bluuebunny/crossref_metadata_2025_split huggingface dataset:
Crystal structure and ligand-induced folding of the SAM/SAH riboswitch
Authors: Huang Lin , Liao Ting-Wei , Wang Jia , Ha Taekjip , Lilley David M J 
Published: May 2020

Abstract
While most SAM riboswitches strongly discriminate between SAM and SAH, the SAM/SAH riboswitch responds to both ligands with similar apparent affinities. We have determined crystal structures of the SAM/SAH riboswitch bound to SAH, SAM and other variant ligands at high resolution. The riboswitch forms an H-type pseudoknot structure with coaxial alignment of the stem–loop helix (P1) and the pseudoknot helix (PK). An additional three base pairs form at the non-open end of P1, and the ligand is bound at the interface between the P1 extension and the PK helix. The adenine nucleobase is stacked into the helix and forms a trans Hoogsteen–Watson–Crick base pair with a uridine, thus becoming an integral part of the helical structure. The majority of the specific interactions are formed with the adenosine. The methionine or homocysteine chain lies in the groove making a single hydrogen bond, and there is no discrimination between the sulfonium of SAM or the thioether of SAH. Single-molecule FRET analysis reveals that the riboswitch exists in two distinct conformations, and that addition of SAM or SAH shifts the population into a stable state that likely corresponds to the form observed in the crystal. A model for translational regulation is presented whereby in the absence of ligand the riboswitch is largely unfolded, lacking the PK helix so that translation can be initiated at the ribosome binding site. But the presence of ligand stabilizes the folded conformation that includes the PK helix, so occluding the ribosome binding site and thus preventing the initiation of translation.
Cancer survival in kidney transplant recipients in Ireland
Authors: Murray Susan L , O’Leary Eamonn , De Bhailís Áine M , Deady Sandra , Daly Fergus E , O’Kelly Patrick , Williams Yvonne , O’Neill James P , Sexton Donal J , Conlon Peter J 
Published: May 2020

Abstract

Background
Transplantation is a well-known risk factor for malignancy. However, outcomes of cancer in transplant recipients compared with non-transplant recipients are less well studied. We aim to study the survival in kidney transplant recipients who develop cancer and compare this with cancer outcomes in the general population.

Methods
We linked data from the National Cancer Registry Ireland with the National Kidney Transplant Database. The period of observation was from 1 January 1994 until 31 December 2014. Transplant recipients were considered at risk from the time of diagnosing cancer. We administratively censored data at 10 years post-cancer diagnosis. Survival was compared with all patients in the general population that had a recorded diagnosis of cancer.

Results
There were 907 renal transplant recipients and 426679 individuals in the general population diagnosed with cancer between 1 January 1994 and 31 December 2014. In those with non-melanoma skin cancer, the hazard ratio (HR) for 10-year, all-cause mortality [HR = 3.06, 95% confidence interval (CI) 2.66–3.52] and cancer-specific mortality (HR = 3.91, 95% CI 2.57–5.96) was significantly higher among transplant recipients than the general population. Patients who developed non-Hodgkin lymphoma (HR = 2.89, 95% CI 1.96–4.25) and prostate cancer (HR = 4.32, 95% CI 2.39–7.82) had increased all-cause but not cancer-specific mortality. Colorectal, lung, breast and renal cell cancer did not show an increased risk of death in transplant recipients.

