bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of entomopathogenic fungi on growth and nutrition in wheat grown on two calcareous soils: Influence of the fungus application method
Authors: González‐Guzmán Adrián , Sacristán Daniel , Quesada‐Moraga Enrique , Torrent José , del Campillo María Carmen , Sánchez‐Rodríguez Antonio Rafael
Published: April 2020

Entomopathogenic fungi (EF) have so far aroused little interest as plant growth promoters or nutritional enhancers while protecting the plant against insect pests and mites. In this work, we examined the performance of Triticum durum and Triticum aestivum plants pot‐grown on two unsterilized Zn‐poor calcareous Vertisols and inoculated with Beauveria bassiana or Metarhizium brunneum by application to soil or seed dressing. The effects of fungal inoculation were found to depend on crop species, soil type, sampling time and fungus application method. While the height of the control plants tended to be significantly greater than the height of inoculated plants at early and intermediate growth stages, the trend changed at more advanced plant stage of development, 56 days after sowing (DAS). This was supported by the significant increase in aerial dry matter (ADM) in T. aestivum plants treated with B. bassiana by seed dressing (17.4%) or with M. brunneum with soil application and seed dressing (20.6 and 26.9%, respectively) 69 DAS. In T. durum, at harvest, seed dressing with B. bassiana or M. brunneum had an overall positive but not significant effect on ADM or grain yield, whereas direct application to the soil slightly decreased grain yield (6.6 and 5.5%, respectively) and ADM (5.3 and 6.1%, respectively). In T. aestivum, none of the fungus–application method combinations affected yield at harvest significantly. Fungal inoculation had little influence on nutrient uptake, whereas application to soil increased Mn uptake and grain Mn concentration in T. durum. Zinc uptake was significantly increased only in T. aestivum grown on the soil with the lowest Zn content treated with M. brunneum. Grain Zn concentration tended to be inversely related to grain yield. These results support seed dressing with EF as a promising green technology for sustainable crop protection and production with no adverse effects on plant performance.
Activation of epidermal growth factor receptor signaling mediates cellular senescence induced by certain pro‐inflammatory cytokines
Authors: Shang Dongsheng , Sun Danlin , Shi Chunyan , Xu Jun , Shen Mingxiang , Hu Xing , Liu Hanqing , Tu Zhigang
Published: April 2020

It is well established that inflammation in the body promotes organism aging, and recent studies have attributed a similar effect to senescent cells. Considering that certain pro‐inflammatory cytokines can induce cellular senescence, systematically evaluating the effects of pro‐inflammatory cytokines in cellular senescence is an important and urgent scientific problem, especially given the ongoing surge in aging human populations. Treating IMR90 cells and HUVECs with pro‐inflammatory cytokines identified six factors able to efficiently induce cellular senescence. Of these senescence‐inducing cytokines, the activity of five (namely IL‐1β, IL‐13, MCP‐2, MIP‐3α, and SDF‐1α) was significantly inhibited by treatment with cetuximab (an antibody targeting epidermal growth factor receptor [EGFR]), gefitinib (a small molecule inhibitor of EGFR), and EGFR knockdown. In addition, treatment with one of the senescence‐inducing cytokines, SDF‐1α, significantly increased the phosphorylation levels of EGFR, as well as Erk1/2. These results suggested that pro‐inflammatory cytokines induce cellular senescence by activating EGFR signaling. Next, we found that EGF treatment could also induce cellular senescence of IMR90 cells and HUVECs. Mechanically, EGF induced cellular senescence via excessive activation of Ras and the Ras‐BRaf‐Erk1/2 signaling axis. Moreover, EGFR activation induced IMR90 cells to secrete certain senescence‐associated secretory phenotype factors (IL‐8 and MMP‐3). In summary, we report that certain pro‐inflammatory cytokines induce cellular senescence through activation of the EGFR‐Ras signaling pathway. Our study thus offers new insight into a long‐ignored mechanism by which EGFR could regulate cellular senescence and suggests that growth signals themselves may catalyze aging under certain conditions.
Integration of whole‐genome DNA methylation data with RNA sequencing data to identify markers for bull fertility
Authors: Gross Nicole , Peñagaricano Francisco , Khatib Hasan
Published: April 2020

Predicting bull fertility prior to breeding is a current challenge for the dairy industry. The use of molecular biomarkers has been previously assessed. However, the integration of this information has not been performed to extract biologically relevant markers. The goal of this study was to integrate DNA methylation data with previously published RNA‐sequencing results in order to identify candidate markers for sire fertility. A total of 1765 differentially methylated cytosines were found between high‐ and low‐fertility sires. Ten genes associated with 11 differentially methylated cytosines were found in a previous study of gene expression between high‐ and low‐fertility sires. Additionally, two of these genes code for proteins found exclusively in bull seminal plasma. Collectively, our results reveal 10 genes that could be used in the future as a panel for predicting bull fertility.
Continuing a pregnancy after diagnosis of a lethal fetal abnormality: Views and perspectives of Australian health professionals and parents
Authors: Weeks Alice , Saya Sibel , Hodgson Jan
Published: April 2020

Background

Couples who receive a prenatal diagnosis of a fetal anomaly in Victoria, Australia, are generally offered a choice about whether or not to continue with the pregnancy. When a severe or ‘lethal’ abnormality is diagnosed, some couples decide to continue the pregnancy in the knowledge that their baby may die before or shortly after birth. Several Australian parents who published personal accounts of that experience describe a lack of clear clinical pathways, suggesting those who decide to continue a pregnancy following a diagnosis of a ‘lethal fetal abnormality’ (LFA) may not be receiving optimal care.

