bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Characteristics of Imported Cases of Coronavirus Disease 2019 (COVID-19) in Jiangsu Province: A Multicenter Descriptive Study
Authors: Wu Jian , Liu Jun , Zhao Xinguo , Liu Chengyuan , Wang Wei , Wang Dawei , Xu Wei , Zhang Chunyu , Yu Jiong , Jiang Bin , Cao Hongcui , Li Lanjuan
Published: February 2020

Background

We aimed to report the clinical characteristics of imported cases of coronavirus disease 2019 (COVID-19) in Jiangsu Province.

Methods

We retrospectively investigated the clinical, imaging, and laboratory characteristics of confirmed cases of COVID-19 with World Health Organization interim guidance in 3 grade IIIA hospitals of Jiangsu from 22 January to 14 February 2020. Real-time RT-PCR was used to detect the new coronavirus in respiratory samples.

Results

Of the 80 patients infected with COVID-19, 41 were female, with a median age of 46.1 years. Except for 3 severe patients, the rest of the 77 patients exhibited mild or moderate symptoms. Nine patients were unconfirmed until a third nucleic acid test; 38 cases had a history of chronic diseases. The main clinical manifestations of the patients were fever and cough, which accounted for 63 (78.75%) and 51 (63.75%) cases, respectively. Only 3 patients (3.75%) showed liver dysfunction. Imaging examination showed that 55 patients (68.75%) showed abnormal density shadow and 25 cases (31.25%) had no abnormal density shadow in the parenchyma of both lungs. Currently, 21 cases have been discharged from the hospital, and no patient died. The average length of stay for discharged patients was 8 days.

Conclusions

Compared with the cases in Wuhan, the cases in Jiangsu exhibited mild or moderate symptoms and no obvious gender susceptibility. The proportion of patients having liver dysfunction and abnormal CT imaging was relatively lower than that in Wuhan. Notably, infected patients may be falsely excluded based on 2 consecutively negative respiratory pathogenic nucleic acid test results.
A Single Center Experience With Long-Term Ustekinumab Use and Reinduction in Patients With Refractory Crohn Disease
Authors: Bennett Audrey , Evers Carlini Lauren , Duley Caroline , Garrett Ailish , Annis Kim , Wagnon Julianne , Dalal Robin , Scoville Elizabeth , Beaulieu Dawn , Schwartz David , Horst Sara
Published: February 2020

Background

Ustekinumab was approved for moderate and severe Crohn’s disease (CD) in 2016, but little is known about long-term outcomes.

Methods

A retrospective study evaluated all patients with CD treated with ustekinumab, including patients with reinduction. C-reactive protein (CRP), Harvey-Bradshaw Index (HBI), Short Inflammatory Bowel Disease (SIBDQ), and endoscopy outcomes were collected prospectively.

Results

Ninety-six patients received ustekinumab, resulting in improvement in CRP, HBI, and SIBDQ scores with 68% endoscopic improvement/remission. Thirty-four patients underwent reinduction, resulting in improved HBI and CRP.

Conclusions

Ustekinumab in refractory CD results in significant clinical and endoscopic improvement and reinduction may be a viable option to recapture response.
Effect of Constant and Fluctuating Temperature on the Development, Reproduction, Survival, and Sex Ratio of Phenacoccus solenopsis (Hemiptera: Pseudococcidae)
Authors: Waqas Muhammad Saad , Lin Lulu , Shoaib Ali Ahmed Zaky , Cheng Xinlai , Zhang Qianqian , Elabasy Asem Saad Saad , Shi Zuhua
Published: February 2020

Effects of temperature on the development, survival, reproduction, longevity and sex ratio of the cotton mealybug, Phenacoccus solenopsis Tinsley, was assessed at five constant temperatures ranging from 20 to 35°C and five fluctuating temperatures ranging from 15 to 40°C under laboratory conditions. Results showed that nymphal development duration, preoviposition period, oviposition period, fecundity, and adult longevity were reduced significantly with increasing temperature until 30°C, but developmental duration of third female nymphal instar and female adult longevity was longer at 35°C than 30°C, and no males could emerge from pupae at the constant temperature 35°C. Fluctuating temperature, in general, significantly accelerated the nymphal developmental duration, prolonged preoviposition period, shortened oviposition period, reduced fecundity, lowered the survival rate of nymphs, and decreased adult longevity of males and females compared to their mean corresponding constant temperature. Overall, it is suggested that one should be prudent when applying the obtained results under constant and fluctuating temperatures under laboratory conditions.
The Ross procedure is a safe and durable option in adults with infective endocarditis: a multicentre study
Authors: Chauvette Vincent , Bouhout Ismail , Lefebvre Laurence , Tarabzoni Mohammed , Chamberland Marie-Ève , Poirier Nancy , Demers Philippe , Chu Michael W A , Perron Jean , El-Hamamsy Ismail
Published: February 2020

OBJECTIVES

Surgical treatment of infective endocarditis (IE) remains a challenge. The Ross procedure offers the benefit of a living substitute in the aortic position but it is a more complex operation which may lead to increased operative risk. The aim of this study was to assess the safety and late outcomes of the Ross procedure for the treatment of active IE.

