bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultraviolet radiation changes plant color
Authors: Valenta Kim , Dimac-Stohl Kristin , Baines Frances , Smith Todd , Piotrowski Greg , Hill Norman , Kuppler Jonas , Nevo Omer 
Published: June 2020

Abstract
Background
Plant absorption of ultraviolet (UV) radiation can result in multiple deleterious effects to plant tissues. As a result, plants have evolved an array of strategies to protect themselves from UV radiation, particularly in the UV-B range (280–320 nm). A common plant response to UV exposure is investment in phenolic compounds that absorb damaging wavelengths of light. However, the inverse phenomenon – plant reflectance of UV to protect plant tissues – has not previously been explored. In a paired experiment, we expose half of our sample (N = 108) of insect-pollinated plants of the cultivar Zinnia Profusion Series to UV radiation, and protect the other half from all light < 400 nm for 42 days, and measure leaf and flower reflectance using spectroscopy. We compare UV-B reflectance in leaves and flowers at the beginning of the experiment or flowering, and after treatment.

Results
We find that plants protected from UV exposure downregulate UV-B reflectance, and that plants exposed to increased levels of UV show trends of increased UV-B reflectance.

Conclusions
Our results indicate that upregulation of UV-B reflecting pigments or structures may be a strategy to protect leaves against highly energetic UV-B radiation.
The minimal informative monitoring interval of N-terminal pro-B-type natriuretic peptide in patients with stable heart failure
Authors: Dai Zhehao , Asano Taku , Takahashi Osamu , Komiyama Nobuyuki , Ohde Sachiko 
Published: June 2020

Abstract
Background
N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a potential biomarker for monitoring the status of heart failure. However, the optimal monitoring interval of NT-proBNP is unknown. This study sought to investigate the minimal informative monitoring interval of NT-proBNP in patients with stable chronic heart failure.

Methods
This retrospective cohort study included patients who were admitted due to heart failure and subsequently followed with serial NT-proBNP measurements in a tertiary hospital. We analyzed NT-proBNP measured between six months after discharge and the earliest timepoint of: an alteration of medication regimen, readmission due to worsening of heart failure, or all-cause death. To distinguish progression of the disease from biological variability and measurement error, the signal-to-noise ratio method was applied with a random-effects model.

Results
In the 368 patients included, NT-proBNP was measured for a median 6 times. In the random-effects model, signal (progression of disease) exceeded noise (biological variability and measurement error) at 7.9 months (95% confidence interval [CI]: 5.1–9.6), while noise corresponded to a 61% increase from baseline. In stratified analysis using the AHEAD risk score, the minimal informative monitoring interval shortened as the risk score increased (0–1 point: 12.2 months [95%CI: 10.3–14.4]; 2–3 points: 8.0 months [95%CI: 6.8–9.7]; 4–5 points: 3.3 months [95%CI: 3.0–3.8]).

Conclusions
In patients with stable chronic heart failure, the minimal informative monitoring interval of NT-proBNP measurement was 7.9 months in the current population, which varied with underlying risks. The optimal monitoring interval could be lengthened for patients at lower risks.
Bedside testing of CYP2C19 gene for treatment of patients with PCI with antiplatelet therapy
Authors: Al-Rubaish Abdullah M. , Al-Muhanna Fahad A. , Alshehri Abdullah M. , Al-Mansori Mohammed A. , Alali Rudaynah A. , Khalil Rania M. , Al Faraidy Khalid A. , Cyrus Cyril , Sulieman Mohammed M. , Vatte Chittibabu , Claassens Daniel M. F. , ten Berg Jurriën M. , Asselbergs Folkert W. , Al-Ali Amein K. 
Published: June 2020

Abstract
Background
To mitigate the risk of stent thrombosis, patients treated by percutaneous coronary intervention (PCI) are administered dual anti-platelet therapy comprising aspirin and a platelet P2Y12 receptor inhibitor. Clopidogrel is a prodrug requiring activation by the cytochrome P450 enzyme, CYP2C19. In Saudi Arabia, it has been reported that approximately 26% of the population carries CYP2C19*2 and/or *3 loss-of-function polymorphisms in addition to a high prevalence of CVD.

