bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kinetics of crystalloid fluid in hyperglycemia; an open‐label exploratory clinical trial
Authors: Hahn Robert G. , Svensson Robert , Zdolsek Joachim H. 
Published: May 2020

BackgroundInfusion with 0.9% saline is a mainstay in the treatment of severe hyperglycemia, but the kinetics of the saline volume in this setting has not been studied.MethodsAn intravenous infusion of 1 L of 0.9% saline over 30 minutes was given on 31 occasions to 17 patients with hyperglycemia due to poorly controlled diabetes (mean age 51 years). A two‐volume kinetic model was fitted to serial data on the hemodilution and urinary excretion, using mixed‐effects modeling software.ResultsPlasma glucose was 36 ± 9 mmol/L on arrival to the hospital. The central volume of distribution (the plasma) was only 2.38 L (mean; 95% confidence interval 1.73‐3.04) on the day of admission. Uptake into a remote compartment, believed to be the cells, amounted to 300 mL of the first liter of saline, although only small amounts of insulin were given. Plasma glucose, plasma bicarbonate, urine glucose, and plasma creatinine served as covariates in the kinetic model and mathematically affected the urinary excretion. For example, elimination of the infused fluid tripled from an increase in plasma glucose from 5 to 35 mmol/L and doubled from a reduction in plasma bicarbonate from 24 to 5 mmol/L.ConclusionsThe excretion of 0.9% saline was increased depending on the degree of hyperglycemia. The kinetics was characterized by glucose‐accelerated diuresis, and an intracellular uptake that occurred at two thirds the urine flow rate. These data could help to determine appropriate volumes and rates of infusion of crystalloids in hyperglycemia.
The impact of local smoke‐free policies on smoking behaviour among adults in Indonesia: a quasi‐experimental national study
Authors: Septiono Wahyu , Kuipers Mirte A. G. , Ng Nawi , Kunst Anton E. 
Published: May 2020

AbstractAimsTo investigate to what extent the adoption of local smoke‐free policies (SFPs) in Indonesia in 2007–13 was associated with changes in adult smoking behaviour.DesignA quasi‐experimental study.SettingIndonesia, 2007 and 2013.ParticipantsA total of 1 052 611 > 25‐year‐old adults. Data were derived from the 2007 and 2013 Indonesian national health survey.MeasurementsFor both years, provincial and district SFPs were identified from government documents in 497 districts in 33 provinces. Multi‐level logistic regression analysis assessed the association of adoption of provincial and district SFPs between 2007 and 2013 with smoking continuation (among ever‐smokers), current smoking and high smoking intensity (among current smokers). We controlled for survey year, SFP in 2007, socio‐demographics and district characteristics.FindingsProvincial SFP exposure was associated with lower odds of smoking continuation [strong SFP versus no SFP: odds ratio (OR) = 0.71, 95% confidence interval (CI) = 0.66–0.76] and smoking intensity (strong SFP: OR= 0.91, 95% CI = 0.86–0.97), but also with higher odds of current smoking (strong SFP versus no SFP: OR = 1.08; 95% CI = 1.04–1.12). District SFP exposure was associated with higher odds of smoking continuation (strong SFP versus no SFP: OR = 1.07, 95% CI = 1.01–1.14) and current smoking (strong SFP versus no SFP: OR = 1.09, 95% CI = 1.05–1.14), but with lower odds of smoking intensity (moderately strong SFP versus no SFP: OR = 0.95, 95% CI = 0.91–0.99).ConclusionsThere may be an association between the adoption of local smoke‐free policies in Indonesia and decreased adult smoking intensity. However, the evidence is inconsistent, which may reflect problems with policy implementation and enforcement,
Variants in ALX4 and their association with genitourinary defects
Authors: Chen Ching H. , Bournat Juan C. , Wilken Nathan , Rosenfeld Jill A. , Zhang Jason , Seth Abhishek , Jorgez Carolina J. 
Published: May 2020