METHODS

From 2000 to 2019, a total of 31 consecutive patients underwent a Ross procedure to treat active IE (mean age 43 ± 12 years, 84% male). All patients were followed up prospectively. Four patients (13%) were intravenous (IV) drug users and 6 patients (19%) had prosthetic IE. The most common infective organism was Streptococcus (58%). Median follow-up was 3.5 (0.9–4.5) years and 100% complete.

RESULTS

There were no in-hospital deaths. One patient suffered a postoperative stroke (3%) and 1 patient (3%) required reintervention for bleeding. Three patients had a new occurrence endocarditis: 2 patients were limited to the pulmonary homograft and successfully managed with IV antibiotics, whereas 1 IV drug user patient developed concomitant autograft and homograft endocarditis. Overall, cumulative incidence of IE recurrence was 13 ± 8% at 8 years. The cumulative incidence for autograft endocarditis was 5 ± 4% at 8 years. Two patients (6%) died during follow-up, both from drug overdoses. At 8 years, actuarial survival was 88 ± 8%.

CONCLUSIONS

In selected patients with IE, the Ross procedure is a safe and reasonable alternative with good mid-term outcomes. Freedom from recurrent infection on the pulmonary autograft is excellent, labelporting the notion that a living valve in the aortic position provides good resistance to infection. Nevertheless, in IV drug user patients, pulmonary homograft endocarditis remains a challenge. Continued follow-up is needed to ascertain the long-term benefits of this approach.
Aortic valve-sparing root replacement in patients with bicuspid aortic valve: long-term outcome with the David I procedure over 20 years
Authors: Beckmann Erik , Martens Andreas , Krüger Heike , Korte Wilhelm , Kaufeld Tim , Stettinger Alissa , Haverich Axel , Shrestha Malakh Lal
Published: February 2020

OBJECTIVES

Aortic valve-sparing root replacement is an excellent treatment option for patients with intact tricuspid aortic valves. However, the durability in patients with bicuspid aortic valves is still a matter of debate. The aim of this study was to analyse the short- and long-term outcomes in patients with bicuspid aortic valves.

METHODS

Between July 1993 and October 2015, a total of 582 patients underwent the David I procedure, 50 of whom had a bicuspid aortic valve. In these patients, the mean age was 46 ± 13 years, and 80% (n = 40) were men. Follow-up was complete for 100% of patients and comprised a total of 552 patient-years with a mean follow-up time of 11 ± 5.2 years.

RESULTS

In addition to the David procedure, cusp plication was performed in 34% (n = 17) of patients and commissure repair in 8% (n = 4) of patients. There were no in-hospital deaths, and 1 patient (2%) had a perioperative stroke. The 1-, 5-, 10- and 20-year survival rates of patients after discharge were 98%, 94%, 88% and 84%, respectively. The rates for freedom from valve-related reoperation at 1, 5, 10 and 20 years after initial surgery were 98%, 88%, 79% and 74%, respectively. Long-term freedom from reoperation was comparable to that of patients with tricuspid aortic valves (P = 0.2).

CONCLUSIONS

The David procedure has excellent short-term results in patients with a bicuspid aortic valve. In this study, the long-term durability of reimplanted bicuspid aortic valves was comparable to that of tricuspid valves. However, careful patient selection might have contributed to this, and further studies might be needed to definitely clarify this issue.
Microhabitats are associated with diversity–productivity relationships in freshwater bacterial communities
Authors: Schmidt Marian L , Biddanda Bopaiah A , Weinke Anthony D , Chiang Edna , Januska Fallon , Props Ruben , Denef Vincent J
Published: February 2020

Eukaryotic communities commonly display a positive relationship between biodiversity and ecosystem function (BEF) but the results have been mixed when assessed in bacterial communities. Habitat heterogeneity, a factor in eukaryotic BEFs, may explain these variable observations but it has not been thoroughly evaluated in bacterial communities. Here, we examined the impact of habitat on the relationship between diversity assessed based on the (phylogenetic) Hill diversity metrics and heterotrophic productivity. We sampled co-occurring free-living (more homogenous) and particle-associated (more heterogeneous) bacterial habitats in a freshwater, estuarine lake over three seasons: spring, summer and fall. There was a strong, positive, linear relationship between particle-associated bacterial richness and heterotrophic productivity that strengthened when considering dominant taxa. There were no observable BEF trends in free-living bacterial communities for any diversity metric. Biodiversity, richness and Inverse Simpson's index, were the best predictors of particle-associated production whereas pH was the best predictor of free-living production. Our findings show that heterotrophic productivity is positively correlated with the effective number of taxa and that BEF relationships are associated with microhabitats. These results add to the understanding of the highly distinct contributions to diversity and functioning contributed by bacteria in free-living and particle-associated habitats.
Process Evaluation of a Combined Lifestyle Intervention for Community-Dwelling Older Adults: ProMuscle in Practice
Authors: van Dongen Ellen J I , Doets Esmée L , de Groot Lisette C P G M , Dorhout Berber G , Haveman-Nies Annemien
Published: February 2020

Background and Objectives

The ProMuscle in Practice intervention combines resistance exercise training and dietary protein intake for community-dwelling older adults, implemented by health care professionals (HCPs). This study aimed to evaluate implementation and context of this intervention in Dutch health care practice.