Aims

This study aimed to provide empirical Australian evidence of views and experiences of care provision from health professionals (HPs) and parents.

Materials and Methods

Two sequential phases of this qualitative study purposively recruited a range of key HPs and parents. Semi‐structured interviews were thematically analysed.

Results

Findings reveal that current care provision following prenatal diagnosis of an LFA is ‘ad hoc’ with both participant groups identifying disparities between parents’ needs and available care. However, the goodwill and good intentions of all HPs involved was apparent. There was strong support from both groups for considering a model of perinatal palliative care (PPC) based on existing programs overseas.

Conclusions

Future care provision in this setting needs to be redefined. A formal PPC program could ensure better and more consistent experiences of support for parents as well as the HPs working in the field.
Good at heart: Developing a tertiary perinatal cardiac service; the first eight years of experience
Authors: Heland Sarah , de Chellis Adam , Rieder Wawrzyniec , Sleeman Matthew , Johns Jennifer , Lancefield Terase , Robinson Andrew , Fung Alison , Walker Susan
Published: April 2020

Background

Maternal cardiac disease is the most common cause of indirect maternal death, and women with pre‐existing cardiac disease have complex medical, obstetric and anaesthetic requirements. Our hospital commenced a multidisciplinary perinatal cardiac service in 2009 to optimise outcomes in women with cardiac disease.

Aim

To assess the maternal and perinatal outcomes of women referred to the clinic to evaluate clinical practice and inform future service provision.

Materials and Methods

This is a single‐centre retrospective study of women referred to the perinatal cardiac service between 2009–2016. Data collected included: demographic details; cardiac diagnosis; pregnancy outcomes, including anaesthetic and delivery complications, and admission to intensive care unit (ICU)/high dependency unit (HDU).

Results

One hundred and fifty‐two women were referred for care in 165 pregnancies. Congenital heart disease was the most common indication for referral (35%), followed by maternal cardiac arrhythmia (26%) and valvular disease (18%). The perinatal mortality rate was 2%, median gestational age at delivery was 38 weeks 4 days, fetal growth restriction (customised birthweight <10th centile) was 9% although 25 (17%) pregnancies resulted in preterm birth, 36% of which were spontaneous and 64% were iatrogenic. Maternal outcomes were favourable and there were no maternal deaths. However, 51% of women required a caesarean section, and 23% who achieved a live birth required ICU/HDU admission.

Conclusion

This study confirmed that women with cardiac disease are at increased risk of preterm birth, and high acuity in the peripartum period but otherwise good maternal and perinatal outcomes. An integrated multidisciplinary perinatal cardiac service can optimise perinatal outcomes in these women.
Retail‐bank efficiency: Nonstandard goals and environmental determinants
Authors: Burgstaller Johann
Published: April 2020

This paper analyzes technical and scale efficiency of Austrian savings and cooperative banks. Non‐profit objectives are also considered with respect to input–output choice, which contributes to adequate performance measurements for alternative banks. Efficiency score estimates obtained via Data Envelopment Analysis (DEA) reveal considerable potential for improvement in terms of intermediation efficiency. Several environmental determinants prove significant, but the cumulative predictive content of exogenous factors is rather modest. Bank efficiency improves in both underdeveloped and prosperous markets, while increased rival size and distance appear to be detriments to efficiency. A concluding discussion of confounding factors reveals the managerial, stakeholder, and policy implications of the results.
Native parasitic plants: Biological control for plant invasions?
Authors: Těšitel Jakub , Cirocco Robert M , Facelli José M , Watling Jennifer R
Published: April 2020

Plant invasions cause biodiversity loss and degradation in ecosystems worldwide. The invasive species involved may be introduced, or native invaders, and controlling them is a major global challenge. Here, we highlight an emerging role for native parasitic plants in suppressing invasive species, thus aiding in restoration of affected habitats. Compelling empirical evidence is provided by three study systems located in Central Europe, southern Australia and eastern China. Further cases of parasitism of invasive plants have been recorded across five continents. We propose including the interactions between parasitic and invasive plants into the theoretical framework of the biotic resistance hypothesis concerning generalist interactions between invaders and native biota. Among parasitic plants, numerous root hemiparasites, mistletoes and parasitic vines show low host specificity and exert substantial negative effects on their hosts. These parasitic plants may interfere with key traits of invaders such as symbiotic nitrogen fixation or clonal propagation which provide them with competitive advantage over native species. We contend that some parasitic plants may present a cost‐effective environmentally sustainable component of invasion management schemes. Therefore, we encourage exploration of this potential and the development of methods for practical applications in ecological restoration and nature conservation.
Bridging the Gap between Clinical Practice and Research Part I: Findings of a Pilot Study on Daniel Stern's ‘Moments of Meeting’ from the UKCP's Practitioner Research Network
Authors: Harris Tirril , Lepper Georgia , Cheetham Brian , Crowther Catherine , King Desmond , Ryde Julia
Published: April 2020

