bluuebunny/crossref_metadata_2025_split huggingface dataset:
Catalytic activity of human guanylate‐binding protein 1 coupled to the release of structural restraints imposed by the C‐terminal domain
Authors: Ince Semra , Zhang Ping , Kutsch Miriam , Krenczyk Oktavian , Shydlovskyi Sergii , Herrmann Christian 
Published: April 2020

Human guanylate‐binding protein 1 (hGBP‐1) shows a dimer‐induced acceleration of the GTPase activity yielding GDP as well as GMP. While the head‐to‐head dimerization of the large GTPase (LG) domain is well understood, the role of the rest of the protein, particularly of the GTPase effector domain (GED), in dimerization and GTP hydrolysis is still obscure. In this study, with truncations and point mutations on hGBP‐1 and by means of biochemical and biophysical methods, we demonstrate that the intramolecular communication between the LG domain and the GED (LG:GED) is crucial for protein dimerization and dimer‐stimulated GTP hydrolysis. In the course of GTP binding and γ‐phosphate cleavage, conformational changes within hGBP‐1 are controlled by a chain of amino acids ranging from the region near the nucleotide‐binding pocket to the distant LG:GED interface and lead to the release of the GED from the LG domain. This opening of the structure allows the protein to form GED:GED contacts within the dimer, in addition to the established LG:LG interface. After releasing the cleaved γ‐phosphate, the dimer either dissociates yielding GDP as the final product or it stays dimeric to further cleave the β‐phosphate yielding GMP. The second phosphate cleavage step, that is, the formation of GMP, is even more strongly coupled to structural changes and thus more sensitive to structural restraints imposed by the GED. Altogether, we depict a comprehensive mechanism of GTP hydrolysis catalyzed by hGBP‐1, which provides a detailed molecular understanding of the enzymatic activity connected to large structural rearrangements of the protein.DatabaseStructural data are available in RCSB Protein Data Bank under the accession numbers: 1F5N, 1DG3, 2B92.
Clinging on to alpine life: Investigating factors driving the uphill range contraction and population decline of a mountain breeding bird
Authors: Ewing Steven R. , Baxter Alistair , Wilson Jeremy D. , Hayhow Daniel B. , Gordon James , Thompson Des B. A. , Whitfield D. Philip , van der Wal René 
Published: April 2020

AbstractClimate change and anthropogenic nitrogen deposition are widely regarded as important drivers of environmental change in alpine habitats. However, due to the difficulties working in high‐elevation mountain systems, the impacts of these drivers on alpine breeding species have rarely been investigated. The Eurasian dotterel (Charadrius morinellus) is a migratory wader, which has been the subject of uniquely long‐term and spatially widespread monitoring effort in Scotland, where it breeds in alpine areas in dwindling numbers. Here we analyse data sets spanning three decades, to investigate whether key potential drivers of environmental change in Scottish mountains (snow lie, elevated summer temperatures and nitrogen deposition) have contributed to the population decline of dotterel. We also consider the role of rainfall on the species' wintering grounds in North Africa. We found that dotterel declines—in both density and site occupancy of breeding males—primarily occurred on low and intermediate elevation sites. High‐elevation sites mostly continued to be occupied, but males occurred at lower densities in years following snow‐rich winters, suggesting that high‐elevation snow cover displaced dotterel to lower sites. Wintering ground rainfall was positively associated with densities of breeding males two springs later. Dotterel densities were reduced at low and intermediate sites where nitrogen deposition was greatest, but not at high‐elevation sites. While climatic factors explained variation in breeding density between years, they did not seem to explain the species' uphill retreat and decline. We cannot rule out the possibility that dotterel have increasingly settled on higher sites previously unavailable due to extensive snow cover, while changes associated with nitrogen deposition may also have rendered lower lying sites less suitable for breeding. Causes of population and range changes in mountain‐breeding species are thus liable to be complex, involving multiple anthropogenic drivers of environmental change acting widely across annual and migratory life cycles.
Helicobacter pylori test‐and‐treat strategy for second‐year junior high school students aimed at the prevention of gastric cancer in Takatsuki City
Authors: Kaji Emiri , Yoden Atsushi , Otani Masano , Okuhira Takeru , Aomatsu Tomoki , Tamai Hiroshi , Ashida Akira 
Published: April 2020