Methods
This prospective (April 2013–December 2020) parallel assignment clinical trial focuses on ST-Elevation Myocardial Infarction (STEMI) patient outcomes. The clinical trial includes 1500 STEMI patients from two hospitals in the Eastern Province of Saudi Arabia. Patients are assigned to one of two groups; the control arm receives conventional therapy with clopidogrel, while in the active arm the Spartan RX CYP2C19 assay is used to determine the *2 genotype. Carriers of a CYP2C19*2 loss-of-function allele receive prasugrel or ticagrelor, while non-carriers are treated with clopidogrel. Follow-up is one year after primary PCI. The primary end point is the number of patients who develop an adverse major cardiovascular event, including recurrent MI, non-fatal stroke, cardiovascular death, or major bleeding one year after PCI.

Discussion
The risk of stent thrombosis in PCI patients is usually reduced by dual anti-platelet therapy, comprising aspirin and a P2Y12 inhibitor, such as clopidogrel. However, clopidogrel requires activation by the cytochrome P450 enzyme, CYP2C19. Approximately 20% of the population are unable to activate clopidogrel as they possess the CYP2C19*2 loss-of function (LoF) allele. The primary goal of this trial is to study the benefits of treating only those patients that cannot activate clopidogrel with an alternative that has shown to be a more effective platelet inhibitor and does not require bioactivation by the cytochrome P450 enzyme. We expect an improvement in net clinical benefit outcome in the active arm patients, thus supporting pharmacogenetic testing in PCI patients post STEMI.

Trial registration
Trial registration name is “Bedside Testing of CYP2C19 Gene for Treatment of Patients with PCI with Antiplatelet Therapy” (number NCT01823185) retrospectively registered with clinicaltrials.gov on April 4, 2013. This trial is currently at the patient recruitment stage.
Comparison of four algorithms on establishing continuous reference intervals for pediatric analytes with age-dependent trend
Authors: Li Kun , Hu Lixin , Peng Yaguang , Yan Ruohua , Li Qiliang , Peng Xiaoxia , Song Wenqi , Ni Xin 
Published: June 2020

Abstract
Background
Continuous reference intervals (RIs) allow for more precise consideration of the dynamic changes of physiological development, which can provide new strategies for the presentation of laboratory test results. Our study aimed to establish continuous RIs using four different simulation methods so that the applicability of different methods could be further understood.

Methods
The data of alkaline phosphatase (ALP) and serum creatinine (Cr) were obtained from the Pediatric Reference Interval in China study (PRINCE), in which healthy children aged 0–19 years were recruited. The improved non-parametric method, the radial smoothing method, the General Additive Model for Location Scale and Shape (GAMLSS), and Lambda-Median-Sigma (LMS) were used to develop continuous RIs. The accuracy and goodness of fit of the continuous RIs were evaluated based on the out of range (OOR) and Akaike Information Criterion (AIC) results.

Results
Samples from 11,517 and 11,544 participants were used to estimate the continuous RIs of ALP and Cr, respectively. Time frames were partitioned to fulfill the following two criteria: sample size = 120 in each subgroup and mean difference = 2 between adjacent time frames. Cubic spline or penalized spline was used for curve smoothing. The RIs estimated by the four methods approximately overlapped. However, more obvious edge effects were shown in the curves fit by the non-parametric methods than the semi-parametric method, which may be attributed to insufficient sample size. The OOR values of all four methods were smaller than 10%.

Conclusions
All four methods could be used to establish continuous RIs. GAMLSS and LMS are more reliable than the other two methods for dealing with edge effects.
No one accelerometer-based physical activity data collection protocol can fit all research questions
Authors: Bergman Patrick , Hagströmer Maria 
Published: June 2020

