bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sequence analysis and variant identification at the APOC3 gene locus indicates association of rs5218 with BMI in a sample of Kuwaiti’s
Authors: Malalla Zainab H. , Al-Serri Ahmad E. , AlAskar Huda M. , Al-Kandari Wafaa Y. , Al-Bustan Suzanne A. 
Published: December 2019

AbstractBackgroundAPOC3 is important in lipid transport and metabolism with limited studies reporting genetic sequence variations in specific ethnic groups. The present study aimed to analyze the fullAPOC3sequence among Kuwaiti Arabs and test the association of selected variants with lipid levels and BMI.MethodsVariants were identified by Sanger sequencing the entireAPOC3gene in 100 Kuwaiti Arabs. Variants and their genotypes were fully characterized and used to construct haplotype blocks. Four variants (rs5128, rs2854117, rs2070668, KUAPOC3N3 g.5196 A > G) were selected for testing association with serum lipid levels and BMI in a cohort (n = 733).ResultsAPOC3sequence (4.3 kb) of a Kuwaiti Arab was deposited in Genbank (accession number KJ437193). Forty-two variants including 3 novels were identified including an “A” insertion at genomic positions 116,700,599–116,700,600 (promoter region) and two substitutions in intron 1 at genomic positions 116,700,819 and 116,701,159. Only three variants, (rs5128, rs2854117, and rs2070668) were analyzed for association of which rs5128 showed a trend for association with increased BMI, TG and VLDL levels that was further investigated using multivariate analysis. A significant association of rs5128 with BMI (p <  0.05) was observed following a dominant genetic model with increased risk by an OR of 4.022 (CI: 1.13–14.30).ConclusionThe present study is the first to report sequence analysis ofAPOC3in an Arab ethnic group. This study supports the inclusion of rs5128 as a marker for assessing genetic risk to dyslipidemia and obesity and the inclusion of the novel variant g.5196 A > G for population stratification of Arabs.
Outcome preferences of older people with multiple chronic conditions and hypertension: a cross-sectional survey using best-worst scaling
Authors: Aschmann Hélène E. , Puhan Milo A. , Robbins Craig W. , Bayliss Elizabeth A. , Chan Wiley V. , Mularski Richard A. , Wilson Renée F. , Bennett Wendy L. , Sheehan Orla C. , Yu Tsung , Yebyo Henock G. , Leff Bruce , Tabano Heather , Armacost Karen , Glover Carol , Maslow Katie , Mintz Suzanne , Boyd Cynthia M. 
Published: December 2019

Abstract
Background
Older people with hypertension and multiple chronic conditions (MCC) receive complex treatments and face challenging trade-offs. Patients’ preferences for different health outcomes can impact multiple treatment decisions. Since evidence about outcome preferences is especially scarce among people with MCC our aim was to elicit preferences of people with MCC for outcomes related to hypertension, and to determine how these outcomes should be weighed when benefits and harms are assessed for patient-centered clinical practice guidelines and health economic assessments.

Methods
We sent a best-worst scaling preference survey to a random sample identified from a primary care network of Kaiser Permanente (Colorado, USA). The sample included individuals age 60 or greater with hypertension and at least two other chronic conditions. We assessed average ranking of patient-important outcomes using conditional logit regression (stroke, heart attack, heart failure, dialysis, cognitive impairment, chronic kidney disease, acute kidney injury, fainting, injurious falls, low blood pressure with dizziness, treatment burden) and studied variation across individuals.

Results
Of 450 invited participants, 217 (48%) completed the survey, and we excluded 10 respondents who had more than two missing choices, resulting in a final sample of 207 respondents. Participants ranked stroke as the most worrisome outcome and treatment burden as the least worrisome outcome (conditional logit parameters: 3.19 (standard error 0.09) for stroke, 0 for treatment burden). None of the outcomes were always chosen as the most or least worrisome by more than 25% of respondents, indicating that all outcomes were somewhat worrisome to respondents. Predefined subgroup analyses according to age, self-reported life-expectancy, degree of comorbidity, number of medications and antihypertensive treatment did not reveal meaningful differences.

