bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novelin vitroplatform for the study of SN38-induced mucosal damage and the development of Toll-like receptor 4-targeted therapeutic options
Authors: Wardill Hannah R , Gibson Rachel J , Van Sebille Ysabella ZA , Secombe Kate R , Logan Richard M , Bowen Joanne M 
Published: April 2016

Tight junction and epithelial barrier disruption is a common trait of many gastrointestinal pathologies, including chemotherapy-induced gut toxicity. Currently, there are no validated in vitro models suitable for the study of chemotherapy-induced mucosal damage that allow paralleled functional and structural analyses of tight junction integrity. We therefore aimed to determine if a transparent, polyester membrane insert supports a polarized T84 monolayer with the phenotypically normal tight junctions. T84 cells (passage 5–15) were seeded into either 0.6 cm2, 0.4 µm pore mixed-cellulose transwell hanging inserts or 1.12 cm2, 0.4 µm pore polyester transwell inserts at varying densities. Transepithelial electrical resistance was measured daily to assess barrier formation. Immunofluoresence for key tight junction proteins (occludin, zonular occludens-1, claudin-1) and transmission electron microscopy were performed to assess tight junction integrity, organelle distribution, and polarity. Reverse transcription-polymerase chain reaction was performed to determine expression of toll-like receptor 4 (TLR4). Liquid chromatography was also conducted to assess SN38 degradation in this model. Polyester membrane inserts support a polarized T84 phenotype with functional tight junctions in vitro. Transmission electron microscopy indicated polarity, with apico-laterally located tight junctions. Immunofluorescence showed membranous staining for all tight junction proteins. No internalization was evident. T84 cells expressed TLR4, although this was significantly lower than levels seen in HT29 cells ( P = .0377). SN38 underwent more rapid degradation in the presence of cells (−76.04 ± 1.86%) compared to blank membrane (−48.39 ± 4.01%), indicating metabolic processes. Polyester membrane inserts provide a novel platform for paralleled functional and structural analysis of tight junction integrity in T84 monolayers. T84 cells exhibit the unique ability to metabolize SN38 as well as expressing TLR4, making this an excellent platform to study clinically relevant therapeutic interventions for SN38-induced mucosal damage by targeting TLR4.
Evaluation of a bilayered, micropatterned hydrogel dressing for full-thickness wound healing
Authors: Magin Chelsea M , Neale Dylan B , Drinker Michael C , Willenberg Bradley J , Reddy Shravanthi T , La Perle Krista MD , Schultz Gregory S , Brennan Anthony B 
Published: April 2016

Nearly 12 million wounds are treated in emergency departments throughout the United States every year. The limitations of current treatments for complex, full-thickness wounds are the driving force for the development of new wound treatment devices that result in faster healing of both dermal and epidermal tissue. Here, a bilayered, biodegradable hydrogel dressing that uses microarchitecture to guide two key steps in the proliferative phase of wound healing, re-epithelialization, and revascularization, was evaluated in vitro in a cell migration assay and in vivo in a bipedicle ischemic rat wound model. Results indicate that the Sharklet™-micropatterned apical layer of the dressing increased artificial wound coverage by up to 64%, P = 0.024 in vitro. In vivo evaluation demonstrated that the bilayered dressing construction enhanced overall healing outcomes significantly compared to untreated wounds and that these outcomes were not significantly different from a leading clinically available wound dressing. Collectively, these results demonstrate high potential for this new dressing to effectively accelerate wound healing.
Phospholipid transfer protein deficiency in mice impairs macrophage reverse cholesterol transportin vivo
Authors: Si Yanhong , Zhang Ying , Chen Xiaofeng , Zhai Lei , Zhou Guanghai , Yu Ailing , Cao Haijun , Shucun Qin 
Published: April 2016