AbstractBackgroundMore than 90% of gastric cancer cases are caused by Helicobacter pylori infections. To prevent gastric cancer, an H pylori test‐and‐treat strategy targeting young people has been implemented in various places in Japan. In this study, we evaluated the effectiveness of an H pylori test‐and‐treat strategy for second‐year junior high school students in Takatsuki City.Materials and MethodsIn 2014‐2017, a urine‐based H pylori test was used for initial screening. The final infection status was determined by a 13C‐urea breath test (13C‐UBT). Successful H pylori eradication was confirmed by 13C‐UBT 3 months after treatment. First‐line eradication therapy was changed from 10 mg of rabeprazole, 750 mg of amoxicillin, and 200 mg of clarithromycin twice daily for 7 days in 2014 to 20 mg of vonoprazan, 750 mg of amoxicillin, and 200 mg of clarithromycin twice daily for 7 days in 2015‐2017. Second‐line eradication therapy included 10 mg of rabeprazole, 750 mg of amoxicillin, and 250 mg of metronidazole twice daily for 7 days.ResultsIn total, 8067 of 13 055 students participated this project and 206 students were diagnosed with H pylori infection. The success rate of first‐line therapy was 45.9% in 2014 and 83.8% after the revised first‐line therapy was administered. The final eradication rate was 98.5%. There were no severe side effects.ConclusionOur results support the use of the H pylori test‐and‐treat strategy for junior high school students as a safe approach for the prevention of gastric cancer. H pylori eradication therapy with vonoprazan could be a standard therapy in children.
Potential interaction between timing of infant complementary feeding and breastfeeding duration in determination of early childhood gut microbiota composition and BMI
Authors: Differding Moira K. , Doyon Myriam , Bouchard Luigi , Perron Patrice , Guérin Renée , Asselin Claude , Massé Eric , Hivert Marie‐France , Mueller Noel T. 
Published: April 2020

SummaryBackgroundIntroducing complementary foods other than breastmilk or formula acutely changes the infant gut microbiota composition. However, it is unknown whether the timing of introduction to complementary foods (early vs. late) in infancy is associated with early childhood gut microbiota and BMI, and if these associations depend on breastfeeding duration.ObjectiveOur primary objective was to investigate whether timing of infant complentary feeding with solid foods is associated with early childhood gut microbiota composition and BMI‐z, and whether these associations differ by duration of breastfeeding.MethodsWe used data from a Canadian pre‐birth cohort followed till age 5 years. We examined timing of introduction to solid foods with the gut microbiota, determined by 16S rRNA gene sequencing of stool collected at 5 years of age, and age‐and‐sex specific BMI‐z. We conducted analyses before and after stratifying by breastfeeding duration, and adjusted for delivery mode, gestational age and birth weight.ResultsOf the 392 children in the analysis, 109 (27.8%) had early (≤4 months) solids. The association between early (vs later) solids and BMI‐z at 5 years was modified by breastfeeding status at 4 months (P = .06). Among children breastfed >4 months, early (vs later) solids were associated with differential relative abundance of 6 bacterial taxa, including lower Roseburia, and 0.30 higher BMI‐z (95% CI: 0.05, 0.55) at 5 years. In children breastfed <4 months, early solids were associated with differential relative abundance of 9 taxa, but not with child BMI‐z.ConclusionsEarly (vs. later) introduction to solid foods in infancy is associated with altered gut microbiota composition and BMI in early childhood, however these associations differ by duration of breastfeeding.
Validation of the Dutch translation of the Cardiff wound impact schedule for evaluation of the health‐related quality of life of patients with chronic wounds
Authors: van Doorn Louk P. , Sijberden Jasper P. , Brouwers Jeroen J. W. M. , Goossens Lisa Dominique , Hamming Jaap F. 
Published: April 2020

AbstractThe aim of this study was to validate a Dutch translation of the Cardiff wound impact schedule (CWIS), a disease‐specific instrument to measure the health‐related quality of life (HRQoL) in patients with chronic leg ulcers. To achieve this, the original instrument was translated. A total of 83 patients with chronic lower leg ulcers were included and completed the translated instrument and SF36 at baseline after assessment of their wound severity. Follow‐up was performed 1 week after inclusion. The psychometric properties of the instrument were assessed. Construct validity was positively evaluated by an expert panel. Face validity was positively evaluated in a cognitive debriefing of a pilot group. Discriminant validity was assessed by correlating 1‐year amputation risk according to the Wound, Ischaemia, foot Infection classification system with the instrument scores. Significant correlation could not be proven. Criterion validity was assessed by correlating domain scores of the instrument with domain scores of the gold standard: SF36. Moderate to high correlation was calculated for most domains of the instrument. Test‐retest reliability and internal consistency were evaluated as acceptable. In conclusion, the Dutch translation of the CWIS is a valid and reliable disease‐specific instrument to assess the HRQoL in patients with chronic lower leg ulcers.
A cross‐sectional multisite exploration of Italian paediatric nurses’ reported burnout and its relationship to perceptions of clinical safety and adverse events using the RN4CAST@IT‐Ped
Authors: Bagnasco Annamaria , Dasso Nicoletta , Rossi Silvia , Timmins Fiona , Watson Roger , Aleo Giuseppe , Catania Gianluca , Zanini Milko , Sasso Loredana 
Published: April 2020

