bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanical properties of low‐diameter balloon expandable covered stents
Authors: Blais Benjamin , Carr Karen , Sinha Sanjay P , Salem Morris M , Levi Daniel S
Published: December 2020

Objectives

To determine over‐dilation potential of commercially available covered stents.

Background

Covered stents including the Atrium iCast, Gore VBX, and Lifestream stents (LS) can treat ruptures, dissections, and aneurysms in small vessels. Especially in growing patients, stents often require serial dilations beyond their implant or nominal diameters. Tolerance of serial dilations is clinically important information for interventionalists.

Methods

Serial dilations of 5–12 mm iCast, VBX, and LS covered stents were performed in 1–2 mm increments (up to 20 mm). With each dilation, foreshortening and recoil were measured, and stent strut and covering integrity were assessed. High‐pressure balloons were used to expand the stents until they fractured or could not be further expanded.

Results

The 5–8 mm LS tolerated dilation to 14.5–16 mm. The 10–12 mm LS stents tolerated dilation to 18 mm and fractured on the 20 mm balloon. LS stents foreshortened 35%–45% on average after 8 mm of over‐dilation and had 5%–10% recoil on <6 mm over‐dilation. All iCast stents tolerated dilation to 12–13 mm and required fracture for dilation to >14 mm. ICast stents foreshortened 19%–29% at maximum dilation, with 3–6% recoil on <2 mm over‐dilation, and < 3% thereafter. VBX stents over‐dilated to 2.9–4.7 mm above nominal, foreshortening 40%–50% after 4–6 mm of over‐dilation before collapsing into a ring. VBX stent recoil was <2.5% on all dilations.

Conclusions

LS stents had the greatest over‐dilation potential. VBX stents had the least recoil but tended to foreshorten significantly 3–4 mm above nominal. Regardless of nominal size, all iCast stents (including the 5 mm) tolerated dilation to a maximum of 12–13 mm.
Early diagnosis and antibiotic treatment for fulminant Clostridium difficile infection
Authors: Fukushima Kazutaka , Inokuchi Ryota , Hirayama Ichiro , Hiruma Takahiro , Doi Kent
Published: December 2020

In fulminant Clostridium difficile infection (CDI), early diagnosis is important, and early diagnosis could save fulminant CDI patients that do not qualify for surgery due to severe complicating conditions by conservative antibiotic therapy.
Researcher Development of Doctoral Students: Supports and Barriers Across Time
Authors: Borders L. DiAnne , Wester Kelly L. , Driscoll Kathleen H.
Published: December 2020

We used content analysis to analyze 42 counseling doctoral students' reports of supports and barriers influencing their researcher development across 3 years. In line with social cognitive career theory, the students named cognitive‐person, environmental, and social‐context influences. Analyses indicated no differences in frequencies of supports and barriers across time but significant differences by cohort.
Ni2P Nanoalloy as an Air‐Stable and Versatile Hydrogenation Catalyst in Water: P‐Alloying Strategy for Designing Smart Catalysts
Authors: Fujita Shu , Yamaguchi Sho , Yamasaki Jun , Nakajima Kiyotaka , Yamazoe Seiji , Mizugaki Tomoo , Mitsudome Takato
Published: December 2020

Non‐noble metal‐based hydrogenation catalysts have limited practical applications because they exhibit low activity, require harsh reaction conditions, and are unstable in air. To overcome these limitations, herein we propose the alloying of non‐noble metal nanoparticles with phosphorus as a promising strategy for developing smart catalysts that exhibit both excellent activity and air stability. We synthesized a novel nickel phosphide nanoalloy (nano‐Ni2P) with coordinatively unsaturated Ni active sites. Unlike conventional air‐unstable non‐noble metal catalysts, nano‐Ni2P retained its metallic nature in air, and exhibited a high activity for the hydrogenation of various substrates with polar functional groups, such as aldehydes, ketones, nitriles, and nitroarenes to the desired products in excellent yields in water. Furthermore, the used nano‐Ni2P catalyst was easy to handle in air and could be reused without pretreatment, providing a simple and clean catalyst system for general hydrogenation reactions.
Development of an Improved Guanidine‐Based Rac1 Inhibitor with in vivo Activity against Non‐Small Cell Lung Cancer
Authors: Ciarlantini Matías S. , Barquero Andrea , Bayo Juan , Wetzler Diana , Dodes Traian Martín M. , Bucci Hernán A. , Fiore Esteban J. , Gandolfi Donadío Lucía , Defelipe Lucas , Turjanski Adrián , Ramírez Javier A. , Mazzolini Guillermo , Comin Maria J.
Published: December 2020

The Rho GTPase Rac1 is involved in the control of cytoskeleton reorganization and other fundamental cellular functions. Aberrant activity of Rac1 and its regulators is common in human cancer. In particular, deregulated expression/activity of Rac GEFs, responsible for Rac1 activation, has been associated to a metastatic phenotype and drug resistance. Thus, the development of novel Rac1‐GEF interaction inhibitors is a promising strategy for finding new preclinical candidates. Here, we studied structure–activity relationships within a new family of N,N’‐disubstituted guanidine as Rac1 inhibitors. We found that compound 1D‐142, presents superior antiproliferative activity in human cancer cell lines and higher potency as Rac1‐GEF interaction inhibitor in vitro than parental compounds. In addition, 1D‐142 reduces Rac1‐mediated TNFα‐induced NF‐κB nuclear translocation during cell proliferation and migration in NSCLC. Notably, 1D‐142 allowed us to show for the first time the application of a Rac1 inhibitor in a lung cancer animal model.
Psychotherapy and youth suicide prevention: An interpretative phenomenological analysis of specialist clinicians' experiences
Authors: Janackovski Atanas , Deane Frank P. , Hains Alex
Published: December 2020

