bluuebunny/crossref_metadata_2025 huggingface dataset:
Hyperuricemia Is Not an Independent Predictor of Erectile Dysfunction
Authors: Tuokko Antti T. , Murtola Teemu , Korhonen Päivi , Kaipia Antti
Published: February 2021

Introduction

Erectile dysfunction (ED) is strongly associated with physiological and metabolic disturbances, and hyperuricemia has been proposed to predict the onset of ED.

Aim

To investigate if hyperuricemia is an independent predictor for ED when all relevant confounding factors are taken into account.

Methods

This is a cross-sectional study of men aged between 45 and 70 years. The population was well characterized for established cardiovascular risk factors, metabolic syndrome, as well as kidney function, depression, and socioeconomic factors. Analysis was limited to 254 men with complete data and also serum uric acid (SUA) measurements were available. This included 150 men with and 104 without ED. The presence and severity of ED was evaluated using International Index of Erectile Function-5 questionnaire. Risk of ED by SUA level was calculated using univariate and multivariable-adjusted logistic regression. Effect modification by participant characteristics were evaluated in subgroup analyses.

Main Outcome measures

The main outcome measures of this study are prevalence and severity of erectile dysfunction.

Results

Patients with ED (59% of the study population) were older than men without ED (59 vs 54 years) and had lower serum testosterone (14.3, 95% CI 11.3–17.3 vs 15.1 nmol/l, 95% CI 12.1–18.8, respectively). Regarding all other variables, the groups were comparable. No significant difference was found for SUA by ED. SUA was not associated with ED risk in univariate or multivariable analysis (multivariable-adjusted OR 1.14, 95% CI 0.59–2.19, P = .7) for SUA level higher than median compared with median or lesser (OR 1.00, 95% CI 0.997–1.006, P = .7 for continuous variable). No subgroup analysis modified the association. After multivariable adjustment age, education level and depression were statistically significant predictors of ED.

Conclusions

Elevated SUA was not found to be an independent risk factor for ED. Metabolic syndrome, glomerular filtration rate, or cardiovascular risk factors did not modify this result. ED cannot be predicted based on the level of SUA.
An Integrated Systems Biology Approach Identifies the Proteasome as a Critical Host Machinery for ZIKV and DENV Replication
Authors: Song Guang , Lee Emily M. , Pan Jianbo , Xu Miao , Rho Hee-Sool , Cheng Yichen , Whitt Nadia , Yang Shu , Kouznetsova Jennifer , Klumpp-Thomas Carleen , Michael Samuel G. , Moore Cedric , Yoon Ki-Jun , Christian Kimberly M. , Simeonov Anton , Huang Wenwei , Xia Menghang , Huang Ruili , Lal-Nag Madhu , Tang Hengli , Zheng Wei , Qian Jiang , Song Hongjun , Ming Guo-li , Zhu Heng
Published: February 2021

The Zika virus (ZIKV) and dengue virus (DENV) flaviviruses exhibit similar replicative processes but have distinct clinical outcomes. A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis. Here we employed three independent systems biology approaches toward this goal. First, protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and 20,240 human proteins revealed multiple conserved cellular pathways and protein complexes, including proteasome complexes. Second, an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process. Third, high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds, including six proteasome inhibitors that suppress both ZIKV and DENV replication. Integrative analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV replication. Our study provides multi-omics datasets for further studies of flavivirus–host interactions, disease pathogenesis, and new drug targets.
The Role of DNA Methylation Reprogramming During Sex Determination and Transition in Zebrafish
Authors: Wang Xinxin , Ma Xin , Wei Gaobo , Ma Weirui , Zhang Zhen , Chen Xuepeng , Gao Lei , Liu Zhenbo , Yuan Yue , Yi Lizhi , Wang Jun , Tokumoto Toshinobu , Huang Junjiu , Chen Dahua , Zhang Jian , Liu Jiang
Published: February 2021

DNA methylation is a prevalent epigenetic modification in vertebrates, and it has been shown to be involved the regulation of gene expression and embryo development. However, it remains unclear how DNA methylation regulates sexual development, especially in species without sex chromosomes. To determine this, we utilized zebrafish to investigate DNA methylation reprogramming during juvenile germ cell development and adult female-to-male sex transition. We reveal that primordial germ cells (PGCs) undergo significant DNA methylation reprogramming during germ cell development, and the methylome of PGCs is reset to an oocyte/ovary-like pattern at 9 days post fertilization (9 dpf). When DNA methyltransferase (DNMT) activity in juveniles was blocked after 9 dpf, the zebrafish developed into females. We also show that Tet3 is involved in PGC development. Notably, we find that DNA methylome reprogramming during adult zebrafish sex transition is similar to the reprogramming during the sex differentiation from 9 dpf PGCs to sperm. Furthermore, inhibiting DNMT activity can prevent the female-to-male sex transition, suggesting that methylation reprogramming is required for zebrafish sex transition. In summary, DNA methylation plays important roles in zebrafish germ cell development and sexual plasticity.
Pediatric and adolescent mood disorders
Authors: Sulley Saanie , Ndanga Memory , Mensah Nana
Published: February 2021

Background:

Mental health is an essential aspect of health and wellbeing that the general population often overlooks. This study aims to utilize a nationwide sample [Healthcare Cost and Utilization Project (HCUP) Kid's Inpatient Database (KID)] to analyze the factors affecting inpatient mood disorder admissions in the United States.