AbstractAimTo explore Italian paediatric nurses’ reported burnout and its relationship to their perceptions of safety and adverse events.DesignA cross‐sectional study using the RN4CAST@IT‐Ped database with a web‐based survey design.MethodsThe RN4CAST@IT‐Ped questionnaire was used to collect data in 2017. This comprised three main components: three dimensions (22 items) of the Maslach Burnout Inventory including emotional exhaustion, depersonalization and personal accomplishment. Participants also scored an overall grade of patient safety and estimated the occurrence of adverse clinical events.ResultsNurses (N = 2,243) reported high levels of burnout. Most rated clinical safety as high. The risk of adverse events ranged from 1.3–12.4%. The degree of burnout appeared to influence the perception of safety and adverse events.ConclusionThe association between nurses’ burnout and perceptions of higher rates of adverse events and reduced safety in clinical practice is an important finding. However, it is unclear whether this was influenced by a negative state of mind, and whether reduced safety and increased adverse events negatively influenced nurses’ well‐being, thus leading to burnout. Regardless, the association between nurses’ burnout and these quality concepts needs further exploration to examine the effect, if any, on burnout and safety, and identify supportive mechanisms for nurses.ImpactThe association between reported burnout and perception of safety and risk of adverse events in Italian paediatric nurses has been reported for the first time. Nurses reporting burnout are at greater risk of intensely negative perceptions of clinical safety and adverse events. This is an important finding as perceptions can influence practice and behaviours. Quality measures in children's clinical environments need to go beyond obvious indicators to examine nurses’ well‐being as this also influences quality and safety.
Climatic refugia boosted allopatric diversification in Western Mediterranean vipers
Authors: Martínez‐Freiría Fernando , Freitas Inês , Zuffi Marco A. L. , Golay Philippe , Ursenbacher Sylvain , Velo‐Antón Guillermo 
Published: April 2020

AbstractAimThe ecological dimension of evolutionary processes has been scarcely addressed in phylogeographic studies. We reconstruct the historical biogeography of Western Mediterranean vipers to discover the role of climate in fostering diversification.LocationWestern Mediterranean Basin.TaxonVipera aspis and Vipera latastei‐monticola complex.MethodsWe used nearly range‐wide phylogeographic analyses of three mitochondrial genes followed by geographic assignment of 4,056 records to genetic units to test phylogenetic niche conservatism, under a 3D hypervolume approach, and reconstruct paleoclimatic scenarios for the diversification of main lineages during Pleistocene.ResultsBayesian inferences from mtDNA recovered three Miocene clades and nine Pliocene lineages that diversified during the Pleistocene. Diversification was mostly restricted to southern regions of Iberian and Italian peninsulas and to the north‐western African mountains until the late Pliocene. Some lineages expanded northwards during the Pleistocene. Accordingly, genetic diversity was higher in southern regions. Ecological niche tests mostly supported allopatric diversification with niche conservatism, although niche shifts occurred with two divergence events. Palaeoclimatic models identified particular requirements for the current distribution of main lineages and distinct responses to the cooling and warming events of the Pleistocene. Areas of climatic stability during the Pleistocene were identified for main lineages; however, climatic stability was weakly correlated with haplotype diversity.Main conclusionsIn the Western Mediterranean biodiversity hotspot, palaeo‐tectonic and palaeo‐climatic factors drove diversification since the Miocene. Comparisons among patterns of diversification, haplotype diversity, and climatic stability suggest that southern Iberian and Italian peninsulas, and north‐western African mountains acted as refugia since the Pliocene, while some northern areas favoured population persistence during the Pleistocene. Climate adaptation likely played a secondary role in the diversification of some lineages.
Longitudinal control of blood pressure among a cohort of Ghanaians with hypertension: A multicenter, hospital‐based study
Authors: Sarfo Fred S. , Mobula Linda , Plange‐Rhule Jacob , Gebregziabher Mulugeta , Ansong Daniel , Sarfo‐Kantanka Osei , Arthur Lynda , Sablah Jasper , Gavor Edith , Burnham Gilbert , Ofori‐Adjei David 
Published: April 2020