Psychotherapists continue to be wary of researchers who enter the clinical domain and their methodologies, which can seem opaque and alien to clinical practice. The following is a report on a pilot project, supported and enabled through the Practice Research Network of the UK Council for Psychotherapy (UKCP), to explore whether adopting the role of researcher on the therapy process, using their own clients, could help to dissipate this discomfort. Findings were anticipated concerning two groups of issues. First, we sought to examine whether, and how, a ‘moment of meeting’ (MoM) might impact on the therapy, and its outcomes. Second, whether, and how, undertaking the role of researcher with one's own clients might affect clinical practice, and how systematic reflection on observations from clinical practice might provide rich evidence in the development of the MoM concept. We report on two broad issues arising from the project. First, using the data collected by the research team in a mixed method study of their own cases, we examine the relationship of the process variable MoM to clinical outcome. Relationships between other process variables were also investigated, using both established measures and a new, post‐therapy interview developed by the team during the project. Second we explore the experience of the participant clinicians undertaking research on their own, and their colleagues’, clinical practice. Finally we consider the learning taken from this pilot project, making recommendations for taking our experience of clinician–research collaboration further.
Insights into the functional aspects of poly(ADP‐ribose) polymerase‐1 (PARP‐1) in mitochondrial homeostasis in Dictyostelium discoideum
Authors: Kadam Ashlesha , Jubin Tina , Roychowdhury Rittwika , Garg Abhishek , Parmar Nishant , Palit Sayantani Pramanik , Begum Rasheedunnisa
Published: April 2020

Background information

Poly(ADP‐ribose) Polymerase‐1 (PARP‐1) is predominantly a nuclear protein and involved in various cellular processes like DNA repair, cell death, development, chromatin modulation etc. PARP‐1 utilizes NAD+ and adds negatively charged PAR moieties on the target proteins. Over‐activation of PARP‐1 has been shown to cause energy crisis mediated cell death in which mitochondrial homeostasis is also affected. Moreover, the presence of mitochondrial NAD+ pools highlights the role of PARP‐1 in mitochondria. The aim of present study is to understand the physiological role of PARP‐1 in regulating mitochondrial functioning by varying the levels of PARP‐1 in Dictyostelium discoideum. Intra‐mitochondrial PARylation was analyzed by indirect immunofluorescence. Further, the effect of altered levels of PARP‐1 i.e. overexpression, downregulation, knockout and its chemical inhibition was studied on mitochondrial respiration, reactive oxygen species (ROS) levels, ATP production, mitochondrial fission‐fusion, mitochondrial morphology and mitochondrial DNA (mtDNA) content of D. discoideum.

Results

Our results show intra‐mitochondrial PARylation under oxidative stress. Altered levels of PARP‐1 caused impairment in the mitochondrial respiratory capacity, leading to elevated ROS levels and reduced ATP production. Moreover, PARP‐1 affects the mitochondrial morphology and mtDNA content, alters the mitochondrial fission‐fusion processes in lieu of preventing cell death under physiological conditions.

Conclusion

The current study highlights the physiological role of PARP‐1 in mitochondrial respiration, its morphology, fission‐fusion processes and mtDNA maintenance in D. discoideum.

Significance

This study would provide new clues on the PARP‐1's crucial role in mitochondrial homeostasis, exploring the therapeutic potential of PARP‐1 in various mitochondrial diseases.
Edematous myositis: a clinical presentation first suggesting dermatomyositis diagnosis
Authors: Duchesne Mathilde , Leonard‐Louis Sarah , Landon‐Cardinal Océane , Anquetil Céline , Mariampillai Kuberaka , Monzani Quentin , Benveniste Olivier , Allenbach Yves
Published: April 2020

Aims: Edema of the limbs is uncommon in idiopathic inflammatory myopathies (IIM). The few reported cases have been associated with severe and refractory dermatomyositis (DM), sometimes in association with cancers. We aimed to determine if edematous myositis is a homogeneous subtype based on clinical, serological and pathological features. Methods: This is a retrospective observational study performed between 2008 and 2015 in the French national referral center for myositis. All adult patients with an inflammatory muscle biopsy and upper limbs edema were included as well as IIM cases without limb edema as controls. Clinical, biological and pathological features were collected. Results: Seventeen edematous myositis were included and compared to 174 IIM without edema, including 50 DM controls. Edema was the first manifestation in 23% of patients. Muscle weakness was severe and symmetric, 71% of patients presented dysphagia and a restrictive ventilatory pattern was found in 40%. Fifty‐two percent of patients had a typical DM skin rash and 23% had cancer within 3 years of diagnosing myositis. Fifty‐three percent of patients presented a myositis specific antibody and only DM‐specific antibodies were detected. Classic pathological DM features (perifascicular atrophy, perifascicular/perimysial perivascular inflammation) were uncommon but capillary C5b‐9 deposition and MxA expression were seen in 79% and 73% of cases, respectively. A perimysial edema was found in 82% of cases. Seventeen percent of patients died (median follow up of 18 months). Edematous myositis demonstrated more marked capillary C5b‐9 deposition compared to IIM controls. There was no clinical, biological or pathological difference with DM controls except for limb edema. Conclusion: Our study underlines that limb edema could be a symptom of IIM and that edematous myositis are mostly DM. The vasculopathy seems to play a key role in its pathophysiology. Limb edema associated with muscle impairment should suggest the diagnosis of DM in clinical settings.
Budget impact analysis of treatment‐free remission in nilotinib‐treated Japanese chronic myeloid leukemia patients
Authors: Yamazaki Kiyotaka , Inagaki Naohito , Moldaver Daniel , Viana Ricardo , Kimura Shinya
Published: April 2020