Research Design and Methods

We conducted a randomized controlled multicenter intervention study in 5 Dutch municipalities. Eighty-two older adults received the 12-week intensive support intervention (resistance exercise training and individual dietary counseling) and the optional 12-week moderate support intervention (resistance exercise training and a nutrition course). Mixed method data were collected from both participants and HCPs (n = 37) on process indicators recruitment, dose received, acceptability, fidelity, applicability, and context.

Results

Overall, the intervention was feasible to implement and accepted by participants and HCPs. About two thirds of participants continued with the moderate support intervention after the first 12 weeks. The mean dose received for the training sessions was 83.6% in the intensive intervention, 63.6% in the moderate intervention, >90% for individual dietitian consultations, and 76.8% for the nutrition course. The intensive support intervention was implemented with high fidelity, whereas for the moderate support intervention resistance exercise trainings varied in implementation between exercise providers.

Discussion and Implications

A combined resistance exercise training and dietary protein intervention for community-dwelling older adults can be successfully implemented in practice. Well-tailored interventions, intensive supervision by skilled HCPs, social aspects, fidelity, and fit within real-world settings appeared essential for successful implementation. These elements are important for continuous intervention optimization to accomplish broader and successful implementation.
Chromosomal-level assembly of Juglans sigillata genome using Nanopore, BioNano, and Hi-C analysis
Authors: Ning De-Lu , Wu Tao , Xiao Liang-Jun , Ma Ting , Fang Wen-Liang , Dong Run-Quan , Cao Fu-Liang
Published: February 2020

Background

Juglans sigillata, or iron walnut, belonging to the order Juglandales, is an economically important tree species in Asia, especially in the Yunnan province of China. However, little research has been conducted on J. sigillata at the molecular level, which hinders understanding of its evolution, speciation, and synthesis of secondary metabolites, as well as its wide adaptability to its plateau environment. To address these issues, a high-quality reference genome of J. sigillata would be useful.

Findings

To construct a high-quality reference genome for J. sigillata, we first generated 38.0 Gb short reads and 66.31 Gb long reads using Illumina and Nanopore sequencing platforms, respectively. The sequencing data were assembled into a 536.50-Mb genome assembly with a contig N50 length of 4.31 Mb. Additionally, we applied BioNano technology to identify contacts among contigs, which were then used to assemble contigs into scaffolds, resulting in a genome assembly with scaffold N50 length of 16.43 Mb and contig N50 length of 4.34 Mb. To obtain a chromosome-level genome assembly, we constructed 1 Hi-C library and sequenced 79.97 Gb raw reads using the Illumina HiSeq platform. We anchored ~93% of the scaffold sequences into 16 chromosomes and evaluated the quality of our assembly using the high contact frequency heat map. Repetitive elements account for 50.06% of the genome, and 30,387 protein-coding genes were predicted from the genome, of which 99.8% have been functionally annotated. The genome-wide phylogenetic tree indicated an estimated divergence time between J. sigillata and Juglans regia of 49 million years ago on the basis of single-copy orthologous genes.

Conclusions

We provide the first chromosome-level genome for J. sigillata. It will lay a valuable foundation for future research on the genetic improvement of J. sigillata.
Inversion of the reflected SV-wave for density and S-wave velocity structures
Authors: Zhang Feng , Li Xiang-yang
Published: February 2020

Density is one of the most essential properties that determines the dynamic behavior of the Earth. Besides, density has been commonly used to investigate the mineral composition, porosity and fluid content of rock. Therefore, a reliable estimation of the density structure is one of the most important objectives in both global seismology and seismic exploration. However, seismic inversions of independent density estimates are ill-posed because density has a large trade-off with velocities. Shear wave propagation is sensitive to both density and the S-wave velocity. We show that the reflected SV-wave (SV-to-SV wave) at an incident angle of 22.5o depends only on density contrast, and at incident angle 30o it depends only on S-wave velocity contrast. Thus, density as well as S-wave velocity can be directly inverted from the reflected SV-wave as separate and independent parameters. The forward modelling has high accuracy, the inverse problem is well-posed and the misfit function can be easily regularized. Field data application demonstrates the proposed method can efficiently recover reliable and high-resolution density and S-wave velocity of fine sturctures. Thus, this method has great potential in geological interpretation including understanding regional Moho structure, crustal and mantle formation and evolution, and rock lithologic composition and fluid-filled porosity.
The invention of tradition: Same-sex marriage and its discontents in Hong Kong
Authors: Wan Marco
Published: February 2020