Conclusion
Cancer-attributable mortality is higher in kidney transplant recipients with non-melanoma skin cancer compared with non-transplant patients. The American Joint Committee on Cancer staging should reflect the increased hazard of death in these immunosuppressed patients.
US Parties Abroad: Partisan Mobilising in a Federal Context
Authors: Kalu Vivian , Scarrow Susan E 
Published: May 2020

AbstractIn the early 2000s, some observers predicted that the US parties’ overseas association would play an increasing role in US politics (Dark 2003). Changes since then, including the growth of the expatriate population, would seem to make such developments more likely. Yet many features of the US political system mitigate against party efforts to mobilise expatriate supporters, including single-member district elections and candidate-centred contests (Van Haute and Kernalegenn, 2020). What, then, has been the 21st century trajectory of US party abroad activity? This article investigates this question, comparing the recent evolution Democrat and Republican party abroad efforts. It shows that the parties have taken different paths, with the Democrats’ organisation focussing more on electoral mobilisation, while the Republicans’ organisation has focussed more on issue advocacy and non-electoral representation. These different operational modes reflect the opportunities for, and constraints on, mobilising US expatriates for partisan purposes.
Predicting Pain-Related 30-Day Emergency Department Return Visits in Middle-Aged and Older Adults
Authors: Sheikh Sophia , Booth-Norse Ashley , Smotherman Carmen , Kalynych Colleen , Lukens-Bull Katryne , Guerrido Erika , Henson Morgan , Gautam Shiva , Hendry Phyllis 
Published: May 2020

Abstract

Objective
The objective of this study was to determine predictive factors for pain-related emergency department returns in middle-aged and older adults. Design, Setting, and Subjects. This was a subanalysis of patients &gt; 55 years of age enrolled in a prospective observational study of adult patients presenting within 30 days of an index visit to a large, urban, academic center.

Methods
Demographic and clinical data were collected and compared to determine significant differences between patients who returned for pain and those who did not. Multiple logistic regressions were used to determine significant predictive variables for return visits.

Results
The majority of the 130 enrolled patients &gt; 55 years of age returned for pain (57%), were African American (78%), were younger (55–64 years old, 67%), had a high emergency department acuity level (level 1 or 2) at their index visit (56%), had low health literacy (Rapid Estimate of Adult Literacy in Medicine [REALM] score, 62%), lived in an area of extreme deprivation (69%), and were admitted (61%) during their index visit. Age (odds ratio [OR] = 0.9, 95% CI = 0.8–0.9, P = 0.047), health literacy (REALM scores; OR = 3.1, 95% CI = 1.3–7.5, P = 0.011), and index visit pain scores (OR = 1.1, 95% CI = 1.0–1.2, P = 0.004) were predictive of emergency department returns for pain in middle-aged and older adults.

Conclusions
The likelihood of emergency department return visits for pain in middle-aged and older adults decreased with older age, increased with higher health literacy (REALM scores), and increased with increase in pain scores.
The State of American Federalism 2019–2020: Polarized and Punitive Intergovernmental Relations
Authors: Goelzhauser Greg , Konisky David M 
Published: May 2020

AbstractThe state of American federalism is characterized by polarization and punitiveness. As in previous years, political polarization continues to shape intergovernmental relations. But we also identify punitiveness as an increasingly prevalent aspect of vertical power sharing. Punitive federalism describes the national government’s use of threats and punishment to suppress state and local actions that run contrary to its policy preferences. In this Annual Review of American Federalism overview article, we introduce the concept of punitive federalism and discuss its application to contemporary public policy. We also highlight federalism implications concerning the COVID-19 pandemic; discuss recent policy developments concerning the environment, gender identity, health care, immigration, reproductive choice, and sexual orientation; and review recent Supreme Court decisions that impact intergovernmental relations.
Comparison of serum cytokine profiles in macrophage activation syndrome complicating different background rheumatic diseases in children
Authors: Mizuta Mao , Shimizu Masaki , Irabu Hitoshi , Usami Masaaki , Inoue Natsumi , Nakagishi Yasuo , Wada Taizo , Yachie Akihiro 
Published: May 2020

Abstract

Objectives
To compare the cytokines involved in the development of macrophage activation syndrome (MAS) in different background rheumatic diseases and to identify serum biomarkers for MAS diagnosis.