AbstractBackgroundGenitourinary anomalies occur in approximately 1% of humans, but in most cases, the cause is unknown. Aristaless‐like homeobox 4 (ALX4) is an important homeodomain transcription factor. ALX4 mutations in humans and mouse have been associated with craniofacial defects and genitourinary anomalies such as cryptorchidism and epispadias.ObjectivesTo investigate the presence and the functional impact of ALX4 variants in patients with genitourinary defects.Materials and methodsTwo separate patient cohorts were analyzed. One includes clinical exome‐sequencing (ES) data from 7500 individuals. The other includes 52 ALX4 Sanger‐sequenced individuals with bladder exstrophy‐epispadias complex (BEEC). Dual luciferase assays were conducted to investigate the functional transcriptional impact of ALX4 variants in HeLa cells and HEK293 cells.ResultsA total of 41 distinct ALX4 heterozygous missense variants were identified in the ES cohort with 15 variants present as recurrent in multiple patients. p.G369E and p.L373F were the only two present in individuals with genitourinary defects. A p.L373F heterozygous variant was also identified in one of the 52 individuals in the BEEC cohort. p.L373F and p.G369E were tested in vitro as both are considered damaging by MutationTaster, although only p.G369E was considered damaging by PolyPhen‐2. p.L373F did not alter transcriptional activity in HeLa and HEK293 cells. p.G369E caused a significant 3.4‐ and 1.8‐fold decrease in transcriptional activities relative to wild‐type ALX4 in HEK293 and HeLa cells, respectively.Discussion and conclusionsOur study supports the idea that transcription factors like ALX4 could influence the normal development of the GU tract in humans as demonstrated in mouse models as ALX4 variant p.G369E (predicted pathogenic by multiple databases) affects ALX4 function in vitro. Variant p.L373F (predicted pathogenic by only MutationTaster) did not affect ALX4 function in vitro. Exon‐sequence information and mouse genetics provide important insights into the complex mechanisms driving genitourinary defects allowing the association of transcriptional defects with congenital disorders.
Public Health Agency of Sweden's Brief Report: Pregnant and postpartum women with severe acute respiratory syndrome coronavirus 2 infection in intensive care in Sweden
Authors: Collin Julius , Byström Emma , Carnahan AnnaSara , Ahrne Malin 
Published: May 2020

AbstractThe Public Health Agency of Sweden has analyzed how many pregnant and postpartum women with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection have been treated in intensive care units (ICU) in Sweden between 19 March and 20 April 2020 compared with non‐pregnant women of similar age. Cases were identified in a special reporting module within the Swedish Intensive Care Registry (SIR). Fifty‐three women aged 20‐45 years with SARS‐CoV‐2 were reported in SIR, and 13 of these women were either pregnant or postpartum (<1 week). The results indicate that the risk of being admitted to ICU may be higher in pregnant and postpartum women with laboratory‐confirmed SARS‐CoV‐2 in Sweden, compared with non‐pregnant women of similar age.
Comparison of the effectiveness of conbercept and ranibizumab treatment for retinopathy of prematurity
Authors: Cheng Yong , Zhu Xuemei , Linghu Dandan , Liang Jianhong 
Published: May 2020

AbstractPurposeTo compare the effectiveness of intravitreal conbercept and ranibizumab treatment for retinopathy of prematurity (ROP).MethodsIn this retrospective study, the date of patients with ROP treated with intravitreal conbercept or ranibizumab from July 2012 to March 2018 with at least 12 months of follow‐up at the Eye Center in People’s Hospital of Peking University were analysed. Regression, progression or recurrence and peripheral retina vascularization were evaluated.ResultsIn total, 283 eyes (145 infants) with conbercept treatment and 916 eyes (480 infants) with ranibizumab treatment were enrolled. In zone I ROP and aggressive posterior ROP (APROP), the recurrence prevalence was 49.09% (108/220 eyes) and 28.57% (10/33 eyes), and the recurrence interval was 7.87 ± 0.65 (5.5–9.5) weeks and 10.6 ± 1.53 (10.5–13) weeks in the ranibizumab and conbercept groups, respectively. In zone II ROP disease, the recurrence prevalence was 23.56% (164/696 eyes) and 13.31% (33/248 eyes), and the interval of recurrence was 8.40 ± 0.88 (6–10.5) weeks and 11.4 ± 1.35 (11–13.5) weeks in the ranibizumab and conbercept groups, respectively. The recurrence prevalence was significantly higher with ranibizumab in Zone I ROP and APROP (p = 0.006) and Zone II ROP (p < 0.001), and the recurrence interval was significantly longer in the conbercept group than that in the ranibizumab (p < 0.001). There was no significant difference in the rate of retinal vascularization (p = 0.441).ConclusionConbercept and ranibizumab are effective for treating ROP. Compared with ranibizumab, conbercept resulted in less recurrence and longer treatment intervals.
Cystic fibrosis transmembrane conductance regulator‐dependent bicarbonate entry controls rat cardiomyocyte ATP release via pannexin1 through mitochondrial signalling and caspase activation
Authors: Wang Yongshun , Zhao Junjun , Cai Yin , Ballard Heather J. 
Published: May 2020

