bluuebunny/crossref_metadata_2025 huggingface dataset:
Neural and behavioral measures suggest that cognitive and affective functioning interactions mediate risk for psychosis‐proneness symptoms in youth with chromosome 22q11.2 deletion syndrome
Authors: Linton Samantha R. , Popa Abbie M. , Luck Steven J. , Bolden Khalima , Carter Cameron S. , Niendam Tara A. , Simon Tony J.
Published: April 2020

Behavioral components of chromosome 22q11.2 deletion syndrome (22q), caused by the most common human microdeletion, include cognitive and adaptive functioning impairments, heightened anxiety, and an elevated risk of schizophrenia. We investigated how interactions between executive function and the largely overlooked factor of emotion regulation might relate to the incidence of symptoms of psychotic thinking in youth with 22q. We measured neural activity with event‐related potentials (ERPs) in variants of an inhibitory function (Go/No‐Go) experimental paradigm that presented affective or non‐affective stimuli. The study replicated inhibition impairments in the 22q group that were amplified in the presence of stimuli with negative, more than positive affective salience. Importantly, the anterior N2 conflict monitoring ERP significantly increased when youth with 22q viewed angry and happy facial expressions, unlike the typically developing participants. This suggests that youth with 22q may require greater conflict monitoring resources when controlling their behavior in response to highly salient social signals. This evidence of both behavioral and neurophysiological differences in affectively influenced inhibitory function suggests that frequently anxious youth with 22q may struggle more with cognitive control in emotionally charged social settings, which could influence their risk of developing symptoms of psychosis.
Complementary approach for analysis of phospholipids by liquid chromatography hyphenated to elemental and molecular mass spectrometry
Authors: Vosse Christian , Thyssen Georgina M. , Sperling Michael , Karst Uwe , Hayen Heiko
Published: April 2020

Phospholipids are one of the most important lipid categories with multiple functions in biological systems. Their analysis can contribute to a better understanding of metabolomic and kinetic processes in living cells. Comprehensive methods based on liquid chromatography coupled to mass spectrometry are available for phospholipid identification and quantification. However, quantification of phospholipids using electrospray ionization‐mass spectrometry with internal standards is still challenging due to several reasons. In particular, the detector response of phospholipid species differs with variation of the head group as well as the fatty acid chain length and double bond number. Inductively coupled plasma‐tandem mass spectrometry (ICP‐MS/MS) provides an alternative approach for their absolute quantification with universal detector response for phosphorus independent of its chemical form and proportional to its quantity. Therefore, a quantification method based on compound‐independent calibration using hydrophilic interaction liquid chromatography (HILIC) coupled to ICP‐MS/MS was developed. An inverse gradient system was implemented for constant mobile phase composition after HILIC separation, which provides steady plasma ionization conditions. Isobaric phosphorus interferences were decreased by using the oxygen reaction mode of the triple quadrupole based ICP‐MS/MS instrument. Complementary molecular information was obtained by ESI‐high‐resolution MS and MS/MS. The applicability of this approach was demonstrated in a proof of concept by complementary analysis of a total lipid extract of baker's yeast.
Experimental study and modelling of effective parameters on removal of Cd(II) from water by halloysite/graphene quantum dots magnetic nanocomposite as an adsorbent using response surface methodology
Authors: Zare Pirhaji Jamileh , Moeinpour Farid , Mirhoseini Dehabadi Abolghasem , Yasini Ardakani Seyed Ali
Published: April 2020

Graphene quantum dots (GQDs) were covalently immobilized onto the NiFe2O4‐halloysite nanotubes (NiFe2O4‐HNTs) surface to fabricate a nanocomposite material utilized as an active adsorbent to eliminate Cd(II) ions from water. NiFe2O4 nanoparticles were synthesized and simultaneously deposited on HNTs. Then, the material surface was coated by APTES (aminopropyltriethoxysilane) to cause GQDs be connected to the external layer via an amide bond. The prepared nanomaterial structure was identified by TEM, XRD, FT‐IR, BET isotherm, EDS analysis and VSM (vibrating sample magnetometry). Box–Behnken design incorporated with response surface method (RSM) was utilized to find out the impact of pH, time, initial concentration of Cd(II) and adsorbent dose on cadmium removal. Study discovered that adsorption operation is the quasi‐second‐order kinetic model and adapted more precisely with Langmuir adsorption model. The Langmuir highest uptake capacity of 34.72 mg/g at 298 K was acquired. The Elovich model recommended that the process is a kind of chemisorption. The calculated thermodynamic variables verified that the uptake process is endothermic and spontaneous. Additionally, the adsorbent can be simply separated with the aid of a magnet. In this study, we have suggested a practical method for the synthesis of the NiFe2O4/halloysite nanotubes/graphene quantum dots magnetic nanoparticles for cadmium removal from water.
From brittle‐to‐ductile fracture of polymer composites: The incorporation of energy dissipation mechanisms by carbon nanotubes‐based multilayered interface
Authors: Fioravante André , de Oliveira Paula Campos , Siqueira Eder José , Vitorino Luísa Sá , Brito Pedro Paiva , Oréfice Rodrigo Lambert , Isaac Augusta
Published: April 2020