Methods
Serum neopterin, IL-6, IL-18 and soluble TNF receptor (sTNFR) type I (sTNFR-I) and type II (sTNFR-II) levels were determined using ELISA in 12 patients with SLE, including five with MAS; 12 patients with JDM, including four with MAS; 75 patients with Kawasaki disease (KD), including six with MAS; and 179 patients with systemic JIA (s-JIA), including 43 with MAS. These results were compared with the clinical features of MAS.

Results
Serum neopterin, IL-18 and sTNFR-II levels were significantly higher during the MAS phase than during the active phase in patients with all diseases. Furthermore, serum sTNFR-I levels were significantly higher during the MAS phase than during the active phase in patients with SLE, KD and s-JIA. Receiver operating characteristic (ROC) curve analysis revealed that serum sTNFR-I levels for SLE, serum IL-18 levels for JDM, and serum sTNFR-II levels for KD and s-JIA had the highest areas under the ROC curve. Serum levels of these cytokines were significantly and positively correlated with serum ferritin levels.

Conclusions
Overproduction of IFN-γ, IL-18 and TNF-α might be closely related to the development of MAS. Serum levels of sTNFR-I for SLE, IL-18 for JDM, and sTNFR-II for KD and s-JIA might be useful diagnostic markers for the transition from active phase to MAS.
Sodium aescinate and its bioactive components induce degranulation via oxidative stress in RBL-2H3 mast cells
Authors: Huang Xian-Ju , Wang Da Gui , Ye Li-Chun , Li Jun , Akhtar Muhammad , Saleem Shahzad , Shi Zhao-Hua , Ihsan Awais 
Published: May 2020

Abstract
Sodium aescinate (SA) is a vital salt of sodium escin from Aesculus wilsonii Rehd seeds. SA injection (SAI) has received great success in treating cerebral edema, venous reflux disease and other inflammatory conditions. Recently, high incidences of immediate hypersensitivity reactions were reported after SA infusion, which raised questions on safety and risk associated with its clinical application. This study was designed to check whether SAI and its four components induce degranulation using RBL-2H3 mast cells. For this purpose, we evaluated different treatment levels of SAI (20, 40, 60, 80 and 100 μg ml−1) and its four characteristic components, SA-A, SA-B, SA-C and SA-D, at 60 μg ml−1 in different tests including cell viability test, β-hexosaminidase and histamine assays, oxidative stress indices, apoptosis analysis and intracellular calcium ions in RBL-2H3 cells. Our results demonstrated that SAI at 80 μg ml−1 and 100 μg ml−1, and its two components (SA-B and SA-D) at 60 μg ml−1 were responsible for disturbing cell morphology and cell viability, elevated levels of β-hexosaminidase, histamine, modulation of oxidative stress indices, induced apoptosis and increase in intracellular calcium ions in RBL-2H3 cells, when compared with the control. Our results demonstrated for the first time that SAI was more likely to induce immediate hypersensitivity reactions attributable to degranulation via oxidative stress caused by SA-B and SA-D components. These results would not only be useful for the safety of end user but also for the industry to improve the quality of SA infusion.
Ephedrine versus Phenylephrine Effect on Cerebral Blood Flow and Oxygen Consumption in Anesthetized Brain Tumor Patients
Authors: Koch Klaus U. , Mikkelsen Irene K. , Aanerud Joel , Espelund Ulrick S. , Tietze Anna , Oettingen Gorm v. , Juul Niels , Nikolajsen Lone , Østergaard Leif , Rasmussen Mads 
Published: May 2020

Background
Studies in anesthetized patients suggest that phenylephrine reduces regional cerebral oxygen saturation compared with ephedrine. The present study aimed to quantify the effects of phenylephrine and ephedrine on cerebral blood flow and cerebral metabolic rate of oxygen in brain tumor patients. The authors hypothesized that phenylephrine reduces cerebral metabolic rate of oxygen in selected brain regions compared with ephedrine.