Conclusions
Although some outcomes were more worrisome to patients than others, our results indicate that none of the outcomes should be disregarded for clinical practice guidelines and health economic assessments.
The prognostic capacities of CBP and p300 in locally advanced rectal cancer
Authors: Rühlmann Felix , Windhof-Jaidhauser Indra Maria , Menze Cornelius , Beißbarth Tim , Bohnenberger Hanibal , Ghadimi Michael , Dango Sebastian 
Published: December 2019

AbstractBackgroundCREB-binding protein (CBP) and p300 represent histone acetyltransferases (HATs) and transcriptional coactivators that play essential roles in tumour initiation and progression. Both proteins are generally thought to function as tumour suppressors, although their distinct roles in colorectal cancer (CRC) remain inconsistent and ambiguous.Thus, we analysed the expression of these two HATs in human tissue samples from patients with locally advanced rectal cancer via immunohistochemistry and evaluated their potential impacts on future CRC diagnosis and treatment.MethodsIn our analysis, we included ninety-three (n = 93) patients diagnosed with adenocarcinoma in the upper third of the rectum. None of the patients received preoperative chemoradiotherapy, but the patients did undergo primary resection of the tumour within the phase II GAST-05 trial. By using H-scores, the expression of both proteins was visualised via immunohistochemistry in resected specimens from the patients. CBP and p300 expression were correlated with clinical and follow-up data.ResultsOur analysis showed that high expression of CBP was significantly associated with prolonged cancer-specific survival (CSS;p = 0.002). In univariate analysis, CBP was an independent prognostic parameter for CSS (p = 0.042). High nuclear CBP expression was observed in two-thirds of patients. In contrast, we could not find any significant correlation between the expression of p300 and cancer-specific survival in this cohort of patients (p = 0.09). We did not observe any cooperation between CBP and p300 in our analysis.ConclusionsHigh expression of CBP was significantly associated with improved oncological outcomes. This finding could help to stratify patients in the future for CRC treatment. Histone deacetylase (HDAC) inhibitors are increasingly playing a role in oncological treatment and could additionally become therapeutic options in CRC. Our findings need to be further evaluated and verified in future clinical analyses.
A live-cell imaging system for visualizing the transport of Marburg virus nucleocapsid-like structures
Authors: Takamatsu Yuki , Dolnik Olga , Noda Takeshi , Becker Stephan 
Published: December 2019

Abstract
Background
Live-cell imaging is a powerful tool for visualization of the spatio-temporal dynamics of moving signals in living cells. Although this technique can be utilized to visualize nucleocapsid transport in Marburg virus (MARV)- or Ebola virus-infected cells, the experiments require biosafety level-4 (BSL-4) laboratories, which are restricted to trained and authorized individuals.

Methods
To overcome this limitation, we developed a live-cell imaging system to visualize MARV nucleocapsid-like structures using fluorescence-conjugated viral proteins, which can be conducted outside BSL-4 laboratories.

Results
Our experiments revealed that nucleocapsid-like structures have similar transport characteristics to those of nucleocapsids observed in MARV-infected cells, both of which are mediated by actin polymerization.

Conclusions
We developed a non-infectious live cell imaging system to visualize intracellular transport of MARV nucleocapsid-like structures. This system provides a safe platform to evaluate antiviral drugs that inhibit MARV nucleocapsid transport.
Sustainment, Sustainability, and Spread Study (SSaSSy): protocol for a study of factors that contribute to the sustainment, sustainability, and spread of practice changes introduced through an evidence-based quality-improvement intervention in Canadian nursing homes
Authors: Berta Whitney B. , Wagg Adrian , Cranley Lisa , Doupe Malcolm B. , Ginsburg Liane , Hoben Matthias , MacEachern Lauren , Chamberlain Stephanie , Clement Fiona , Easterbrook Adam , Keefe Janice M. , Knopp-Sihota Jennifer , Rappon Tim , Reid Colin , Song Yuting , Estabrooks Carole A. 
Published: December 2019

