bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between arterial stiffness and circadian pattern of blood pressure
Authors: Park Jin-Sun , Shin Joon-Han , Park Jeong-Bae , Choi Dong-Ju , Youn Ho-Joong , Park Chang-Gyu , Kwan Jun , Ahn Youngkeun , Kim Dong-Woon , Rim Se-Joong , Park Seung-Woo , Sung Jidong , Bae Jang-Ho 
Published: March 2019

Abstract
Arterial stiffness is a risk factor for cardiovascular morbidity and mortality. The relationship between the arterial stiffness and the circadian pattern of blood pressure (BP) has been controversial. The objective of the present study was to investigate the relationship between arterial stiffness by pulse wave analysis (PWA) and variables of 24-hour ambulatory BP monitoring (ABPM) in patients with high normal BP or hypertension (HTN).
Five hundred forty-eight patients (304 males, 48 ± 12-year-old) with high normal BP or HTN were enrolled. BP was measured at the outpatient clinic and 24-hour ABPM was performed. Using radial applanation tonometry, PWA was performed for evaluation of systemic arterial stiffness. Patients were classified into four groups according to the dipping patterns: a nocturnal dipping group, an isolated systolic non-dipping group, an isolated diastolic non-dipping group and a both systolic and diastolic non-dipping group. For adjustment of age, population was divided to 2 groups: old group ≥55 year-old (n = 158, 75 males), young group <55 year-old (n = 390, 229 males).
According to the dipping patterns, augmentation pressure (AP), augmentation index (AI) and heart rate (75 bpm) adjusted AI (AI@HR75) showed statistically significant difference (P = .011, .009, and .018, respectively). Multivariate analysis showed that isolated diastolic non-dipping was correlated with arterial stiffness expressed as AI and AI@HR 75, only in young group (β-coefficient = 12.6, P = .04 and β-coefficient = 7.503, P = .028, respectively).
Arterial stiffness might be closely related with the pattern of non-dipping in young patients with HTN and high normal BP.
Opioid induced adrenal insufficiency: what is new?
Authors: Donegan Diane 
Published: March 2019

Purpose of reviewDespite the declaration of an opioid epidemic, opioid use remains prevalent. Side-effects of chronic opioid use continue to be problematic. Opioid-induced endocrinopathies have been well documented, yet opioid-induced adrenal insufficiency (OIAI) remains underappreciated. This review summarizes what is currently known regarding the prevalence, predictive factors for the development and effect of treatment of OIAI.Recent findingsAlthough several case reports have highlighted the development of adrenal crisis among those receiving chronic opioids, only a few studies have systematically assessed patients for OIAI. The heterogeneity of these small studies presents challenges when trying to assess prevalence of or potential risk factors for OIAI. The estimated prevalence of OIAI among those treated with chronic opioids ranges from 8.3 to 29% and is more likely in those receiving higher doses of opioids. Reduced health-related quality of life variables and altered pain perception has been associated with lower cortisol levels; however, the effect of glucocorticoid replacement on the parameters remains unknown.SummaryFurther research is critical to better identify those at greatest risk and guide optimal management of OIAI. Frontline providers should remain vigilant for possibility of OIAI among chronic opioid users.
Neutrophil-to-lymphocyte ratio is independently associated with inflammatory activity and fibrosis grade in nonalcoholic fatty liver disease
Authors: Khoury Tawfik , Mari Amir , Nseir Wiliam , Kadah Anas , Sbeit Wisam , Mahamid Mahmud 
Published: March 2019

Background and aim
The progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis (NASH) is believed to be the driver for future development of fibrosis and cirrhosis. Nevertheless, there remains a lack of noninvasive methods for the diagnosis of NASH. The aim of the present study was to determine the role of neutrophil-to-lymphocyte ratio (NLR) in predicting histological severity in NAFLD.

Patients and methods
We performed a single-center retrospective study in EMMS Nazareth Hospital from July 2014 to May 2017. Liver biopsies were evaluated using the steatosis, activity, and fibrosis scoring system, which includes three components: (i) steatosis (0–3), (ii) activity grade (0–4), and (iii) fibrosis (0–4). Patients were divided into two groups. The first group was considered to have NAFLD when fibrosis grade was 0–1 and inflammatory activity was 0–1, whereas the second group included patients with fibrosis grade of 2–4 and inflammatory activity grade of 2–3, considered to have NASH.