Interfaces can have a great influence on the behavior and properties of polymer composites. In this work, the versatile and low‐cost layer‐by‐layer technique was used for depositing layers of poly(diallyldimethylammonium chloride) (PDDA) and poly(sodium 4‐styrenesulfonate) (PSS) containing oxidized multiwalled carbon nanotubes (MWCNT‐COOH) on the surface of woven glass fibers (GFs); and polypropylene composites containing the modified GFs were prepared by compression molding. The effect of this novel hybrid multilayered interface on the mechanical properties and fracture behavior of the GF reinforced polymer (GFRP) composites was systematically investigated. For that, in situ tensile tests of the composites were monitored by using the high‐resolution phase‐contrast tomography. We found that the GFRP composites with multilayered interface (GFRP multilayered) exhibited exceptional increase in ductility and fracture toughness (about 25 and 130%, respectively), when compared to the composites without interfacial modification (GFRP untreated). Whereas the failure characteristics of the GFRP‐untreated composites were typical of fragile systems (mainly, delamination), the GFRP‐multilayered exhibited additional toughening mechanisms such as crazing and fibrillation as result of the enhanced interfacial adhesion. Our results clearly indicate that the multilayered interface of PDDA/PSS/MWCNT‐COOH led to a more efficient load transfer from the matrix to the GFs, culminating with the brittle‐to‐ductile transition in the failure mode.
Synthesis, anti‐inflammatory activity, and molecular docking studies of some novel Mannich bases of the 1,3,4‐oxadiazole‐2(3H)‐thione scaffold
Authors: Ozyazici Tugce , Gurdal Enise E. , Orak Duygu , Sipahi Hande , Ercetin Tuba , Gulcan Hayrettin O. , Koksal Meric
Published: April 2020

A series of novel ibuprofen and salicylic acid‐based 3,5‐disubstituted‐1,3,4‐oxadiazole‐2(3H)‐thione derivatives was synthesized, and they were evaluated as potential anti‐inflammatory agents. Following the structure identification studies employing IR, 1H nuclear magnetic resonance (NMR), 13C NMR, and elemental analysis, the title compounds were tested by cyclooxygenase (COX)‐1 and COX‐2 inhibition assays concomitant to lipopolysaccharide (LPS)‐induced nitric oxide and prostaglandin production prevention experiments. The results indicated that the majority of the compounds displayed either a superior or comparable activity in preventing both LPS‐induced NO production and COX‐1 activity in comparison to the activities of the reference molecules. Furthermore, docking studies were also performed to reveal possible interactions with the COX enzymes.
Experience of Trauma and PTSD Symptoms in Autistic Adults: Risk of PTSD Development Following DSM‐5 and Non‐DSM‐5 Traumatic Life Events
Authors: Rumball Freya , Happé Francesca , Grey Nick
Published: April 2020

Research to date suggests that individuals with autistic spectrum disorder (ASD) may be at increased risk of developing post‐traumatic stress disorder (PTSD) following exposure to traumatic life events. It has been posited that characteristics of ASD may affect perceptions of trauma, with a wider range of life events acting as possible catalysts for PTSD development. This study set out to explore the nature of “trauma” for adults with ASD and the rates of self‐reported PTSD symptomatology following DSM‐5 and non‐DSM‐5 traumas—the latter being defined as those that would not meet the standard DSM‐5 PTSD trauma Criterion A. Fifty‐nine adults with ASD who reported exposure to traumatic events took part in the study, which involved completing a series of online questionnaires. Thirty‐three individuals reported experiencing a “DSM‐5” traumatic event (i.e., an event meeting DSM‐5 PTSD Criterion A) and 35 reported a “non‐DSM‐5” traumautic event. Trauma‐exposed ASD adults were found to be at increased risk of PTSD development, compared to previous general population statistics, with PTSD symptom scores crossing thresholds suggestive of probable PTSD diagnosis for more than 40% of ASD individuals following DSM‐5 or non‐DSM‐5 traumas. A broader range of life events appear to be experienced as traumatic and may act as a catalyst for PTSD development in adults with ASD. Assessment of trauma and PTSD symptomatology should consider possible non‐DSM‐5 traumas in this population, and PTSD diagnosis and treatment should not be withheld simply due to the atypicality of the experienced traumatic event.

Lay Summary

This study explored the experience of trauma and rates of probable post‐traumatic stress disorder (PTSD) in adults with autistic spectrum disorder (ASD). We asked 59 autistic adults to complete online questionnaires about their experiences of stressful or traumatic events and related mental health difficulties. Autistic adults experienced a wide range of life events as traumatic, with over 40% showing probable PTSD within the last month and over 60% reporting probable PTSD at some point in their lifetime. Many of the life events experienced as traumas would not be recognized in some current diagnostic systems, raising concerns that autistic people may not receive the help they need for likely PTSD.
Subcutaneous in situ gel delivered leuprolide acetate's consistent and prolonged drug delivery maintains effective testosterone suppression independent of age and weight in men with prostate cancer
Authors: Renzulli Joseph F. , Tagawa Scott T. , Atkinson Stuart N. , Boldt‐Houle Deborah M. , Moul Judd W.
Published: April 2020

Objectives

To assess the impact of patient age and weight on the pharmacokinetics (PK), testosterone (T) suppression and safety from four fixed dosing regimens (7.5, 22.5, 30, or 45 mg for 1‐, 3‐, 4‐, or 6‐months, respectively) of subcutaneous in situ gel delivered leuprolide acetate (Gel‐LA) injected via the ATRIGEL Delivery System in patients with prostate cancer (PCa).