The study explored psychologists' experiences in delivering short‐term psychotherapy for suicidal adolescents and sought to clarify how these experiences fit with empirically supported interventions and the interpersonal psychological theory of suicide. Semistructured interviews were conducted with 12 psychologists' who provided short‐term psychotherapy in a suicide prevention programme for youth (12‐ to 25‐year‐olds). Interview transcripts were analysed using interpretative phenomenological analysis. Three superordinate themes were identified: (i) understand the experience and context of the suicidality and the importance of a formulation‐based approach to engagement and individualized treatment planning; (ii) involve broad support systems, and in particular families, to help the young person reduce feelings of burdensomeness and increase safety, connectedness and belonging; and (iii) improve affect regulation and reflective functioning, important not only for the young person but also for the support system to maximize the positive impact of supports via emotional coregulation and effective problem‐solving. Interventions and approaches as well as the potential underlying processes of change being targeted are discussed in light of these findings. As an example, the development of a suicide safety plan was an intervention that traversed these themes. When used as a process tool, it helped foster a collaborative, formulation, dimensional and biopsychosocial approach to treat psychopathology and suicidality and extended beyond the therapist–client dyad. Moreover, treatment needs to be extended beyond the therapist–client dyad to allow therapists to facilitate a systemic treatment response, as this was seen as a major component of interventions for suicidal youth.
Clinical assessment of non‐suicidal self‐injury: A systematic review of instruments
Authors: Faura‐Garcia Juan , Orue Izaskun , Calvete Esther
Published: December 2020

There has been an increase in the number of assessment instruments for non‐suicidal self‐injury (NSSI). However, previous reviews are inconsistent and do not provide a comprehensive psychometric assessment of the instruments. This study aimed to systematically assess and compare the psychometric properties of clinically relevant instruments to measure NSSI in any population. Through a systematic review guided by COSMIN and PRISMA, two searches were conducted in English and Spanish in February 2020 in 13 databases including grey literature. Of the 7,813 initial records, 152 validations were extracted. From these, 83 instruments (22 versions or adaptations) were excluded for not measuring NSSI, having no potential clinical utility or not including psychometric properties. Finally, 26 (22 versions, 35 adaptations and 19 creations) instruments measuring NSSI were included. Predominantly, the studies were North American self‐reports in English for community adolescents, adaptations or versions emanating from a small number of instruments. Twenty‐six indicators were categorized to assess NSSI. The most frequent instruments are structured interviews, and their indicators were related to NSSI function and topography. Evidence of validity and reliability was positive but limited. Despite the high number of instruments and diversity of evaluations, we found no instrument with sufficient evidence for clinical assessment. Findings broadly overview NSSI assessment instruments' current use and future improvement in clinical and research settings.
Exploring the effectiveness of a specialized therapy programme for burnout using subjective report and biomarkers of stress
Authors: Orosz Ariane , Federspiel Andrea , Eckert Anne , Seeher Christian , Dierks Thomas , Tschitsaz Armita , Cattapan Katja
Published: December 2020

The increasing prevalence of stress‐related disorders such as burnout urges the need for specialized treatment approaches. Programmes combining psychotherapy and regenerative interventions emerge to be the most successful. However, evaluated therapy programmes are scarce and usually involve subjective symptom quantification without consideration of physiologic parameters. The aim of the present exploratory, single‐group study was the multimodal investigation of the effectiveness of a specialized holistic therapy programme by assessing symptoms and biological markers of chronic stress. Seventy‐one in‐patients (39 men/32 women; age 46.8 ± 9.9 years) of a specialized burnout ward with the additional diagnosis of burnout (Z73.0) in conjunction with a main diagnosis of depressive disorder (F32 or F33) according to the International Classification of Diseases (ICD)‐10 were included in the study. In addition to symptomatology, the stress‐responsive biomarkers heart rate variability (HRV) and serum brain‐derived neurotrophic factor (BDNF) were measured in patients at admittance to and discharge from the burnout ward applying a 6‐week specialized treatment programme. At discharge, patients showed a significant reduction of symptom burden and a significant increase in serum BDNF, while HRV remained unchanged. The findings implicate that the therapy programme may have beneficial effects on symptomatology and neuroplasticity of patients with burnout. As therapy was often supplemented by psychopharmacological treatment, a relevant influence of antidepressant medication especially on BDNF has to be considered.
Impact of Hepatic CYP3A4 Ontogeny Functions on Drug–Drug Interaction Risk in Pediatric Physiologically‐Based Pharmacokinetic/Pharmacodynamic Modeling: Critical Literature Review and Ivabradine Case Study
Authors: Lang Jennifer , Vincent Ludwig , Chenel Marylore , Ogungbenro Kayode , Galetin Aleksandra
Published: December 2020