Results
Ninety-one (91) patients with biopsy-proven fatty liver were included. The average age was 42.13 ± 11.5 (18–74) years. Fifty-seven (62.6%) patients were male. Univariate analysis revealed several factors to be associated with advanced fibrosis and inflammatory activity, including NLR, C-reactive protein, and HOMA-IR, which correlated with fibrosis [odds ratio (OR): 1.405, 95% confidence interval (CI): 1.21–1.63, P < 0.0001; OR: 1.329, 95% CI: 1.05–1.68, P = 0.016; and OR: 1.922, 95% CI: 1.18–3.11, P = 0.007, respectively], and NLR, triglycerides, and HOMA-IR, which correlated with hepatocyte inflammation (OR: 1.210, 95% CI: 1.08–1.35, P = 0.0009; OR: 0.984, 95% CI: 0.97–0.99, P = 0.01; and OR: 2.069, 95% CI: 1.28–3.34, P = 0.003, respectively). On multivariate logistic regression analysis, NLR remains independently associated with advanced fibrosis grade and inflammatory activity (OR: 0.734, 95% CI: 0.631–0.854, P < 0.0001, area under the curve: 0.8622 and OR: 0.836, 95% CI: 0.74–0.95, P = 0.006, area under the curve: 0.7845, respectively). Our second major finding was defining an NLR cut-off point that was associated with inflammatory activity and fibrosis grade using receiver operating characteristic analysis based on the Youden index (J), which is defined by the maximal sensitivity and specificity.

Conclusion
NLR showed significant independent correlation with advanced inflammation and fibrosis in patients with NAFLD. This simple available laboratory tool may be incorporated into future diagnostic scores.
Bile acid alterations in nonalcoholic fatty liver disease, obesity, insulin resistance and type 2 diabetes: what do the human studies tell?
Authors: Chávez-Talavera Oscar , Haas Joel , Grzych Guillaume , Tailleux Anne , Staels Bart 
Published: March 2019

Purpose of review
The purpose of this review is to discuss the influence of obesity, insulin resistance, type 2 diabetes (T2D), and nonalcoholic fatty liver disease (NAFLD) on bile acid metabolism and to analyze whether these findings reinforce current beliefs about the role of bile acids in the pathophysiology of these diseases.

Recent findings
Discordant results on plasma bile acid alterations in NAFLD patients have been reported. Obesity, insulin resistance, and T2D, common comorbidities of NAFLD, have been associated with bile acid changes, but the individual bile acid species variations differ between studies (summarized in this review), perhaps because of clinicobiological differences between the studied patient populations and the heterogeneity of statistical analyses applied.

Summary
The regulatory role of bile acids in metabolic and cellular homeostasis renders bile acids attractive candidates as players in the pathophysiology of NAFLD. However, considering the complex relationship between NAFLD, obesity, insulin resistance and T2D, it is difficult to establish clear and independent associations between bile acid alterations and these individual diseases. Though bile acid alterations may not drive NAFLD progression, signaling pathways activated by bile acids remain potent therapeutic targets for its treatment. Further studies with appropriate matching or adjustment for potential confounding factors are necessary to determine which pathophysiological conditions drive the alterations in bile acid metabolism.
Long-term ventilation for children with chronic lung disease of infancy
Authors: Baker Christopher D. 
Published: March 2019

Purpose of review
Modern medical advances have resulted in an increased survival after extremely preterm birth. However, some infants will develop severe bronchopulmonary dysplasia (BPD) and fail to wean from invasive or noninvasive positive pressure support. It remains unclear which infants will benefit from tracheostomy placement for chronic ventilation. Once the decision to pursue chronic ventilation has been made, questions remain with respect to the timing of tracheotomy surgery, optimal strategies for mechanical ventilation, and multidisciplinary care in both the inpatient and outpatient settings. The appropriate time for weaning mechanical ventilation and tracheostomy decannulation has similarly not been determined.

Recent findings
Although there remains a paucity of randomized controlled trials involving infants with severe BPD, a growing body of evidence suggests that chronic ventilation via tracheostomy is beneficial to support the growth and development of severely affected preterm children. However, delivering such care is not without risk. Chronic ventilation via tracheostomy requires complex care coordination and significant resource utilization.