In Leung Chun Kwong v. Secretary for the Civil Service, the Hong Kong Court of Final Appeal held that the government unlawfully discriminated against a gay civil servant by refusing to recognize his same-sex marriage—entered into abroad—when considering the granting of local spousal benefits and joint tax assessment. The year before, in QT v. Director of Immigration, the court had ruled against the government for denying the partner of a British lesbian a dependant visa on the basis of her sexual orientation. QT and Leung Chun Kwong are landmarks in the rapidly evolving jurisprudence on same-sex marriage in the territory. This article presents an analysis of the Hong Kong cases relating to gay rights and same-sex marriage. It contends that, even though the need to protect traditional marriage is cited as a reason against marriage equality in many jurisdictions, the claim is particularly problematic in Hong Kong, given the city’s unique marriage history. It draws on the historian Eric Hobsbawm’s notion of “the invention of tradition” to argue that the rhetoric of traditional marriage conjures up an imagined past that displaces a vast and varied set of long-standing marital practices. By exploring government reports and records pertaining to Chinese marriages in colonial Hong Kong, this article then examines these forgotten traditions and demonstrates their significance for understanding the marriage equality debate in the territory in our own time.
Technological revolution, democratic recession, and climate change: The limits of law in a changing world
Authors: Barroso Luís Roberto
Published: February 2020

Law is a universal institution that has pretensions of being ubiquitous and complete. However, in a complex, plural and volatile world, its limits and possibilities are shaken by the speed, depth and extent of ongoing transformations, its resulting ethical dilemmas, and the difficulties of forming consensus in the political universe. This article provides a reflection on how the law has attempted to deal with some of the main afflictions of our time, facing demands that include the needs to (i) keep the technological revolution on an ethical and humanitarian track, (ii) avoid democracy being perverted by populist and authoritarian adventures, and (iii) prevent solutions to climate change from coming when it is too late. At a time when even the near future has become unpredictable, the law cannot provide a priori solutions to multiplying problems and anxieties. When this happens, we must set clear goals for the future of humanity, basing them on the essential and perennial values that have followed us since antiquity.
The impact of cardiopulmonary bypass management on outcome: a propensity matched comparison between minimally invasive and conventional valve surgery
Authors: Vandewiele Korneel , De Somer Filip , Vandenheuvel Michael , Philipsen Tine , Bové Thierry
Published: February 2020

OBJECTIVES

Research concerning cardiopulmonary bypass (CPB) management during minimally invasive cardiac surgery (MICS) is scarce. We investigated the effect of CPB parameters such as pump flow, haemoglobin concentration and oxygen delivery on clinical outcome and renal function in a propensity matched comparison between MICS and median sternotomy (MS) for atrioventricular valve surgery.

METHODS

A total of 356 patients undergoing MICS or MS for atrioventricular valve surgery between 2006 and 2017 were analysed retrospectively. Propensity score analysis matched 90 patients in the MS group with 143 in the MICS group. Logistic regression analysis was performed to investigate independent predictors of cardiac surgery-associated acute kidney injury in patients having MICS.

RESULTS

In MICS, CPB (142.9 ± 39.4 vs 101.0 ± 38.3 min; P < 0.001) and aortic cross-clamp duration (89.9 ± 30.6 vs 63.5 ± 23.0 min; P < 0.001) were significantly prolonged although no differences in clinical outcomes were detected. The pump flow index was lower [2.2 ± 0.2 vs 2.4 ± 0.1 l⋅(min⋅m2)−1; P < 0.001] whereas intraoperative haemoglobin levels were higher (9.25 ± 1.1 vs 8.8 ± 1.2; P = 0.004) and the nadir oxygen delivery was lower [260.8 ± 43.5 vs 273.7 ± 43.7 ml⋅(min⋅m2)−1; P = 0.029] during MICS. Regression analysis revealed that the nadir haemoglobin concentration during CPB was the sole independent predictor of cardiac surgery-associated acute kidney injury (odds ratio 0.67, 95% confidence interval 0.46–0.96; P = 0.029) in MICS but not in MS.

CONCLUSIONS

Specific cannulation-related issues lead to CPB management during MICS being confronted with flow restrictions because an average pump flow index ≤2.2 l/min/m2 is achieved in 40% of patients who have MICS compared to those who have a conventional MS. This study showed that increasing the haemoglobin level might be helpful to reduce the incidence of cardiac surgery-associated acute kidney injury after minimally invasive mitral valve surgery.
Manuscript Preparation for Submission and Publication
Authors: Iverson Cheryl
Published: February 2020

The Manuscript Preparation chapter of the 11th edition of the AMA Manual of Style considers each element of a manuscript (with the exception of references and figures, tables, and boxes, which are dealt with in separate chapters): titles and subtitles, author bylines and end-of-text signatures, notes, running heads and running feet, abstracts, key words, epigraphs, headings and subheadings and side headings, addenda, acknowledgments, appendixes, online-only supplementary material, and ancillary educational and promotional material. Guidance is directed to both authors, for manuscript preparation and submission, and editors, for manuscript publication. Requirements of specific journals as well as reporting guidelines such as EQUATOR are taken into account. For some sections, both print and online examples are provided.
References
Authors: Fischer Lauren , Frank Paul
Published: February 2020

The References chapter of the 11th edition of the AMA Manual of Style contains detailed guidance on what should be included in a reference and how references should be styled and formatted. Sample references to both books and journals, in print and online, include formats for sometimes complex citations that include non-English words and phrases, names of organisms, discontinuous pagination, journals without volume or issue numbers, a special department of a journal, discussants, online comments, special collections, package inserts, patents, conference proceedings, personal communications, material submitted but not yet accepted or published, and transcripts. Many examples of how to cite social media and other electronic resources, including podcasts, apps and interactive games, preprints, databases, and data repositories, are included. New recommendations: a DOI should be included for journal references if available, and it is no longer necessary to include the publisher’s location in references to books.
Tables, Figures, and Multimedia
Authors: Christiansen Stacy , Manno Connie
Published: February 2020