AbstractBackgroundMeasuring physical activity and sedentary behavior accurately remains a challenge. When describing the uncertainty of mean values or when making group comparisons, minimising Standard Error of the Mean (SEM) is important. The sample size and the number of repeated observations within each subject influence the size of the SEM. In this study we have investigated how different combinations of sample sizes and repeated observations influence the magnitude of the SEM.MethodsA convenience sample were asked to wear an accelerometer for 28 consecutive days. Based on the within and between subject variances the SEM for the different combinations of sample sizes and number of monitored days was calculated.ResultsFifty subjects (67% women, mean ± SD age 41 ± 19 years) were included. The analyses showed, independent of which intensity level of physical activity or how measurement protocol was designed, that the largest reductions in SEM was seen as the sample size were increased. The same magnitude in reductions to SEM was not seen for increasing the number of repeated measurement days within each subject.ConclusionThe most effective way of reducing the SEM is to have a large sample size rather than a long observation period within each individual. Even though the importance of reducing the SEM to increase the power of detecting differences between groups is well-known it is seldom considered when developing appropriate protocols for accelerometer based research. Therefore the results presented herein serves to highlight this fact and have the potential to stimulate debate and challenge current best practice recommendations of accelerometer based physical activity research.
Serosurvey of Treponema pallidum infection among children with skin ulcers in the Tarangire-Manyara ecosystem, northern Tanzania
Authors: Lubinza Clara K. C. , Lueert Simone , Hallmaier-Wacker Luisa K. , Ngadaya Esther , Chuma Idrissa S. , Kazwala Rudovick R. , Mfinanga Sayoki G. M. , Failing Klaus , Roos Christian , Knauf Sascha 
Published: June 2020

Abstract
Background
The first yaws eradication campaign reduced the prevalence of yaws by 95%. In recent years, however, yaws has reemerged and is currently subject to a second, ongoing eradication campaign. Yet, the epidemiological status of Tanzania and 75 other countries with a known history of human yaws is currently unknown. Contrary to the situation in humans in Tanzania, recent infection of nonhuman primates (NHPs) with the yaws bacterium Treponema pallidum subsp. pertenue (TPE) have been reported. In this study, we consider a One Health approach to investigate yaws and describe skin ulcers and corresponding T. pallidum serology results among children living in the Tarangire-Manyara ecosystem, an area with increasing wildlife-human interaction in northern Tanzania.

Methods
To investigate human yaws in Tanzania, we conducted a cross-sectional study to screen and interview skin-ulcerated children aged 6 to 15 years, who live in close proximity to two national parks with high numbers of naturally TPE-infected monkeys. Serum samples from children with skin ulcers were tested for antibodies against the bacterium using a treponemal (Treponema pallidum Particle Agglutination assay) and a non-treponemal (Rapid Plasma Reagin) test.

Results
A total of 186 children aged between 6 and 15 years (boys: 10.7 ± 2.1 (mean ± SD), N = 132; girls: 10.9 ± 2.0 (mean ± SD), N = 54) were enrolled. Seven children were sampled at health care facilities and 179 at primary schools. 38 children (20.4%) reported active participation in bushmeat hunting and consumption and 26 (13.9%) reported at least one physical contact with a NHP. None of the lesions seen were pathognomonic for yaws. Two children tested positive for treponemal antibodies (1.2%) in the treponemal test, but remained negative in the non-treponemal test.

Conclusions
We found no serological evidence of yaws among children in the Tarangire-Manyara ecosystem. Nevertheless, the close genetic relationship of human and NHPs infecting TPE strains should lead to contact prevention with infected NHPs. Further research investigations are warranted to study the causes and possible prevention measures of spontaneous chronic ulcers among children in rural Tanzania and to certify that the country is free from human yaws.
A case with Behçet’s disease involving erosive Metacarpophalangeal joint arthritis: the value of ultrasonography in the diagnosis of an Erosion
Authors: MÜLKOĞLU Cevriye , AYHAN F. Figen 
Published: June 2020

Abstract
Background
Behçet’s disease (BD) is a chronic multisystemic vasculitis that may emerge with musculoskeletal system involvements, oral-genital recurrent aphthae, mucocutaneous lesions, and ocular symptoms. Arthritis in BD is usually non-erosive and not related to crippling disease. Erosive arthropathy is a very rare manifestation of BD.

Case presentation
Herein, we present a 60-year-old male patient suffering from BD for 33 years with erosive arthritis in his second metacarpophalangeal joint. After we assessed his finger by X-ray, we diagnosed erosive arthropathy quickly by musculoskeletal ultrasonography. In addition, a systematic literature search was performed via the PubMed and Scopus databases using the keywords, ‘Behçet’s disease [AND] erosive/destructive arthritis’.