Treatment‐free remission (TFR), in which patients discontinue pharmacotherapy and remain in molecular remission, is an emerging treatment goal for patients with chronic myeloid leukemia (CML). Attainment of TFR requires an increased frequency of molecular monitoring, to ensure that patients maintain a deep molecular response. The objective of this analysis was to assess the economic impact of stopping nilotinib among Japanese TFR‐eligible patients. A Markov model evaluated the economic impact of TFR among the study population, TFR‐eligible CML patients diagnosed since 2012. The model compared patients who had discontinued tyrosine kinase inhibitor (TKI) treatment (ie, attempted TFR) with patients that continued TKI treatment. A 3‐y time horizon was modeled from a Japanese public payer perspective. Costs associated with drug treatment, hospital/physician visits, and molecular monitoring were considered. TFR‐eligible patients were calculated from Japanese CML incidence rates and efficacy was derived from nilotinib trials. Japanese co‐payment maximums were utilized to assess the patient perspective. An estimated 761 and 140 patients were eligible for first‐ and second‐line nilotinib, respectively, in 2019. Assuming that 100% of eligible patients complied, TFR was associated with cost savings of ¥7 625 174 640 (US$66 567 775) over 3 y. In scenarios with reduced willingness to attempt TFR, cost savings persisted. Achievement of TFR was estimated to markedly reduce out‐of‐pocket expenses for CML patients, regardless of the timing of relapse. Stopping nilotinib for TFR‐eligible patients in Japan may result in significant cost savings to both payers and patients. Monitoring costs contributed little to overall annual costs and decreased over time.
Obesity predicts persistence of resistant hypertension after surgery in patients with primary aldosteronism
Authors: Nakamaru Ryo , Yamamoto Koichi , Rakugi Hiromi , Akasaka Hiroshi , Kurihara Isao , Ichijo Takamasa , Takeda Yoshiyu , Katabami Takuyuki , Tsuiki Mika , Wada Norio , Ogawa Yoshihiro , Kawashima Junji , Sone Masakatsu , Yoshimoto Takanobu , Okamoto Ryuji , Fujita Megumi , Kobayashi Hiroki , Tamura Kouichi , Kamemura Kohei , Okamura Shintaro , Kakutani Miki , Tanabe Akiyo , Naruse Mitsuhide ,   JPAS/JRAS Study Group
Published: April 2020

Objective

Primary aldosteronism (PA) is considered a major cause of resistant hypertension (RHT). The prevalence of RHT has been recently reported to reach 18% in general hypertension. However, little is known about the prevalence and the outcomes after adrenalectomy of RHT in PA. Therefore, we aimed to clarify the prevalence and surgical outcomes in patients with both PA and RHT.

Patients and Design

Among 550 patients who underwent adrenalectomy for unilateral PA in the Japan PA Study, RHT was defined as an uncontrolled blood pressure (≥140/90 mm Hg) despite treatment with at least any three antihypertensives or hypertension controlled with at least four drugs. Surgical outcome was assessed by the biochemical and clinical outcome.

Results

Although 40 (7.3%) patients fulfilled the criteria for preoperative RHT, this should be underestimated because only 36% of patients with postoperative RHT were classified as having preoperative RHT. The prevalence of preoperative RHT was approximately 20% when estimated using the total number of patients with postoperative RHT and the ratio of postoperative RHT in patients with preoperative RHT. Although an improvement in hypertension was achieved in approximately 80% of patients with preoperative RHT, 20% of these exhibited persistent RHT. These patients were more obese than those for whom RHT improved after surgery. Notably, body mass index of ≥25 kg/m2 was an independent predictor of postoperative RHT.

Conclusions

The prevalence of RHT in PA was lower than expected even with the adjustment for underestimation. Furthermore, obesity is an independent factor predicting the postoperative persistence of RHT.
ADAMTS19‐associated heart valve defects: Novel genetic variants consolidating a recognizable cardiac phenotype
Authors: Massadeh Salam , Alhashem Amal , van de Laar Ingrid M.B.H. , Alhabshan Fahad , Ordonez Natalia , Alawbathani Salem , Khan Suliman , Kabbani Mohamed S. , Chaikhouni Farah , Sheereen Atia , Almohammed Iman , Alghamdi Bader , Frohn‐Mulder Ingrid , Ahmad Salim , Beetz Christian , Bauer Peter , Wessels Marja W. , Alaamery Manal , Bertoli‐Avella Aida M.
Published: April 2020