Patients and methods

Two patient populations were specified for analysis: a small cohort of surgically castrated PCa patients and a large, pooled population of PCa patients from four pivotal trials of Gel‐LA. Two separate analyses of the impact of age and weight on study endpoints were conducted: (1) PK and safety of a single monthly dose of Gel‐LA in a Phase 1 study with PCa patients who had undergone bilateral surgical orchiectomy (“Bilaterally orchiectomized male study”); (2) PK/pharmacodynamic (PD) effects and safety using pooled data from four pivotal trials assessing 1‐, 3‐, 4‐, and 6‐month dosing of Gel‐LA in patients with advanced PCa, stratified by age and body weight (pivotal trials).

Results

Eight orchiectomized patients from the “Bilaterally orchiectomized male study” and 438 patients from the pivotal trials were included in the analyses. Age and body weight did not appear to affect the PK results in the orchiectomized patient population. Pooled pivotal trial data showed that serum T levels did not appear to be influenced by age or weight; ≥90% of patients across all age groups and ≥92% of patients across all weight groups achieved T ≤ 50 ng/dL by week 4. Median T levels for castration (T ≤ 50 ng/dL) were maintained from week 3 until the end of the study and all subgroups achieved median T ≤ 20 ng/dL by week 4. Patients from the orchiectomized patient study did not report any serious treatment‐related adverse events (AEs) and there were no AE‐related withdrawals from the study. The most common AEs were hot flashes and injection site events. The safety profiles from pivotal trials have been previously described and, as expected, were consistent with known effects of LHRH agonist therapy and suppression of T levels.

Conclusion

PK and PD of Gel‐LA appear to be unaffected by age and body weight, as demonstrated by persistence of effective drug levels through the dosing period and consistent T suppression across different ages and body weights.
Noteworthy idiosyncrasies of 1α,25‐dihydroxyvitamin D3 kinetics for extrapolation from mouse to man: Commentary
Authors: Noh Keumhan , Yang Qi Joy , Sekhon Lavtej , Quach Holly P. , Chow Edwin C.Y. , Pang K. Sandy
Published: April 2020

Calcitriol or 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] is the active ligand of the vitamin D receptor (VDR) that plays a vital role in health and disease. Vitamin D is converted to the relatively inactive metabolite, 25‐hydroxyvitamin D3 [25(OH)D3], by CYP27A1 and CYP2R1 in the liver, then to 1,25(OH)2D3 by a specific, mitochondrial enzyme, CYP27B1 (1α‐hydroxylase) that is present primarily in the kidney. The degradation of both metabolites is mostly carried out by the more ubiquitous mitochondrial enzyme, CYP24A1. Despite the fact that calcitriol inhibits its formation and degradation, allometric scaling revealed strong interspecies correlation of the net calcitriol clearance (CL estimated from dose/AUC∞), production rate (PR), and basal, plasma calcitriol concentration with body weight (BW). PBPK‐PD (physiologically based pharmacokinetic‐pharmacodynamic) modeling confirmed the dynamic interactions between calcitriol and Cyp27b1/Cyp24a1 on the decrease in the PR and increase in CL in mice. Close scrutiny of the literature revealed that basal levels of calcitriol had not been taken into consideration for estimating the correct AUC∞ and CL after exogenous calcitriol dosing in both animals and humans, leading to an overestimation of AUC∞ and underestimation of the plasma CL. In humans, CL was decreased in chronic kidney disease but increased in cancer. Collectively, careful pharmacokinetic data analysis and improved definition are achieved with PBPK‐PD modeling, which embellishes the complexity of dose, enzyme regulation, and disease conditions. Allometric scaling and PBPK‐PD modeling were applied successfully to extend the PBPK model to predict calcitriol kinetics in cancer patients.
A review of the uses of virtual reality in engineering education
Authors: di Lanzo Jaiden A. , Valentine Andrew , Sohel Ferdous , Yapp Angie Y. T. , Muparadzi Kudakwashe C. , Abdelmalek Merkorios
Published: April 2020

The use of virtual environments as pedagogical tools within the domain of education has become an increasingly popular phenomenon over the last few decades especially. However, the uses and effects of virtual environments as pedagogical tools within the specific domain of engineering education have not been explored in extensive detail. The limited body of current research regarding the uses of virtual environments in engineering education affords a unique opportunity. This review provides an overview and synthesis of the uses of virtual reality within the domain of engineering education through the systematic analysis of journal articles and conference proceedings published across two databases (IEEE Xplore and Scopus) between 2015 and 2019. In summary, 17 studies were analysed utilising a systematic approach and using a coding scheme including four main categories and 12 binary items. The findings indicate an escalation in the use of virtual classroom environments as supplementary to traditional teaching environments, as well as reported substantial benefits to cognitive and skill‐based learning outcomes. The findings suggest that evaluation metrics and processes that lack clarity, together with unrealistic virtual scenarios and small evaluation sample sizes, may confound comparison and, hence, the reported substantive and beneficial use of virtual reality environments in engineering education. Scholars and educators within the domain of engineering education should continue investigating the uses and merits of virtual reality environments as pedagogical tools, taking these issues into consideration.
Sex‐dependent least toxic timing of irinotecan combined with chronomodulated chemotherapy for metastatic colorectal cancer: Randomized multicenter EORTC 05011 trial
Authors: Innominato Pasquale F. , Ballesta Annabelle , Huang Qi , Focan Christian , Chollet Philippe , Karaboué Abdoulaye , Giacchetti Sylvie , Bouchahda Mohamed , Adam René , Garufi Carlo , Lévi Francis A.
Published: April 2020

The least toxic time (LTT) of irinotecan varied by up to 8 hours according to sex and genetic background in mice. The translational relevance was investigated within a randomized trial dataset, where no LTT stood out significantly in the whole population.

