bluuebunny/crossref_metadata_2025_split huggingface dataset:
New models of atherosclerosis and multi-drug therapeutic interventions
Authors: Parton Andrew , McGilligan Victoria , Chemaly Melody , O’Kane Maurice , Watterson Steven 
Published: December 2018

Abstract

Motivation
Atherosclerosis is amongst the leading causes of death globally. However, it is challenging to study in vivo or in vitro and no detailed, openly-available computational models exist. Clinical studies hint that pharmaceutical therapy may be possible. Here, we develop the first detailed, computational model of atherosclerosis and use it to develop multi-drug therapeutic hypotheses.

Results
We assembled a network describing atheroma development from the literature. Maps and mathematical models were produced using the Systems Biology Graphical Notation and Systems Biology Markup Language, respectively. The model was constrained against clinical and laboratory data. We identified five drugs that together potentially reverse advanced atheroma formation.

Availability and implementation
The map is available in the Supplementary Material in SBGN-ML format. The model is available in the Supplementary Material and from BioModels, a repository of SBML models, containing CellDesigner markup.

Supplementary information
Supplementary data are available at Bioinformatics online.
7-hydroxyfrullanolide, isolated from Sphaeranthus indicus, inhibits colorectal cancer cell growth by p53-dependent and -independent mechanism
Authors: Pandey Praveen , Singh Deepika , Hasanain Mohammad , Ashraf Raghib , Maheshwari Mayank , Choyal Kuldeep , Singh Akhilesh , Datta Dipak , Kumar Brijesh , Sarkar Jayanta 
Published: December 2018

Abstract
Sphaeranthus indicus Linn. is commonly used in Indian traditional medicine for management of multiple pathological conditions. However, there are limited studies on anticancer activity of this plant and its underlying molecular mechanisms. Here, we isolated an active constituent, 7-hydroxyfrullanolide (7-HF), from the flowers of this plant, which showed promising chemotherapeutic potential. The compound was more effective in inhibiting in vitro proliferation of colon cancers cells through G2/M phase arrest than other cancer cell lines that were used in this study. Consistent with in vitro data, 7-HF caused substantial regression of tumour volume in a syngeneic mouse model of colon cancer. The molecule triggered extrinsic apoptotic pathway, which was evident as upregulation of DR4 and DR5 expression as well as induction of their downstream effector molecules (FADD, Caspase-8). Concurrent activation of intrinsic pathway was demonstrated with loss of ΔΨm to release pro-apoptotic cytochrome c from mitochondria and activation of downstream caspase cascades (Caspase -9, -3). Loss of p53 resulted in decreased sensitivity of cells towards pro-apoptotic effect of 7-HF with increased number of viable cells indicating p53-dependent arrest of cancer cell growth. This notion was further supported with 7-HF-mediated elevation of endogenous p53 level, decreased expression of MDM2 and transcriptional upregulation of p53 target genes in apoptotic pathway. However, 7-HF was equally effective in preventing progression of HCT116 p53+/+ and p53−/− cell derived xenografts in nude mice, which suggests that differences in p53 status may not influence its in vivo efficacy. Taken together, our results support 7-HF as a potential chemotherapeutic agent and provided a new mechanistic insight into its anticancer activity.
Hemispheric Module-Specific Influence of the X Chromosome on White Matter Connectivity: Evidence from Girls with Turner Syndrome
Authors: Zhao Chenxi , Yang Liyuan , Xie Sheng , Zhang Zhixin , Pan Hui , Gong Gaolang 
Published: December 2018

AbstractTurner syndrome (TS) is caused by the congenital absence of all or part of one of the X chromosomes in females, offering a valuable human “knockout model” to study the functioning patterns of the X chromosome in the human brain. Little is known about whether and how the loss of the X chromosome influences the brain structural wiring patterns in human. We acquired a multimodal MRI dataset and cognitive assessments from 22 girls with TS and 21 age-matched control girls to address these questions. Hemispheric white matter (WM) networks and modules were derived using refined diffusion MRI tractography. Statistical comparisons revealed a reduced topological efficiency of both hemispheric networks and bilateral parietal modules in TS girls. Specifically, the efficiency of right parietal module significantly mediated the effect of the X chromosome on working memory performance, indicating that X chromosome loss impairs working memory performance by disrupting this module. Additionally, TS girls showed structural and functional connectivity decoupling across specific within- and between-modular connections, predominantly in the right hemisphere. These findings provide novel insights into the functional pathways in the brain that are regulated by the X chromosome and highlight a module-specific genetic contribution to WM connectivity in the human brain.
Effects of Planting Date on Thrips (Thysanoptera: Thripidae) in Cotton
Authors: Kerns Cody D , Greene Jeremy K , Reay-Jones Francis P F , Bridges William C 
Published: December 2018