Clinical assessment of drug–drug interactions (DDIs) in children is not a common practice in drug development. Therefore, physiologically‐based pharmacokinetic (PBPK) modeling can be beneficial for informing drug labeling. Using ivabradine and its metabolite (both cytochrome P450 3A4 enzyme (CYP3A4) substrates), the objectives were (i) to scale ivabradine‐metabolite adult PBPK/PD to pediatrics, (ii) to predict the DDIs with a strong CYP3A4 inhibitor, and (iii) to compare the sensitivity of children to DDIs using two CYP3A4 hepatic ontogeny functions: Salem and Upreti. A scaled parent‐metabolite PBPK/PD model from adults to children satisfactorily predicted pharmacokinetics (PK) and pharmacodynamics (PD) in 74 children (0.5–18 years) regardless of CYP3A4 hepatic ontogeny function applied. However, using the Salem ontogeny, mean predicted parent and metabolite area under the concentration‐time curve over 12 hours (AUC12h) and heart rate change from baseline were 2‐fold, 1.5‐fold, and 1.4‐fold higher in young children (0.5–3 years old) compared with Upreti ontogeny, respectively. Despite these differences, choice of appropriate hepatic CYP3A4 ontogeny was challenging due to sparse PK and PD data. Different sensitivity to ivabradine–ketoconazole DDIs was simulated in young children relative to adults depending on the choice of hepatic CYP3A4 ontogeny. Predicted ivabradine and metabolite AUCDDI/AUCcontrol were 2‐fold lower in the youngest children (0.5–1 year old) compared with adults (Salem function). In contrast, the Upreti function predicted comparable ivabradine DDIs across all age groups, although predicted metabolite AUCDDI/AUCcontrol was 1.3‐fold higher between the youngest children and adults. In the case of PD, differences in predicted DDIs were minor across age groups and between both functions. Current work highlights the importance of careful consideration of hepatic CYP3A4 ontogeny function and implications on labeling recommendations in the pediatric population.
Stability of synthetic cathinones in clinical and forensic toxicological analysis—Where are we now?
Authors: Aldubayyan Abdulaziz A. , Castrignanò Erika , Elliott Simon , Abbate Vincenzo
Published: December 2020

Understanding the stability of analyzed drugs in biological samples is a crucial part for an appropriate interpretation of the analytical findings. Synthetic cathinones, as psychoactive stimulants, belong to a major class of new psychoactive substances. As they are subject to several degradation pathways, they are known to clinical and forensic toxicologists as unstable analytes in biological samples. When interpreting analytical data of synthetic cathinones in biological samples, analysts must be aware that the concentration of analytes may not accurately reflect the levels at the time they were acquired owing to many factors. This review provides (i) an overview of the current scientific knowledge on the stability of synthetic cathinones and/or metabolites in various human biological samples with a focus on factors that may deteriorate their stability—such as storage temperature, length of storage, matrix, pH, type of preservatives, concentration of analytes, and the chemistry of the analytes—and (ii) possible solutions on how to avoid such degradation. The PubMed database as well as Google Scholar was thoroughly searched to find published studies on the stability of synthetic cathinones since 2007 by searching specific keywords. A total of 23 articles met the inclusion criteria and were included in this review. Synthetic cathinones that carry methylenedioxy or N‐pyrrolidine ring showed higher degradation resistance over other substituted groups. Acidification of samples pH plays a crucial role at increasing the stability of cathinones even with analytes that were frequently considered as poorly stable. This review also provides several recommendations for best practice in planning the experimental design, preservation, and storage conditions in order to minimize synthetic cathinones' degradation in human biological samples.
Disordered eating attitudes and body shape concerns among North Indian Kathak dancers
Authors: Kulshreshtha Monika , Babu Nandita , Goel Neha J. , Chandel Shivani
Published: December 2020

Objective

To determine the prevalence and association between disordered eating attitudes and body shape concerns in a sample of North Indian Kathak dancers.

Method

Participants were 206 Kathak female dancers and 235 healthy controls, ages 18–45 years. Participants completed questionnaires assessing demographics, disordered eating attitudes, and body dissatisfaction. Pearson correlations assessed the association between the disordered eating attitudes and body dissatisfaction, and binary logistic regression identified the risk of having a possible eating disorder.

Results

Kathak dancers reported significantly greater disordered eating attitudes compared to controls (12.1% vs. 5.9%, p = .023). Dancers endorsed greater dieting behaviors (M = 5.6 vs. 4.5, p = .031), and binge eating episodes (p < .001) relative to their counterparts. Body dissatisfaction was significantly positively correlated with disordered eating attitudes among the dancers (p < .001). Dancers with elevated body shape concerns were five times more likely to report disordered eating attitudes, relative to their peers (p < .001).

Discussion

Disordered eating attitudes and body shape concerns are prevalent among North Indian Kathak dancers. Future research should aim to develop targeted prevention and intervention programs that focus on reducing these behaviors and promoting a positive body image to mitigate the risk of disordered eating among this group.
The project COMPASS protocol: Optimizing mindfulness and acceptance‐based behavioral treatment for binge‐eating spectrum disorders
Authors: Juarascio Adrienne S. , Felonis Christina R. , Manasse Stephanie M. , Srivastava Paakhi , Boyajian Laura , Forman Evan M. , Zhang Fengqing
Published: December 2020