130 male and 63 female eligible patients with metastatic colorectal cancer were randomized to receive chronomodulated Irinotecan with peak delivery rate at 1 of 6 clock hours staggered by 4 hours on day 1, then fixed‐time chronomodulated Fluorouracil‐Leucovorin‐Oxaliplatin for 4 days, q3 weeks. The sex‐specific circadian characteristics of grade (G) 3‐4 toxicities were mapped with cosinor and time*sex interactions confirmed with Fisher's exact test.

Baseline characteristics of male or female patients were similar in the six treatment groups. Main grade 3‐4 toxicities over six courses were diarrhea (males vs females, 39.2%; vs 46.0%), neutropenia (15.6% vs 15.0%), fatigue (11.5% vs 15.9%), and anorexia (10.0% vs 7.8%). They were reduced following irinotecan peak delivery in the morning for males, but in the afternoon for females, with statistically significant rhythms (P < .05 from cosinor) and sex*timing interactions (Fisher's exact test, diarrhea, P = .023; neutropenia, P = .015; fatigue, P = .062; anorexia, P = .032). Irinotecan timing was most critical for females, with grades 3‐4 ranging from 55.2% of the patients (morning) to 29.4% (afternoon) for diarrhea, and from 25.9% (morning) to 0% (afternoon) for neutropenia.

The study results support irinotecan administration in the morning for males and in the afternoon for females, in order to minimize adverse events without impairing efficacy.
Lifestyle associated factors and risk of urinary bladder cancer: A prospective cohort study from Norway
Authors: Hektoen Helga H. , Robsahm Trude E. , Andreassen Bettina K. , Stenehjem Jo S. , Axcrona Karol , Mondul Alison , Gislefoss Randi E.
Published: April 2020

A number of lifestyle associated factors, such as high body mass index (BMI), low physical activity, and related metabolic disorders, are associated with increased risk of cancer at several sites. For urinary bladder cancer (BC), such studies show inconsistent results, which could result from inadequate adjustment for smoking and occupational exposure. In the population‐based Janus Cohort (n = 292 851), we investigated the independent and combined impact of BMI, physical activity, blood pressure, and blood lipids on the risk of BC, by thorough adjustment for smoking and potential occupational exposure. We used cox proportional hazard regression to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for the associations between the lifestyle associated factors and BC risk. The associations observed were dependent on smoking status and gender. Among men, diastolic blood pressure (DBP) (HR 1.07, 95% CI 1.02‐1.12) and systolic blood pressure (SBP) (HR 1.04, 95% CI 1.01‐1.07) were positively associated with BC risk. Stratification by smoking status revealed a positive association between DBP and BC risk in never smokers (HR 1.14, 95% CI 1.00‐1.30), while no association was seen for current and former smokers. A risk score, integrating information across the lifestyle factors was positively associated with BC risk in men (ptrend = 0.043). In women, physical activity was associated with a decreased BC risk, but only among never smokers (HR 0.65, 95% CI 0.45‐0.94). In conclusion, relations between lifestyle associated factors and BC risk were most evident in never smokers, suggesting that smoking dominates the relation in current smokers.
Management of ST‐segment‐elevation myocardial infarction during the coronavirus disease 2019 (COVID‐19) outbreak: Iranian“247” National Committee's position paper on primary percutaneous coronary intervention
Authors: Sadeghipour Parham , Talasaz Azita H. , Eslami Vahid , Geraiely Babak , Vojdanparast Mohammad , Sedaghat Mojtaba , Moosavi Abouzar Fakhr , Alipour‐Parsa Saeed , Aminian Bahram , Firouzi Ata , Ghaffari Samad , Ghasemi Massoud , Saleh Davood Kazemi , Khosravi Alireza , Kojuri Javad , Noohi Feridoun , Pourhosseini Hamid , Salarifar Mojtaba , Salehi Mohamad Reza , Sezavar Hashem , Shabestari Mahmoud , Soleimani Abbas , Tabarsi Payam , Parsa Amir Farhang Zand , Abdi Seifollah
Published: April 2020

World Health Organization has designated coronavirus disease 2019 (COVID‐19) as a pandemic. During the past several weeks, a considerable burden has been imposed on the Iranian's healthcare system. The present document reviewed the latest evidence and expert opinion regarding the management of ST‐segment‐elevation myocardial infarction during the outbreak of COVID‐19 and outlines a practical algorithm for it.
Impact of body mass index on outcome and health status after chronic total occlusion percutaneous coronary intervention: Insights from the OPEN‐CTO study
Authors: Patterson Christian , Sapontis James , Nicholson William J. , Lombardi William , Karmpaliotis Dimitri , Moses Jeffrey , Gosch Kensey L. , Grantham J. Aaron , Hirai Taishi ,   OPEN CTO Study Group
Published: April 2020

Background

The effect of body mass index (BMI) on the procedural outcomes and health status (HS) change after chronic total occlusion (CTO) percutaneous coronary intervention (PCI) is largely unknown.