Methods:

A total of 295,472 cases ages 1–20 were identified to meet the criteria (Appendix A) for the selected mood disorders from the HCUP KID 2016 dataset. We conducted descriptive statistics of the individual diagnosis. We evaluated the relationships with variables such as age (grouped), sex, region, disposition, household income, race, rural-urban demographics, and mean charges. We also conducted association tests for the variables of interest.

Results:

An average of six days LOS was observed for mood disorders compared to four days LOS for other pediatric inpatient admissions nationwide. The highest prevalence rate (per 100,000) of single (5050), recurrent (2284) episode MDD and bipolar disorder (2445) was observed among no charge (uninsured) populations. The native American population had the highest rate prevalence of single episode MDD (3274) and highest extreme and significant loss of function at presentation. The highest manic episode presentation rate was observed among Black (12) and Native American (9) populations. Manic episodes and bipolar disorder were higher among young adults (47 and 4554); teenagers (13–17) showed a higher presentation rate for all other mood disorders.

Conclusion:

No charge (uninsured), teenagers (13–17), females, native Americans, and south and midwest regions showed a higher rate of mood disorder presentations among the population. Understanding these variances could play a vital role in highlighting the need for new innovative care approaches. Comprehensive mental health programs in collaboration with educational and community organizations and other stakeholders could be vital to addressing mood and mental health among these populations. This approach tackles several social influencers such as stigma and support to ensure effectiveness and sustainability.conclusion.
The role of m6A modification in the biological functions and diseases
Authors: Jiang Xiulin , Liu Baiyang , Nie Zhi , Duan Lincan , Xiong Qiuxia , Jin Zhixian , Yang Cuiping , Chen Yongbin
Published: February 2021

N6-methyladenosine (m6A) is the most prevalent, abundant and conserved internal cotranscriptional modification in eukaryotic RNAs, especially within higher eukaryotic cells. m6A modification is modified by the m6A methyltransferases, or writers, such as METTL3/14/16, RBM15/15B, ZC3H3, VIRMA, CBLL1, WTAP, and KIAA1429, and, removed by the demethylases, or erasers, including FTO and ALKBH5. It is recognized by m6A-binding proteins YTHDF1/2/3, YTHDC1/2 IGF2BP1/2/3 and HNRNPA2B1, also known as “readers”. Recent studies have shown that m6A RNA modification plays essential role in both physiological and pathological conditions, especially in the initiation and progression of different types of human cancers. In this review, we discuss how m6A RNA methylation influences both the physiological and pathological progressions of hematopoietic, central nervous and reproductive systems. We will mainly focus on recent progress in identifying the biological functions and the underlying molecular mechanisms of m6A RNA methylation, its regulators and downstream target genes, during cancer progression in above systems. We propose that m6A RNA methylation process offer potential targets for cancer therapy in the future.
Viromes outperform total metagenomes in revealing the spatiotemporal patterns of agricultural soil viral communities
Authors: Santos-Medellin Christian , Zinke Laura A , ter Horst Anneliek M , Gelardi Danielle L , Parikh Sanjai J , Emerson Joanne B
Published: February 2021

Viruses are abundant yet understudied members of soil environments that influence terrestrial biogeochemical cycles. Here, we characterized the dsDNA viral diversity in biochar-amended agricultural soils at the preplanting and harvesting stages of a tomato growing season via paired total metagenomes and viral size fraction metagenomes (viromes). Size fractionation prior to DNA extraction reduced sources of nonviral DNA in viromes, enabling the recovery of a vaster richness of viral populations (vOTUs), greater viral taxonomic diversity, broader range of predicted hosts, and better access to the rare virosphere, relative to total metagenomes, which tended to recover only the most persistent and abundant vOTUs. Of 2961 detected vOTUs, 2684 were recovered exclusively from viromes, while only three were recovered from total metagenomes alone. Both viral and microbial communities differed significantly over time, suggesting a coupled response to rhizosphere recruitment processes and/or nitrogen amendments. Viral communities alone were also structured along an 18 m spatial gradient. Overall, our results highlight the utility of soil viromics and reveal similarities between viral and microbial community dynamics throughout the tomato growing season yet suggest a partial decoupling of the processes driving their spatial distributions, potentially due to differences in dispersal, decay rates, and/or sensitivities to soil heterogeneity.
Synergistic epistasis enhances the co-operativity of mutualistic interspecies interactions
Authors: Turkarslan Serdar , Stopnisek Nejc , Thompson Anne W , Arens Christina E , Valenzuela Jacob J , Wilson James , Hunt Kristopher A , Hardwicke Jessica , de Lomana Adrián López García , Lim Sujung , Seah Yee Mey , Fu Ying , Wu Liyou , Zhou Jizhong , Hillesland Kristina L , Stahl David A , Baliga Nitin S
Published: February 2021