Summary
When chronic respiratory insufficiency limits a preterm infant's ability to grow and develop, chronic invasive ventilation may facilitate neurodevelopmental progress and may lead to an improved long-term outcome.
Repurposing Food and Drug Administration–Approved Drugs to Promote Antitumor Immunity
Authors: Sukhatme Vidula V. , Ramalingam Suresh S. , Ahmed Rafi , Sukhatme Vikas P. 
Published: March 2019

Abstract
There has been a major resurgence of interest in immune-based approaches to treat cancer, based largely on the success of checkpoint inhibitors (anti–cytotoxic T-lymphocyte–associated antigen 4, anti–programmed cell death 1, and anti–programmed cell death ligand 1 antibodies) in several malignancies. However, not all tumors respond to checkpoint therapy, and there is clearly a need for additional approaches for enhancing tumor immunity. We summarize the critical elements necessary for mounting an efficacious T-cell response to a tumor. We cite drugs approved by the Food and Drug Administration for no-cancer indications that could be repurposed and used as part of an antitumor immune cocktail. We also list cancer drugs not initially intended to impact tumor immunity (soft repurposing) but that have been found to modulate the immune system. We highlight those drugs that might be used in combination with checkpoint inhibitors to increase response rates and survival of cancer patients. Our focus will be on drugs for which there are limited but existing human data. We cite supporting mechanistic mouse data as well. Repurposing drugs to modulate antitumor immunity is an opportunity to rapidly bring new, effective, and affordable treatments to cancer patients.
Refractory Cutaneous Dermatomyositis With Severe Scalp Pruritus Responsive to Apremilast
Authors: Charlton Devon , Moghadam-Kia Siamak , Smith Kristin , Aggarwal Rohit , English Joseph C. , Oddis Chester V. 
Published: March 2019

Abstract
Dermatomyositis (DM) is a subset of idiopathic inflammatory myopathy with characteristic cutaneous manifestations and muscle weakness. Conventional treatments for DM include glucocorticoids and other immunosuppressive or immunomodulatory agents including hydroxychloroquine, methotrexate, azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine, and intravenous immunoglobulin. Refractory patients require more aggressive or novel therapies. Apremilast has not been studied for the management of refractory cutaneous DM. We report a case of a patient with refractory DM with severe scalp pruritus treated with apremilast who demonstrated significant improvement in her skin disease and complete resolution of scalp pruritus.
A Bibliometric Analysis of the Most Cited Articles in Global Reconstructive Surgery
Authors: Čebron Urška , Zuo Kevin J. , Kasrai Leila 
Published: March 2019

Background
A substantial global inequality exists between surgical need and the availability of safe, affordable surgical care. Low- and middle-income countries have the greatest burden of untreated surgical disease and addressing this inequity is the goal of the Global Surgery movement. Reconstructive surgery is a fundamental component of Global Surgery as it is central to the appropriate treatment of trauma, burns, wounds, and congenital malformations. The objective of this study was to analyze the most frequently cited articles in the field of global reconstructive surgery to understand the main publication trends.

Methods
The 25 most cited articles relating to global reconstructive surgery were identified from all available journals through the Web of Science online database. The following data were extracted from each included article: title, source journal, publication year, total citations, average citations per year, authors, main subject, reconstructive surgery subspecialty, country, and institution of origin.

Results
The average number of citations per article was 21.7 (median, 19; range, 10–40). Most articles originated from the United States, and only 1 originated from a low-income country. The majority of the articles focused on cleft lip and palate (CLP) (72%), with few articles discussing burns or trauma. The main discussion themes were the quality of care provided in low- and middle-income countries both by local and visiting teams, the burden of diseases in relation to global reconstructive surgery, and the impact of surgical interventions economically and on patients.