Methods

Thousand consecutive patients enrolled in a 12‐center prospective CTO PCI study (Outcomes, Patient Health Status, and Efficiency in Chronic Total Occlusion Hybrid Procedures [OPEN‐CTO]) were categorized into three groups by baseline BMI (obese ≥30, overweight 25–30, and normal 18.5–25), after excluding seven patients with BMI <18.5. Baseline and follow‐up HS at 1 year were quantified using the Seattle Angina Questionnaire, Rose Dyspnea Score, and Personal Health Questionnaire‐8 (PHQ‐8). Hierarchical, multivariable logistic, and repeated measures linear regression models were used to assess procedural success, major adverse cardiovascular and cerebrovascular events (MACCE), and HS outcomes, as appropriate.

Results

The obese and overweight were 47.6% and 37.4%, respectively. While procedure time and contrast dose were similar among the groups, total radiation dose (mGy) was higher with increased BMI (3,019 ± 2,027, 2,267 ± 1,714, 1,642 ± 1,223, p < .01). Procedural success rates, as well as MACCE rates, were similar among the three groups (obese 83.1%, overweight 79.8%, normal 81.9%, p = .47 and 5.1, 8.4, and 8.7%, p = .11). These rates remained similar after adjustment for baseline characteristics. The HS improvement from baseline to 12 months after adjustment was similar in obese and overweight patients compared to normal weight patients.

Conclusions

CTO PCI in obese and overweight patients can be performed with similar success and complication rates. Obese and overweight patients derive similar HS benefit from CTO PCI compared to normal weight patients.
Three strikes? Failed vascular access in mechanical thrombectomy
Authors: Walker Melanie , Levitt Michael R. , Ghodke Basavaraj V.
Published: April 2020

Anatomic variability in the posterior circulation and small, fragile, or otherwise treacherous origins of vertebral arteries can create a challenge to acute endovascular intervention. We report a case of unsuccessful reperfusion due to inability to access the posterior circulation in a patient with acute basilar artery occlusion.
Some Aspects of Combining Data and Models in Process Engineering
Authors: Heese Raoul , Nies Julia , Bortz Michael
Published: April 2020

Observing phenomena under defined conditions and building mathematical models to make further predictions are essential ingredients of natural and engineering sciences. Recent technological and methodical advances make large and high‐dimensional simulation data accessible to model building and therefore to optimization. In this article, selected machine learning methods are highlighted and applied to example data from simple flow sheet simulations. Furthermore, the essential outcomes of the workshop dealing with combination of data and models during the Tutzing Symposium 2019 are summarized.
Effects of acupuncture versus cognitive behavioral therapy on cognitive function in cancer survivors with insomnia: A secondary analysis of a randomized clinical trial
Authors: Liou Kevin T. , Root James C. , Garland Sheila N. , Green Jamie , Li Yuelin , Li Q. Susan , Kantoff Philip W. , Ahles Tim A. , Mao Jun J.
Published: April 2020

Background

Cancer‐related cognitive impairment is a prevalent, disruptive condition potentially exacerbated by sleep disturbances. The current study was performed to evaluate the effects of acupuncture versus cognitive behavioral therapy for insomnia (CBT‐I) on objective and subjective cognitive function in cancer survivors with insomnia.

Methods

Using data from a randomized clinical trial (160 survivors) that compared acupuncture versus CBT‐I for insomnia occurring in cancer survivors, the authors analyzed cognitive outcomes and their relationship to insomnia symptoms. Analysis was limited to 99 patients who reported baseline cognitive difficulties. Interventions were delivered over 8 weeks. Objective attention, learning, and memory were evaluated using the Buschke Selective Reminding Test. Subjective cognitive function was assessed using the Brown Attention‐Deficit Disorder Scales. Insomnia symptoms were assessed using the Insomnia Severity Index. All outcomes were collected at baseline, week 8, and week 20.

Results

From baseline to week 8, acupuncture produced statistically significant within‐group improvements in objective attention (Cohen D, 0.29), learning (Cohen D, 0.31), and memory (Cohen D, 0.33) that persisted to week 20 (all P < .05), whereas CBT‐I produced a statistically significant within‐group improvement in objective attention from baseline to week 20 (Cohen D, 0.50; P < .05); between‐group differences were not statistically significant. Both interventions produced statistically significant within‐group improvements in subjective cognitive function at weeks 8 and 20 compared with baseline (all P < .001); between‐group differences were not statistically significant. In the acupuncture group, patients with clinically meaningful responses with regard to insomnia symptoms demonstrated a significantly greater improvement in subjective cognitive function compared with those without clinically meaningful insomnia responses (P = .006).