Early evolution of mutualism is characterized by big and predictable adaptive changes, including the specialization of interacting partners, such as through deleterious mutations in genes not required for metabolic cross-feeding. We sought to investigate whether these early mutations improve cooperativity by manifesting in synergistic epistasis between genomes of the mutually interacting species. Specifically, we have characterized evolutionary trajectories of syntrophic interactions of Desulfovibrio vulgaris (Dv) with Methanococcus maripaludis (Mm) by longitudinally monitoring mutations accumulated over 1000 generations of nine independently evolved communities with analysis of the genotypic structure of one community down to the single-cell level. We discovered extensive parallelism across communities despite considerable variance in their evolutionary trajectories and the perseverance within many evolution lines of a rare lineage of Dv that retained sulfate-respiration (SR+) capability, which is not required for metabolic cross-feeding. An in-depth investigation revealed that synergistic epistasis across pairings of Dv and Mm genotypes had enhanced cooperativity within SR− and SR+ assemblages, enabling their coexistence within the same community. Thus, our findings demonstrate that cooperativity of a mutualism can improve through synergistic epistasis between genomes of the interacting species, enabling the coexistence of mutualistic assemblages of generalists and their specialized variants.
Solid-phase synthesis of peptide Mn(i)–carbonyl bioconjugates and their CO release upon visible light activation
Authors: Zhou Yi , Chen Yonglu , He Chunmao
Published: February 2021

A streamlined one-pot solid-phase synthetic route for peptide–MnCO bioconjugates, which release CO upon exposure to visible light, was developed.
Glycoengineering: scratching the surface
Authors: Critcher Meg , O'Leary Timothy , Huang Mia L.
Published: February 2021

At the surface of many cells is a compendium of glycoconjugates that form an interface between the cell and its surroundings; the glycocalyx. The glycocalyx serves several functions that have captivated the interest of many groups. Given its privileged residence, this meshwork of sugar-rich biomolecules is poised to transmit signals across the cellular membrane, facilitating communication with the extracellular matrix and mediating important signalling cascades. As a product of the glycan biosynthetic machinery, the glycocalyx can serve as a partial mirror that reports on the cell's glycosylation status. The glycocalyx can also serve as an information-rich barrier, withholding the entry of pathogens into the underlying plasma membrane through glycan-rich molecular messages. In this review, we provide an overview of the different approaches devised to engineer glycans at the cell surface, highlighting considerations of each, as well as illuminating the grand challenges that face the next era of ‘glyco-engineers’. While we have learned much from these techniques, it is evident that much is left to be unearthed.
Comprehensive fault simulation method in active distribution network with the consideration of cyber security
Authors: Sheng Wanxing , Liu Keyan , Liang Ying
Published: February 2021

With the many characteristics of cyber–physical systems (CPS), including the complex evolution of various dynamic processes in distribution networks (DNs), communication modes and serious network security events have become important issues. From the perspective of DN analysis, traditional electrical digital simulations cannot access current models of communication systems and cyber network security events. The interactions between cyber and physical networks cannot be simulated and analysed simultaneously, which is challenging to the development of CPS simulations of DNs. To evaluate the impact of cyber networks on physical networks, a CPS simulation platform that contains physical, communication and control layers is discussed. Three‐phase short‐circuit fault processing and islanding operation control are simulated by data interactions among three‐layer models that are used to analyse the impact of communication data tampering on fault handling processes. The influence of data tampering on fault processing and the influence of false data injection and data interception on islanding operation control processes are analysed. The simulation results show that the network information security has a large impact on fault protection and islanding operation control, which leads to the expansion of the outage scope and the failure of islanding operation frequency adjustment. This article also provides a simulation basis for the analysis of CPS operation characteristics and the identification and prevention of cyber network security events.
A novel multi‐objective optimization method for the optimization of interior permanent magnet synchronous machines
Authors: Tong Wenming , Wei Haiyang , Li Shiqi , Zheng Jigui
Published: February 2021

A novel hybrid multi‐objective optimization method which combines the Taguchi method with multi‐level Kriging model is developed for optimization of interior permanent magnet synchronous machines (IPMSMs). This method is capable to sharply reduce the finite element analysis calculations for the given multi‐objective optimization problem compared with the conventional optimization method. The method is applied to maximize the power density and the efficiency of an IPMSM under constraints. After adopting the method in the optimization process, the power density of the IPMSM is significantly improved and the volume of the IPMSM is sharply reduced. And the contrast scheme shows that this method can improve the efficiency while increasing the power density. Besides, a prototype is manufactured to verify the feasibility of this method.
Energy supply reliability assessment of the integrated energy system considering complementary and optimal operation during failure
Authors: Li Zhenkun , Wang Zhifeng , Fu Yang , Zhao Nan
Published: February 2021

Integrated energy system (IES) is an effective solution for energy and environment problems. In view of the difficulty of traditional reliability assessment methods to reasonably and effectively assess the reliability of the IES, an energy supply reliability assessment method based on sequential Monte Carlo simulation is proposed in this study. The optimal operation of the system is realised by mobilising the multi‐energy complementary characteristics during device failure. The reliability of the system under three different operation objectives is compared and analysed. Three new reliability indices are proposed, which take into account the supply of multiple energy loads and the differences among different energy. Finally, through the analysis of energy supply reliability under different objectives, the reasonability of the proposed indices and the flexible scheduling of energy flow under different objectives are verified; therefore, the IES can realise adaptive and targeted operation strategy during device failure. Also, the influence of different device faults on the system's energy supply reliability is ranked, which is of great significance to find the weak parts of the system and provide a reference for the system to improve energy supply reliability.
Analysis and design of a S/PS compensated IPT system with constant current output
Authors: Xu Ziwei , Yang Lin , Li Xiaoming , Liu Sheng , Dong Zifan , Wu Yuanbao
Published: February 2021