Methods
In this double-blinded, randomized clinical trial, 24 anesthetized patients with brain tumors were randomly assigned to ephedrine or phenylephrine treatment. Positron emission tomography measurements of cerebral blood flow and cerebral metabolic rate of oxygen in peritumoral and normal contralateral regions were performed before and during vasopressor infusion. The primary endpoint was between-group difference in cerebral metabolic rate of oxygen. Secondary endpoints included changes in cerebral blood flow, oxygen extraction fraction, and regional cerebral oxygen saturation.

Results
Peritumoral mean ± SD cerebral metabolic rate of oxygen values before and after vasopressor (ephedrine, 67.0 ± 11.3 and 67.8 ± 25.7 μmol · 100 g−1 · min−1; phenylephrine, 68.2 ± 15.2 and 67.6 ± 18.0 μmol · 100 g−1 · min−1) showed no intergroup difference (difference [95% CI], 1.5 [−13.3 to 16.3] μmol · 100 g−1 · min−1 [P = 0.839]). Corresponding contralateral hemisphere cerebral metabolic rate of oxygen values (ephedrine, 90.8 ± 15.9 and 94.6 ± 16.9 μmol · 100 g−1 · min−1; phenylephrine, 100.8 ± 20.7 and 96.4 ± 17.7 μmol · 100 g−1 · min−1) showed no intergroup difference (difference [95% CI], 8.2 [−2.0 to 18.5] μmol · 100 g−1 · min−1 [P = 0.118]). Ephedrine significantly increased cerebral blood flow (difference [95% CI], 3.9 [0.7 to 7.0] ml · 100 g−1 · min−1 [P = 0.019]) and regional cerebral oxygen saturation (difference [95% CI], 4 [1 to 8]% [P = 0.024]) in the contralateral hemisphere compared to phenylephrine. The change in oxygen extraction fraction in both regions (peritumoral difference [95% CI], −0.6 [−14.7 to 13.6]% [P = 0.934]; contralateral hemisphere difference [95% CI], −0.1 [− 12.1 to 12.0]% [P = 0.989]) were comparable between groups.

Conclusions
The cerebral metabolic rate of oxygen changes in peritumoral and normal contralateral regions were similar between ephedrine- and phenylephrine-treated patients. In the normal contralateral region, ephedrine was associated with an increase in cerebral blood flow and regional cerebral oxygen saturation compared with phenylephrine.

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Salvianolic acid B decreases interleukin-1β-induced colitis recurrence in mice
Authors: Feng Pan-Pan , Fang Xue-Sheng , Zhao Si-Hui , Fu Jun-Yan , Zhang Hui-Ting , Yi Yan-Lin , Li Chang-Yi , Jiang Chun-Ling , Chen Da-Peng 
Published: May 2020

Abstract

Background
Degree of mucosal recovery is an important indicator for evaluating the therapeutic effects of drugs in treatment of inflammatory bowel disease (IBD). Increasing evidences has proved that tight junction (TJ) barrier dysfunction is one of the pathological mechanisms of IBD. The aim of this study was to observe whether enhancement of TJ can decrease colitis recurrence.

Methods
Eighty C57BL/6 mice were randomly divided into four groups including normal group, colitis group, sulfasalazine (SASP) treated group, and traditional Chinese drug salvianolic acid B (Sal B) treated group. Colitis was established in mice by free drinking water containing dextran sulfate sodium, after treatments by SASP and Sal B, recombinant human interleukin-1β (IL-1β) was injected intraperitoneally to induce colitis recurrence.