Outcomes from cognitive behavioral therapy for binge‐eating spectrum disorders are suboptimal, possibly due in part to deficits in self‐regulation (i.e., the ability to control behavior in pursuit of long‐term goals despite internal challenges). Mindfulness and acceptance‐based treatments (MABTs) integrate behavioral treatment with psychological strategies designed to enhance self‐regulation, yet little is known about how and for whom they are effective. The present study will utilize the multiphase optimization strategy to identify which of four MABT components (mindful awareness, distress tolerance, emotion modulation, values‐based decision making) to include in a fully powered clinical trial. Participants (n = 256) will be randomized to 16 sessions in one of 16 conditions, each a different combination of MABT components being included or excluded from a base behavioral treatment. Our primary aim is to evaluate each component's independent efficacy on disordered eating symptoms. Our secondary aims are to confirm each component's target engagement (i.e., whether each component improves the targeted variable and outcomes), and test that each component's efficacy is moderated by baseline weaknesses in the same component (e.g., that participants with poor distress tolerance at baseline benefit most from the distress tolerance component). Our exploratory aim is to quantify the component interaction effects.
Effects of fire on ground‐dwelling arthropods in a shrub‐dominated grassland
Authors: Butler Anna , Davis Craig A. , Fuhlendorf Samuel D. , Wilder Shawn M.
Published: December 2020

Arthropods are abundant and diverse animals in many terrestrial food webs. In western Oklahoma, some shrublands are interspersed with discrete, dense thickets of tall, woody vegetation, known as mottes. Some of these shrublands are managed with prescribed burning. The goal of this study was to examine whether prescribed burning interacted with habitat type (i.e., shrubland versus mottes) to affect ground‐dwelling arthropod communities. Arthropods were collected in pitfall traps at four sampling locations in relation to mottes; in the center of mottes, and three plot location in shrublands; 1 m, 15 m, and 50 m away from the edge of the motte. There were three treatment levels for burning: one year postburn (burned in dormant months of 2017), two years postburn (burned in dormant months of 2016), and unburned (burned in dormant season of 2014 and prior). There were no significant interactions between prescribed burning and habitat type. Mottes had a different community of arthropods compared with the surrounding shrubland. Mottes also had lower overall abundance, but a higher diversity of arthropods. In terms of fires, arthropod communities one year after burning were different from those two or more years after burning. There was no effect of burning on overall arthropod abundance, but plots that were one year since burning had significantly lower diversity compared with plots that were two or more years postburn. The results of this study suggest that both fire and mottes can independently facilitate heterogeneity in arthropod communities, but they do not appear to interact with one another.
Increased mortality and worse cardiac outcome of acute myocardial infarction during the early COVID‐19 pandemic
Authors: Primessnig Uwe , Pieske Burkert M. , Sherif Mohammad
Published: December 2020

Aims

This study aimed to evaluate the impact of coronavirus disease 2019 (Covid‐19) outbreak on admissions for acute myocardial infarction (AMI) and related mortality, severity of presentation, major cardiac complications and outcome in a tertiary‐care university hospital in Berlin, Germany.

Methods and results

In a single‐centre cross‐sectional observational study, we included 355 patients with AMI containing ST‐elevation or non‐ST‐elevation myocardial infarction (STEMI or NSTEMI), admitted for emergency cardiac catheterization between January and April 2020 and the equivalent time in 2019. During the early phase of the Covid‐19 pandemic (e‐COV) in Berlin (March and April 2020), admissions for AMI halved compared with those in the pre‐Covid‐19 time (January and February 2020; pre‐COV) and with those in the corresponding months in 2019. However, mortality for AMI increased substantially from 5.2% pre‐COV to 17.7% (P < 0.05) during e‐COV. Severity of presentation for AMI was more pronounced during e‐COV [increased levels of cardiac enzymes, reduced left ventricular ejection fraction (LVEF), an increase in the need of inotropic support by 25% (P < 0.01)], while patients' demographic and angiographic characteristics did not differ between pre‐COV and e‐COV. Time from symptom onset to first medical contact was prolonged in all AMI during e‐COV (presentation > 72 h +21% in STEMI, p = 0.04 and presentation > 72 h in NSTEMI +22%, p = 0.02). Door to balloon time was similar in STEMI patients, while time from first medical contact to revascularization was significantly delayed in NSTEMI patients (p = 0.02). Major cardiac complications after AMI occurred significantly more often, and cardiac recovery was worse in e‐COV than in pre‐COV, demonstrated by a significantly lower LVEF (39 ± 16 vs. 46 ± 16, p < 0.05) at hospital discharge and substantially higher NTproBNP levels.

Conclusions

The Covid‐19 outbreak affects hospital admissions for acute coronary syndromes. During the first phase of the pandemia, significantly less patients with AMI were admitted, but those admitted presented with a more severe phenotype and had a higher mortality, more complications, and a worse short‐term outcome. Therefore, our data indicate that Covid‐19 had relevant impact on non‐infectious disease states, such as acute coronary syndromes.
Two year outcome in nonagenarians undergoing percutaneous mitral valve repair
Authors: Christidi Aikaterini , Haschemi Jafer , Spieker Maximilian , Bönner Florian , Kelm Malte , Westenfeld Ralf , Horn Patrick
Published: December 2020

Aims

Percutaneous mitral valve repair (PMVR) has emerged as standard treatment in selected patients with clinically relevant mitral regurgitation (MR) and increased surgical risk. We aimed to evaluate the safety and clinical outcomes in nonagenarians undergoing PMVR.