Load‐independent constant current (CC) output with high‐system efficiency is required in many cases of Wireless power transfer (WPT) applications. However, the existing topologies with CC output are hard to achieve both simple structure and enough design freedom. In this study, the series/parallel–series (S/PS) topology, which has three compensation capacitors, is presented to achieve CC output. The constant output current of the proposed S/PS topology is free from the constraint of the coils' self‐inductance of the loosely coupled transformer (LCT). A thorough analysis of the proposed S/PS topology that implements CC and ZPA is provided. Besides, ZVS can also be obtained by reasonably setting the value of compensation capacitors. An experimental prototype with 50 V input voltage and 3 A output current is fabricated to validate the practicability and rationality of the proposed topology, and 92.18% power transfer efficiency is achieved. Furthermore, a design example with 2 A output current and the corresponding experimental results are provided to verify that the CC output of the proposed S/PS topology is free from the constraint of the LCT parameters. Finally, a comprehensive comparison with several existing topologies for CC output is conducted to reveal the advantages of the proposed S/PS topology.
Capture of a dipolar magnetic field by laser-produced plasma
Authors: Efimov M.A. , Chibranov A.A. , Berezutsky A.G. , Rumenskikh M.S. , Posukh V.G. , Zakharov Yu.P. , Boyarintsev E.L. , Trushin P.A. , Smolina E.V. , Miroshnichenko I.B. , Shaikhislamov I.F.
Published: February 2021

We describe an experiment on the interaction of a dipolar magnetic field with the laser plasma flow produced inside of a laboratory magnetosphere. This interaction is found to exhibit two dynamic stages: after a prompt displacement of the dipole field by the laser plasma, the magnetic field is captured and carried outside of the magnetosphere. The resultant data confirm the results of previous measurements carried out far beyond the magnetosphere and provide additional information about the new process of capturing the dipolar magnetic field by the internal magnetospheric plasma flow.
Type-II GaAsBi QDs/GaSb for middle-wave and long-wave infrared lasers
Authors: Zhang Zhongyue , Zhang Liyao , Zhang Mingxuan , Yao Shuang , Yu Peng , Li Xiaodan
Published: February 2021

A GaSb/GaAsBi type-II quantum dot structure is proposed for fabricating middle-wave infrared (MWIR) and long-wave infrared (LWIR) lasers. The finite element method is employed to investigate the train distributions and band structures of the proposed structures with different Bi contents and QD sizes. It is found that the strain component εxx
decreases with Bi contents and heights, and increases with the diameter, while the component εzz
inversely changes. The charge carriers recombine between the electrons in GaAsBi QDs and the holes in GaSb. The energy of the ground states of electrons of GaAsBi QDs decreases and the emission wavelength increases with the Bi contents and QD sizes. The emission wavelength can cover MWIR and LWIR ranges with proper Bi contents and QD sizes. The proposed structure provides a feasible way to fabricate MWIR and LWIR lasers.
SUV39H2 epigenetic silencing controls fate conversion of epidermal stem and progenitor cells
Authors: Balmer Pierre , Hariton William V.J. , Sayar Beyza S. , Jagannathan Vidhya , Galichet Arnaud , Leeb Tosso , Roosje Petra , Müller Eliane J.
Published: February 2021

Epigenetic histone trimethylation on lysine 9 (H3K9me3) represents a major molecular signal for genome stability and gene silencing conserved from worms to man. However, the functional role of the H3K9 trimethylases SUV39H1/2 in mammalian tissue homeostasis remains largely unknown. Here, we use a spontaneous dog model with monogenic inheritance of a recessive SUV39H2 loss-of-function variant and impaired differentiation in the epidermis, a self-renewing tissue fueled by stem and progenitor cell proliferation and differentiation. Our results demonstrate that SUV39H2 maintains the stem and progenitor cell pool by restricting fate conversion through H3K9me3 repressive marks on gene promoters encoding components of the Wnt/p63/adhesion axis. When SUV39H2 function is lost, repression is relieved, and enhanced Wnt activity causes progenitor cells to prematurely exit the cell cycle, a process mimicked by pharmacological Wnt activation in primary canine, human, and mouse keratinocytes. As a consequence, the stem cell growth potential of cultured SUV39H2-deficient canine keratinocytes is exhausted while epidermal differentiation and genome stability are compromised. Collectively, our data identify SUV39H2 and potentially also SUV39H1 as major gatekeepers in the delicate balance of progenitor fate conversion through H3K9me3 rate-limiting road blocks in basal layer keratinocytes.
Phosphorylation of SNX27 by MAPK11/14 links cellular stress–signaling pathways with endocytic recycling
Authors: Mao Lejiao , Liao Chenyi , Qin Jiao , Gong Yanqiu , Zhou Yifei , Li Shasha , Liu Zhe , Deng Huaqing , Deng Wankun , Sun Qingxiang , Mo Xianming , Xue Yu , Billadeau Daniel D. , Dai Lunzhi , Li Guohui , Jia Da
Published: February 2021