Conclusions

Among cancer survivors with insomnia, both acupuncture and CBT‐I produced significant improvements in objective and subjective cognitive function. However, the effect sizes varied and only survivors in the acupuncture group demonstrated a significant relationship between cognitive and sleep outcomes. These preliminary findings warrant further investigation to guide the personalized management of patients with cancer‐related cognitive impairment.
11p15.5 epimutations in children with Wilms tumor and hepatoblastoma detected in peripheral blood
Authors: Fiala Elise M. , Ortiz Michael V. , Kennedy Jennifer A. , Glodzik Dominik , Fleischut Megan Harlan , Duffy Kelly A. , Hathaway Evan R. , Heaton Todd , Gerstle Justin T. , Steinherz Peter , Shukla Neerav , McNeer Nicole , Tkachuk Kaitlyn , Bouvier Nancy , Cadoo Karen , Carlo Maria I. , Latham Alicia , Dubard Gault Marianne , Joseph Vijai , Kemel Yelena , Kentsis Alex , Stadler Zsofia , La Quaglia Michael , Papaemmanuil Elli , Friedman Danielle , Ganguly Arupa , Kung Andrew , Offit Kenneth , Kalish Jennifer M. , Walsh Michael F.
Published: April 2020

Background

Constitutional or somatic mosaic epimutations are increasingly recognized as a mechanism of gene dysregulation resulting in cancer susceptibility. Beckwith‐Wiedemann syndrome is the cancer predisposition syndrome most commonly associated with epimutation and is extremely variable in its phenotypic presentation, which can include isolated tumors. Because to the authors' knowledge large‐scale germline DNA sequencing studies have not included methylation analysis, the percentage of pediatric cancer predisposition that is due to epimutations is unknown.

Methods

Germline methylation testing at the 11p15.5 locus was performed in blood for 24 consecutive patients presenting with hepatoblastoma (3 patients) or Wilms tumor (21 patients).

Results

Six individuals with Wilms tumor and 1 patient with hepatoblastoma were found to have low‐level gain of methylation at imprinting control 1, and a child with hepatoblastoma was found to have loss of methylation at imprinting control 2. The loss of methylation at imprinting control 2 was found to be maternally inherited, despite not being associated with any detectable genomic alteration.

Conclusions

Overall, 33% of patients (8 of 24 patients) with Wilms tumor or hepatoblastoma were found to have an epigenetic susceptibility that was detectable in the blood. It is interesting to note that low‐level gain of methylation at imprinting control 1 predominantly was detected in females with bilateral Wilms tumors. Further studies in larger cohorts are needed to determine the efficacy of testing all patients with Wilms tumor or hepatoblastoma for 11p15.5 epimutations in the blood as part of DNA analysis because this hallmark of predisposition will not be detected by sequencing‐based approaches and detecting a cancer predisposition may modify treatment.
Multiplexed fluorescence in situ hybridization–based detection of circulating tumor cells: A novel liquid‐based technology to facilitate accurate and early identification of non–small cell lung cancer patients
Authors: Zhu Yili , Lowe Alarice Cheng‐Yi
Published: April 2020

Multiplexed fluorescence in situ hybridization–based circulating tumor cell (CTC) technology detects cytogenetic abnormalities in patients who are at risk for non–small cell lung cancer with high accuracy. Combined with low‐dose computed tomography, this CTC technology can efficiently rule out malignancy in at‐risk patients with benign pulmonary nodules.
Effects and Safety of Statin and Ezetimibe Combination Therapy in Patients with Chronic Kidney Disease: A Systematic Review and Meta‐Analysis
Authors: Lin Yi‐Chih , Lai Tai‐Shuan , Wu Hon‐Yen , Chou Yu‐Hsiang , Chiang Wen‐Chih , Lin Shuei‐Liong , Chen Yung‐Ming , Chu Tzong‐Shinn , Tu Yu‐Kang
Published: April 2020

The efficacy and safety of statin and ezetimibe combination therapy in patients with chronic kidney disease (CKD) remains unclear. To assess the effect of statin and ezetimibe combination therapy on controlling lipid profiles and reducing cardiovascular events in patients with CKD, we conducted a systematic review and meta‐analysis. We selected randomized controlled trials comparing this combination therapy with statin monotherapy or placebo in patients with CKD from the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases published before September 1, 2018 on the Internet. Eight articles on seven studies, with a total of 14,016 patients with CKD, were selected from 412 full‐text articles. Statin and ezetimibe combination therapy had beneficial effects on serum total cholesterol (weighted mean difference (WMD) −20.31 mg/dL, 95% confidence interval (CI), −26.87 to −13.75 mg/dL, P < 0.001), low‐density lipoprotein cholesterol (WMD −17.22 mg/dL, 95% CI, −18.93 to −15.51 mg/dL, P < 0.001), and triglycerides (WMD −15.08 mg/dL, 95% CI, −23.41 to −6.75 mg/dL, P < 0.001) compared with statin monotherapy. Statin and ezetimibe combination therapy significantly reduced all‐cause mortality and major adverse cardiovascular events (risk ratio 0.86, 95% CI, 0.77 to 0.97, P = 0.01). The incidence of adverse events was low, with no significant difference between statin and ezetimibe combination therapy and statin monotherapy. In conclusion, the statin and ezetimibe combination therapy significantly improved serum lipid profiles and reduced risks of all‐cause deaths and major adverse cardiovascular events compared with the control group in patients with CKD.
Using Healthcare Databases to Replicate Trial Findings for Supplemental Indications: Adalimumab in Patients with Ulcerative Colitis
Authors: Spoendlin Julia , Desai Rishi J. , Franklin Jessica M. , Glynn Robert J. , Payne Emma , Schneeweiss Sebastian
Published: April 2020