Methods and results

Altogether, 493 patients with severe MR who were treated with PMVR were included in this open‐label prospective study and followed up for 2 years. We treated 25 patients with PMVR aged 90 years or above, 185 patients aged 80–89 years, and 283 patients aged <80 years. PMVR in nonagenarians was safe and did not differ from PMVR in younger patients in terms of safety endpoints. Device success did not differ among the groups (100% in nonagenarians, 95.7% in octogenarians, and 95.1% in septuagenarians, P = 0.100). Unadjusted 2 year mortality was 28% in nonagenarians, 32.4% in octogenarians, and 19.8% in septuagenarians (P = 0.008). Kaplan–Meier curves confirmed similar 2 year survival in the nonagenarian and octogenarian groups (P = 0.657). In the multivariate analysis, age [hazard ratio (HR) 1.031, 95% confidence interval (CI) 1.002–1.060, P = 0.034], higher post‐procedural transmitral valve gradients (HR 1.187, 95% CI 1.104–1.277, P = 0.001), and post‐procedural acute kidney injury (HR 2.360, 95% CI 1.431–3.893, P = 0.001) were independent predictors of 2 year mortality. Altogether, 89.4% of the nonagenarians, 85.9% of the octogenarians, and 86.4% of the septuagenarians had MR grade of 2+ or less at 1 year after PMVR (P = 0.910). New York Heart Association functional class improved in the vast majority of patients, irrespective of age (P = 0.129). After 1 year, 9.5% of the nonagenarians, 22.3% of the octogenarians, and 25.2% of the septuagenarians (each P = 0.001 compared with baseline) suffered from New York Heart Association Functional Class III or IV. The rate of heart failure rehospitalization in the first 12 months after PMVR did not differ among the groups (16% in the nonagenarians, 16.7% in the octogenarians, and 17.7% in the septuagenarians) (P = 0.954). Quality of life assessed by the Minnesota Living with Heart Failure Questionnaire before and at 1 year after PMVR improved in all age groups (P = 0.001).

Conclusions

Percutaneous mitral valve repair in carefully selected nonagenarians is feasible and safe with intermediate‐term beneficial effects comparable with those in younger patients.
Study on Structural and Thermal Characteristics of Heteroleptic Yttrium Complexes as Potential Precursors for Vapor Phase Deposition
Authors: Beer Sebastian M. J. , Krusenbaum Annika , Winter Manuela , Vahlas Constantin , Devi Anjana
Published: December 2020

Yttrium oxide (Y2O3) thin films are implemented as a functional component in a broad field of applications such as optics, electronics or thermal barrier coatings. Atomic layer deposition (ALD) is a promising technique to fabricate high‐quality thin films with atomic level precision in which the precursor choice plays a crucial role in process development. The limited number of suitable yttrium precursors available for ALD of Y2O3 has triggered increasing research activity seeking new or modified precursors. In this study, heteroleptic compounds of yttrium bearing the cyclopentadienyl (Cp) ligand in combination with the chelating amidinate or guanidinate ligands were targeted as potential precursors for ALD. In this context, a systematic and comparative study of the structure and thermal characteristics of (bis‐cyclopentadienyl‐(N,N'‐diisopropyl‐2‐methyl‐amidinato)yttrium) [YCp2(dpamd)] 1 and (bis‐cyclopentadienyl‐(N,N'‐diisopropyl‐2‐dimethylamido‐guanidinato)yttrium) [YCp2(dpdmg)] 2 was performed. Complementary characterization tools such as 1H‐NMR, elemental analysis, electron‐impact mass spectrometry (EI‐MS) and single‐crystal X‐ray diffraction (XRD) confirmed the spectroscopic purity and the monomeric nature of the metalorganic compounds. Hirshfeld surface analysis revealed influence of the ligand choice on the intermolecular interactions of the compounds. The important figures of merit for a precursor, namely the thermal properties were investigated via thermogravimetric analysis. Thus, the volatility, transport behavior and thermal stability were examined and compared to their homoleptic counterparts [YCp3], [Y(dpamd)3] or [Y(dpdmg)3].
Brain parcellation driven by dynamic functional connectivity better capture intrinsic network dynamics
Authors: Fan Liangwei , Zhong Qi , Qin Jian , Li Na , Su Jianpo , Zeng Ling‐Li , Hu Dewen , Shen Hui
Published: December 2020

Until now, dynamic functional connectivity (dFC) based on functional magnetic resonance imaging is typically estimated on a set of predefined regions of interest (ROIs) derived from an anatomical or static functional atlas which follows an implicit assumption of functional homogeneity within ROIs underlying temporal fluctuation of functional coupling, potentially leading to biases or underestimation of brain network dynamics. Here, we presented a novel computational method based on dynamic functional connectivity degree (dFCD) to derive meaningful brain parcellations that can capture functional homogeneous regions in temporal variance of functional connectivity. Several spatially distributed but functionally meaningful areas that are well consistent with known intrinsic connectivity networks were identified through independent component analysis (ICA) of time‐varying dFCD maps. Furthermore, a systematical comparison with commonly used brain atlases, including the Anatomical Automatic Labeling template, static ICA‐driven parcellation and random parcellation, demonstrated that the ROI‐definition strategy based on the proposed dFC‐driven parcellation could better capture the interindividual variability in dFC and predict observed individual cognitive performance (e.g., fluid intelligence, cognitive flexibility, and sustained attention) based on chronnectome. Together, our findings shed new light on the functional organization of resting brains at the timescale of seconds and emphasized the significance of a dFC‐driven and voxel‐wise functional homogeneous parcellation for network dynamics analyses in neuroscience.
Metabolic Landscape of the Mouse Liver by Quantitative 31P Nuclear Magnetic Resonance Analysis of the Phosphorome
Authors: Bernardo‐Seisdedos Ganeko , Bilbao Jon , Fernández‐Ramos David , Lopitz‐Otsoa Fernando , Gutierrez de Juan Virginia , Bizkarguenaga Maider , Mateos Borja , Fondevila Marcos F. , Abril‐Fornaguera Jordi , Diercks Tammo , Lu Shelly C. , Nogueiras Rubén , Mato José M. , Millet Oscar
Published: December 2020

Background and Aims

The liver plays a central role in all metabolic processes in the body. However, precise characterization of liver metabolism is often obscured by its inherent complexity. Phosphorylated metabolites occupy a prominent position in all anabolic and catabolic pathways. Here, we develop a 31P nuclear magnetic resonance (NMR)–based method to study the liver “phosphorome” through the simultaneous identification and quantification of multiple hydrophilic and hydrophobic phosphorylated metabolites.