The Tables, Figures, and Multimedia chapter of the 11th edition of the AMA Manual of Style begins with guidance on when to use tables vs figures or tables vs text. Descriptions of various table types (eg, matrix, box, sidebar, and other nontabular material) and examples of each illustrate advice on organization of information, use of footnotes, alignment, titles, column and row headings, and treatment of punctuation, abbreviations, and units of measure. Descriptions of assorted figures (statistical graphs, diagrams, maps, illustrations, and clinical imaging), each with examples, provide advice on scales, axis labels, and error bars, as well as titles and legends. New with this edition is sentence-style capitalization for table column headings and graph axis labels. Consent for identifiable patients is covered, and helpful guidelines for preparing both figures and tables are included. Detailed specifications on acceptable video and audio file formats, optimal video quality, and filming and copyright considerations complete the chapter.
Ethical and Legal Considerations
Authors: Flanagin Annette
Published: February 2020

The Ethical and Legal Considerations chapter of the 11th edition of the AMA Manual of Style summarizes best practices and cites examples of the determinants of ethical behavior and legal concerns as they relate to scientific publication. Topics covered include authorship responsibility; acknowledgments; duplicate publication; scientific misconduct; conflicts of interest; intellectual property: access, rights, and management; confidentiality; protecting research participants’ and patients’ rights in scientific publication; defamation and libel; editorial freedom and integrity; editorial responsibilities, roles, procedures, and policies; advertisements, advertorials, sponsorship, supplements, reprints, and e-prints; and release of information to the public and journal/author relations with the news media. Several new policies: mandate for a single corresponding author has been relaxed; designations such as co–first authorship or co–senior authorship may be allowed; the ICMJE policy on sharing clinical trial data is now being followed; and a new option is presented for retraction and replacement in cases of pervasive error without evidence of misconduct or invalid science.
Punctuation
Authors: Iverson Cheryl
Published: February 2020

The Punctuation chapter of the 11th edition of the AMA Manual of Style includes guidance on usage of many punctuation marks, as well as examples to illustrate the style. Included are the period, question mark, and exclamation point; comma, semicolon, and colon; hyphens and dashes; forward slash (virgule); parentheses and brackets; quotation marks; apostrophe; and ellipses. Expanded guidance on punctuation within lists or enumerations has been added, as have several policy changes: no hyphen in email and no period in the reference list after a URL or a DOI if either of these is the final item in the reference.
Nomenclature
Authors: Iverson Cheryl
Published: February 2020

The Nomenclature chapter of the 11th edition of the AMA Manual of Style attempts to explain not how names for specific entities should be devised (although the sources of such rules are cited whenever possible) but rather which names should be used and how they should be styled. Official systems of nomenclature are not universally observed to the letter (literally or figuratively), but there is an attempt to be consistent with official guidelines. The work of international groups, tradition, and flexibility combine to provide an approach that attempts to balance official systems and actual usage. Guidelines for nomenclature in the following areas are covered: blood groups, platelet antigens, and granulocyte antigens; cancer; cardiology; drugs; equipment, devices, and reagents; genetics; hemostasis; immunology; isotopes; molecular medicine; neurology; obstetrics; ophthalmology; organisms and pathogens; psychiatry; pulmonary, respiratory, and blood gas terminology; and radiology. A preview of a new section on nephrology is also included.
Numbers and Percentages
Authors: Livingston Edward H.
Published: February 2020

The Numbers and Percentages chapter of the 11th edition of the AMA Manual of Style tackles the difficult question of when to use numerals and when to use words, and how to combine the two. Many examples are given, including exceptions to the rules. Also addressed are different forms of numbers: fractions, mixed fractions, and decimals; numbers as measures of time, temperature, and currency; percentages and proportions; rates and ratios; and digit spans. Special attention is given to the number one (1), enumerations, and rounding numbers.
Simulation modeling validity and utility in colorectal cancer screening delivery: A systematic review
Authors: Smith Heather , Varshoei Peyman , Boushey Robin , Kuziemsky Craig
Published: February 2020

Objective

This study sought to assess the impact and validity of simulation modeling in informing decision making in a complex area of healthcare delivery: colorectal cancer (CRC) screening.

Materials and Methods

We searched 10 electronic databases for English-language articles published between January 1, 2008, and March 1, 2019, that described the development of a simulation model with a focus on average-risk CRC screening delivery. Included articles were reviewed for evidence that the model was validated, and provided real or potential contribution to informed decision making using the GRADE EtD (Grading of Recommendations Assessment, Development, and Evaluation Evidence to Decision) framework.

Results

A total of 43 studies met criteria. The majority used Markov modeling (n = 31 [72%]) and sought to determine cost-effectiveness, compare screening modalities, or assess effectiveness of screening. No study reported full model validation and only (58%) reported conducting any validation. Majority of models were developed to address a specific health systems or policy question; few articles report the model’s impact on this decision (n = 39 [91%] vs. n = 5 [12%]). Overall, models provided evidence relevant to every element important to decision makers as outlined in the GRADE EtD framework.

