernatants from WT AIEC (but not the isogenic, pduC-deficient clone) promoted ex vivo Th17 cell polarization and metabolomics analysis (LC-MS) of these supernatants defined PduC-dependent metabolites capable of promoting Th17 polarization. These studies reveal a link between AIEC microbial metabolism and inflammatory Th17 cells with the potential to serve as a therapeutic target in the treatment of Crohn’s disease.
P162 CRITICAL ROLES OF DIETARY SIMPLE SUGARS IN COLITIS PATHOGENESIS
Authors: Godfrey Victoria , Zaki Hasan 
Published: January 2020

Abstract
The incidence of inflammatory bowel disease (IBD) is strikingly high in Western countries, implicating the role of Western diet in its etiology and pathogenesis. Western diet is characterized by high fat, low fiber, and high sugar. Despite clinical evidence of an association between high sugar diet and IBD susceptibility, the precise role of dietary simple sugars such as glucose, fructose, and sucrose in colitis pathogenesis is unknown. Using dextran sodium sulfate (DSS) and IL10-deficient mouse models of colitis, we studied the effect of simple sugars in colitis susceptibility. Mice were given high glucose, fructose or sucrose in their drinking water or left untreated before and during colitis induced by DSS. Sugar-fed mice exhibited increased colitis susceptibility evidenced by higher body weight loss, diarrhea, rectal bleeding, and severe histopathological changes in the colon as compared to those of sugar-untreated colitic mice. Pre-colitis dietary habit of sugar consumption was critical since sugar pretreated mice were susceptible to DSS-induced colitis even without high sugar diet intake during DSS administration. Consistent with these findings, there were higher incidence of spontaneous colitis development in Il10-/- mice following consumption of high sugar. To understand the underlying mechanism, we evaluated the effect of high sugar diet on intestinal epithelial cell death, inflammation, epithelial barrier permeability, and gut microbiota composition in healthy mice. We did not observe any major pathological changes and apoptosis in the colon of sugar-fed mice. Inflammatory responses, activation of inflammatory signaling pathways, and the expression of tight junction proteins were comparable between control and sugar-fed mice. Interestingly, gut microbiota composition of sugar-fed mice was altered as measured by 16S rRNA gene sequencing of DNA isolated from feces. Microbial species richness was reduced and relative abundance of several bacterial species was either increased or decreased in sugar-fed mice. We further confirmed that sugar-induced alteration of gut microbiota is responsible for exacerbated colitis by using antibiotics or germ-free mice. Mice receiving antibiotics during high-sugar intake did not show increased DSS-colitis susceptibility. Similarly, high-sugar diet did not induce overt colitis pathogenesis in germ-free mice. These findings demonstrate a critical role of dietary caloric sugars in the predisposition and promotion of colitis and could be implicated in the treatment and management of IBD.