AbstractAt-plant applications of insecticides are the most common method to manage thrips in upland cotton, Gossypium hirstutum L. Because the primary pest species, tobacco thrips, Frankliniella fusca (Hinds), has developed resistance to commonly used neonicotinoid insecticides used in producing cotton, alternative control options are needed for sustainable thrips management programs. A 3-year study (2015–2017) showed that densities of thrips, feeding injury from thrips, cotton growth, and yield varied among 10 planting dates. Densities of thrips were lowest in seedling cotton planted after mid-May in all years. Thrips injury ratings in all years were highest in cotton planted in April, lowest in cotton planted in June, and below intermediate injury (intermediate corresponded to a 3 on the 0–5 scale) levels in cotton planted after mid-May. Cotton planted during May, rather than in April or June, had the highest yield potential, regardless of variety. Results of the study indicated that altering planting date could potentially be useful in mitigating injury and losses from thrips in upland cotton.
Clinical valve thrombosis and subclinical leaflet thrombosis in transcatheter aortic heart valves: clinical manifestations, diagnosis, and treatment
Authors: Rosseel Liesbeth , De Backer Ole , Søndergaard Lars 
Published: December 2018

Abstract
During the last decade, transcatheter aortic valve replacement (TAVR) has rapidly expanded as an alternative to surgical aortic valve replacement (SAVR) in patients with symptomatic severe aortic valve stenosis (AS) and increased surgical risk. In TAVR, a bioprosthetic valve is positioned within the stenotic native aortic valve. Although favorable short- and medium-term outcomes have been reported, thrombosis of the transcatheter heart valve (THV) has occurred, with two different entities being described: clinical valve thrombosis and subclinical leaflet thrombosis. In clinical valve thrombosis, an increase in transvalvular gradient appears as a result of obstructive thrombus formation, which eventually leads to symptoms of heart failure. Subclinical leaflet thrombosis is an incidental finding, characterized by a thin layer of thrombus covering the aortic site of the leaflet—called hypo-attenuating leaflet thickening (HALT)—as described on and defined by 4-dimensional computed tomography (4DCT) imaging. This phenomenon may affect motion of the leaflets and is then classified as hypo-attenuation affecting motion (HAM). Even in the case of HAM, the transvalvular pressure gradient remains within the normal range. Clinical valve thrombosis requires treatment, whereas the clinical impact and need for intervention in subclinical leaflet thrombosis is uncertain. Anticoagulant therapy protects against and resolves both clinical valve thrombosis and subclinical leaflet thrombosis, but studies exploring different antithrombotic strategies after TAVR are ongoing. This review summarizes currently available literature within the field of THV thrombosis and provides recommendations for a patient-tailored approach in TAVR patients, although guidelines are still lacking.
Uneven Patterns of Inequality: An Audit Analysis of Hiring-Related Practices by Gendered and Classed Contexts
Authors: Yavorsky Jill E 
Published: December 2018

AbstractDespite women’s uneven entrances into male-dominated occupations, limited scholarship has examined whether and how employers in different occupational classes unevenly discriminate against women during early hiring practices. This article argues that intersecting gendered and classed features of occupations simultaneously shape hiring-related practices and generate uneven patterns of inequality. Using data derived from comparative white-collar (N = 3,044 résumés) and working-class (N = 3,258 résumés) correspondence audits and content-coded analyses of more than 3,000 job advertisements, the author analyzes early hiring practices among employers across two gendered occupational dimensions: (1) sex composition (male- or female-dominated jobs) and (2) gender stereotyping (masculinized or feminized jobs, based on the attributes that employers emphasize in job advertisements). Broadly, findings suggest a polarization of early sorting mechanisms in which discrimination against female applicants is concentrated in male-dominated and masculinized working-class jobs, whereas discrimination against male applicants at early job-access points is more widespread, occurring in female-dominated and feminized jobs in both white-collar and working-class contexts. Interestingly, discrimination further compounds for male and female applicants—depending on the classed context—when these occupational dimensions align in the same gendered direction (e.g., male-dominated jobs that also have masculinized job advertisements). These findings have implications for the study of gender and work inequality and indicate the importance of a multidimensional approach to hiring-related inequality.
Switching Immunosuppression From Cyclosporine to Tacrolimus in Kidney Transplant Recipients Based on CYP3A5 Genotyping
Authors: Wang Xuebin , Yang Yunyun , Liu Zhengyue , Xiao Chengwu , Gao Lihong , Zhang Wenjing , Zhang Wenwen , Wang Zhuo 
Published: December 2018