Endocytosed proteins can be delivered to lysosomes for degradation or recycled to either the trans-Golgi network or the plasma membrane. It remains poorly understood how the recycling versus degradation of cargoes is determined. Here, we show that multiple extracellular stimuli, including starvation, LPS, IL-6, and EGF treatment, can strongly inhibit endocytic recycling of multiple cargoes through the activation of MAPK11/14. The stress-induced kinases in turn directly phosphorylate SNX27, a key regulator of endocytic recycling, at serine 51 (Ser51). Phosphorylation of SNX27 at Ser51 alters the conformation of its cargo-binding pocket and decreases the interaction between SNX27 and cargo proteins, thereby inhibiting endocytic recycling. Our study indicates that endocytic recycling is highly dynamic and can crosstalk with cellular stress–signaling pathways. Suppression of endocytic recycling and enhancement of receptor lysosomal degradation serve as new mechanisms for cells to cope with stress and save energy.
Filament evanescence of myosin II and smooth muscle function
Authors: Wang Lu , Chitano Pasquale , Seow Chun Y.
Published: February 2021

Smooth muscle is an integral part of hollow organs. Many of them are constantly subjected to mechanical forces that alter organ shape and modify the properties of smooth muscle. To understand the molecular mechanisms underlying smooth muscle function in its dynamic mechanical environment, a new paradigm has emerged that depicts evanescence of myosin filaments as a key mechanism for the muscle’s adaptation to external forces in order to maintain optimal contractility. Unlike the bipolar myosin filaments of striated muscle, the side-polar filaments of smooth muscle appear to be less stable, capable of changing their lengths through polymerization and depolymerization (i.e., evanescence). In this review, we summarize accumulated knowledge on the structure and mechanism of filament formation of myosin II and on the influence of ionic strength, pH, ATP, myosin regulatory light chain phosphorylation, and mechanical perturbation on myosin filament stability. We discuss the scenario of intracellular pools of monomeric and filamentous myosin, length distribution of myosin filaments, and the regulatory mechanisms of filament lability in contraction and relaxation of smooth muscle. Based on recent findings, we suggest that filament evanescence is one of the fundamental mechanisms underlying smooth muscle’s ability to adapt to the external environment and maintain optimal function. Finally, we briefly discuss how increased ROCK protein expression in asthma may lead to altered myosin filament stability, which may explain the lack of deep-inspiration–induced bronchodilation and bronchoprotection in asthma.
Stability of 10-mg/mL and 50-mg/mL ketamine oral solutions
Authors: Ancedy Dimitri , Sebti Maria , Postaire Martine , Vidal Fabrice , Cisternino Salvatore , Schlatter Joël
Published: February 2021

Purpose

Ketamine is an anesthetic agent commonly used for the induction of anesthesia. Ketamine is also given to control pain, for treatment of posttraumatic stress disorder, and to induce bronchodilation in refractory asthma. Moreover, ketamine therapy is gaining ground as an intervention for patients with treatment-resistant depression and individuals who have depression with serious suicidal ideation. Recently, the drug has been used to disrupt maladaptive reward memories in individuals with harmful alcohol consumption behaviors. The stability of 10-mg/mL and 50-mg/mL ketamine solutions stored at ambient and refrigeration temperatures was assessed over 90 days.

Methods

Three batches of 10-mg/mL and 50-mg/mL ketamine solutions were stored for 90 days under two temperature conditions (2°C-8°C and 22°C-25°C) in amber plastic bottles. Chemical stability was assessed using a stability-indicating high-performance liquid chromatography assay. At each study time, visual inspection and pH assessments of ketamine concentration and pH were conducted.

Results

For all solutions tested at each condition, the ketamine concentration remaining was at least 98% of the initial concentration over 90 days of storage. Throughout the study period, solution pH remained stable and the color and odor of the suspensions remained unchanged.

Conclusion

Extemporaneously compounded 10-mg/mL and 50-mg/mL oral solutions of ketamine prepared in a flavored suspending excipient and stored in amber polypropylene plastic bottles were stable for at least 90 days at both ambient and refrigeration temperatures.
Health-system implementation of a collaborative core curriculum for advanced pharmacy experiential education during the COVID-19 pandemic
Authors: Montepara Courtney A , Schoen Rebecca R , Guarascio Anthony J , McConaha Jamie L , Horn Paula J
Published: February 2021

Purpose

A collaborative advanced pharmacy practice experience (APPE) education model established within a healthcare institution during the coronavirus disease 2019 (COVID-19) pandemic is described.

The COVID-19 pandemic caused a nationwide disruption of APPE pharmacy education. Healthcare institutions faced the challenge of educating APPE students while attempting to simultaneously de-densify work areas and reduce transmission risk for employees and patients. A pharmacist coordinator and pharmacist academic partners at a large teaching hospital created a collaborative common core curriculum model for resourceful implementation of APPE education. Healthcare network pharmacists, clinical pharmacist academic partners, and pharmacy residents delivered the curriculum to 35 pharmacy students over a 9-week time period. Main components of the curriculum included patient case discussions, topic discussions, journal club presentations, live continuing education (CE) webinars, and development of pharmacy technician CE programs. A majority of students reported positive experiences working with a variety of preceptors from different specialties (81%) and collaborating with students from other universities (62%).