AbstractAimCystic fibrosis transmembrane conductance regulator (CFTR) is expressed in the heart, but its function there is unclear. CFTR regulates an ATP release pore in many tissues, but the identity and regulatory mechanism of the pore are unknown. We investigated the role of CFTR in ATP release from primary cardiomyocytes and ventricular wall in vivo.MethodsProteins involved in the signalling pathway for ATP release during simulated ischaemia (lactic acid treatment) were investigated using inhibitors and siRNA; colocalization was identified by coimmunofluorescence and proximity ligation assays; changes in near‐membrane pH and calcium were identified with total internal reflection microscopy; in vivo ATP release was investigated using interstitial microdialysis of rat heart.ResultsLactic acid‐induced CFTR‐dependent ATP release from cultured cardiomyocytes and left ventricle in vivo. Lactic acid entry elevated near‐membrane calcium, which involved Na/H‐ and Na/Ca‐exchangers colocalized with CFTR. Calcium entry‐induced CFTR activation, which involved cAMP, protein kinase A, FAK, Pyk2 and Src. Removal of extracellular bicarbonate abolished cardiomyocyte ATP release induced by lactic acid or CFTR activators. Bicarbonate stimulated cytochrome c expression, cytochrome c release and ATP release from isolated cardiomyocyte mitochondria. Pannexin 1 (Panx1) colocalized with CFTR. Lactic acid increased cardiomyocyte caspase activity: caspase inhibitors or Panx1 siRNA abolished cardiomyocyte ATP release, while pannexin inhibition abolished cardiac ATP release in vivo.ConclusionDuring simulated ischaemia, CFTR‐dependent bicarbonate entry stimulated ATP and cytochrome c release from mitochondria; in the cytoplasm, cytochrome c‐activated caspase 3, which in turn activated Panx1, and ATP was released through the opened Panx1 channel.
Drug monitoring for mycophenolic acid in graft‐vs‐host disease prophylaxis in cord blood transplantation
Authors: Muranushi Hiroyuki , Kanda Junya , Arai Yasuyuki , Shindo Takero , Hishizawa Masakatsu , Yamamoto Takashi , Kondo Tadakazu , Yamashita Kohei , Matsubara Kazuo , Takaori‐Kondo Akifumi 
Published: May 2020

AimsWe performed the retrospective analysis to clarify the significance of drug monitoring for mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), in prophylaxis for graft‐vs‐host disease (GVHD) in cord blood transplantation.MethodsWe retrospectively analysed the data of 46 patients who underwent first cord blood transplantation and received GVHD prophylaxis with tacrolimus plus MMF. MPA levels were measured on days 7 and 21, and 24‐hour areas under the curve (AUC0–24) were estimated.ResultsThe engraftment and 3‐year overall survival rates of all patients were 94% and 78%, respectively. The cumulative incidence of sepsis before engraftment was higher in patients with AUC0–24 on day 7 of >60 μg h/mL than in other patients (33 vs 6%, P = .02). The cumulative incidence of grade II–IV acute GVHD was higher in patients with AUC0–24 on day 21 of ≤30 μg h/mL than in other patients (80 vs 50%, P = .04). The cumulative incidence of human herpesvirus 6 reactivation was higher in patients with AUC0–24 on day 21 of ≤48 μg h/mL (median) than in other patients (50 vs 19%, P = .03).ConclusionBlood level of MPA was associated with risk of acute GVHD and infection. A prospective trial evaluating the benefit of personalized MMF dosing using MPA levels is needed.
A pharmacokinetic‐pharmacodynamic study of a single dose of febuxostat in healthy subjects
Authors: Kamel Bishoy , Graham Garry G. , Stocker Sophie L. , Liu Zhixin , Williams Kenneth M. , Carland Jane E. , Pile Kevin D. , Day Richard O. 
Published: May 2020