Conclusions
The number of research articles and citations related to global reconstructive surgery are limited. Despite having a lower incidence than burns or trauma, there is a preponderance of reports focusing on missions treating CLP. These findings suggest that more research funding could be invested in global reconstructive surgery for conditions other than CLP.
Everolimus Initiation With Early Calcineurin Inhibitor Withdrawal in De Novo Heart Transplant Recipients: Long-term Follow-up From the Randomized SCHEDULE Study
Authors: Gustafsson Finn , Andreassen Arne K. , Andersson Bert , Eiskjær Hans , Rådegran Göran , Gude Einar , Jansson Kjell , Solbu Dag , Karason Kristjan , Arora Satish , Dellgren Göran , Gullestad Lars 
Published: March 2019

Background.
A calcineurin inhibitor (CNI)-free immunosuppressive regimen has been demonstrated to improve renal function early after heart transplantation, but long-term outcome of such a strategy has not been well described.

Methods.
In the randomized SCHEDULE trial, de novo heart transplant recipients received (1) everolimus with reduced-exposure CNI (cyclosporine) followed by CNI withdrawal at week 7–11 posttransplant or (2) standard-exposure cyclosporine, both with mycophenolate mofetil and corticosteroids; 95/115 randomized patients were followed up at 5–7 years posttransplant.

Results.
Mean measured glomerular filtration rate was 74.7 mL/min and 62.4 mL/min with everolimus and CNI, respectively. The mean difference was in favor of everolimus by 11.8 mL/min in the intent-to-treat population (P = 0.004) and 17.2 mL/min in the per protocol population (n = 75; P < 0.001). From transplantation to last follow-up, the incidence of biopsy-proven acute rejection (BPAR) was 77% (37/48) and 66% (31/47) (P = 0.23) with treated BPAR in 50% and 23% (P < 0.01) in the everolimus and CNI groups, respectively; no episode led to hemodynamic compromise. Coronary allograft vasculopathy (CAV) assessed by coronary intravascular ultrasound was present in 53% (19/36) and 74% (26/35) of everolimus- and CNI-treated patients, respectively (P = 0.037). Graft dimensions and function were similar between the groups. Late adverse events were comparable.

Conclusions.
These results suggest that de novo heart transplant patients randomized to everolimus and low-dose CNI followed by CNI-free therapy maintain significantly better long-term renal function as well as significantly reduced CAV than patients randomized to standard CNI treatment. Increased BPAR in the everolimus group during year 1 did not impair long-term graft function.
Advance in genetics of migraine
Authors: de Boer Irene , van den Maagdenberg Arn M.J.M. , Terwindt Gisela M. 
Published: March 2019

Purpose of review
Migraine is a primary headache disorder and one of the most common and disabling neurological diseases worldwide. Genome-wide association studies have identified ≈40 genetic loci associated with migraine. How these and other genetic findings are used to expand our knowledge on the pathophysiological mechanism of common migraine and rare migraine variants will be discussed.

Recent findings
The genetic load, based on common polygenic variation, is higher in familial migraine cases than in nonfamilial cases, and higher for migraine with aura and hemiplegic migraine. Migraine shares common genetic variant risks with depression. Specific clinical features of common migraine seem to be determined by genetic factors. A stronger family history of migraine is associated with lower age-at-onset, higher frequency and number of medication days and the migraine with aura subtype. Mild hemiplegic migraine is likely caused by complex polygenic interaction of multiple gene variants and environmental factors, like in common migraine subtypes. Phenotypical features in hemiplegic migraine patients may guide physicians in providing adequate genetic counseling.

Summary
Integration of genetic, phenotypic and epigenetic data will help to identify the biological mechanisms by which genetic factors contribute to migraine pathogenesis. Recent studies show the impact of genetics on clinical features and comorbidities in migraine and may guide clinicians to an adequate genetic advice for patients.
Variations in Structural MRI Quality Significantly Impact Commonly-Used Measures of Brain Anatomy
Authors: Gilmore Alysha , Buser Nicholas , Hanson Jamie L. 
Published: March 2019