Conclusion

A health system can leverage institutional, network-wide, and academic partner resources to implement a collaborative APPE curriculum during challenging times such as those experienced during the COVID-19 pandemic.
Genome size evolution is associated with climate seasonality and glucosinolates, but not life history, soil nutrients or range size, across a clade of mustards
Authors: Cacho N Ivalú , McIntyre Patrick J , Kliebenstein Daniel J , Strauss Sharon Y
Published: February 2021

Background and Aims

We investigate patterns of evolution of genome size across a morphologically and ecologically diverse clade of Brassicaceae, in relation to ecological and life history traits. While numerous hypotheses have been put forward regarding autecological and environmental factors that could favour small vs. large genomes, a challenge in understanding genome size evolution in plants is that many hypothesized selective agents are intercorrelated.

Methods

We contribute genome size estimates for 47 species of Streptanthus Nutt. and close relatives, and take advantage of many data collections for this group to assemble data on climate, life history, soil affinity and composition, geographic range and plant secondary chemistry to identify simultaneous correlates of variation in genome size in an evolutionary framework. We assess models of evolution across clades and use phylogenetically informed analyses as well as model selection and information criteria approaches to identify variables that can best explain genome size variation in this clade.

Key Results

We find differences in genome size and heterogeneity in its rate of evolution across subclades of Streptanthus and close relatives. We show that clade-wide genome size is positively associated with climate seasonality and glucosinolate compounds. Model selection and information criteria approaches identify a best model that includes temperature seasonality and fraction of aliphatic glucosinolates, suggesting a possible role for genome size in climatic adaptation or a role for biotic interactions in shaping the evolution of genome size. We find no evidence supporting hypotheses of life history, range size or soil nutrients as forces shaping genome size in this system.

Conclusions

Our findings suggest climate seasonality and biotic interactions as potential forces shaping the evolution of genome size and highlight the importance of evaluating multiple factors in the context of phylogeny to understand the effect of possible selective agents on genome size.
COPS8 in cutaneous melanoma: an oncogene that accelerates the malignant development of tumor cells and predicts poor prognosis
Authors: Sun Liangliang
Published: February 2021

This study aimed to investigate the roles of COP9 signalosome subunit 8 (COPS8) and its underlying mechanism in cutaneous melanoma. Bioinformatics tools were utilized to analyze the expression of COPS8 in cutaneous melanoma, while Kaplan–Meier analysis was employed to assess the correlation between COPS8 and patients’ overall survival. The proliferation, migration, and invasion of cells were estimated by CCK8, colony formation, and Transwell assays. Western blot was used to check the expression of epithelial–mesenchymal transition (EMT)-related proteins. Results showed that COPS8 was up-regulated and predicted a poor clinical outcome for cutaneous melanoma patients. Knockdown of COPS8 inhibited cutaneous melanoma cell proliferation, migration and invasion, whereas overexpression of COPS8 resulted in the opposite outcomes. The up-regulation of E-cadherin and down-regulation of N-cadherin, vimentin, and snail were caused by silencing COPS8 while their expression showed contrary trends in cells with overexpressed COPS8. Collectively, COPS8 is up-regulated and promotes cutaneous melanoma progression via regulating EMT.
Polymethoxyflavones in orange peel extract prevent skeletal muscle damage induced by eccentric exercise in rats
Authors: Suzuki Toshihide , Shimizu Makoto , Yamauchi Yoshio , Sato Ryuichiro
Published: February 2021

Polymethoxyflavones (PMFs) contained in the peel of citrus fruits have anti-inflammatory, anticancer, and antidepressant effects. However, their effects on skeletal muscle are unknown. We investigated whether PMFs could prevent skeletal muscle damage induced by eccentric exercise in rats. Downhill running for 90 min increased the levels of the inflammatory cytokines, monocyte chemotactic protein-1 (MCP-1), and interleukin-1β (IL-1β) in skeletal muscles, especially in vastus lateralis, and the plasma creatine kinase levels. These increases were attenuated by a single oral administration of orange peel extract (OPE) 30 min before downhill running. A mixture of nobiletin, sinensetin, 3,5,6,7,8,3′,4′-heptamethoxyflavone, and tangeretin, which are the major PMFs of OPE, also showed similar effects on muscle damage. These results suggest that OPE has a protective effect against eccentric exercise-induced skeletal muscle damage, and that the effects may be attributed to the 4 major PMFs.
The analytical method to identify the nitrogen source for nitric oxide synthesis
Authors: Nasuno Ryo , Yoshikawa Yuki , Takagi Hiroshi
Published: February 2021

Nitric oxide (NO) is a ubiquitous signaling molecule synthesized from various nitrogen sources. An analytical method to identify a nitrogen source for NO generation was developed using liquid chromatography with tandem mass spectrometry in combination with stable isotope labeling. Our method successfully detected the 15N-labeled NO-containing compound generated from 15N-labeled substrate nitrite in vitro and in vivo.
Failure to rescue patients after emergency laparotomy for large bowel perforation: analysis of the National Emergency Laparotomy Audit (NELA)
Authors: Peacock O , Yanni F , Kuryba A , Cromwell D , Lockwood S , Anderson I , Vohra R S ,   NELA Project Team, Cripps P , Eugene N , Goodwin J , Hare S , Grocott M , Davies E , Bassett M , Johnston C , Lourtie J , Moonesinghe R , Murray D , Papadimitriou D , Peden C , Poulton T , Salih T , Walker K , Warren S , Cripps M , Drake S , Oliver M
Published: February 2021

Background

Past studies have highlighted variation in in-hospital mortality rates among hospitals performing emergency laparotomy for large bowel perforation. The aim of this study was to investigate whether failure to rescue (FTR) contributes to this variability.