Recently, ADAMTS19 was identified as a novel causative gene for autosomal recessive heart valve disease (HVD), affecting mainly the aortic and pulmonary valves. Exome sequencing and data repository (CentoMD) analyses were performed to identify patients with ADAMTS19 variants (two families). A third family was recognized based on cardiac phenotypic similarities and SNP array homozygosity. Three novel loss of function (LoF) variants were identified in six patients from three families. Clinically, all patients presented anomalies of the aortic/pulmonary valves, which included thickening of valve leaflets, stenosis and insufficiency. Three patients had (recurrent) subaortic membrane, suggesting that ADAMTS19 is the first gene identified related to discrete subaortic stenosis. One case presented a bi‐commissural pulmonary valve. All patients displayed some degree of atrioventricular valve insufficiency. Other cardiac anomalies included atrial/ventricular septal defects, persistent ductus arteriosus, and mild dilated ascending aorta. Our findings confirm that biallelic LoF variants in ADAMTS19 are causative of a specific and recognizable cardiac phenotype. We recommend considering ADAMTS19 genetic testing in all patients with multiple semilunar valve abnormalities, particularly in the presence of subaortic membrane. ADAMTS19 screening in patients with semilunar valve abnormalities is needed to estimate the frequency of the HVD related phenotype, which might be not so rare.
Emerging illegal wildlife trade issues: A global horizon scan
Authors: Esmail Nafeesa , Wintle Bonnie C. , t Sas‐Rolfes Michael , Athanas Andrea , Beale Colin M. , Bending Zara , Dai Ran , Fabinyi Michael , Gluszek Sarah , Haenlein Cathy , Harrington Lauren A. , Hinsley Amy , Kariuki Kennedy , Lam Jack , Markus Matthew , Paudel Kumar , Shukhova Sofiya , Sutherland William J. , Verissimo Diogo , Wang Yifu , Waugh John , Wetton Jon H. , Workman Catherine , Wright Joss , Milner‐Gulland Eleanor J.
Published: April 2020

Illegal wildlife trade is gaining prominence as a threat to biodiversity, but addressing it remains challenging. To help inform proactive policy responses in the face of uncertainty, in 2018 we conducted a horizon scan of significant emerging issues. We built upon existing iterative horizon scanning methods, using an open and global participatory approach to evaluate and rank issues from a diverse range of sources. Prioritized issues related to three themes: developments in biological, information, and financial technologies; changing trends in demand and information; and socioeconomic, geopolitical shifts and influences. The issues covered areas ranging from changing demographic and economic factors to innovations in technology and communications that affect illegal wildlife trade markets globally; the top three issues related to China, illustrating its vital role in tackling emerging threats. This analysis can support national governments, international bodies, researchers, and nongovernmental organizations as they develop strategies for addressing the illegal wildlife trade.
Litigation risk and firm performance: The effect of internal and external corporate governance
Authors: Wu Wuqing , Peng Fei , Shan Yuan George , Zhang Lu
Published: April 2020

Research Question/Issue

We argue that findings regarding litigation risk in the United States are not applicable in the Chinese context because Chinese firms are more dependent on debt financing for their operations compared with US firms. Thus, we raise the following research questions to test potential differences: Is litigation risk associated with firm performance? Does effective internal control of governance improve the performance of lawsuit firms? Do financial analysts improve the performance of lawsuit firms? Does debt financing mediate the effect of litigation risk on firm performance?

Research Findings/Insights

Our results indicate that litigation claims for large monetary amounts are negatively associated with firm performance, whereas internal governance and analyst following moderate the negative effects of litigation risk. We further examine the mediating effect of debt financing on the relationship between litigation risk and firm performance, finding that litigation risk is negatively associated with firm performance through excessive leverage, increased cost of debt, reduced bank borrowing, and trade credit.

Theoretical/Academic Implications

By empirically testing the mediation effect of debt financing, this study enhances the understanding of the underlying causes of the association between a firm's litigation risk and its performance.

Practitioner/Policy Implications

The findings will help firm managers to review litigation risks, better understand the economic mechanisms of litigation risk, and promote risk control to regulate their behaviors. We also find that financial analysts can correct the adverse effects of litigation risk; thus, we recommend that the financial analyst profession be further normalized.
Population Pharmacokinetics of Metoclopramide in Infants, Children, and Adolescents
Authors: Ge Shufan , Mendley Susan R. , Gerhart Jacqueline G. , Melloni Chiara , Hornik Christoph P. , Sullivan Janice E. , Atz Andrew , Delmore Paula , Tremoulet Adriana , Harper Barrie , Payne Elizabeth , Lin Susan , Erinjeri Jinson , Cohen‐Wolkowiez Michael , Gonzalez Daniel ,   Best Pharmaceuticals for Children Act – Pediatric Trials Network Steering Committee
Published: April 2020