AbstractSubject motion can introduce noise into neuroimaging data and result in biased estimations of brain structure. In-scanner motion can compromise data quality in a number of ways and varies widely across developmental and clinical populations. However, quantification of structural image quality is often limited to proxy or indirect measures gathered from functional scans; this may be missing true differences related to these potential artifacts. In this study, we take advantage of novel informatic tools, the CAT12 toolbox, to more directly measure image quality from T1-weighted images to understand if these measures of image quality: 1) relate to rigorous quality-control checks visually completed by human raters; 2) are associated with sociodemographic variables of interest; 3) influence regional estimates of cortical surface area, cortical thickness, and subcortical volumes from the commonly-used Freesurfer tool suite. We leverage public-access data that includes a community-based sample of children and adolescents, spanning a large age-range (N=388; ages 5-21). Interestingly, even after visually inspecting our data, we find image quality significantly impacts derived cortical surface area, cortical thickness, and subcortical volumes from multiple regions across the brain (∼23.4% of all areas investigated). We believe these results are important for research groups completing structural MRI studies using Freesurfer or other morphometric tools. As such, future studies should consider using measures of image quality to minimize the influence of this potential confound in group comparisons or studies focused on individual differences.
Dictyostelium discoideumflotillin homologues are essential for phagocytosis and participate in plasma membrane recycling and lysosome biogenesis
Authors: Bosmani Cristina , Bach Frauke , Leuba Florence , Hanna Nabil , Burdet Frédéric , Pagni Marco , Hagedorn Monica , Soldati Thierry 
Published: March 2019

ABSTRACTThe metazoan flotillins are lipid rafts residents involved in membrane trafficking and recycling of plasma membrane proteins.Dictyostelium discoideum, a social soil amoeba, uses phagocytosis to digest, kill and feed on bacteria.D. discoideumpossesses three flotillin-like proteins, termed VacA, VacB and the recently identified VacC. All three vacuolins gradually accumulate on postlysosomes and, like flotillins, are strongly associated with membranes and partly with lipid rafts. Vacuolins are absolutely required for uptake of various particles. Their absence impairs particle recognition possibly because of defective recycling of plasma membrane or cortex-associated proteins. In addition, vacuolins are involved in phagolysosome biogenesis, although this does not impact digestion and killing of a wide range of bacteria. Furthermore, vacuolin knockout affects early recruitment of the WASH complex on phagosomes, suggesting that vacuolins may be involved in the WASH-dependent plasma membrane recycling. Altogether, these results indicate that vacuolins act as the functional homologues of flotillins inD. discoideum.
Region-specific blood-brain barrier transporter changes leads to increased sensitivity to amisulpride in Alzheimer’s disease
Authors: Sekhar Gayathri Nair , Fleckney Alice L. , Boyanova Sevda Tomova , Rupawala Huzefa , Lo Rachel , Wang Hao , Farag Doaa B. , Rahman Khondaker Miraz , Broadstock Martin , Reeves Suzanne , Thomas Sarah Ann 
Published: March 2019

AbstractResearch into amisulpride use in Alzheimer’s disease (AD) implicates blood-brain barrier (BBB) dysfunction in antipsychotic sensitivity. Solute carrier function in AD has not been widely studied. This study tests the hypothesis that organic cation transporters contribute to the BBB delivery of antipsychotics and is disrupted in AD.In vitroBBB studies indicated that [3H]amisulpride and [3H]haloperidol were transported by OCT1. Amisulpride also utilized PMAT. Molecular docking predicted that amisulpride and haloperidol are OCT1, PMAT and MATE1 substrates, and amisulpride is not a P-gp substrate. Amisulpride brain uptake increased in 3xTgAD compared to wildtype mice. PMAT and MATE1 expression was reduced in brain from AD patients compared to controls. The increased sensitivity of Alzheimer’s patients to amisulpride is related to previously unreported changes in OCT1, PMAT and MATE1 function/expression at the BBB. Dose adjustments may be required for drugs that are substrates of these transporters when prescribing for AD patients.
CRISPR-BEST: a highly efficient DSB-free base editor for filamentous actinomycetes
Authors: Tong Yaojun , Robertsen Helene L. , Blin Kai , Klitgaard Andreas K. , Weber Tilmann , Lee Sang Yup 
Published: March 2019

AbstractFilamentous actinomycetes serve as major producers of various natural products including antimicrobial compounds. Although CRISPR-Cas9 systems have been developed for more robust genetic manipulations, concerns of genome instability caused by the DNA double-strand breaks (DSB) and the toxicity of Cas9 remain. To overcome these limitations, here we report development of the DSB-free, single-nucleotide resolution genome editing system CRISPR-BEST (CRISPR-Base Editing SysTem). Specifically targeted by an sgRNA, the cytidine deaminase component of CRISPR-BEST efficiently converts C:G to T:A within a window of approximately seven-nucleotides. The system was validated and successfully used in different Streptomyces species.