Phospholipid transfer protein is expressed in various cell types and secreted into plasma, where it transfers phospholipids between lipoproteins and modulates the composition of high-density lipoprotein particles. Phospholipid transfer protein deficiency in vivo can lower high-density lipoprotein cholesterol level significantly and impact the biological quality of high-density lipoprotein. Considering high-density lipoprotein was a critical determinant for reverse cholesterol transport, we investigated the role of systemic phospholipid transfer protein deficiency in macrophage reverse cholesterol transport in vivo. After the littermate phospholipid transfer protein KO and WT mice were fed high-fat diet for one month, they were injected intraperitoneally with3H-cholesterol-labeled and acLDL-loaded macrophages. Then the appearance of3H-tracer in plasma, liver, bile, intestinal wall, and feces over 48 h was determined. Plasma lipid analysis indicated phospholipid transfer protein deficiency lowered total cholesterol, high-density lipoprotein-C and apolipoprotein A1 levels significantly but increased triglyceride level in mice. The isotope tracing experiment showed3H-cholesterol of plasma was decreased by 68% for male and 62% for female, and3H-tracer of bile was decreased by 37% for male and 21% for female in phospholipid transfer protein KO mice compared with WT mice. However, there was no difference in liver, and3H-tracer of intestinal wall was increased by 43% for male and 27% for female. Finally,3H-tracer of fecal excretion in phospholipid transfer protein KO mice was reduced significantly by 36% for male and 43% for female during 0–24 h period, but there was no significant difference during 24–48 h period. Meanwhile, Western Blot analysis showed the expressions of reverse cholesterol transport -related protein liver X receptor α (LXRα), ATP binding cassette transporter A1, and cholesterol 7α-hydroxylase A1 were upregulated in liver of phospholipid transfer protein KO mice compared with WT mice. These data reveal that systemic phospholipid transfer protein deficiency in mice impairs macrophage-specific reverse cholesterol transport in vivo.
Management of Acute Mesenteric Ischemia
Authors: Zhao Yang , Yin Henghui , Yao Chen , Deng Jiong , Wang Mian , Li Zilun , Chang Guangqi 
Published: April 2016

Background: Acute mesenteric ischemia (AMI) due to a sudden loss or decrease in blood perfusion to the mesentery represents a highly lethal condition. However, the optimal surgical management remains debatable and merits a more clear recommendation based on a higher level of evidence. Methods: A systematic review of articles published between 2000 and 2013 was performed. Patients were divided into endovascular treatment (ET), open surgery (OS), and hybrid technique (HT) groups. Data of patients’ demographics, procedural information, clinical outcomes including mortality, morbidity, primary patency rate, technique success, primary intestinal resection rate, and second-look laparotomy rate, and follow-up were all retrieved. Comparison between the ET and the OS groups was made using 2-sided Student t test and 2-sided χ2 test or Fisher exact test where appropriate. Results: Twenty-eight articles with a total of 1110 patients were included for the review. The ET group had lower in-hospital mortality and morbidity but similar survival rate during follow-up compared to the OS group. The primary patency rate was higher in the ET group. The overall bowel resection rate was lower in the ET group, and nearly every patient in the cohort who required second-look laparotomy required bowel resection. The HT group seemed to have the lowest mortality and acceptable second-look laparotomy rate and morbidity. Comparison between the HT group and other groups was not possible due to the limited number of cases available for review. Conclusion: Endovascular treatment may serve as a first-line therapy for select patients when there is a low suspicion for intestinal necrosis. Open surgery should be reserved for emergency conditions requiring exploratory laparotomy. Hybrid technique may be an especially effective approach for treating AMI, with low morbidity and mortality, although further studies are required comparing it to OS and ET.
The Dynamicity of Steenbeek Foot Abduction Brace for Clubfoot in Dorsiflexion and Pronation
Authors: Agarwal Anil , Kumar Anubrat , Shaharyar Abbas , Mishra Madhusudan 
Published: April 2016