Metoclopramide is commonly used for gastroesophageal reflux. The aims of the present study were to develop a pediatric population pharmacokinetic (PopPK) model, which was applied to simulate the metoclopramide exposure following dosing used in clinical practice. Opportunistic pharmacokinetic data were collected from pediatric patients receiving enteral or parenteral metoclopramide per standard of care and these data were simultaneously fitted using NONMEM. Allometric scaling with body weight was included a priori in the model. Using the final model, the steady‐state maximum concentrations (Css,max) and the area under the metoclopramide plasma concentration‐time curve at steady state from 0 to 6 hours (AUCss,0–6h) were simulated following 0.1 or 0.15 mg/kg orally every 6 hours in virtual patients, and compared with previously reported ranges associated with toxicity or the efficacy for gastroesophageal reflux in infants. A two‐compartment model with first‐order absorption best characterized 87 concentration measurements from 50 patients (median [range] postnatal age of 8.89 years [0.01–19.13]). There were 20 infants (≤ 2 years), 9 children (2 years to age ≤ 12 years), and 21 adolescents (> 12 years). Body weight was the only covariate included in the final model. For > 75% of virtual patients, simulated Css,max and AUCss,0–6h estimates were within the range associated with efficacy for gastroesophageal reflux in infants; however, slightly lower exposures were predicted in virtual patients < 2 years. Our study suggests that a metoclopramide enteral dose of 0.1 mg/kg every 6 hours, which was previously recommended for pediatric patients, results in simulated exposure generally within suggested ranges for the treatment of gastroesophageal reflux.
The intergenerational transmission of mathematics achievement in middle childhood: A prospective adoption design
Authors: Borriello Giulia A. , Ramos Amanda M. , Natsuaki Misaki N. , Reiss David , Shaw Daniel S. , Leve Leslie D. , Neiderhiser Jenae M.
Published: April 2020

The present study uses a parent–offspring adoption design to examine the dual roles of heritable and environmental influences on children's mathematics achievement. Linked sets (N = 195) of adopted children, adoptive parents, and birth parents each completed a measure of mathematics fluency (i.e., simple computational operations). Birth parent mathematics achievement and adoptive father mathematics achievement positively correlated with child achievement scores at age 7, whereas adoptive mother and adopted child mathematics achievement scores were not significantly associated with one another. Additionally, findings demonstrated no significant effects of gene–environment interactions on child mathematics achievement at age 7. These results indicate that both heritable and rearing environmental factors contribute to children's mathematics achievement and identify unique influences of the paternal rearing environment on mathematics achievement in middle childhood.
Endoscopic stenting for colorectal cancer obstruction as a bridge‐to‐surgery strategy
Authors: Lovero Rosa , Losurdo Giuseppe , La Fortezza Rosa Federica , Spirito Fulvio , Di Leo Alfredo , Andriulli Angelo , Gentile Marco
Published: April 2020

Background

Acute obstructive colorectal cancer requires prompt decompression commonly by emergency surgery (ES). However, self‐expanding metal stents (SEMS) have been increasingly used as a bridge‐to‐surgery (BTS) strategy.

Materials and methods

In an 8‐year period, consecutive patients with acute left‐sided colonic obstruction, due to locally advanced colorectal cancer, underwent ES or SEMS implantation. We evaluated technical/clinical success of SEMS, adverse events, and overall (OS) and disease‐free survival (DFS) of the two therapeutic options.

Results

Forty‐five patients underwent ES (n = 23) or SEMS (n = 22). The two groups were comparable for sex, age, ASA score and cancer site/stage. Technical and clinical successes of SEMS were 100% and 72.7%, respectively. Clinical success correlated with neutrophil‐lymphocyte ratio (NLR) at baseline (OR = 0.65, 95% CI 0.43‐0.98, P = .04). SEMS allowed primary anastomosis in the 45.5% of cases (0% in ES). SEMS implantation allowed a higher rate of surgery carried out by a laparoscopic approach: 36.4% vs 13.0% in ES. Performance of a definitive stoma and complications were similar. Median OS (34 in SEMS; 45 in ES, P = .33) and DFS (36 in SEMS; 35 in ES, P = .35) did not differ between the two groups. At univariate analysis, DFS was positively associated with primary anastomosis (HR = 2.44, 95% CI 1.4‐16.6, P = .04) and laparoscopic surgery (HR = 8.33, 95% CI 1.08‐50, P = .04), and inversely associated with a NLR > 3.6 (HR = 0.59, 95% CI 0.16‐0.92, P = .03). At multivariate analysis, no feature retained an independent predictive power.

Conclusion

SEMS is an effective and safe procedure, equivalent to emergency surgery in terms of complications, OS and DFS, providing the chance of a primary anastomosis in the majority of patients.
Cold adaptation across the elevation gradient in an alpine butterfly species complex
Authors: Nève Gabriel , Després Laurence
Published: April 2020

1. Temperature acts as a major factor on the timing of activity and behaviour in butterflies, and it might represent a key driver of butterfly diversification along elevation gradients. Under this hypothesis, local adaptation should be found along the elevation gradient, with butterflies from high elevation populations able to remain active at lower ambient temperature than those from low elevation.

2. The warming‐up rate and the thoracic temperature at take‐off of 123 individuals of the Alpine butterfly species complexCoenonympha arcania – C. macromma – C. gardettawere recorded in controlled conditions.

3. Warming‐up rate increased with elevation inC. arcania: high‐elevation males ofC. arcaniawere able to warm up more quickly compared to low‐elevation ones.

4. High‐elevationC. gardettahad a darker underwing pattern than low‐elevation ones. This high‐elevation species was significantly smaller (lower weight and wing surface) than the two other species and had a faster warming‐up rate.