AbstractBackgroundImplementation scientists and practitioners, alike, recognize the importance of sustaining practice change, however post-implementation studies of interventions are rare. This is a protocol for the Sustainment, Sustainability and Spread Study (SSaSSy). The purpose of this study is to contribute to knowledge on the sustainment (sustained use), sustainability (sustained benefits), and spread of evidence-based practice innovations in health care. Specifically, this is apost-implementationstudy of an evidence-informed, Care Aide-led, facilitation-based quality-improvement intervention called SCOPE (Safer Care for Older Persons (in long-term care) Environments). SCOPE has been implemented in nursing homes in the Canadian Provinces of Manitoba (MB), Alberta (AB) and British Columbia (BC). Our study has three aims: (i) to determine the role that adaptation/contextualization plays in sustainment, sustainability and spread of the SCOPE intervention; (ii) to study the relative effects on sustainment, sustainability and intra-organizational spread of high-intensity and low-intensity post-implementation “boosters”, and a “no booster” condition, and (iii) to compare the relative costs and impacts of each booster condition.Methods/designSSaSSy is a two-phase mixed methods study. The overarching design is convergent, with qualitative and quantitative data collected over a similar timeframe in each of the two phases, analyzed independently, then merged for analysis and interpretation. Phase 1 is a pilot involving up to 7 units in 7 MB nursing homes in which SCOPE was piloted in 2016 to 2017, in preparation for phase 2. Phase 2 will comprise a quasi-experiment with two treatment groups of low- and high-intensity post-implementation “boosters”, and an untreated control group (no booster), using pretests and post-tests of the dependent variables relating to sustained care and management practices, and resident outcomes. Phase 2 will involve 31 trial sites in BC (17 units) and AB (14 units) nursing homes, where the SCOPE trial concluded in May 2019.DiscussionThis project stands to advance understanding of the factors that influence the sustainment of practice changes introduced through evidence-informed practice change interventions, and their associated sustainability. Findings will inform our understanding of the nature of the relationship of fidelity and adaptation to sustainment and sustainability, and afford insights into factors that influence the intra-organizational spread of practice changes introduced through complex interventions.
A hybrid automated treatment planning solution for esophageal cancer
Authors: Ling Chifang , Han Xu , Zhai Peng , Xu Hao , Chen Jiayan , Wang Jiazhou , Hu Weigang 
Published: December 2019

Abstract
Objective
This study aims to investigate a hybrid automated treatment planning (HAP) solution that combines knowledge-based planning (KBP) and script-based planning for esophageal cancer.

Methods
In order to fully investigate the advantages of HAP, three planning strategies were implemented in the present study: HAP, KBP, and full manual planning. Each method was applied to 20 patients. For HAP and KBP, the objective functions for plan optimization were generated from a dose–volume histogram (DVH) estimation model, which was based on 70 esophageal patients. Script-based automated planning was used for HAP, while the regular IMRT inverse planning method was used for KBP. For full manual planning, clinical standards were applied to create the plans. Paired t-tests were performed to compare the differences in dose-volume indices among the three planning methods.

Results
Among the three planning strategies, HAP exhibited the best performance in all dose-volume indices, except for PTV dose homogeneity and lung V5. PTV conformity and spinal cord sparing were significantly improved in HAP (P < 0.001). Compared to KBP, HAP improved all indices, except for lung V5. Furthermore, the OAR sparing and target coverage between HAP and full manual planning were similar. Moreover, HAP had the shortest average planning time (57 min), when compared to KBP (63 min) and full manual planning (118 min).

Conclusion
HAP is an effective planning strategy for obtaining a high quality treatment plan for esophageal cancer.
Reliability of synovial fluid alpha-defensin and leukocyte esterase in diagnosing periprosthetic joint infection (PJI): a systematic review and meta-analysis
Authors: Chen Yisheng , Kang Xueran , Tao Jie , Zhang Yunpeng , Ying Chenting , Lin Weiwei 
Published: December 2019

Abstract
Background
Synovial fluid proteins had been applied as diagnostic biomarkers for periprosthetic joint infection (PJI) in recent research papers. Thus, this meta-analysis aimed to estimate the diagnostic efficiency of synovial fluid α-defensin and leukocyte esterase (LE) for PJI.