Purpose. Steenbeek foot abduction brace (SFAB) has been widely used in various national clubfoot programs. The aim of the study was to define effectiveness and dynamicity of SFAB in terms of dorsiflexion and pronation for the corrected clubfoot. Methods. Differences in foot dorsiflexion and pronation measurement with brace in knee flexed and extended position were recorded as dynamicity1 and dynamicity2, respectively. The residual soft tissue stretch lag despite brace use was calculated by determining the difference between maximum foot dorsiflexion (stretchlag1) and pronation (stretchlag2) achievable without and with brace in knee flexed. Statistical difference between measurements were calculated using paired t tests. Results. There were a total of 63 feet in 40 patients. The mean foot dorsiflexion with brace on in knee extension was 7.57° and in flexion was 15.20°. The foot pronation with brace on in knee extension was 9.46° and in flexion was 16.77°. Thus, SFAB exerted statistically significant differences in foot dorsiflexion and pronation between the knee extended and flexed positions. Dynamicity1 and dynamicity2 were 7.63° and 7.31°, respectively. Stretchlag1 was 18.47° and stretchlag2 was 17.63°. Conclusions. SFAB demonstrates effective dynamicity in maintaining corrected foot dorsiflexion and pronation. There is a residual soft tissue stretch lag both in dorsiflexion and pronation in corrected clubfoot despite use of SFAB. Levels of Evidence: Therapeutic, Level IV: Case series
Propofol-associated QTc prolongation
Authors: Scalese Michael J. , Herring Holly R. , Rathbun R. Chris , Skrepnek Grant H. , Ripley Toni L. 
Published: April 2016

Objectives: Propofol is a preferred agent for sedation in patients in the intensive care unit (ICU) due, in part, to its established safety profile. Despite this, recent case reports have suggested a potential for prolongation of the corrected QT interval (QTc) in ICU patients receiving propofol, though limited empirical work has been conducted to evaluate this association. As such, the purpose of this study was to assess the relationship between propofol infusion and QTc prolongation in a historical cohort of ICU patients. Methods: A single-center, historical, observational, pre-post cohort analysis of medical records from admitted patients ⩾18 years old with cardiovascular disease was conducted, involving cases who received propofol infusion for ⩾3 hours with sequential electrocardiogram monitoring from 2006 to 2012. A multivariable, generalized linear model regression was employed to assess the primary outcome of on-propofol QTc interval (QTc2), controlling for various demographic and clinical factors. Results: A total of 96 patients met inclusion criteria, averaging 56.1 ± 14.1 years of age and 86.1 ± 25.0 kg, with 37.5% being female. A mean prolongation in QTc interval of 30.4 ± 55.5 ms ( p < 0.001) was observed during the propofol infusion, with 43.8% of cases exhibiting an on-infusion QTc2 of ⩾ 500 ms. Regression analyses suggested that prolongation in on-propofol QTc was independently associated with baseline QTc interval and amiodarone use, while weight as inversely associated with QTc2 ( p < 0.05). Conclusion: This historical cohort analysis of adult ICU patients receiving propofol suggests that on-infusion QTc prolongation was associated with increasing baseline QTc interval and with amiodarone use. Further research is needed to evaluate the clinical significance and cause-and-effect relationship between potential QTc changes and propofol use in the ICU.
Factors associated with antidepressant use in residents with and without dementia in Australian aged care facilities
Authors: Hiltunen Henna , Tan Edwin C. K. , Ilomäki Jenni , Hilmer Sarah N. , Visvanathan Renuka , Emery Tina , Robson Leonie , Jones Mary J. , Hartikainen Sirpa , Bell J. Simon 
Published: April 2016

Objective: Depressive symptoms are highly prevalent in residential aged care facilities (RACFs). The prevalence of antidepressant use is increasing but the effectiveness of antidepressants in people with dementia is uncertain. The objective of the study was to investigate factors associated with antidepressant use in residents with and without dementia. Methods: This was a prospective cross-sectional study of 383 residents in six Australian RACFs. Data on health status, medications and demographics were collected by trained study nurses from April to August 2014. Logistic regression was used to compute adjusted odds ratios (AORs) and 95% confidence intervals (CIs) for factors associated with antidepressant use. Analyses were stratified by dementia and depression. Results: Overall, 183 (47.8%) residents used antidepressants. The prevalence of antidepressant use was similar among residents with and without dementia. Clinician-observed pain was inversely associated with antidepressant use in the main analysis (AOR = 0.56, 95% CI = 0.32–0.99) and in subanalyses for residents with documented depression (AOR = 0.51, 95% CI = 0.27–0.96). In residents with dementia, moderate quality of life was associated with a lower odds of antidepressant use compared with poor quality of life (AOR = 0.35, 95% C I= 0.13–0.95). In residents without dementia, analgesic use was associated with antidepressant use (AOR = 2.34, 95% CI = 1.07–5.18). Conclusions: The prevalence of antidepressant use was similar in residents with and without dementia. Clinician-observed pain was inversely associated with antidepressant use but there was no association between self-reported pain and antidepressant use.
Medication safety in neonatal care: a review of medication errors among neonates
Authors: Krzyzaniak Natalia , Bajorek Beata 
Published: April 2016