5. This study's results suggest that the ability to warm up quickly and to take flight at a high body temperature evolved adaptively in the high‐altitudeC. gardettaand that low temperature at high altitude may explain the absence ofC. arcania, while the hybrid nature ofC. macrommais probably the explanation of its elevation overlap with both the other species and its local replacement ofC. gardetta.
A multi‐trait, field‐based examination of personality in a semi‐aquatic turtle
Authors: Roth Timothy C. , Rosier Maxwell , Krochmal Aaron R. , Clark Lisa
Published: April 2020

Studies documenting and quantifying personality traits are common in animal behavior. Such studies often consider the nature of individual variation and personality as correlated with a variety of natural history, physiological, or ecological traits, and therefore consider the importance of personality for strategies in wild systems. Though such studies have contributed markedly to our understanding of the important aspects of personality that may covary with a variety of factors that might affect fitness, much of the research on animal personalities is taxonomically limited. To supplement and compliment the laboratory study of reptile personality, we examined the patterns of multiple personality traits in wild Eastern painted turtles (Chrysemys picta) in the field. We examined patterns of aggression, sociability, and boldness across these traits in different contexts in 103 adult, wild‐caught turtles. We found strong correlations both within and among the focal behavioral axes, representing robust evidence for personality in this species. Specifically, we found strong relationships among many measures of aggression, as well as relationships between aggression and our measures of boldness. Finally, we note a tendency for sociability in our turtles, with animals scoring high on sociability showing lower tendency toward aggression. Overall, our study provides robust evidence for correlated suites of behavioral traits, or personality, in a semi‐aquatic turtle surveyed in the wild. Future work should continue to expand the range of traits examined to more fully consider the ecological consequences of variation in personality in this and similar species.
What's in a Family? Family Conceptualizations of Flemish College‐Aged Students (1997–2018)
Authors: De Coninck David , Matthijs Koen , Dekeyser Graziela
Published: April 2020

Objective

Inspired by previous research, we investigated how perceptions about family have changed among first‐year university students at KU Leuven (Flanders, Belgium) between 1997 and 2018.

Background

The question of what constitutes a family has puzzled scholars for years, yet empirical information on this topic, especially from young adults, is limited. The perceptions are important because studies have found a link between perceptions about families and family behavior.

Method

We collected a convenience sample of first‐year university students at KU Leuven in 1997 (n = 674) and 2018 (n = 471) via online and offline questionnaires. Using cross‐tabulation analysis, we compared the data to consider changes in perceptions about families and investigate differences.

Discussion

We found that students in 2018 are more receptive to postdivorce arrangements, pets, and deceased family members in their conceptualizations of family. Also, we noted that the conceptualization of families including friends was not widespread, indicating that the “framily” is not yet established among the university students in this group. We found that women, students who report their parents as having a lower socioeconomic status, and students from nonintact families held more inclusive family views.

Implications

Our findings contribute to a better understanding of how Flemish college‐age students perceive families. This information, however limited, can provide valuable information for policymakers, opinion leaders, and (family) therapists.
Omics‐derived hepatocellular carcinoma risk biomarkers for precision care of chronic liver diseases
Authors: Fujiwara Naoto , Qian Tongqi , Koneru Bhuvaneswari , Hoshida Yujin
Published: April 2020

Precise hepatocellular carcinoma (HCC) risk prediction will play increasingly important roles with the contemporary HCC etiologies, that is, non‐alcoholic fatty liver disease and resolved hepatitis C virus infection. Because the HCC incidence rate in this emerging patient population is relatively low (~1% per year), identification of a subset of patients at the highest risk is critical to concentrate the effort and resources of regular HCC screening to those who most need it. Omics profiling has been derived using several candidate HCC risk biomarkers, which could refine HCC screening by enabling individual risk‐based personalized or risk‐stratified patient management. Various types of biomolecules have been explored as sources of information to predict HCC risk at various time horizons. Germline DNA polymorphisms likely reflect race/ethnicity‐ and/or etiology‐specific susceptibility to HCC development or chronic liver disease progression toward carcinogenesis. Transcriptomic dysregulations in the diseased liver capture functional molecular status supporting oncogenesis such as inflammatory pathway and myofibroblast activation. Circulating nucleic acids, proteins, and metabolites could serve as less‐invasive measures of molecular HCC risk. Characterization of gut microbiota could also inform HCC risk estimation. Each biomarker could have its niche of clinical application depending on logistics of use, performance, and costs with a goal to eventually improve patient prognosis as a part of the whole algorithm of chronic liver disease management.
Eriodictyonangustifolium extract, but not Eriodictyon californicum extract, reduces human hair greying
Authors: Taguchi N. , Hata T. , Kamiya E. , Homma T. , Kobayashi A. , Aoki H. , Kunisada T.
Published: April 2020

Objective

Yerba Santa (Eriodictyon angustifolium and Eriodictyon californicum) has been used for many years in traditional medicine. However, the effect of Yerba Santa on melanogenesis has not yet been investigated. We aimed to assess the biological effects of Yerba Santa on hair pigmentation.

Methods

Yerba Santa extracts were assessed for their cytological effects following X‐ray irradiation treatment and then tested directly for the prevention of human hair greying. Ultra‐performance liquid chromatography (UPLC) was utilized to identify the individual extract components.