Results
Compared with sham control, cell apoptosis in colitis group was increased from 100.85 ± 3.46% to 162.89 ± 11.45% (P = 0.0038), and TJ dysfunction marker myosin light chain kinase (MLCK) was also significantly increased from 99.70 ± 9.29% to 296.23 ± 30.78% (P = 0.0025). The increased cell apoptosis was reversed by both SASP (125.99 ± 8.45% vs. 162.89 ± 11.45%, P = 0.0059) and Sal B (104.27 ± 6.09% vs. 162.89 ± 11.45%, P = 0.0044). High MLCK expression in colitis group was reversed by Sal B (182.44 ± 89.42% vs. 296.23 ± 30.78%, P = 0.0028) but not influenced by SASP (285.23 ± 41.04% vs. 296.23 ± 30.78%, P > 0.05). The recurrence rate induced by recombinant human IL-1β in Sal B-treated group was significantly lower than that in SASP-treated group.

Conclusions
These results suggested a link between intestinal mucosal barrier dysfunction, especially TJ barrier dysfunction, and colitis recurrence. The TJ barrier dysfunction in remission stage of colitis increased the colitis recurrence. This study might provide potential treatment strategies for IBD recurrence.
Patient Reported Outcomes in Microbial Keratitis
Authors: Tuohy Megan M. , Niziol Leslie M. , I. Mian Shazhad , Ballouz Dena , Bosch David , Woodward Maria A. 
Published: May 2020

Purpose:
The aim of this investigation was to study the patient-reported outcomes of patients with microbial keratitis (MK) using the 9-item National Eye Institute-Visual Function Questionnaire (NEI VFQ-9).

Methods:
Using the Sight Outcomes Research Collaborative ophthalmology electronic health record repository, patients with MK and control patients who completed the NEI VFQ-9 within 7 days of their appointment were identified. The questionnaire is scored as a mean of the 9 items on a scale from 0 to 100, with higher scores indicating better functioning. Composite and individual item scores were compared between groups using the analysis of variance.

Results:
In total, 916 questionnaires were completed from patients with acute MK (n = 84), nonacute MK (n = 30), MK with a corneal transplant (n = 21), from controls seen in a satellite comprehensive ophthalmology clinic (n = 528), and controls seen at a subspecialty ophthalmology clinic (n = 253). The mean NEI VFQ-9 composite scores per group were 66.6 (SD = 26.8), 78.1 (SD = 17.1), 58.6 (SD =21.6), 88.0 (SD = 10.2), and 83.5 (SD = 13.0), respectively (P < 0.0001). Both patients with acute MK and patients with MK requiring transplant reported significantly worse function than nonacute MK, comprehensive, and specialty patients. Patients with nonacute MK reported significantly worse function than comprehensive control patients (all Tukey-adjusted P < 0.05).

Discussion:
Patients who had or eventually require corneal transplant for management of their MK report worse visual function than patients with nonacute MK. This may be important in helping physicians counsel their patients.
Efficacy of Amphotericin B in Corneal Preservation Media After Extended Frozen Storage
Authors: Huh Doowon , Tran Khoa D. , Straiko Megan M. W. , McCarthy Matthew W. , Loo Angela S. , Walsh Thomas J. , Sales Christopher S. 
Published: May 2020

Purpose:
To investigate the antimycotic activity of amphotericin B deoxycholate that has been previously frozen for 28 days before supplementation of Optisol-GS.

Methods:
Triplicate Optisol-GS samples were inoculated with 106 colony-forming units (CFU) of Candida albicans. Each set of triplicate cultures was supplemented with 2.5 μg/mL of amphotericin B that was either freshly resuspended and never frozen, frozen overnight at −20°C and thawed, or frozen at −20°C for 4 weeks and thawed. The cultures were stored at 4°C, with aliquots taken at 0, 6, 24, and 72 hours for quantification. The efficacy of each preparation of amphotericin B in reducing C. albicans growth was assessed at these time points.

Results:
Six hours after antifungal supplementation, there was a 1.33 log10 CFU reduction with freshly resuspended amphotericin B, compared with a 1.31 log10 reduction with amphotericin B that was frozen overnight (P = 0.20) and a 1.18 log10 reduction with amphotericin B that was frozen for 4 weeks (P = 0.05). After 72 hours, there was a 2.72 log10 CFU reduction with freshly resuspended amphotericin B, a 2.64 log10 CFU reduction with amphotericin B that was frozen overnight (P = 0.45), and a 2.18 log10 CFU reduction with amphotericin B that was frozen for 4 weeks (P = 0.05).