Discussion and Conclusion

Simulation modeling contributes evidence that is considered valuable to decision making in CRC screening delivery, particularly in assessing cost-effectiveness and comparing screening modalities. However, the actual impact on decisions and validity of models is lacking in the literature. Greater validity testing, impact assessment, and standardized reporting of both is needed to understand and demonstrate the reliability and utility of simulation modeling.
Microbiologique Microfilm™ EBEc – a Rapid Method for the Simultaneous Enumeration of Enterobacteriaceae and Escherichia coli
Authors: Mai Tam L , Ming Ziwen , Nguyen Van , Shapovalova Anna , Samadpour Mansour
Published: February 2020

Background

The Enterobacteriaceae and generic Escherichia coli are routinely enumerated in foods as part of product release criteria, or in the case of swabs, for environmental monitoring.

Objective

Microbiologique Microfilm™ EBEc is intended to provide a rapid and easy-to-use method for simultaneous enumeration of Enterobacteriaceae and E. coli on foods and environmental surfaces. Methods: This study evaluated the performance of Microfilm™ EBEc against ISO methods (ISO 21528-2:2017 for Enterobacteriaceae and ISO 16649-2: 2001 for E. coli) in 20 food matrixes and two environmental surfaces. Inclusivity, exclusivity, lot-to-lot reproducibility, ruggedness and stability studies were also performed on Microfilm™ EBEc.

Results

No significant differences and high correlation coefficients (R2) were observed between the Microfilm™ EBEc and the corresponding ISO methods in spiked food matrixes and environmental samples. Inclusivity studies showed expected results for all the E. coli and Enterobacteriaceae strains tested. In terms of exclusivity testing, all the strains tested failed to grow on Microfilm™ EBEc. A lot-to-lot study showed no significant differences in mean difference (log10) counts among the three lots of the Microfilm™ EBEc. Ruggedness studies showed no significant differences in mean difference (log10) counts at varying incubation temperatures and times. Stability studies on the Microfilm™ EBEc showed that it is stable at 2–25°C for 12 months, and at 45°C for 6 weeks.

Conclusions

The results of this study indicate that the Microfilm™ EBEc is equivalent to the corresponding ISO methods for enumeration of Enterobacteriaceae and E. coli. Highlights: Microfilm™ EBEc offers a convenient and relatively fast test method for simultaneous enumeration of Enterobacteriaceae and E. coli in 24 h and has an advantage over the corresponding ISO methods that require two assays on the same sample for enumeration of Enterobacteriaceae and E. coli Gram-negative indicator groups.
Testing for Stanozolol, Using UPLC–MS-MS and Confirmation by UPLC–q-TOF-MS, in Hair Specimens Collected from Five Different Anatomical Regions
Authors: Gheddar Laurie , Raul Jean-Sébastien , Kintz Pascal
Published: February 2020

An athlete challenged the result from an in-competition doping test which returned with an adverse analytical finding for stanozolol, claiming it was due to supplement contamination. Her lawyer asked the laboratory to analyze several hair specimens simultaneously collected from five different anatomical regions, head, arm, leg, pubis and armpit, to document the pattern of drug exposure. A specific UPLC–MS-MS method was developed. After decontamination with dichloromethane, stanozolol was extracted from hair in the presence of stanozolol-d3 used as internal standard, under alkaline conditions, with diethyl ether. Linearity was observed for concentrations ranging from 5 pg/mg to 10 ng/mg. The method has been validated according to linearity, precision and matrix effect. Concentrations of stanozolol in head hair, pubic hair, arm hair, leg hair and axillary hair were 73, 454, 238, 244 and 7,100 pg/mg, respectively. The concentration of stanozolol in head hair is in accordance with data published in the literature. When comparing the concentrations, body hair concentrations were higher than the concentration found in head hair. These results are consistent with a better incorporation rate of stanozolol in body hair when compared to head hair. The simultaneous positive concentrations in different hair types confirm the adverse analytical finding in urine of the top athlete, as the measured concentrations do not support the theory of contamination. For the first time, an anabolic agent was simultaneously tested in hair collected from five different anatomical regions from the same subject, with a large distribution of concentrations, due to anatomical variations, and these findings will help interpretation in further doping cases when documented with hair.
A58 REGULATION OF INTESTINAL EPITHELIAL THYMIC STROMAL LYMPHOPOIETIN GENE EXPRESSION BY RETINOIC ACID RECEPTOR ALPHA
Authors: Mahmood R , Chan R , Beck P , Jijon H
Published: February 2020

Background

We have targeted the retinoic acid receptor alpha (RARα) isoform in murine intestinal epithelial cells (IECs) to explore the role of epithelial intrinsic retinoid signaling in intestinal immune homeostasis. We noted a significant decrease in the CD11c+ and CD103+ dendritic cell (DC) subpopulations in the intestines of intestinal-epithelial specific RARα-deficient (RARα villin) mice. In the present study, we identified Thymic Stromal Lymphopoietin (TSLP) as a contributing factor that influences intrinsic RARα signaling within IECs. This cytokine preferentially stimulates CD103+ DCs to a more tolerogenic phenotype in the GI tract, induces Tregs and drives TH2 polarization. TSLP also influences immune homeostasis by modulating the activation of myeloid cells, inhibition of proinflamamtory DCs, and production of IL-12. Notably, TSLP levels are decreased in Crohn’s disease (CD) where inflammation is driven by IL-12.