Results

Eriodictyon angustifolium extract significantly increased melanin synthesis in the melanoma cell line through activation of the WNT/MITF/tyrosinase‐signalling pathway. In contrast, E. californicum had no effect on melanin synthesis. E. angustifolium extract also demonstrated a protective effect against the damage induced by X‐ray irradiation in human keratinocytes. Application of the extracts to subjects who had grey beards demonstrated a reduced number of grey beard hair per year specifically with the E. angustifolium extract. A significant decrease in grey head hair was also observed after application of E. angustifolium extract. Upregulation of gene expression related to melanin production and WNT signalling was observed after the application of E. angustifolium extract. Sterubin was the most abundant flavonoid detected by UPLC in E. angustifolium extract. In addition, sterubin showed the highest difference in terms of quantity, between E. angustifolium and E. californicum extract.

Conclusion

Eriodictyon angustifolium extract, which is abundant in sterubin, may be suitable as a potential cosmetic and medical agent for the prevention and improvement of hair greying.
Warfarin vs non‐vitamin K oral anticoagulants for left atrial appendage thrombus: A meta‐analysis
Authors: Murtaza Ghulam , Turagam Mohit K. , Atti Varunsiri , Garg Jalaj , Boda Urooge , Velagapudi Poonam , Akella Krishna , Natale Andrea , Gopinathannair Rakesh , Lakkireddy Dhanunjaya
Published: April 2020

Introduction

Novel oral anticoagulants (NOACs) are commonly used for thromboembolic risk reduction and treatment of pulmonary embolism and deep venous thrombosis. However, data regarding their efficacy and safety in comparison to warfarin for left atrial appendage thrombus is limited.

Methods

A comprehensive literature search in PubMed, Google Scholar, and Cochrane Review from inception to 30 October 2019 was performed. Studies reporting clinical outcomes comparing warfarin vs NOACs were included. Two investigators independently extracted the data and individual quality assessment was performed. A meta‐analysis was performed using random‐effects model to calculate risk ratio (RR) and 95% confidence interval (CI). The analysis was performed using RevMan 5.3.

Results

Four studies met inclusion criteria and a total of 322 patients were included of whom 141 were in the NOAC arm and 181 were in the warfarin arm. There was no significant difference in thrombus resolution between the two groups (RR, 1.00; 95% CI [0.77‐1.29; P = .98]). There was no significant difference in major bleeding (RR, 1.30; 95% CI [0.14‐12.21; P = .82]) or stroke (RR, 0.42; 95% CI [0.09‐2.06; P = .29]) between the two groups.

Conclusion

The results of our meta‐analysis show that NOACs are as efficacious and safe as warfarin in the treatment of left atrial appendage thrombus in patients with non‐valvular atrial fibrillation.
Esophageal injury associated with catheter ablation for atrial fibrillation: Determinants of risk and protective strategies
Authors: Assis Fabrizio R. , Shah Rushil , Narasimhan Bharat , Ambadipudi Sravya , Bhambhani Hrithika , Catanzaro John N. , Calkins Hugh , Tandri Harikrishna
Published: April 2020

Catheter ablation has become an important element in the management of atrial fibrillation. Several technical advances allowed for better safety profiles and lower recurrence rates, leading to an increasing number of ablations worldwide. Despite that, major complications are still reported, and esophageal thermal injury remains a significant concern as atrioesophageal fistula (AEF) is often fatal. Recognition of the mechanisms involved in the process of esophageal lesion formation and the identification of the main determinants of risk have set the grounds for the development and improvement of different esophageal protective strategies. More sensitive esophageal temperature monitoring, safer ablation parameters and catheters, and different energy sources appear to collectively reduce the risk of esophageal thermal injury. Adjunctive measures such as the prophylactic use of proton‐pump inhibitors, as well as esophageal cooling or deviation devices, have emerged as complementary methods with variable but promising results. Nevertheless, as a multifactorial problem, no single esophageal protective measure has proven to be sufficiently effective to eliminate the risk, and further investigation is still warranted. Early screening in the patients at risk and prompt intervention in the cases of AEF are important risk modifiers and yield better outcomes.
Tissue‐selective regulation of protein homeostasis and unfolded protein response signalling in sporadic ALS
Authors: Montibeller Luigi , Tan Li Yi , Kim Joo Kyung , Paul Praveen , de Belleroche Jacqueline
Published: April 2020

Amyotrophic lateral sclerosis (ALS) is a disorder that affects motor neurons in motor cortex and spinal cord, and the degeneration of both neuronal populations is a critical feature of the disease. Abnormalities in protein homeostasis (proteostasis) are well established in ALS. However, they have been investigated mostly in spinal cord but less so in motor cortex. Herein, we monitored the unfolded protein (UPR) and heat shock response (HSR), two major proteostasis regulatory pathways, in human post‐mortem tissue derived from the motor cortex of sporadic ALS (SALS) and compared them to those occurring in spinal cord. Although the UPR was activated in both tissues, specific expression of select UPR target genes, such as PDIs, was observed in motor cortex of SALS cases strongly correlating with oligodendrocyte markers. Moreover, we found that endoplasmic reticulum‐associated degradation (ERAD) and HSR genes, which were activated predominately in spinal cord, correlated with the expression of neuronal markers. Our results indicate that proteostasis is strongly and selectively activated in SALS motor cortex and spinal cord where subsets of these genes are associated with specific cell type. This study expands our understanding of convergent molecular mechanisms occurring in motor cortex and spinal cord and highlights cell type–specific contributions.