Methods
We conducted our systematic review by searching the keywords in online databases such as PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to October 2018. Inclusion criteria were as follows: patients who have undergone knee, hip, or shoulder joint replacements; α-defensin or leukocyte esterase (LE strip) of synovial fluid was detected as the biomarker for PJI diagnosis; and Musculoskeletal Infection Society (MSIS) or utilizing a combination of clinical data was considered as the gold standard. Diagnostic parameters including sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary of receiver operating characteristics curve (AUSROC) were calculated for the included studies to evaluate the synovial fluid α-defensin and LE for PJI diagnosis.

Results
After full-text review, 28 studies were qualified for this systematic review, 16 studies used α-defensin and the other 12 were conducted using LE strip. The pooled sensitivity, specificity, and DOR of LE strip were 87% (95% CI 84–90%), 96% (95% CI 95–97%), and 170.09 (95% CI 97.63–296.32), respectively, while the pooled sensitivity, specificity, and DOR of α-defensin were 87% (95% CI 83–90%), 97% (95% CI 96–98%), and 158.18 (95% CI 74.26–336.91), respectively. The AUSROC for LE strip and α-defensin were 0.9818 and 0.9685, respectively.

Conclusion
Both LE strip and α-defensin of synovial fluid provide rapid and convenient diagnosis for PJI. Sensitivity of α-defensin and LE strip are the same, while both these two methods have high specificity in clinical practice.
Mandibuloacral dysplasia type B (MADB): a cohort of eight patients from Suriname with a homozygous founder mutation in ZMPSTE24 (FACE1), clinical diagnostic criteria and management guidelines
Authors: Hitzert M. M. , van der Crabben S. N. , Baldewsingh G. , van Amstel H. K. Ploos , van den Wijngaard A. , van Ravenswaaij-Arts C. M. A. , Zijlmans C. W. R. 
Published: December 2019

Abstract
Background
Mandibuloacral Dysplasia with type B lipodystrophy (MADB) is a rare premature aging disorder with an autosomal recessive inheritance pattern. MADB is characterized by brittle hair, mottled, atrophic skin, generalized lipodystrophy, insulin resistance, metabolic complications and skeletal features like stunted growth, mandibular and clavicular hypoplasia and acro-osteolysis of the distal phalanges. MADB is caused by reduced activity of the enzyme zinc metalloprotease ZMPSTE24 resulting from compound heterozygous or homozygous mutations in ZMPSTE24.

Methods
In 2012, and again in 2018, eight related patients from the remote tropical rainforest of inland Suriname were analysed for dysmorphic features. DNA analysis was performed and clinical features were documented. We also analysed all previously reported genetically confirmed MADB patients from literature (n = 12) for their clinical features. Based on the features of all cases (n = 20) we defined major criteria as those present in 85–100% of all MADB patients and minor criteria as those present in 70–84% of patients.

Results
All the Surinamese patients are of African descent and share the same homozygous c.1196A > G, p.(Tyr399Cys) missense variant in the ZMPSTE24 gene, confirming MADB. Major criteria were found to be: short stature, clavicular hypoplasia, delayed closure of cranial sutures, high palate, mandibular hypoplasia, dental crowding, acro-osteolysis of the distal phalanges, hypoplastic nails, brittle and/or sparse hair, mottled pigmentation, atrophic and sclerodermic skin, and calcified skin nodules. Minor criteria were (generalized or partial) lipoatrophy of the extremities, joint contractures and shortened phalanges. Based on our detailed clinical observations, and a review of previously described cases, we propose that the clinical diagnosis of MADB is highly likely if a patient exhibits ≥4 major clinical criteria OR ≥ 3 major clinical criteria and ≥ 2 minor clinical criteria.

Conclusions
We report on eight related Surinamese patients with MADB due to a homozygous founder mutation in ZMPSTE24. In low-income countries laboratory facilities for molecular genetic testing are scarce or lacking. However, because diagnosing MADB is essential for guiding clinical management and for family counselling, we defined clinical diagnostic criteria and suggest management guidelines.
Detailed statistical analysis plan for the SafeBoosC III trial: a multinational randomised clinical trial assessing treatment guided by cerebral oxygenation monitoring versus treatment as usual in extremely preterm infants
Authors: Hansen Mathias Lühr , Pellicer Adelina , Gluud Christian , Dempsey Eugene , Mintzer Jonathan , Hyttel-Sorensen Simon , Heuchan Anne Marie , Hagmann Cornelia , Dimitriou Gabriel , Pichler Gerhard , Naulaers Gunnar , Cheng Guoqiang , Vilan Ana , Tkaczyk Jakub , Kreutzer Karen B. , Fumagalli Monica , Claris Olivier , Fredly Siv , Szczapa Tomasz , Lange Theis , Jakobsen Janus Christian , Greisen Gorm 
Published: December 2019