Regulators wish to understand whether real world evidence can be used for secondary indications of biologics. Using the secondary indication of adalimumab for ulcerative colitis (UC) as an example, we aimed to replicate the ULTRA‐2 randomized controlled trial finding on the effectiveness of adalimumab in patients with UC using realworld data analyses. Adalimumab, a TNF‐alpha receptor inhibitor initially approved for Crohn’s disease, was approved for moderate to severe UC in 2012. The ULTRA‐2 trial had shown improved remission against placebo in patients with UC. Using claims data (2006–2012), we conducted a cohort study of patients with UC who initiated adalimumab and compared them with (i) nonusers and (ii) new users of infliximab using propensity score matching. The coprimary end points were corticosteroid (CS) discontinuation within 8 weeks and 1 year of treatment. We computed hazard ratios (HRs) and 95% confidence intervals (CIs). We identified 398 matched pairs of adalimumab users vs. nonusers and 326 pairs of adalimumab vs. infliximab users. Adalimumab users were 28% more likely to achieve CS‐discontinuation compared with nonusers over 1 year (HR = 1.28; 95% CI 0.94–1.73). However, unlike in ULTRA‐2, this effect was not observed in the first 8 weeks (HR = 0.79; 95% CI 0.65–0.97). Compared with infliximab, adalimumab initiators showed no incremental benefit over 1 year (HR = 1.08; 95% CI 0.80–1.04), but showed a 22% reduction (HR = 0.78; 95% CI 0.64–0.95) during the first 8 weeks of treatment. In summary, our results highlight opportunities and some limitations of database analysis to identify treatment effects for secondary indications.
Risks of ACE Inhibitor and ARB Usage in COVID‐19: Evaluating the Evidence
Authors: Sriram Krishna , Insel Paul A.
Published: April 2020

Concerns have been raised regarding the safety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease of 2019 (COVID‐19), based on the hypothesis that such medications may raise expression of ACE2, the receptor for severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). We conducted a literature review of studies (n = 12) in experimental animals and human subjects (n = 12) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses of ACEIs or ARBs than are typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID‐19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.
Mutations in the HvMKK3 and HvAlaAT1 genes affect barley preharvest sprouting and after‐ripened seed dormancy
Authors: Vetch Justin M. , Walling Jason G. , Sherman Jamie , Martin John M. , Giroux Michael J.
Published: April 2020

Preharvest sprouting (PHS) is a natural phenomenon that negatively impacts various crops across the globe when late‐season rainfall causes seeds to germinate prior to harvest. Prevention of PHS in small grains such as barley (Hordeum vulgare L.) and wheat (Triticum aestivum L.) is of particular importance because of the large acreage devoted to them. Barley is the fourth most grown cereal crop and is often susceptible to PHS damage, which limits the regions in which barley can be grown without heavy losses. Preharvest sprouting damage could be mitigated by incorporation of genetic alleles that impart desired levels of dormancy at specific times in grain maturity, ideally high dormancy at harvest with a fast loss of dormancy upon after‐ripening. Toward this goal, 114 barley varieties were assessed for dormancy at physiological maturity and in after‐ripened grains. Three genes previously associated with dormancy in barley or wheat (HvAlaAT1, HvMKK3, and HvMFT) were sequenced from all lines and assessed for allelic diversity. The resulting alleles were assessed for association with dormancy at each of the maturity time points. In total, seven missense mutations were discovered across the three genes. It was observed that a single missense mutation in HvAlaAT1 (L214F) is associated with loss of dormancy in after‐ripened grain, while a single missense mutation in HvMKK3 (E165Q) is associated with a large loss of dormancy starting around physiological maturity. This study suggests that different genes may be associated with dormancy at different time points in grain maturity, which would allow for selective breeding of specific dormancy time periods.
Joint beam selection and user association strategy for beam space millimetre wave downlink systems
Authors: Jayakumar Roscia Jeya Shiney , Ganesan Indumathi
Published: April 2020

Beam space multiple‐input multiple‐output (B‐MIMO) systems operating at mmWave frequency in downlink uses different beam selection techniques for reducing the required number of radio frequency chains without apparent performance loss. In this paper, a joint beam selection and user association scheme with the objective of sum rate maximization is proposed. The proposed work on beam selection is based on a norm and uncorrrelation based approach, which considers channel correlation among the users so as to avoid inter‐user interference. Two different methods for beam user association with one modelled as a balanced assignment problem based on average sum assignment method and the other method that associates an optimal beam to every user by considering their channel gain values are also proposed along with beam selection. The proposed beam assignment methods are less complex and efficient in finding a suitable beam to every user within the cell. Simulation results show that the proposed method accomplish comparable performance in terms of sum rate and energy efficiency with appreciably low computational complexity relative to the existing methods in a correlated environment.
Human‐mediated dispersal and disturbance shape the metapopulation dynamics of a long‐lived herb
Authors: Bullock James M. , Wichmann Matthias C. , Hails Rosemary S. , Hodgson David J. , Alexander Matt J. , Morley Kathryn , Knopp Tatjana , Ridding Lucy E. , Hooftman Danny A. P.
Published: April 2020