Objective: The objective of this study was to describe the medication errors in hospitalized patients, comparing those in neonates with medication errors across the age spectrum. Method: In tier 1, PubMed, Embase and Google Scholar were searched, using selected MeSH terms relating to hospitalized paediatric, adult and elderly populations. Tier 2 involved a search of the same electronic databases for literature relating to hospitalized neonatal patients. Results: A total of 58 articles were reviewed. Medication errors were well documented in each patient group. Overall, prescribing and administration errors were most commonly identified across each population, and mostly related to errors in dosing. Errors due to patient misidentification and overdosing were particularly prevalent in neonates, with 47% of administration errors involving at least tenfold overdoses. Unique errors were identified in elderly patients, comprising duplication of therapy and unnecessary prescribing of medicines. Overall, the medicines most frequently identified with error across each patient group included: heparin, antibiotics, insulin, morphine and parenteral nutrition. While neonatal patients experience the same types of medication errors as other hospitalized patients, the medication-use process within this group is more complex and has greater consequences resulting from error. Suggested strategies to help overcome medication error most commonly involved the integration of a clinical pharmacist into the treating team. Conclusion: This review highlights that each step of the medication-use process is prone to error across the age spectrum. Further research is required to develop targeted strategies relevant to specific patient groups that integrate key pharmacy services into wards.
Seasonal variations in calcidiol and parathyroid hormone levels in healthy children and adolescents in Navarre, Spain: a cross-sectional study
Authors: Durá-Travé Teodoro , Gallinas-Victoriano Fidel 
Published: April 2016

Objective To analyze the seasonal variations in calcidiol and parathyroid hormone serum levels along a natural year in a paediatric population living in a region of the north of Spain considering a normal nutrition status. Design A cross-sectional study. Setting Navarra Hospital Complex, Pamplona, Spain. Participants A total of 413 Caucasian individuals (aged 3.1 to 15.4 years): 227 school children (96 males and 131 females) and 186 adolescents (94 males and 92 females), with normal nutritional status. Main outcome measures Clinical examination (sex, age, weight, height and body mass index) and blood testing (calcium, phosphate, alkaline phosphatase, calcidiol and parathyroid hormone) during the year 2014. Results Calcidiol levels were lower during spring (25.96 ± 6.64 ng/mL) and reached its maximum level in summer (35.33 ± 7.51 ng/mL); parathyroid hormone levels were lower in summer (27.13 ± 7.89 pg/mL) and reached maximum level in autumn (34.73 ± 15.38 pg/mL). Hypovitaminosis D prevalence was 14.3% in summer and 75.3% in spring. Parathyroid hormone levels were compatible with secondary hyperparathyroidism in eight individuals (1.9%). There is a correlation ( p < 0.01) between calcidiol and parathyroid hormone ( r = −0.336). Logistic regression showed significant increased risk of hypovitaminosis in females (OR:1.63) and adolescents (OR:1.77), and when blood samples taken in autumn (OR:12.22), winter (OR:8.54) and spring (OR:19.72). Conclusions There is a high prevalence of hypovitaminosis D in the paediatric population with a healthy nutrition situation in Navarre, mainly during the months of autumn and winter, and, especially, in spring time. Given the difficulties in maintaining a sufficient amount of body vitamin D content along the year, it should be considered to give vitamin supplements and/or increase the intake of its natural dietary sources or vitamin D fortified foods.
The association between trainee demographic factors and self-reported experience: Analysis of General Medical Council National Training Survey 2014 and 2015 data
Authors: Gill Dipender 
Published: April 2016