Background:
Kidney transplant recipients on long-term cyclosporine (CsA) therapy may develop multiple adverse drug events, and immunosuppression conversion from CsA to tacrolimus (Tac) is an option. Genetic variations, especially cytochrome P450 (CYP) 3A5*3, affects Tac dosing. However, little information is available to guide the conversion with regards to patients' pharmacogenomics. We aimed to investigate whether CYP3A5, CYP3A4, and ABCB1 genotyping could contribute to a more precise and individualized initial dosing of Tac at the time of immunosuppressant conversion.

Methods:
Genotypes of 5 candidate genes (CYP3A5*3, CYP3A4*1G, ABCB1C1236T, ABCB1C3435T, and ABCB1G2677T/A) were investigated by polymerase chain reaction and restriction fragment-length polymorphism methods in 46 adult kidney transplant recipients requiring immunosuppressant conversion from CsA to TAC. Associations between these functional genetic polymorphisms and the dose-adjusted trough concentrations of CsA and Tac were evaluated, retrospectively.

Results:
Based on the linear regression analysis, CYP3A5 expressers (*1/*1 and *1/*3) had lower Tac dose-adjusted trough concentrations on days 7, 14, 21, and 28, and they required 1.40- to 1.75-fold higher daily dose to reach the target concentration compared with nonexpressers (*3/*3) on day 28 [0.07 (0.06–0.09) mg/kg/d versus 0.05 (0.02–0.06) mg/kg/d, P = 0.001]. CYP3A4*1G or ABCB1 genetic polymorphisms had no effect on the Tac dose-adjusted trough concentrations.

Conclusions:
Our preliminary study supports the use of CYP3A5 genotyping to guide the initial dosing of Tac when converting the immunosuppression therapy from CsA to Tac.
Targeted Proteomic Analysis Detects Acute T Cell–Mediated Kidney Allograft Rejection in Belatacept-Treated Patients
Authors: van der Zwan Marieke , Hesselink Dennis A. , Clahsen-van Groningen Marian C. , Baan Carla C. 
Published: December 2018

Background:
There is an unmet need for reliable minimally invasive diagnostic biomarkers for immunological allograft monitoring and for the detection of acute kidney transplant rejection. Here, targeted proteomic analysis was applied to compare 92 proteins in sera of belatacept-treated patients who had biopsy-proven, acute T-cell–mediated rejection (aTCMR) with patients without aTCMR.

Methods:
Proximity extension immunoassay was used to measure 92 inflammation-related protein concentrations in the prerejection and rejection sera of 11 patients with aTCMR and 9 patients without aTCMR. This assay uses 2 matched oligonucleotide-labeled antibody probes for each protein and polymerase chain reaction to measure normalized protein expression values.

Results:
Five proteins (CD5, CD8A, NCR1, TNFRSF4, and TNFRSF9) were expressed significantly higher in samples with aTCMR compared with samples without aTCMR (adjusted P-value < 0.014) and had a good predictive capacity for aTCMR [area under the curve in a receiver–operator curve ranged from 0.83 to 0.91 (P < 0.014)]. These proteins are associated with CD8+ cytotoxic T-cell and NK cell functions. Nonhierarchical clustering analysis showed distinct clustering of samples with aTCMR and samples without aTCMR. This clustering was not found in prerejection samples (1 month after transplantation). In prerejection samples, IFN-γ was expressed at a significantly lower level (normalized protein expression value median −0.15, interquartile range: −0.27 to 0.04) than in samples of patients without rejection (median 0.13, interquartile range: −0.07 to 0.15, adjusted P-value = 0.00367).