Approach and Results

We applied this technique to define the metabolic landscape in livers from a mouse model of the rare disease disorder congenital erythropoietic porphyria (CEP) as well as two well‐known murine models of nonalcoholic steatohepatitis: one genetic, methionine adenosyltransferase 1A knockout mice, and the other dietary, mice fed a high‐fat choline‐deficient diet. We report alterations in the concentrations of phosphorylated metabolites that are readouts of the balance between glycolysis, gluconeogenesis, the pentose phosphate pathway, the tricarboxylic acid cycle, and oxidative phosphorylation and of phospholipid metabolism and apoptosis. Moreover, these changes correlate with the main histological features: steatosis, apoptosis, iron deposits, and fibrosis. Strikingly, treatment with the repurposed drug ciclopirox improves the phosphoromic profile of CEP mice, an effect that was mirrored by the normalization of liver histology.

Conclusions

In conclusion, these findings indicate that NMR‐based phosphoromics may be used to unravel metabolic phenotypes of liver injury and to identify the mechanism of drug action.
A novel algorithm for the computation of systems containing different types of integral and integro‐differential equations
Authors: Khan Noor Saeed , Ali Liaqat , Ali Rohail , Kumam Poom , Thounthong Phatiphat
Published: December 2020

An easy and efficient technique is applied to get a reliable analytic approximate solution of linear and nonlinear integral and integro‐differential equations arising in the phenomena of everyday life. The proposed technique consists of a series only in which the unknown constants are determined in the usual way. The obtained results by this technique are in good agreement with the exact solution and it is proved that this technique is effective and easy to apply. Some problems are solved to prove the above claims and also the results are compared with exact solutions as well as with the results obtained by already existing different techniques.
Inhibiting phosphoglycerate dehydrogenase counteracts chemotherapeutic efficacy againstMYCN‐amplified neuroblastoma
Authors: Arlt Birte , Zasada Christin , Baum Katharina , Wuenschel Jasmin , Mastrobuoni Guido , Lodrini Marco , Astrahantseff Kathy , Winkler Annika , Schulte Johannes H. , Finkler Sabine , Forbes Martin , Hundsdoerfer Patrick , Guergen Dennis , Hoffmann Jens , Wolf Jana , Eggert Angelika , Kempa Stefan , Deubzer Hedwig E.
Published: December 2020

Here we sought metabolic alterations specifically associated withMYCNamplification as nodes to indirectly target theMYCNoncogene. Liquid chromatography‐mass spectrometry‐based proteomics identified seven proteins consistently correlated with MYCN in proteomes from 49 neuroblastoma biopsies and 13 cell lines. Among these was phosphoglycerate dehydrogenase (PHGDH), the rate‐limiting enzyme in de novo serine synthesis. MYCN associated with two regions in thePHGDHpromoter, supporting transcriptionalPHGDHregulation by MYCN. Pulsed stable isotope‐resolved metabolomics utilizing13C‐glucose labeling demonstrated higher de novo serine synthesis inMYCN‐amplified cells compared to cells with diploidMYCN. An independence ofMYCN‐amplified cells from exogenous serine and glycine was demonstrated by serine and glycine starvation, which attenuated nucleotide pools and proliferation only in cells with diploidMYCNbut did not diminish these endpoints inMYCN‐amplified cells. Proliferation was attenuated inMYCN‐amplified cells by CRISPR/Cas9‐mediatedPHGDHknockout or treatment with PHGDH small molecule inhibitors without affecting cell viability. PHGDH inhibitors administered as single‐agent therapy to NOG mice harboring patient‐derivedMYCN‐amplified neuroblastoma xenografts slowed tumor growth. However, combining a PHGDH inhibitor with the standard‐of‐care chemotherapy drug, cisplatin, revealed antagonism of chemotherapy efficacy in vivo. Emergence of chemotherapy resistance was confirmed in the genetic PHGDH knockout model in vitro. Altogether, PHGDH knockout or inhibition by small molecules consistently slows proliferation, but stops short of killing the cells, which then establish resistance to classical chemotherapy. Although PHGDH inhibition with small molecules has produced encouraging results in other preclinical cancer models, this approach has limited attractiveness for patients with neuroblastoma.
Prospective assessment of a nasopharyngeal carcinoma risk score in a population undergoing screening
Authors: Chen Geng‐Hang , Liu Zhiwei , Ji Ming‐Fang , Pfeiffer Ruth M. , Huang Qi‐Hong , Lu Yu‐Qiang , Xie Shang‐Hang , Lin Chu‐Yang , Chen Wen‐Jie , Chen Xiao‐Xia , Ling Wei , Fan Yu‐Ying , Yu Xia , Wu Biao‐Hua , Wei Kuang‐Rong , Rao Hui‐Lian , Guo Xiang , Hong Ming‐Huang , Ma Jun , Liu Qing , Hildesheim Allan , Cao Su‐Mei
Published: December 2020