Aims

We hypothesize that RA intrinsic signaling within IECs modulates TSLP expression via activation of RARα. We sought to generate a RARα -/- murine intestinal epithelial cell line utilizing the CRISPR/CAS9 system to examine the effects of RARa ablation. Second, we aim to establish RARα’s role in regulating intestinal epithelial TSLP expression in both the RARα villin mice and the CRISPR-generated RARα -/- cell line.

Methods

Exon 5 in the open reading frame of the RARα gene in Mode-K murine IECs was targeted using CRISPR/CAS9. CRISPR cleavage and knockdown of RARα activity was confirmed via surveyor/luciferase assays. The cell lines were phenotyped with regards to their morphology, proliferative ability, and viability. Next, we examined TSLP mRNA expression in the colons of RARα villin mice and the CRISPR RARα -/- knockout cell line via qRT-PCR under baseline and stimulated conditions. Wild-type (WT) and RARα-/- cells were stimulated with RARα-selective agonist, BMS753, and muramyl dipeptide (MDP), a NOD2-selective agonist.

Results

TSLP expression in surface colonic epithelium was elevated 2.3-fold in RARα villin mice compared to WT litter mates. TSLP expression was elevated 10-fold in the Mode-K RARα-/- cells versus parent cells at baseline. BMS753 stimulation resulted in a 15-fold increase in TSLP expression in the RARα-/- cells compared to baseline. When stimulated with MDP, a NOD2-selective agonist known to stimulate TSLP expression, TSLP expression was elevated 60-fold in the RARα-/- cells, but significantly impaired compared to the WT cells (400-fold).

Conclusions

TSLP expression is controlled by RARα in colonic IECs where it may act as a repressor of TSLP promoter transactivation under baseline conditions. This suggests an important role for RA on myeloid and T cell function via effects on intestinal epithelial TSLP expression.

Funding Agencies

CCCUniversity of Calgary, Department of Medicine
A83 INTESTINAL EPITHELIAL CELL STEMNESS AND DIFFERENTIATION ARE REGULATED BY THE HIPPO PATHWAY EFFECTOR YAP1
Authors: Fallah S , Beaulieu J
Published: February 2020

Background

The high rate of cell turnover in the intestinal epithelium is supported by the LGR5+ crypt base columnar (CBC) stem cells, which are located at the lower part of the gland. Among of the various factors and signals like Wnt and Notch, YAP1 (yes associated protein) also plays an important role in stemness of CBC stem cells. YAP1 is the effector of the Hippo pathway. Hippo Pathway restricts the cells proliferation, tissues overgrowth and cancer formation through the phosphorylation and inactivation of the YAP1 protein. When active, YAP1 transfers into nucleus, forms the complex with TEADs transcription factors and promotes the transcription of genes involved in cell growth and proliferation.

Aims

In the present study, we investigated the role of the YAP1 in the colorectal cancer multipotent HT29 cell line, which contain cancer stem cells (CSC).

Methods

For approaching to this goal, YAP1 expression was knocked down using shRNAs in HT29 cells. Then stem cells and intestinal cell lineages (secretory goblet, Paneth and enteroendocrine and absorptive) markers expression was analyzed using qPCR and Western blot.

Results

The results showed the reduction of the expression of stem cells markers including LGR5 in YAP1 knockdown HT29 cells compare with control. Expression of the goblet cells markers (MUC2 and trefoil factor 3) and absorptive cells markers (sucrase-isomaltase and dipeptidylpeptidase IV) were significantly increased in YAP1 knockdown cells but Paneth (DEFA5 and lysozyme) and enteroendocrine (CHGA) were not detected. Finally, examination of the main transcription factors for intestinal differentiation revealed an increase in CDX2 expression.

Conclusions

These results suggest that YAP1 is involved in the maintenance of colorectal cancer stem cells while preventing intestinal differentiation in both secretory and absorptive lineages through the repression of CDX2.

Funding Agencies

CIHR
A91 SARCOMATOID CARCINOMA OF THE COLON PRESENTING AS IRON DEFICIENCY ANEMIA
Authors: Masckauchan M , Soulellis C A
Published: February 2020

Background

Gastrointestinal malignancy is a common cause of iron deficiency and occult gastrointestinal bleeding among adults in developed countries. Given the high prevalence of colorectal cancer and adenomatous polyps in our population, it is imperative that these patients undergo early colonoscopy. Sarcomatoid carcinoma (SCA) of the colon is a very rare condition, with less than 30 cases reported in the literature. Given the highly aggressive nature of this neoplasm, it is important to familiarize oneself with its presentation, histopathology and treatment options.

Aims

Describe a case of SCA of the colon in a cirrhotic patient, presenting initially as iron deficiency anemia of unknown etiology.