As anthropogenic impacts on the natural world escalate, there is increasing interest in the role of humans in dispersing seeds. But the consequences of this Human‐Mediated Dispersal (HMD) on plant spatial dynamics are little studied. In this paper, we ask how secondary dispersal by HMD affects the dynamics of a natural plant metapopulation. In addition to dispersal between patches, we suggest within‐patch processes can be critical. To address this, we assess how variation in local population dynamics, caused by small‐scale disturbances, affects metapopulation size. We created an empirically based model with stochastic population dynamics and dispersal among patches, which represented a real‐world, cliff‐top metapopulation of wild cabbage Brassica oleracea. We collected demographic data from multiple populations by tagging plants over eight years. We assessed seed survival, and establishment and survival of seedlings in intact vegetation vs. small disturbances. We modeled primary dispersal by wind using field data and used experimental data on secondary HMD by hikers. We monitored occupancy patterns over a 14‐yr period in the real metapopulation. Disturbance had large effects on local population growth rates, by increasing seedling establishment and survival. This meant that the modeled metapopulation grew in size only when the area disturbed in each patch was above 35%. In these growing metapopulations, although only 0.2% of seeds underwent HMD, this greatly enhanced metapopulation growth rates. Similarly, HMD allowed more colonizations in declining metapopulations under low disturbance, and this slowed the rate of decline. The real metapopulation showed patterns of varying patch occupancy over the survey years, which were related to habitat quality, but also positively to human activity along the cliffs, hinting at beneficial effects of humans. These findings illustrate that realistic changes to dispersal or demography, specifically by humans, can have fundamental effects on the viability of a species at the landscape scale.
Hypokalaemia and outcomes in older patients hospitalized for heart failure
Authors: Valentova Miroslava , Patel Samir , Lam Phillip H. , Faselis Charles , Arundel Cherinne , Fonarow Gregg C. , Cheng Yan , Allman Richard M. , von Haehling Stephan , Anker Stefan D. , Ahmed Ali
Published: April 2020

Aims

Hypokalaemia is a risk factor for ventricular arrhythmias and sudden death in ambulatory patients with chronic heart failure (HF). The objective of this study was to examine the association between hypokalaemia and outcomes in hospitalized patients with decompensated HF in whom sudden death is less common.

Methods and results

Of the 5881 hospitalized patients with HF, 1052 had consistent hypokalaemia (both admission and discharge serum potassium <4.0 mmol/L), and 2538 had consistent normokalaemia (both admission and discharge serum potassium 4.0–5.0 mmol/L). Propensity scores for consistent hypokalaemia, estimated for each of 3590 (1052 + 2538) patients, were used to assemble a matched cohort of 971 pairs of patients with consistent hypokalaemia vs. consistent normokalaemia, balanced on 54 baseline characteristics (mean age, 75 years; 60% women; 28% African American). We repeated the above process to assemble 2327 pairs of patients with discharge potassium <4.0 vs. 4.0–5.0 mmol/L and 449 pairs of patients with discharge serum potassium <3.5 vs. 4.0–5.0 mmol/L. Hazard ratios (HR) and 95% confidence intervals (CIs) associated with hypokalaemia were estimated in matched cohorts. 30 day all‐cause mortality occurred in 5% and 4% of patients with consistent normokalaemia vs. consistent hypokalaemia, respectively (HR, 0.78; 95% CI, 0.52–1.18; P = 0.241). HRs (95% CI) for 30 day mortality associated with discharge serum potassium <4.0 and <3.5 mmol/L were 0.90 (0.70–1.16; P = 0.419) and 1.69 (0.94–3.04; P = 0.078), respectively. Hypokalaemia (<4.0 or <3.5 mmol/L) had no association with long‐term mortality or other outcomes.

Conclusions

In hospitalized older patients with HF, compared with normokalaemia (serum potassium 4.0–5.0 mmol/L), hypokalaemia (<4.0 or <3.5 mmol/L) had no significant associations with outcomes.
Ruthenium(II) MOCVD Precursors for Phosphorus‐Doped Ruthenium Layer Formation
Authors: Preuß Andrea , Tamuliene Jelena , Madajska Katarzyna , Szymanska Iwona B. , Korb Marcus , Rüffer Tobias , Jeschke Janine , Melzer Marcel , Bankwitz Jörn , Schulz Stefan E. , Lang Heinrich
Published: April 2020

The synthesis and solid‐state structure of Ru(CO)2(PEt3)2(O2CR)2 (4a–f, R = Me, Et, iPr, tBu, CH2OMe, CF3) is reported. The vapor pressure of 4a–f was measured, ranging from 6.3 mbar (4f) to 14.8 at 190 °C (4e). Complexes 4a–f decompose between 210–350 °C of which 4c shows the lowest (248 °C) and 4e (280 °C) the highest onset temperature. TG‐MS studies (4f) showed subsequent decarbonylation and decarboxylation processes. To determine the gas phase composition VT IR studies were performed. Based on TG‐MS, VT IR and DFT calculations decomposition mechanisms are discussed. Complexes 4a–f are suited as MOCVD precursors, producing dense layers of 25–50 nm thickness, consisting of 57 at‐% Ru, up to 18.2 at‐% P and as impurities C, N and O. A carbon‐free Ru(P) layer was obtained with 4a as CVD precursor.
Nitrosation of Cyanamide: Preparation and Properties of the Elusive E‐ and Z‐N'‐Cyanodiazohydroxides
Authors: Guethner Thomas , Huber Evi , Sans Juergen , Thalhammer Franz
Published: April 2020

Nitrosation of cyanamide leads to unstable E/Z‐cyanodiazohydroxides that easily deprotonate to E/Z‐cyanodiazotates. Pursuing observations of E. Drechsel 145 years ago, the structure and reactivity of those products was determined, mainly in aqueous solution. Depending on the pH, three different thermal decomposition pathways give either N2O + HCN or N2 + HNCO. They were evaluated experimentally and by quantum mechanical calculations.