AbstractThere are limited data on factors associated with longitudinal control of blood pressure (BP) among Ghanaians on antihypertensive treatment. We sought to evaluate associations between prospective BP control and 24 putative factors within socio‐demographic, biological, and organizational domains. This is a cohort study involving 1867 (65%) adults with hypertension and 1006 (35%) with both hypertension and diabetes mellitus at five public hospitals. Clinic BP was measured every 2 months for 18 months of follow‐up. A multivariate logistic regression analysis was fitted via generalized linear mixed models to identify factors associated with clinic BP ≥ 140/90 mm Hg at each clinic visit during follow‐up. Mean age of study participants was 58.9 ± 16.6 years and 76.8% were females. Proportions with controlled BP increased from 46.3% at baseline to 59.8% at month 18, P < .0001. Eight factors with adjusted OR (95% CI) associated prospectively with uncontrolled BP were male gender: 1.37 (1.09‐1.72), secondary education: 1.32 (1.00‐1.74), non‐adherence to antihypertensive treatment: 1.03 (1.00‐1.06), fruit intake: 0.94 (0.89‐1.00), duration of hypertension diagnosis: 1.01 (1.00‐1.02), hypertension with diabetes mellitus: 2.05 (1.72‐2.46), number of antihypertensive medications: 1.63 (1.49‐1.79), and estimated glomerular filtration rate (mL/min rise): 0.82 (0.76‐0.89). Interventions aimed at addressing modifiable factors associated with poorly controlled BP would be critical in prevention of cardiovascular diseases among Ghanaians.
HIP/PAP protects against bleomycin‐induced lung injury and inflammation and subsequent fibrosis in mice
Authors: Zheng Xiaoyan , Li Qian , Tian Hong , Li Hanchao , Lv Yifei , Wang Yanhua , He Lan , Huo Yongwei , Hao Zhiming 
Published: April 2020

AbstractHepatocarcinoma‐intestine‐pancreas/pancreatitis‐associated protein (HIP/PAP), a C‐type lectin, exerts anti‐oxidative, anti‐inflammatory, bactericidal, anti‐apoptotic, and mitogenic functions in several cell types and tissues. In this study, we explored the role of HIP/PAP in pulmonary fibrosis (PF). Expression of HIP/PAP and its murine counterpart, Reg3B, was markedly increased in fibrotic human and mouse lung tissues. Adenovirus‐mediated HIP/PAP expression markedly alleviated bleomycin (BLM)‐induced lung injury, inflammation, and fibrosis in mice. Adenovirus‐mediated HIP/PAP expression alleviated oxidative injury and lessened the decrease in pulmonary superoxide dismutase (SOD) activity in BLM‐treated mice, increased pulmonary SOD expression in normal mice, and HIP/PAP upregulated SOD expression in cultured human alveolar epithelial cells (A549) and human lung fibroblasts (HLF‐1). Moreover, in vitro experiments showed that HIP/PAP suppressed the growth of HLF‐1 and ameliorated the H2O2‐induced apoptosis of human alveolar epithelial cells (A549 and HPAEpiC) and human pulmonary microvascular endothelial cells (HPMVEC). In HLF‐1, A549, HPAEpiC, and HPMVEC cells, HIP/PAP did not affect the basal levels, but alleviated the TGF‐β1‐induced down‐regulation of the epithelial/endothelial markers E‐cadherin and vE‐cadherin and the over‐expression of mesenchymal markers, such as α‐SMA and vimentin. In conclusion, HIP/PAP was found to serve as a potent protective factor in lung injury, inflammation, and fibrosis by attenuating oxidative injury, promoting the regeneration of alveolar epithelial cells, and antagonizing the pro‐fibrotic actions of the TGF‐β1/Smad signaling pathway.
Trametinib potentiates TRAIL‐induced apoptosis via FBW7‐dependent Mcl‐1 degradation in colorectal cancer cells
Authors: Lin Lin , Ding Dapeng , Xiao Xiaoguang , Li Bing , Cao Penglong , Li Shijun 
Published: April 2020