Abstract
Background
Infants born extremely preterm are at high risk of dying or suffering from severe brain injuries. Treatment guided by monitoring of cerebral oxygenation may reduce the risk of death and neurologic complications. The SafeBoosC III trial evaluates the effects of treatment guided by cerebral oxygenation monitoring versus treatment as usual. This article describes the detailed statistical analysis plan for the main publication, with the aim to prevent outcome reporting bias and data-driven analyses.

Methods/design
The SafeBoosC III trial is an investigator-initiated, randomised, multinational, pragmatic phase III trial with a parallel group structure, designed to investigate the benefits and harms of treatment based on cerebral near-infrared spectroscopy monitoring compared with treatment as usual. Randomisation will be 1:1 stratified for neonatal intensive care unit and gestational age (lower gestational age (< 26 weeks) compared to higher gestational age (≥ 26 weeks)). The primary outcome is a composite of death or severe brain injury at 36 weeks postmenstrual age. Primary analysis will be made on the intention-to-treat population for all outcomes, using mixed-model logistic regression adjusting for stratification variables. In the primary analysis, the twin intra-class correlation coefficient will not be considered. However, we will perform sensitivity analyses to address this. Our simulation study suggests that the inclusion of multiple births is unlikely to significantly affect our assessment of intervention effects, and therefore we have chosen the analysis where the twin intra-class correlation coefficient will not be considered as the primary analysis.

Discussion
In line with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines, we have developed and published this statistical analysis plan for the SafeBoosC III trial, prior to any data analysis.

Trial registration
ClinicalTrials.org, NCT03770741. Registered on 10 December 2018.
Typhoidal Salmonella human challenge studies: ethical and practical challenges and considerations for low-resource settings
Authors: Raymond Meriel , Gibani Malick M. , Day Nicholas P. J. , Cheah Phaik Yeong 
Published: December 2019

AbstractTyphoidal Salmonella is a major global problem affecting more than 12 million people annually. Controlled human infection models (CHIMs) in high-resource settings have had an important role in accelerating the development of conjugate vaccines against Salmonella Typhi.The typhoidal Salmonella model has an established safety profile in over 2000 volunteers in high-income settings, and trial protocols, with modification, could be readily transferred to new study sites. To date, a typhoidal Salmonella CHIM has not been conducted in a low-resource setting, although it is being considered.Our article describes the challenges posed by a typhoidal Salmonella CHIM in the high-resource setting of Oxford and explores considerations for an endemic setting.Development of CHIMs in endemic settings is scientifically justifiable as it remains unclear whether findings from challenge studies performed in high-resource non-endemic settings can be extrapolated to endemic settings, where the burden of invasive Salmonella is highest. Volunteers are likely to differ across a range of important variables such as previous Salmonella exposure, diet, intestinal microbiota, and genetic profile. CHIMs in endemic settings arguably are ethically justifiable as affected communities are more likely to gain benefit from the study. Local training and research capacity may be bolstered.Safety was of primary importance in the Oxford model. Risk of harm to the individual was mitigated by careful inclusion and exclusion criteria; close monitoring with online diary and daily visits; 24/7 on-call staffing; and access to appropriate hospital facilities with capacity for in-patient admission. Risk of harm to the community was mitigated by exclusion of participants with contact with vulnerable persons; stringent hygiene and sanitation precautions; and demonstration of clearance of Salmonella infection from stool following antibiotic treatment.Safety measures should be more stringent in settings where health systems, transport networks, and sanitation are less robust.We compare the following issues between high- and low-resource settings: scientific justification, risk of harm to the individual and community, benefits to the individual and community, participant understanding, compensation, and regulatory requirements.We conclude that, with careful consideration of country-specific ethical and practical issues, a typhoidal Salmonella CHIM in an endemic setting is possible.