Conclusions:
Targeted proteomic analysis with proximity extension immunoassay is a promising minimally invasive technique to diagnose aTCMR in kidney transplant recipients.
Bedside respiratory physiology to detect risk of lung injury in acute respiratory distress syndrome
Authors: Beitler Jeremy R. 
Published: December 2018

Purpose of review
The most effective strategies for treating the patient with acute respiratory distress syndrome center on minimizing ventilation-induced lung injury (VILI). Yet, current standard-of-care does little to modify mechanical ventilation to patient-specific risk. This review focuses on evaluation of bedside respiratory mechanics, which when interpreted in patient-specific context, affords opportunity to individualize lung-protective ventilation in patients with acute respiratory distress syndrome.

Recent findings
Four biophysical mechanisms of VILI are widely accepted: volutrauma, barotrauma, atelectrauma, and stress concentration. Resulting biotrauma, that is, local and systemic inflammation and endothelial activation, may be thought of as the final common pathway that propagates VILI-mediated multiorgan failure. Conventional, widely utilized techniques to assess VILI risk rely on airway pressure, flow, and volume changes, and remain essential tools for determining overdistension of aerated lung regions, particularly when interpreted cognizant of their limitations. Emerging bedside tools identify regional differences in mechanics, but further study is required to identify how they might best be incorporated into clinical practice.

Summary
Quantifying patient-specific risk of VILI requires understanding each patient's pulmonary mechanics in context of biological predisposition. Tailoring support at bedside according to these factors affords the greatest opportunity to date for mitigating VILI and alleviating associated morbidity.
Is endoscopic sphincterotomy beneficial for the treatment of acute gallstone pancreatitis with small bile duct stone?
Authors: Kim Sung Bum , Nam Yoon Jeong , Kim Kook Hyun , Kim Tae Nyeun 
Published: December 2018

Background
Acute gallstone pancreatitis occurs when a gallstone is impacted at the ampulla of Vater. The role of endoscopic retrograde cholangiopancreatography in the treatment of small choledocholithiasis in these patients is uncertain. The aim of this study was to compare outcomes of expectant management with endoscopic sphincterotomy for the treatment of small choledocholithiasis (≤5 mm) in patients with acute gallstone pancreatitis.

Patients and methods
Of the 258 patients admitted for acute gallstone pancreatitis from January 2010 to December 2014, 174 patients with small choledocholithiasis were reviewed retrospectively. Patients with coexisting acute cholangitis and/or pancreatobiliary malignancy were excluded. They were divided into an endoscopic sphincterotomy group (n=64) and an expectant management group (n=110). Severity index and outcomes of pancreatitis, complications, and overall mortality were compared.

Results
Age and sex were not significantly different between the two groups. The mean Ranson, acute physiology and chronic health evaluation-II, and bedside index of severity in acute pancreatitis scores were not significantly different between the two groups. The computed tomography severity index score was significantly higher in the expectant management group than in the endoscopic sphincterotomy group (1.6±1.1 vs. 1.0±0.9, P<0.001). Duration of hospitalization, time for normalization of the white blood cell count, and time for oral feeding were similar in both groups. There was no significant difference between two groups in the incidence of development of pseudocyst or walled-off necrosis. In addition, no difference was observed in the rate of recurrence of acute pancreatitis and readmission because of recurrent choledocholithiasis.

Conclusion
Expectant management seems to be effective for the treatment of patients with acute gallstone pancreatitis and size of bile duct stones equal to or less than 5 mm.
Inpatients Sign On
Authors: Kelly Michelle M. , Hoonakker Peter L.T. , Coller Ryan J. 
Published: December 2018

Background:
Inpatient portals are online patient portals linked to electronic health records that provide hospitalized patients and caregivers secure access to real-time clinical information and tools to enhance their communication with providers and hospital experience.

Objective:
The main objective of this commentary was to provide a perspective that inpatient portals are innovative tools poised to engage patients and caregivers during hospitalization and, thus, enhance patient-centered care.

Results:
Inpatient portals are desired by patients and caregivers and may contribute to improved recognition of their inpatient care team, knowledge of their treatment plan and overall inpatient experience. A sociotechnical systems approach is recommended to mitigate potential unintended consequences of inpatient portal use and support effective portal design, implementation and evaluation.