AbstractTrametinib is a MEK1/2 inhibitor and exerts anticancer activity against a variety of cancers. However, the effect of Trametinib on colorectal cancer (CRC) is not well understood. In the current study, our results demonstrate the ability of sub‐toxic doses of Trametinib to enhance TRAIL‐mediated apoptosis in CRC cells. Our findings also indicate that Trametinib and TRAIL activate caspase‐dependent apoptosis in CRC cells. Moreover, Mcl‐1 overexpression can reduce apoptosis in CRC cells treated with Trametinib with or without TRAIL. We further demonstrate that Trametinib degrades Mcl‐1 through the proteasome pathway. In addition, GSK‐3β phosphorylates Mcl‐1 at S159 and promotes Mcl‐1 degradation. The E3 ligase FBW7, known to polyubiquitinate Mcl‐1, is involved in Trametinib‐induced Mcl‐1 degradation. Taken together, these results provide the first evidence that Trametinib enhances TRAIL‐mediated apoptosis through FBW7‐dependent Mcl‐1 ubiquitination and degradation.
Salvianolic acid B inhibits ototoxic drug–induced ototoxicity by suppression of the mitochondrial apoptosis pathway
Authors: Zheng Zhiwei , Wang Yunfeng , Yu Huiqian , Li Wen , Wu Jingfang , Cai Chengfu , He Yingzi 
Published: April 2020

AbstractIt has been claimed that salvianolic acid B (Sal B), a natural bioactive antioxidant, exerts protective effects in various types of cells. This study aims to evaluate the antioxidant and anti‐apoptosis effects of Sal B in a cultured HEI‐OC1 cell line and in transgenic zebrafish (Brn3C: EGFP). A CCK‐8 assay, Annexin V Apoptosis Detection Kit, TUNEL and caspase‐3/7 staining, respectively, examined apoptosis and cell viability. The levels of reactive oxygen species (ROS) were evaluated by CellROX and MitoSOX Red staining. JC‐1 staining was employed to detect the mitochondrial membrane potential (ΔΨm). Western blotting was used to assess expressions of Bax and Bcl‐2. The expression pattern of p‐PI3K and p‐Akt was determined by immunofluorescent staining. We found that Sal B protected against neomycin‐ and cisplatin‐induced apoptotic features, enhanced cell viability and accompanied with decreased caspase‐3 activity in the HEI‐OC1 cells. Supplementary experiments determined that Sal B reduced ROS production (increased ΔΨm), promoted Bcl‐2 expression and down‐regulated the expression of Bax, as well as activated PI3K/AKT signalling pathways in neomycin‐ and cisplatin‐injured HEI‐OC1 cells. Moreover, Sal B markedly decreased the TUNEL signal and protected against neomycin‐ and cisplatin‐induced neuromast HC loss in the transgenic zebrafish. These results unravel a novel role for Sal B as an otoprotective agent against ototoxic drug–induced HC apoptosis, offering a potential use in the treatment of hearing loss.
Distance to Hospital‐based Intrapartum Care and Planned Home Birth in Minnesota
Authors: Parks Santangelo Elise , Osypuk Theresa , Mason Susan M. 
Published: April 2020

IntroductionLoss of hospital‐based intrapartum services is associated with increases in out‐of‐hospital births, but less is known about associations with planned home birth. This study explores the impact of distance to hospital‐based intrapartum care on planned home birth.MethodsPublic‐use Minnesota birth certificate data were merged with Minnesota Hospital Annual Report data (2011‐2016) to test the relationship of miles from maternal residence to hospital‐based intrapartum care with planned home birth in Minnesota. Logistic regression models estimated the odds of a planned home birth versus hospital birth as a function of miles to hospital‐based intrapartum care.ResultsThe number of hospitals offering birth services in Minnesota declined by 11% from 2011 to 2016. Moderate (>20‐50 miles) and great (>50 miles) distances to nearest hospital‐based intrapartum care were associated with increased odds of planned home birth compared with short distances (≤20 miles). Adjusted odds ratios were 3.31 (95% CI, 3.04‐3.61) and 3.89 (95% CI, 2.37‐6.37), respectively, after adjusting for maternal education, age, and race. Planned home birth was the intended birth setting in 4.3% of births among those living great distances from hospital‐based intrapartum care, compared with 1.0% among those living a short distance from hospital‐based intrapartum care.DiscussionBetter understanding of how geographical barriers affect preferred birth settings can inform efforts to reduce the impact of hospital‐based intrapartum service loss on rural women and their birth outcomes.