Conclusions
Erosive arthritis due to BD can be evaluated by ultrasonography in an easy, fast and cost-effective manner. The literature search between 1985 and December 2019 revealed a total of 19 patients with peripheral erosive arthropathy related to BD and the characteristics of the results are summarized in the paper.
Osteoprotegerin gene polymorphisms and otosclerosis: an additional genetic association study, multilocus interaction and meta-analysis
Authors: Bouzid Amal , Tekari Adel , Jbeli Fida , Chakroun Amine , Hansdah Kirtal , Souissi Amal , Singh Neha , Mosrati Mohamed Ali , Achour Imen , Ghorbel Abdelmonem , Charfeddine Ilhem , Ramchander Puppala Venkat , Masmoudi Saber 
Published: June 2020

Abstract
Background
Otosclerosis (OTSC) is among the most common causes of a late-onset hearing loss in adults and is characterized by an abnormal bone growth in the otic capsule. Alteration in the osteoprotegerin (OPG) expression has been suggested in the implication of OTSC pathogenesis.

Methods
A case-control association study of rs2228568, rs7844539, rs3102734 and rs2073618 single nucleotide polymorphisms (SNPs) in the OPG gene was performed in a Tunisian-North African population composed of 183 unrelated OTSC patients and 177 healthy subjects. In addition, a multilocus association and a meta-analysis of existing studies were conducted.

Results
Rs3102734 (p = 0.013) and rs2073618 (p = 0.007) were significantly associated with OTSC, which were predominantly detected in females after multiple corrections. Among the OPG studied SNPs, the haplotypes A-A-C-G (p = 0.0001) and A-A-C-C (p = 0.0004) were significantly associated with OTSC in females. Multilocus association revealed that the SNPs: rs2073618 in OPG, rs1800472 in TGFβ1, rs39335, rs39350 and rs39374 in RELN, and rs494252 in chromosome 11 showed significant OTSC-associated alleles in Tunisian individuals. In addition, meta-analysis of the rs2073618 SNP in Tunisian, Indian and Italian populations revealed evidence of an association with OTSC (OR of 0.826, 95% CI [0.691–0.987], p = 0.035).

Conclusions
Our findings suggest that rs3102734 and rs2073618 variants are associated with OTSC in North African ethnic Tunisian population. Meta-analysis of the rs2073618 in three different ethnic population groups indicated an association with OTSC.
Application of diffusion tensor imaging and blood oxygenation level-dependent magnetic resonance imaging to assess bilateral renal function induced by Iohexol in rabbits
Authors: Wang Zhiqiang , Liu Hongxu , Meng Heng , Zhang Duo 
Published: June 2020

Abstract
Background
Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) and diffusion tensor imaging (DTI) are useful methods for investigating the morphology and function of the kidneys, including revealing unilateral renal damage. Nevertheless, these techniques have not yet been applied for bilateral renal function. The aim of this study was to investigate whether the combination of DTI and BOLD could be used to examine different degrees of contrast-induced acute kidney injury (CI-AKI) in bilateral kidneys compared to standard methods such as serum creatinine (SCr) detection.

Methods
Forty-Two New Zealand white rabbits were divided into two groups: the experimental group and the control group. Physiological saline and iodine contrast agent (iohexol, 1.0 g iodine/kg, 1.0 ml/sec) were injected via the right renal artery. DTI and BOLD-MR data were acquired longitudinally at the baseline and 1, 24, 48, and 72 h after high-pressure syringe injection to measure the apparent diffusion coefficient (ADC), fractional anisotropy (FA) and relative transverse relaxation rate (R2*). After the MR scan at each time point, three rabbits in each group were sacrificed, and changes in SCr and hypoxia-inducible factor-1α (HIF-1α) were analyzed using histopathology and immunochemistry.

Results
Twenty-four hours after iohexol administration, the values of ADC and FA decreased significantly (P < 0.05), while R2* values increased (P < 0.05) in the renal cortex (CO), outer medulla (OM) and inner medulla (IM). Besides, significant negative correlations were observed among ADC, FA, and R2* in CO, OM, and IM (all P < 0.001, r = − 0.654–0.828).

Conclusions
DTI and BOLD can simultaneously and non-invasively assess different degrees of CI-AKI in bilateral kidneys.
Spatio-temporal distribution and associated factors of home delivery in Ethiopia. Further multilevel and spatial analysis of Ethiopian demographic and health surveys 2005–2016
Authors: Tessema Zemenu Tadesse , Tiruneh Sofonyas Abebaw 
Published: June 2020

Abstract
Background
Globally, between 2012 and 2017, 80% of live births occurred at health facilities assisted by skilled health personnel. In Ethiopia, in 2016 only 26% of live births attended by skilled health personal. This study aimed to assess the spatial patterns and associated factors of home delivery in Ethiopia using 2005, 2011, and 2016 Ethiopian Demographic and Health Surveys.