Methods

Patients aged 18 years or over requiring surgery for large bowel perforation between 2013 and 2016 were extracted from the National Emergency Laparotomy Audit (NELA) database. Information on complications were identified using linked Hospital Episode Statistics data and in-hospital deaths from the Office for National Statistics. The FTR rate was defined as the proportion of patients dying in hospital with a recorded complication, and was examined in hospitals grouped as having low, medium or high overall postoperative mortality.

Results

Overall, 6413 patients were included with 1029 (16.0 per cent) in-hospital deaths. Some 3533 patients (55.1 per cent) had at least one complication: 1023 surgical (16.0 per cent) and 3332 medical (52.0 per cent) complications. There were 22 in-hospital deaths following a surgical complication alone, 685 deaths following a medical complication alone, 150 deaths following both a surgical and medical complication, and 172 deaths with no recorded complication. The risk of in-hospital death was high among patients who suffered either type of complication (857 deaths in 3533 patients; FTR rate 24.3 per cent): 172 deaths followed a surgical complication (FTR-surgical rate 16.8 per cent) and 835 deaths followed a medical complication (FTR-medical rate of 25.1 per cent). After adjustment for patient characteristics and hospital factors, hospitals grouped as having low, medium or high overall postoperative mortality did not have different FTR rates (P = 0.770).

Conclusion

Among patients having emergency laparotomy for large bowel perforation, efforts to reduce the risk of in-hospital death should focus on reducing avoidable complications. There was no evidence of variation in FTR rates across National Health Service hospitals in England.
Patient-reported outcomes of immediate implant-based breast reconstruction with and without biological or synthetic mesh
Authors: Sewart E , Turner N L , Conroy E J , Cutress R I , Skillman J , Whisker L , Thrush S , Barnes N , Holcombe C , Potter S ,   implant Breast Reconstruction Evaluation (iBRA) Steering Group and the Breast Reconstruction Research Collaborative
Published: February 2021

Background

Biological and synthetic meshes may improve the outcomes of immediate implant-based breast reconstruction (IBBR) by facilitating single-stage procedures and improving cosmesis. Supporting evidence is, however, limited. The aim of this study was to explore the impact of biological and synthetic mesh on patient-reported outcomes (PROs) of IBBR 18 months after surgery.

Methods

Consecutive women undergoing immediate IBBR between February 2014 and June 2016 were recruited to the study. Demographic, operative, oncological and 3-month complication data were collected, and patients received validated BREAST-Q questionnaires at 18 months. The impact of different IBBR techniques on PROs were explored using mixed-effects regression models adjusted for clinically relevant confounders, and including a random effect to account for clustering by centre.

Results

A total of 1470 participants consented to receive the questionnaire and 891 completed it. Of these, 67 women underwent two-stage submuscular reconstructions. Some 764 patients had a submuscular reconstruction with biological mesh (495 women), synthetic mesh (95) or dermal sling (174). Fourteen patients had a prepectoral reconstruction. Compared with two-stage submuscular reconstructions, no significant differences in PROs were seen in biological or synthetic mesh-assisted or dermal sling procedures. However, patients undergoing prepectoral IBBR reported better satisfaction with breasts (adjusted mean difference +6.63, 95 per cent c.i. 1.65 to11.61; P = 0.009). PROs were similar to those in the National Mastectomy and Breast Reconstruction Audit 2008–2009 cohort, which included two-stage submuscular procedures only.

Conclusion

This study found no difference in PROs of subpectoral IBBR with or without biological or synthetic mesh, but provides early data to suggest improved satisfaction with breasts following prepectoral reconstruction. Robust evaluation is required before this approach can be adopted as standard practice.
Causes of death after emergency general surgical admission: population cohort study of mortality
Authors: Ramsay G , Wohlgemut J M , Bekheit M , Watson A J M , Jansen J O
Published: February 2021

Background

A substantial number of patients treated in emergency general surgery (EGS) services die within a year of discharge. The aim of this study was to analyse causes of death and their relationship to discharge diagnoses, in patients who died within 1 year of discharge from an EGS service in Scotland.

Methods

This was a population cohort study of all patients with an EGS admission in Scotland, UK, in the year before death. Patients admitted to EGS services between January 2008 and December 2017 were included. Data regarding patient admissions were obtained from the Information Services Division in Scotland, and cross-referenced to death certificate data, obtained from the National Records of Scotland.

Results

Of 507 308 patients admitted to EGS services, 7917 died while in hospital, and 52 094 within 1 year of discharge. For the latter, the median survival time was 67 (i.q.r. 21–168) days after EGS discharge. Malignancy accounted for 48 per cent of deaths and was the predominant cause of death in patients aged over 35 years. The cause of death was directly related to the discharge diagnosis in 56.5 per cent of patients. Symptom-based discharge diagnoses were often associated with a malignancy not diagnosed on admission.