AimsTo examine the pharmacokinetic‐phamacodynamic (PK‐PD) relationships of plasma febuxostat and serum urate and the effect of a single dose of the drug on renal excretion and fractional clearance of urate (FCU).MethodsBlood and urine samples were collected at baseline and up to 145 hours following administration of febuxostat (80 mg) to healthy subjects (n = 9). Plasma febuxostat and serum and urinary urate and creatinine concentrations were determined. Febuxostat pharmacokinetics were estimated using a two‐compartment model with first‐order absorption. An Emax PK‐PD model was fitted to mean febuxostat and urate concentrations. Urinary urate excretion and FCU were calculated pre‐ and post‐dose.ResultsMaximum mean plasma concentration of febuxostat (2.7 mg L−1) was observed 1.2 hours after dosage. Febuxostat initial and terminal half‐lives were 2.0 ± 1.0 and 14.0 ± 4.7 hours (mean ± SD), respectively. The majority (81%) of the drug was eliminated in the 9 hours after dosing. Serum urate declined slowly achieving mean nadir (0.20 mmol L−1) at 24 hours. The IC50 (plasma febuxostat concentration that inhibits urate production by 50%) was 0.11 ± 0.09 mg L−1 (mean ± SD). Urinary urate excretion changed in parallel with serum urate. There was no systematic or significant change in FCU from baseline.ConclusionThe PK‐PD model could potentially be used to individualise febuxostat treatment and improve clinical outcomes. A single dose of febuxostat does not affect the efficiency of the kidney to excrete urate. Further investigations are required to confirm the present results following multiple dosing with febuxostat.
The role of informal digital learning of English and L2 motivational self system in foreign language enjoyment
Authors: Lee Ju Seong , Lee Kilryoung 
Published: May 2020

AbstractThis interdisciplinary research examines how Informal Digital Learning of English (IDLE) and the L2 Motivational Self System (consisting of the ideal L2 self and the ought‐to L2 self) are linked with Foreign Language Enjoyment (FLE). Together, these are flourishing research areas in computer‐assisted language learning, second language acquisition and positive psychology. Using a purposive sampling technique, three cohorts of English‐as‐a‐foreign‐language learners (N = 661) are surveyed in South Korea: middle school (n = 173), high school (n = 374) and university students (n = 114). Results of hierarchical regression analyses show that IDLE and the ideal L2 self are significantly predictive of all groups’ FLE, while the ought‐to L2 self predicts only middle school students’ FLE. These results suggest that students’ engagement in extramural digital activities and their motivational mindset (shaped through different socio‐educational contexts) may have influenced their emotions in learning their target language. Informed by these results, teachers can help increase students’ L2 learning enjoyment by supporting their language learning in out‐of‐class digital settings as well as promoting their ideal L2 self‐images. Concurrently, teachers and parents can enhance younger learners’ enjoyment of learning L2—especially in test‐oriented Asian contexts—by setting higher L2 learning expectations.
‘They’re discriminated against, but so are we’: White Australian‐born perceptions of ingroup and immigrant discrimination over time are not zero sum
Authors: Leviston Zoe , Dandy Justine , Jetten Jolanda 
Published: May 2020

We examined whether zero‐sum thinking explains White Australian‐born people’s majority‐culture perceptions of discrimination towards their ingroup and an outgroup (immigrants), and the relationships among perceived discrimination and support for multiculturalism and immigration. Two correlational cross‐sectional studies were conducted among self‐identified White Australians (Study 1, N = 517), and White Americans (Study 2, N = 273), as well as an experiment among White Australians (Study 3, N = 121) in which we manipulated discrimination towards immigrants over time. Our findings did not support a zero‐sum account but revealed that perceptions of group discrimination were positively correlated: a case of ‘they’re discriminated against, but so are we’ rather than ‘if they gain, we lose’. Moreover, concerns about future discrimination of the ingroup were most predictive of opposition to multicultural policy and immigration. We argue our findings are more consistent with a competitive victimhood account of intergroup relations than a zero‐sum thinking account.
TNF‐α enhances TGF‐β‐induced endothelial‐to‐mesenchymal transition via TGF‐β signal augmentation
Authors: Yoshimatsu Yasuhiro , Wakabayashi Ikumi , Kimuro Shiori , Takahashi Naoya , Takahashi Kazuki , Kobayashi Miho , Maishi Nako , Podyma‐Inoue Katarzyna A. , Hida Kyoko , Miyazono Kohei , Watabe Tetsuro 
Published: May 2020