Despite evidence suggesting the utility of Epstein‐Barr virus (EBV) markers to stratify individuals with respect to nasopharyngeal carcinoma (NPC) risk in NPC high‐risk regions, no validated NPC risk prediction model exists. We aimed to validate an EBV‐based NPC risk score in an endemic population undergoing screening for NPC. This prospective study was embedded within an ongoing NPC screening trial in southern China initiated in 2008, with 51 235 adult participants. We assessed the score's discriminatory ability (area under the receiver‐operator‐characteristics curve, AUC). A new model incorporating the EBV score, sex and family history was developed using logistic regression and internally validated using cross‐validation. AUCs were compared. We also calculated absolute NPC risk combining the risk score with population incidence and competing mortality data. A total of 151 NPC cases were detected in 2008 to 2016. The EBV‐based score was highly discriminating, with AUC = 0.95 (95% CI = 0.93‐0.97). For 90% specificity, the score had 87.4% sensitivity (95% CI = 81.0‐92.3%). As specificity increased from 90% to 99%, the positive predictive value increased from 2.4% (95% CI = 1.9‐3.0%) to 12.5% (9.9‐15.5%). Correspondingly, the number of positive tests per detected NPC case decreased from 272 (95% CI = 255‐290) to 50 (41‐59). Combining the score with other risk factors (sex, first‐degree family history of NPC) did not improve AUC. Men aged 55 to 59 years with the highest risk profile had the highest 5‐year absolute NPC risk of 6.5%. We externally validated the discriminatory accuracy of a previously developed EBV score in a high‐risk population. Adding nonviral risk factors did not improve NPC prediction.
Difficult name, cold man: Chinese names, gender stereotypicality and trustworthiness
Authors: Du Xiaopeng , Dong Mengchen , Gu Dian , Xin Zhiyong , Jiang Jiang , Sun Yan
Published: December 2020

Names can play an important role in forming first impressions. While much of the literature has demonstrated how alphabet‐based names influence impression formation, little is known about how character‐based names (e.g., Chinese names) affect interpersonal trust. Across six studies, we demonstrated that a difficult‐to‐recognise Chinese name with less frequently used characters activated masculine perception, which in turn decreased trust in the name holder. The masculine inferences from difficult names were replicated across within‐subjects (Study 1a and 1b) and between‐subjects judgements and maintained irrespective of normative knowledge about difficult names as male names (Study 1c). The mediation of gender stereotypicality was manifested in both measured spontaneous gender inference (Study 2a and Study 2b) and manipulated gender information (Study 2c). The effects of recognisability on masculine and trust perceptions were independent of pronunciationability (Study 2b). This research extends previous research by revealing the implications of character‐based names and pictographic language on the feeling‐as‐information theory, also in terms of interpersonal contexts.
miR‐217 alleviates high‐glucose‐induced vascular smooth muscle cell dysfunction via regulating ROCK1
Authors: Zhou Wan , Ye Shandong , Wang Wei
Published: December 2020

MicroRNA‐217 (miR‐217) has been recently reported to be abnormally expressed during atherosclerosis. Nonetheless, it still remains unknown whether miR‐217 can regulate inflammation, proliferation, migration, and apoptosis of vascular smooth muscle cells (VSMCs) in high‐glucose condition. Sprague Dawley rats were used for establishing diabetic animal models. miR‐217 mimics and miR‐217 inhibitors were transfected into VSMCs. The miR‐217 and ROCK1 expressions were measured by quantitative reverse transcription‐polymerase chain reaction and Western blot. VSMCs’ proliferation, migration, cell cycle, and apoptosis were validated using the Cell Counting Kit‐8 assay, Transwell assay, and flow cytometry analysis, respectively. The binding sites between miR‐217 and the 3′‐untranslated region of ROCK1 were predicted via miRanda, PicTar, TargetScan, and microT databases, and the targeting relationship was confirmed by dual‐luciferase reporter experiments. miR‐217 was found to be upregulated in VSMCs treated by high glucose and aorta VSMCs of diabetic rats. Transfection of miR‐217 mimics significantly induced VSMCs cycle arrest, inhibition of proliferation, reduction of migration, and enhancement of apoptosis. The bioinformatics analysis and dual‐luciferase reporter experiments identified ROCK1 as a direct target of miR‐217. miR‐217 inhibits excessive proliferation and migration of VSMCs induced by high glucose by targeting ROCK1.
The localization number of designs
Authors: Bonato Anthony , Huggan Melissa A. , Marbach Trent G.
Published: December 2020

We study the localization number of incidence graphs of designs. In the localization game played on a graph, the cops attempt to determine the location of an invisible robber via distance probes. The localization number of a graph , written , is the minimum number of cops needed to ensure the robber's capture. We present bounds on the localization number of incidence graphs of balanced incomplete block designs. Exact values of the localization number are given for the incidence graphs of projective and affine planes. Bounds are given for Steiner systems and for transversal designs.
COVID‐19 pandemic: mechanism, diagnosis, and treatment
Authors: Kumar Vinay , Doshi Khushi U , Khan Wajihul H , Rathore Anurag S
Published: December 2020