Conclusions:
This article highlights the potential of using inpatient portals to engage hospitalized patients and caregivers and proposes next steps to evaluate this emerging technology.
Ergonomics in endoscopic sinus surgery
Authors: Ramakrishnan Vijay R. 
Published: December 2018

Purpose of review
Awareness of ergonomics is growing into surgical specialties including otolaryngology. Most otolaryngologists experience occupational physical discomfort, and daily incorporation of standard ergonomic principles may alleviate some of this pain.

Recent findings
Further demonstration of surgery-related physical discomfort has been documented based on surveys of general otolaryngologists and subspecialty rhinologists. One study utilized surface electromyography to document physical findings directly associated with the endoscopic sinus surgery procedure. However, relatively little work has been published on interventions to relieve task-related pain and body discomfort in rhinology.

Summary
Surgeon fatigue and bodily injury is a surprisingly frequent occurrence and is more likely to occur in procedures that are mentally challenging, prolonged, and require the surgeon to operate in a fixed position. Endoscopic sinus and skull base surgeons appear particularly susceptible to task-related physical discomfort, and incorporation of ergonomic principles should be a priority.
The Collaborative Improvement and Innovation Network project to drive quality improvement
Authors: Tosoc-Haskell Henrisa , Sisaithong Kristen , Carrico Robert 
Published: December 2018

Purpose of review
The purpose is to describe an approach for improvement using an organized collaborative improvement framework where participants learn, apply, and share improvement ideas supported through a 3-year Organ Procurement Transplant Network (OPTN) project called Collaborative Improvement and Innovation Network (COIIN). The COIIN project, proposed as an alternative approach to monitoring transplant performance, supported collaboration, and improvement in 58 transplant hospitals and partner organ procurement organizations. The aim was to increase transplantation with a focus on increasing the utilization of moderate-to-high (50–100%) Kidney Donor Profile Index (KDPI) kidneys.

Recent findings
Preliminary findings show increases in transplant rate and utilization of moderate-to-high KDPI kidneys was achieved in many participating organizations. Preliminary COIIN project results suggest that an improvement approach that supports collaborative improvement can be effective in driving improvement.

Summary
The COIIN project involved the development of a change package of key interventions for three key areas: waitlist management, organ-offer acceptance, and care coordination. Additionally, a balanced scorecard approach using outcome, process, and relationship measures, was used and effective in driving improvement. The preliminary COIIN outcome and process results suggest that collaborative improvement does drive improvement and was well received in the transplant community.

Video abstract
In the video, two of the authors describe the content of the review and present the main topics discussed in the article (http://links.lww.com/MOT/A22).
Thrombospondin-1 and Vitamin D in Children With Sickle Cell Anemia
Authors: Adegoke Samuel A. , Smith Olufemi S. , Adeniyi Adewuyi T. , Adekile Adekunle D. 
Published: December 2018

Background:Thrombospondin-1 (TSP-1) and 25-hydroxyvitamin D (25-OHD) play significant roles in the pathogenesis of sickle cell anemia (SCA). TSP-1 enhances cellular adhesion/inflammation, hence contributing to vaso-occlusive crisis (VOC); vitamin D, in contrast, retards inflammation and may lower rate of pain episodes. We determined serum levels of TSP-1 and 25-OHD in Nigerian children with SCA and their matched hemoglobin AA controls; and assess the relationship between the 2 biomarkers.Methods:In total 90 children (32 SCA in steady state, 30 SCA in VOC, and 28 HbAA controls) were studied. Serum TSP-1 and 25-OHD levels were measured with ELISA and HPLC, respectively.Results:The mean TSP-1 of children with VOC was significantly higher than those in steady state (P=0.022) and HbAA controls (P<0.001). Similarly, the mean TSP-1 of those in steady state was higher than the controls (P=0.007). However, mean serum 25-OHD of the children with VOC was significantly lower than those in steady state (28.9±8.2 ng/mL vs. 37.1±12.3 ng/mL,P=0.004). There was a significant inverse correlation between TSP-1 and 25-OHD among the VOC subgroup,r=−0.57,P=0.001. The mean TSP-1 of the 28 children with SCA who had suboptimal vitamin D (213.5±118.6 ng/mL) was higher than 144.2±58.7 ng/mL of the 34 SCA who had normal serum vitamin D,P=0.008.Conclusions:Children with SCA, especially those with VOC, had high serum TSP-1 and low 25-OHD. Also, an inverse relationship exist between serum 25-OHD and TSP-1 in children with VOC. These findings provide basis for further studies into the regulation of TSP-1 by vitamin D.