Conclusions:
Previously frozen amphotericin B remains highly effective against C. albicans. Optisol-GS supplemented with 2.5 μg/mL amphotericin B that was frozen for 4 weeks at −20°C resulted in >90% CFU reduction by 6 hours and >99% reduction by 72 hours.
Limbal Stem Cell Dysfunction in Ichthyosis Follicularis, Alopecia, and Photophobia Syndrome
Authors: Basilious Alfred , Fung Simon S. M. , Ali Asim 
Published: May 2020

Purpose:
To describe the presentation and management of limbal stem cell dysfunction in ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome.

Methods:
A retrospective case report.

Results:
A 6-day-old male infant was diagnosed with IFAP syndrome based on family history and a mutation detected in the MBTPS2 gene. Initial examination showed hyperkeratotic eyelids, madarosis, and lagophthalmos, but otherwise clear corneas. He developed bilateral central corneal epithelial defects spontaneously 6 months later, which were managed with aggressive lubrication, prophylactic antibiotics, and bilateral permanent lateral tarsorrhaphies at 7 months of age. During the procedure, the patient was noted to have bilateral limbal thickening, peripheral corneal pannus with underlying stromal scarring, and late fluorescein staining of the corneal surface. Anterior segment optical coherence tomography demonstrated a significantly abnormal and hyperreflective epithelial surface overlying a thinned corneal stroma, suggestive of limbal stem cell dysfunction. The corneal surface was maintained with lubrication and tarsorrhaphy and has remained stable since.

Conclusions:
The progressive conjunctivalization, spontaneous epithelial defects, and anterior segment optical coherence tomography features are highly suggestive of limbal stem cell dysfunction in IFAP syndrome. Optimizing the ocular surface is of importance in the management of children with this rare disease.
The Association Between E-Cigarette Use Behaviors and Saliva Cotinine Concentration Among Healthy E-Cigarette Users in Malaysia
Authors: Wong Li Ping , Mohd Salim Siti Norfitrah , Alias Haridah , Aghamohammadi Nasrin , Hoe Victor Chee Wai , Isahak Marzuki , Ali Mohd Mustafa 
Published: May 2020

Abstract
Electronic cigarettes (e-cigarettes) have rapidly increased in popularity within the last 2 years in Malaysia. The study aims to understand the association between e-cigarette use behaviors and salivary cotinine (a CYP2AA metabolite of nicotine) concentration to inform the development of future e-cigarette control policies. A convenience sample of saliva from 144 e-cigarette users was obtained between November and December 2015. The study participants used refill liquid containing between 0 and 12 mg/ml of nicotine. The overall median cotinine concentration of the study participants was 81.1 ng/ml (interquartile range = 8.5–195.8). Among the zero-nicotine and single e-cigarette users, the median cotinine level was 51.1 (interquartile range = 8.20–125.35) ng/ml. Factors significantly associated with a higher salivary cotinine concentration were dual use of e-cigarettes and tobacco cigarettes, regular and daily e-cigarette use, a longer duration of e-cigarette use, using a higher amount of e-liquid, and a shorter duration to finish a refill. Multivariate analysis revealed that e-cigarette use of 1–6 and 6–12 months (but not 1 month and below) was significantly associated with a higher cotinine concentration. Cotinine found in zero-nicotine e-liquids implies the importance of stringent regulatory governance for the consistency of labeled nicotine content of e-cigarette liquid in the market. Zero-nicotine e-cigarette users should also be informed of the likelihood of environmental exposure to tobacco smoke. Future studies conducted on larger samples are warranted to validate the association between duration of e-cigarette use and salivary cotinine concentration as well as to investigate underlying mechanisms.