The COVID‐19 pandemic has become a significant global health crisis. The virus has spread to more than 200 countries worldwide and continues to infect more lives and cause more deaths. The second, and possibly the third wave, has begun, with hospitalizations and deaths rising continuously. The impact has galvanized research groups around the world that are working on novel diagnostics, vaccines, biotherapeutics, personal protective equipment, and epidemiological data analysis. This perspective focuses on the biological aspects of COVID‐19 infection, the origin and structure of SARS‐CoV‐2, its genomic variations, mode of transmission, pathogenesis in the human body, symptoms of the infection, mechanism of entry in the host cell, and techniques for clinical diagnosis. Precautionary measures, different treatment options, vaccine development, importance of multidisciplinary research, and political and global prospects of the pandemic have also been addressed. © 2020 Society of Chemical Industry
Enhancement of chromate bioaccumulation by engineered Escherichia coli cells co‐expressing chromate reductase (YieF) and a rice metallothionein isoform (OsMT1)
Authors: Shahpiri Azar , Majnoun Zahra , Kazemi‐Nasab Akram , Zarei Mohsen
Published: December 2020

BACKGROUND

Hexavalent chromium Cr(VI) is a toxic and carcinogenic heavy metal. It is highly water soluble and one of the most widely used metals in industry, resulting in soil and water contamination. Nowadays engineering microbes provide new strategies for remediation of heavy metals.

RESULTS

In the present work, a gene encoding E. coli chromate reductase (YieF) was cloned in pCDF‐1b and was transferred to both cells containing empty pET41a (control strain), and cells containing pET41a‐OsMT1 (R‐MT1) resulted in production of new strains R‐YieF and R‐YieF/MT1, respectively. Both proteins – YieF as His‐tag fusion protein and OsMT1 as glutathione‐S‐transferase fusion protein – appeared in the soluble fraction of R‐YieF/MT1 after induction with isopropyl‐d‐1‐thiogalactopyranoside . The strain R‐YieF/OsMT1 showed high tolerance to Cr6+ and accumulated significantly higher Cr6+ than R‐MT1 (5 mg L−1), R‐YieF (7 mg L−1) and control (2 mg L−1). The accumulation of Cr6+ was dependent on the initial concentration of Cr6+ in the medium, time and the presence of other toxic metals such as Ag+1, Hg+2 and Cd2+.

CONCLUSION

This study demonstrated that the co‐expression of YieF and OsMT1 could effectively enhance the accumulation of Cr(VI) by E. coli cells and opens new insights into bioremediation strategies. © 2020 Society of Chemical Industry
Punishment and its putative fallout: A reappraisal
Authors: Fontes Rafaela M. , Shahan Timothy A.
Published: December 2020

In his book Coercion and Its Fallout Murray Sidman argued against the use of punishment based on concerns about its shortcomings and side effects. Among his concerns were the temporary nature of response suppression produced by punishment, the dangers of conditioned punishment, increases in escape and avoidance responses, punishment‐induced aggression, and the development of countercontrol. This paper revisits Sidman's arguments about these putative shortcomings and side effects by examining the available data. Although Sidman's concerns are reasonable and should be considered when using any form of behavioral control, there appears to be a lack of strong empirical support for the notion that these potential problems with punishment are necessarily ubiquitous, long‐lasting, or specific to punishment. We describe the need for additional research on punishment in general, and especially on its putative shortcomings and side effects. We also suggest the need for more effective formal theories of punishment that provide a principled account of how, why, and when lasting effects of punishment and its potential side effects might be expected to occur or not. In addition to being necessary for a complete account of behavior, such data and theories might contribute to improved interventions for problems of human concern.
The Hamiltonicity of essentially 9‐connected line graphs
Authors: Kaiser Tomáš , Vrána Petr
Published: December 2020

Yang et al proved that every 3‐connected, essentially 11‐connected line graph is Hamilton‐connected. This was extended by Li and Yang to 3‐connected, essentially 10‐connected line graphs. Strengthening their result further, we prove that 3‐connected, essentially 9‐connected line graphs are Hamilton‐connected. We use a method based on quasigraphs in combination with the discharging technique. The result extends to claw‐free graphs.
Evaluating ERA‐Interim, Agri4Cast, and E‐OBS gridded products in reproducing spatiotemporal characteristics of precipitation and drought over a data poor region: The Case of Greece
Authors: Mavromatis Theodoros , Voulanas Dimitrios
Published: December 2020

Gridded climate datasets are among the most used datasets in the study of weather and climate. Given the large range of such products currently available, investigators must consider their strengths and weaknesses. This research evaluated the comparative performance of two reanalysis datasets (ERA‐Interim, and Agri4Cast [e.g. MARS‐STAT]) and one reprocessing dataset (E‐OBS) in replicating selected spatiotemporal characteristics of precipitation and drought at 20 wine production regions in Greece during 1981–2012. The results highlighted the abilities of E‐OBS and Agri4Cast, whose performance varied with season and the specific rainfall characteristic in question. The former product: (1) reproduced better the annual decreasing trends in spring, summer, and autumn, (2) captured a larger portion of the observed monthly variability in spring and summer, associated better and showed the lowest errors with observations, and (3) computed better or equal to Agri4Cast different skill scores applied on the daily time series, replicated better the probabilities of wet and dry days and equally well with Agri4Cast the extreme precipitation indices. Agri4Cast replicated better the monthly cycle of precipitation (underestimating though the station averages) and the increasing trend from SE to NW, on spatial basis. With regards to drought monitoring, frequency and detection of very and extremely wet and dry spells, SPI was superior to SC‐PDSI (the self‐calibrated version of Palmer's index), particularly when E‐OBS data was used. Agri4Cast and E‐OBS are the most appropriate products for use in climate/atmospheric‐related research over Greece.