Objectives To investigate whether demographic factors are associated with self-reported experience amongst medical trainees in the UK. Design Retrospective analysis of survey data. Setting General Medical Council (UK) National Training Survey data for 2014 and 2015. Participants A total of 105,549 responses were provided from 68,551 participants when no data were removed. After removing data to preserve participant anonymity, there were 64,278 participants providing 99,076 responses. Main outcome measures Considered trainee factors were gender, ethnicity, country of primary medical qualification, grade, post specialty and deanery. Self-reported outcome measures were ‘overall satisfaction’, ‘adequate experience’, ‘workload’, ‘clinical supervision’, ‘educational supervision’, and ‘access to educational resources’. Results The experience of medical trainees across various indicators is differentially related to gender, ethnicity, country of primary medical qualification, grade, post specialty and deanery. Conclusions It is demonstrated here that trainee factors are associated with subjective experience across different indicators. Further work is required to explore the reasons behind this, and how this relates to trainee quality of life, work performance and career progression.
Working as a doctor when acutely ill: comments made by doctors responding to United Kingdom surveys
Authors: Smith Fay , Goldacre Michael J , Lambert Trevor W 
Published: April 2016

Summary Objectives We undertook multi-purpose surveys of doctors who qualified in the United Kingdom between 1993 and 2012. Doctors were asked specific questions about their careers and were asked to comment about any aspect of their training or work. We report doctors’ comments about working whilst acutely ill. Design Self-completed questionnaire surveys. Setting United Kingdom. Participants Nine cohorts of doctors, comprising all United Kingdom medical qualifiers of 1993, 1996, 1999, 2000, 2002, 2005, 2008, 2009 and 2012. Main outcome measures Comments made by doctors about working when ill, in surveys one, five and 10 years after graduation. Results The response rate, overall, was 57.4% (38,613/67,224 doctors). Free-text comments were provided by 30.7% (11,859/38,613). Three-hundred and twenty one doctors (2.7% of those who wrote comments) wrote about working when feeling acutely ill. Working with Exhaustion/fatigue was the most frequent topic raised (195 doctors), followed by problems with Taking time off for illness (112), and general comments on Physical/mental health problems (66). Other topics raised included Support from others, Leaving or adapting/coping with the situation, Bullying, the Doctor’s ability to care for patients and Death/bereavement. Arrangements for cover due to illness were regarded as insufficient by some respondents; some wrote that doctors were expected to work harder and longer to cover for colleagues absent because of illness. Conclusions We recommend that employers ensure that it is not unduly difficult for doctors to take time off work when ill, and that employers review their strategies for covering ill doctors who are off work.
Reproducibility of Illumina platform deep sequencing errors allows accurate determination of DNA barcodes in cells
Authors: Beltman Joost B. , Urbanus Jos , Velds Arno , van Rooij Nienke , Rohr Jan C. , Naik Shalin H. , Schumacher Ton N. 
Published: April 2016

Abstract
Background
Next generation sequencing (NGS) of amplified DNA is a powerful tool to describe genetic heterogeneity within cell populations that can both be used to investigate the clonal structure of cell populations and to perform genetic lineage tracing. For applications in which both abundant and rare sequences are biologically relevant, the relatively high error rate of NGS techniques complicates data analysis, as it is difficult to distinguish rare true sequences from spurious sequences that are generated by PCR or sequencing errors. This issue, for instance, applies to cellular barcoding strategies that aim to follow the amount and type of offspring of single cells, by supplying these with unique heritable DNA tags.

Results
Here, we use genetic barcoding data from the Illumina HiSeq platform to show that straightforward read threshold-based filtering of data is typically insufficient to filter out spurious barcodes. Importantly, we demonstrate that specific sequencing errors occur at an approximately constant rate across different samples that are sequenced in parallel. We exploit this observation by developing a novel approach to filter out spurious sequences.

Conclusions
Application of our new method demonstrates its value in the identification of true sequences amongst spurious sequences in biological data sets.