Conclusion

When analysed by subsequent cause of death, EGS is a cancer-based specialty. Adequate follow-up and close links with oncology and palliative care services merit development.
Children with Cerebral Palsy Have Altered Occipital Cortical Oscillations during a Visuospatial Attention Task
Authors: VerMaas Jacy R , Lew Brandon J , Trevarrow Michael P , Wilson Tony W , Kurz Max J
Published: February 2021

Dynamically allocating neural resources to salient features or objects within our visual space is fundamental to making rapid and accurate decisions. Impairments in such visuospatial abilities have been consistently documented in the clinical literature on individuals with cerebral palsy (CP), although the underlying neural mechanisms are poorly understood. In this study, we used magnetoencephalography (MEG) and oscillatory analysis methods to examine visuospatial processing in children with CP and demographically matched typically developing (TD) children. Our results indicated robust oscillations in the theta (4–8 Hz), alpha (8–14 Hz), and gamma (64–80 Hz) frequency bands in the occipital cortex of both groups during visuospatial processing. Importantly, the group with CP exhibited weaker cortical oscillations in the theta and gamma frequency bands, as well as slower response times and worse accuracy during task performance compared to the TD children. Furthermore, we found that weaker theta and gamma oscillations were related to greater visuospatial performance deficits across both groups. We propose that the weaker occipital oscillations seen in children with CP may reflect poor bottom-up processing of incoming visual information, which subsequently affects the higher-order visual computations essential for accurate visual perception and integration for decision-making.
Venoarterial extracorporeal membrane oxygenation as bridge to effective treatment in a 19-year-old woman with acute adrenal crisis: a case report
Authors: Lüsebrink Enzo , Krieg Kathrin , Massberg Steffen , Orban Martin
Published: February 2021

Background

Adrenal crisis is an acute life-threatening exacerbation of the Addison’s disease or primary adrenal insufficiency (PAI) and is associated with a high mortality rate. It can be the first manifestation of adrenal insufficiency and is caused by a critical lack of glucocorticoids.

Case summary

Here, we report the case of a 19-year-old woman presenting to the emergency room with unspecific symptoms, i.e. lethargy, fatigue, arthralgia, dyspnoea, and hypotension. The patient’s examination showed major pericardial effusion resulting in cardiac tamponade requiring immediate pericardiocentesis. In the further course, acute right heart failure and progressive cardiogenic shock occurred. Due to recurrent bradycardia and finally asystole, the patient had to be resuscitated for 15 min in total until return of spontaneous circulation. However, non-invasive haemodynamic stabilization of the patient was not successful. Hence, venoarterial extracorporeal membrane oxygenation (VA-ECMO) was used as salvage intervention to provide temporary circulatory support. We diagnosed an Addison crisis as first manifestation of her previously unknown Addison’s disease. An appropriate substitution therapy with hydrocortisone and fludrocortisone was immediately initiated and the patient’s condition rapidly improved. After a total in-hospital stay of 4 weeks, she recovered completely and could be discharged from hospital.

Discussion 

An Addison crisis requires rapid diagnosis and immediate treatment to end a life-threatening condition caused by critical glucocorticoid deficiency. In patients with non-specific symptoms, such as fatigue, hypotension, weight loss, and hyponatraemia, adrenocortical insufficiency should be considered as differential diagnosis. If patients suffer from an Addison crisis, clinical suspicion requires immediate substitution of hydrocortisone as this is essential for patient’s survival. Venoarterial extracorporeal membrane oxygenation therapy can serve as a bridge to diagnosis and effective treatment in patients requiring temporary cardiopulmonary support, especially as salvage intervention for patients in cardiogenic shock. To our knowledge, this is the first case of a young patient with acute Addison crisis and cardiogenic shock, who was successfully salvaged by VA-ECMO support.
Obstruction of the inferior vena cava following bicaval orthotopic heart transplantation: a case series
Authors: Abudan Anas , Kidd Brent , Hild Peter , Gupta Bhanu
Published: February 2021

Background

Inferior vena cava (IVC) obstruction is a rare complication of orthotopic heart transplantation (OHT) and is unique to bicaval surgical technique. The clinical significance, diagnosis, complications, and management of post-operative IVC anastomotic obstruction have not been adequately described.

Case summary

Two patients with end-stage heart failure presented for bicaval OHT. Post-operative course was complicated with shock refractory to fluid resuscitation and inotropic/vasopressor support. Obstruction at the IVC-right atrial (RA) anastomosis was diagnosed on transoesophageal echocardiography (TOE), prompting emergent reoperation. In both cases, a large donor Eustachian valve was found to be restricting flow across the IVC-RA anastomosis. Resection of the valve resulted in relief of obstruction across the anastomosis and subsequent improvement in haemodynamics and clinical outcome.

Discussion

Presumably rare, we present two cases of IVC obstruction post-bicaval OHT. Inferior vena cava obstruction is an under-recognized cause of refractory hypotension and shock in the post-operative setting. Prompt recognition using TOE is crucial for immediate surgical correction and prevention of multi-organ failure. Obstruction can be caused by a thickened Eustachian valve caught in the suture line at the IVC anastomosis, which would require surgical resection.