Methods

Case report and literature review.

Results

A 69-year-old female presented to the emergency department with complaints of progressive weakness and failure to thrive. Past medical history was significant for chronic kidney disease, NASH cirrhosis Child-Pugh C and recurrent hepatocellular carcinoma despite previous radiofrequency ablation. Investigations demonstrated de novo iron deficiency anemia with the following blood results: hemoglobin of 96, iron of 8.6, iron saturation of 20% and ferritin of 56. Subsequently, gastroenterology was consulted in order to assess for an occult source of bleeding. A gastroscopy was first performed in which no abnormalities were found. She then underwent a colonoscopy, which demonstrated a very large indurated nodular ulcer in the ascending colon, suggestive of invasive neoplasm (Figure A). Indeed, the biopsies demonstrated a malignant spindle cell neoplasm consistent with SCA. On immunohistochemistry, the tumor cells stained positive for keratin AE1/AE3, weakly positive for SMA and S-100, but negative for SMM, HMB45, DOG1, C-KIT and CD31. Given her severe comorbidities, no therapeutic options were available for this patient, thus further staging investigations were not pursued. Unfortunately, the patient rapidly deteriorated and died less than 8 weeks following her diagnosis.

Conclusions

Sarcomatoid carcinoma of the colon is an extremely rare neoplasm with very poor prognosis. Histologically, this tumor is characterized by a typical biphasic pattern, composed of both mesenchymal and epithelial cells. However, as demonstrated in this case, some SCA display a rather predominantly mesenchymal pattern, rendering the diagnosis difficult using morphology only. Immunostaining is therefore used to identify carcinoma features and to rule out similar tumors such as sarcoma, GIST, mesothelioma and melanoma. SCA of the colon is exceedingly aggressive, with remarkably rapid tumor growth and early distant metastasis. Indeed, median survival is reported to be less than 6 months. Given its rarity, no well-defined treatment guidelines exist, however most patients are managed with early radical surgery, adjuvant chemotherapy and close follow-up.

Funding Agencies

None
A110 DGAT1 MUTATION OF LIPID TRAFFICKING ASSOCIATED WITH A RARE CASE OF CONGENITAL DIARRHEA
Authors: Little R , Gonska T
Published: February 2020

Background

Congenital diarrheas and enteropathies (CODEs) are rare and cause severe chronic diarrhea in children under 2 years of age.1 Current genomic research has identified several monogenic defects resulting in epithelial disorders of nutrient and electrolyte transport, enzymes function, metabolism and trafficking.

Aims

To discuss a rare case of congential diarrhea.

Methods

Case Report.

Results

A 10-month-old Ashkenazi Jewish boy was referred to Pediatric Gastroenterology for loose stools and failure to thrive. Born at 27 weeks, he was a NICU inpatient for his first 3 months of life. Explosive loose stools were first noticed after discharge and treated as cow’s milk protein allergy. At aged 10 months he was admitted to his local hospital with irritability, abdominal distension, foul smelling loose stools and developmental delay. Despite an intake of 130kcal/kg/day he failed to gain weight (weight and length < 3rd centile). His abdomen was distended but there was no organomegaly on examination.

On transfer to Sick Kids he underwent extensive work up with low albumin 24 g/L but normal CBC, amylase, lipase and IgA and

anti-TTG negative. The lipid profile showed hypertriglyceridemia 2.98 mmol/L (normal <0.85), low HDL 0.81 mmol/L but normal total cholesterol. Low apoliprotein A1 0.79 g/L (0.92 - 1.96), low apoliprotein B 0.54 g (0.59 - 1.46) and vitamin E deficiency 9.6 umol/L (14.5 - 33.0). Normal fecal elastase (> 500 ug/g stool). Upper GI endoscopy showed duodenal villi blunting with non-specific chronic inactive duodenitis on histopathology.

Due to ongoing poor weight gain he commenced TPN. A repeat endoscopy four weeks after admission revealed patchy villous blunting, crypt hyperplasia and enterocyte vacuolization. However, ultrastructural electron microscopy examination showed normal enterocyte brush border with well-formed microvilli with no inclusions or vesicular bodies. With a differential diagnosis of chylomicron retention disorder, abetalipoproteinemia or hypolipoproteinemia he was commenced on a low-fat diet with MCT feeds. A 72-hour fecal fat collection on this diet was within normal range 5.4 mmol/day (2–7).

One year later his weight is now on 3rd centile and his albumin levels have normalized. However, triglycerides remain elevated. Whole exome sequencing identified two pathogenic variants in the DGAT1 gene; c.629_631delCCT, pSer210del and c751 + 2T>C, IVSB+2T>C.

Conclusions

Diacylglycerol acyltransferase (DGAT)1 catalyzes triglyceride biosynthesis.2 Loss of function DGAT1 gene mutations are described in several cases studies3,4 characterized by electrolyte transport–related diarrhea, protein-losing enteropathy and growth failure. Our cases adds to the understanding of the phenotypic and histological spectrum of DGAT1 mutations. Management strategies currently focus on growth with dietary lipid restriction, while substituting fat-soluble vitamins and essential fatty acids.

Funding Agencies

CAG