AbstractThe tumor microenvironment (TME) consists of various components including cancer cells, tumor vessels, cancer‐associated fibroblasts (CAFs), and inflammatory cells. These components interact with each other via various cytokines, which often induce tumor progression. Thus, a greater understanding of TME networks is crucial for the development of novel cancer therapies. Many cancer types express high levels of TGF‐β, which induces endothelial‐to‐mesenchymal transition (EndMT), leading to formation of CAFs. Although we previously reported that CAFs derived from EndMT promoted tumor formation, the molecular mechanisms underlying these interactions remain to be elucidated. Furthermore, tumor‐infiltrating inflammatory cells secrete various cytokines, including TNF‐α. However, the role of TNF‐α in TGF‐β‐induced EndMT has not been fully elucidated. Therefore, this study examined the effect of TNF‐α on TGF‐β‐induced EndMT in human endothelial cells (ECs). Various types of human ECs underwent EndMT in response to TGF‐β and TNF‐α, which was accompanied by increased and decreased expression of mesenchymal cell and EC markers, respectively. In addition, treatment of ECs with TGF‐β and TNF‐α exhibited sustained activation of Smad2/3 signals, which was presumably induced by elevated expression of TGF‐β type I receptor, TGF‐β2, activin A, and integrin αv, suggesting that TNF‐α enhanced TGF‐β‐induced EndMT by augmenting TGF‐β family signals. Furthermore, oral squamous cell carcinoma‐derived cells underwent epithelial‐to‐mesenchymal transition (EMT) in response to humoral factors produced by TGF‐β and TNF‐α‐cultured ECs. This EndMT‐driven EMT was blocked by inhibiting the action of TGF‐βs. Collectively, our findings suggest that TNF‐α enhances TGF‐β‐dependent EndMT, which contributes to tumor progression.
Clinical and radiological characterization of novel FIG4‐related combined system disease with neuropathy
Authors: Wright Georgia C. , Brown Richard , Grayton Hannah , Livingston John H. , Park Soo‐Mi , Parker Alasdair P.J. , Patel Anjla , Simonic Ingrid , Thomas Adam G. , Vadlamani Gayatri , Horvath Rita , Harijan Pooja D. 
Published: May 2020

AbstractVariants in the FIG4 gene, which encodes a phosphatidylinositol‐3,5‐bisphosphatase lead to obstruction of endocytic trafficking, causing accumulation of enlarged vesicles in murine peripheral neurons and fibroblasts. Bi‐allelic pathogenic variants in FIG4 are associated with neurological disorders including Charcot‐Marie‐Tooth disease type‐4J (CMT4J) and Yunis‐Varón syndrome (YVS). We present four probands from three unrelated families, all homozygous for a recurrent FIG4 missense variant c.506A>C p.(Tyr169Ser), with a novel phenotype involving features of both CMT4J and YVS. Three presented with infant‐onset dystonia and one with hypotonia. All have depressed lower limb reflexes and distal muscle weakness, two have nerve conduction studies (NCS) consistent with severe sensorimotor demyelinating peripheral neuropathy and one had NCS showing patchy intermediate/mildly reduced motor conduction velocities. All have cognitive impairment and three have swallowing difficulties. MRI showed cerebellar atrophy and bilateral T2 hyperintense medullary swellings in all patients. These children represent a novel clinicoradiological phenotype and suggest that phenotypes associated with FIG4 missense variants do not neatly fall into previously described diagnoses but can present with variable features. Analysis of this gene should be considered in patients with central and peripheral neurological signs and medullary radiological changes, providing earlier diagnosis and informing reproductive choices.
Genetic predisposition in type 2 diabetes: A promising approach toward a personalized management of diabetes
Authors: Sirdah Mahmoud M. , Reading N. Scott 
Published: May 2020

AbstractDiabetes mellitus, also known simply as diabetes, has been described as a chronic and complex endocrine metabolic disorder that is a leading cause of death across the globe. It is considered a key public health problem worldwide and one of four important non‐communicable diseases prioritized for intervention through world health campaigns by various international foundations. Among its four categories, Type 2 diabetes (T2D) is the commonest form of diabetes accounting for over 90% of worldwide cases. Unlike monogenic inherited disorders that are passed on in a simple pattern, T2D is a multifactorial disease with a complex etiology, where a mixture of genetic and environmental factors are strong candidates for the development of the clinical condition and pathology. The genetic factors are believed to be key predisposing determinants in individual susceptibility to T2D. Therefore, identifying the predisposing genetic variants could be a crucial step in T2D management as it may ameliorate the clinical condition and preclude complications. Through an understanding the unique genetic and environmental factors that influence the development of this chronic disease individuals can benefit from personalized approaches to treatment. We searched the literature published in three electronic databases: PubMed, Scopus and ISI Web of Science for the current status of T2D and its associated genetic risk variants and discus promising approaches toward a personalized management of this chronic, non‐communicable disorder.