Methods
A total of 33,482 women who gave live birth in the 5 years preceding each survey were included for this study. ArcGIS version 10.7 software was used to visualize the spatial distribution of home delivery. The Bernoulli model was applied using Kilduff SaTScan version 9.6 software to identify significant purely spatial clusters for home delivery in Ethiopia. A multilevel logistic regression model was fitted to identify factors associated with home delivery. A p-value < 0.05 was taken to declare statistically significant predictors.

Results
Home delivery was declined from 94.78% in 2005, 90.05% in 2011, and 73.44% in 2016 in Ethiopia. Among the three surveys, consistently high clustering of home delivery was observed in Amhara and Southern Nations Nationalities and People’s Regions (SNNPR) of Ethiopia. In spatial scan statistics analysis, a total of 128 clusters (RR = 1.04, P-value < 0.001) in 2005, and 90 clusters (RR = 1.11, P-value < 0.001) in 2011, and 55 clusters (RR = 1.29, P-value < 0.001) in 2016 significant primary clusters were identified. Educational status of women and husband, religion, distance to the health facility, mobile access, antenatal care visit, birth order, parity, wealth index, residence, and Region were statistically significant predictors of home delivery.

Conclusion
The spatial distribution of home delivery among the three consecutive surveys were non-random in Ethiopia. Educational status of women and husband, religion, distance to the health facility, wealth index, residence, parity, mobile access, Region, and antenatal care visit were statistically significant predictors of home delivery in Ethiopia. Therefore, an intervention needs to improve the coverage of antenatal care visit, and health care facilities. Ministry of health and other stakeholders should give special attention to women living in Amhara and SNNPR states of Ethiopia.
Up-regulation of GLI1 in vincristine-resistant rhabdomyosarcoma and Ewing sarcoma
Authors: Yoon Joon Won , Lamm Marilyn , Chandler Christopher , Iannaccone Philip , Walterhouse David 
Published: June 2020

Abstract
Background
The clinical significance of GLI1 expression either through canonical Hedgehog signal transduction or through non-canonical mechanisms in rhabdomyosarcoma (RMS) or Ewing sarcoma (EWS) is incompletely understood. We tested a role for Hedgehog (HH) signal transduction and GL11 expression in development of vincristine (VCR) resistance in RMS and EWS.

Methods
We characterized baseline expression and activity of HH pathway components in 5 RMS (RD, Rh18, Ruch-2, Rh30, and Rh41) and 5 EWS (CHLA9, CHLA10, TC32, CHLA258, and TC71) cell lines. We then established VCR-resistant RMS and EWS cell lines by exposing cells to serially increasing concentrations of VCR and determining the IC50. We defined resistance as a ≥ 30-fold increase in IC50 compared with parental cells. We determined changes in gene expression in the VCR-resistant cells compared with parental cells using an 86-gene cancer drug resistance array that included GLI1 and tested the effect of GLI1 inhibition with GANT61 or GLI1 siRNA on VCR resistance.

Results
We found evidence for HH pathway activity and GLI1 expression in RMS and EWS cell lines at baseline, and evidence that GLI1 contributes to survival and proliferation of these sarcoma cells. We were able to establish 4 VCR-resistant cell lines (Ruch-2VR, Rh30VR, Rh41VR, and TC71VR). GLI1 was significantly up-regulated in the Rh30VR, Rh41VR, and TC71VR cells. The only other gene in the drug resistance panel that was significantly up-regulated in each of these VCR-resistant cell lines compared with their corresponding parental cells was the GLI1 direct target and multidrug resistance gene, ATP-binding cassette sub-family B member 1 (MDR1). We established major vault protein (MVP), which was up-regulated in both vincristine-resistant alveolar RMS cell lines (Rh30VR and Rh41VR), as another direct target of GLI1 during development of drug resistance. Treatment of the VCR-resistant cell lines with the small molecule inhibitor GANT61 or GLI1 siRNA together with VCR significantly decreased cell viability at doses that did not reduce viability individually.

Conclusions
These experiments demonstrate that GLI1 up-regulation contributes to VCR resistance in RMS and EWS cell lines and suggest that targeting GLI1 may benefit patients with RMS or EWS by reducing multidrug resistance.