bluuebunny/crossref_metadata_2025 huggingface dataset:
Au, Pd and maghemite nanofunctionalized hydroxyapatite scaffolds for bone regeneration
Authors: Calabrese Giovanna , Petralia Salvatore , Fabbi Claudia , Forte Stefano , Franco Domenico , Guglielmino Salvatore , Esposito Emanuela , Cuzzocrea Salvatore , Traina Francesco , Conoci Sabrina
Published: August 2020

Nanotechnology plays a key role in the development of innovative scaffolds for bone tissue engineering (BTE) allowing the incorporation of nanomaterials able to improve cell proliferation and differentiation. In this study, Mg-HA-Coll type I scaffolds (Mg-HA-based scaffolds) were nanofunctionalized with gold nanorods (Au NRs), palladium nanoparticles (Pd NPs) and maghemite nanoparticles (MAG NPs). Nanofunctionalized Mg-HA-based scaffolds (NF-HA-Ss) were tested for their ability to promote both the proliferation and the differentiation of adipose-derived mesenchymal stem cells (hADSCs). Results clearly highlight that MAG nanofunctionalization substantially improves cell proliferation up to 70% compared with the control (Mg-HA-based scaffold), whereas both Au NRs and Pd NPs nanofunctionalization induce a cell growth inhibition of 94% and 89%, respectively. Similar evidences were found for the osteoinductive properties showing relevant calcium deposits (25% higher than the control) for MAG nanofunctionalization, while a decreasing of cell differentiation (20% lower than the control) for both Au NRs and Pd NPs derivatization. These results are in agreement with previous studies that found cytotoxic effects for both Pd NPs and Au NRs. The excellent improvement of both osteoconductivity and osteoinductivity of the MAG NF-HA-S could be attributed to the high intrinsic magnetic field of superparamagnetic MAG NPs. These findings may pave the way for the development of innovative nanostructured scaffolds for BTE.
International Trade and the Propagation of Merger Waves
Authors: Ahmad Muhammad Farooq , de Bodt Eric , Harford Jarrad
Published: August 2020

Cross-border merger activity is growing in importance. We map the global trade network each year from 1989 to 2016 and compare it to cross-border and domestic merger activity. Trade-weighted merger activity in trading partner countries has statistically and economically significant explanatory power for the likelihood that a given country will be in a merger wave state, at both the cross-border and domestic levels, even controlling for its own lagged merger activity. The role of trade as a channel for transmitting merger waves is confirmed using import tariff cuts and trade sanctions as instruments to mitigate endogeneity. Overall, the full trade network helps our understanding of merger waves and how merger activity propagate across borders.
Changes in the illness perceptions of patients with rheumatoid arthritis over the first year of methotrexate therapy
Authors: Gwinnutt James M , Norton Sam , Hyrich Kimme L , Lunt Mark , Barton Anne , Cordingley Lis  , Verstappen Suzanne M M ,   for the RAMS co-investigators
Published: August 2020

Objectives

To describe the illness perceptions of patients with RA over the first year of MTX treatment, and the association between illness perceptions and outcomes.

Methods

Data came from the Rheumatoid Arthritis Medication Study (RAMS), a UK multicentre cohort study of RA patients starting MTX for the first time. Patients were assessed at baseline, and at 6 and 12 months. Patients completed the Brief Illness Perception Questionnaire (B-IPQ) at each assessment, as well as other patient-reported outcomes (PROs). The inflammation score (2-component DAS28) was calculated. Subgroups of patients with similar trajectories across the eight (B-IPQ) items were identified using a latent class growth model. Predictors of group membership were identified using multinomial logistic regression. Associations between subgroups and PROs over follow-up were assessed using linear mixed models.

Results

Three subgroups were identified in the analysis population (N = 1087): Positive illness perceptions (N = 322), Negative illness perceptions (N = 534) and Improvers (N = 231) who switched from negative to positive illness perceptions over follow-up. Baseline disability was associated with group membership [Positive vs Negative: relative risk ratio (RRR) 0.37, 95% CI: 0.25, 0.54; Improvers vs Negative: RRR 0.60, 95% CI: 0.43, 0.83], as were other PROs (pain, fatigue, anxiety, depression). The Negative group had worse disability, pain and fatigue over follow-up compared with the other groups, controlling for inflammation.

Conclusion

Negative illness perceptions are associated with poor PROs over time. The Improvers subgroup illustrated that illness perceptions can change in RA. Illness perceptions represent a potential therapeutic target that should be assessed using randomized trials.
The Prevalence of Psychotic Experiences in Autism Spectrum Disorder and Autistic Traits: A Systematic Review and Meta-analysis
Authors: Kiyono Tomoki , Morita Masaya , Morishima Ryo , Fujikawa Shinya , Yamasaki Syudo , Nishida Atsushi , Ando Shuntaro , Kasai Kiyoto
Published: August 2020

Several reports have highlighted an association between psychotic experiences (PEs) and autism spectrum disorder/autistic traits; however, no systematic review of the evidence has been done. We searched PubMed, PsycINFO, Web of Science, and Cochrane database on November 20, 2018, for studies providing statistical results on the association between PEs and autism spectrum disorder/autistic traits. Meta-analyses were conducted for both the prevalence of PEs in autism spectrum disorder and the correlation coefficients between PEs and autistic traits. Subgroup analyses were conducted for each PE subtype. Among the 17 included studies, 9 had data about prevalence and 8 had data about correlation. The pooled prevalence of PEs in autism spectrum disorder was 24% (95% confidence interval [CI] 14%–34%). However, subanalyses found that prevalence varied between PE subtypes (hallucinations, 6% [95% CI 1%–11%] and delusions, 45% [95% CI 0%–99%]). Pooled results showed that PEs and autistic traits had a weak to medium correlation (r = .34 [95% CI 0.27–0.41]). Based on our meta-analysis, PEs seem to be more prevalent in individuals with autism spectrum disorder/autistic traits than in the general population, but this finding may vary according to the PE subtype. Future studies should focus on statistical results for each PE subtype separately. More studies should be conducted to clarify the relationship between autism spectrum disorder/autistic traits and PEs by subtype.
Reproductive Care During COVID-19
Authors: McSpedon Corinne
Published: August 2020

The crisis has led to changes in prenatal, maternal, contraceptive, and abortion care.
A Conversation with Monica R. McLemore
Authors: McSpedon Corinne
Published: August 2020

The nurse, scientist, and activist discusses how nurses can work to dismantle racism.
Antegrade Humeral Lengthening With the Motorized Internal Lengthening Nail
Authors: Hassan Sherif Galal , Rozbruch S. Robert
Published: August 2020

Humerus lengthening with internal lengthening nails (ILNs) has been used with success to avoid complications associated with lengthening using external fixators (eg, soft tissue tethering). ILNs can be used in skeletally mature patients with humeral shortening who have an intramedullary canal wide enough to fit the nail, and who has no active infection. Associated deformity (angular or rotational) can be corrected acutely using the ILN as long as it would be tolerated by the neurovascular structures.
Long Bone Lengthening in Children
Authors: Iobst Christopher A.
Published: August 2020

Intramedullary lengthening nails have revolutionized the field of limb lengthening. Although pediatric patients can benefit from this new technology, the size of the bones and the presence of open physes create potential impediments that must be recognized by the surgeon. This review of pediatric intramedullary limb lengthening describes the key elements and nuances that will help guide the surgeon towards a successful outcome.
The Antegrade Femur Technique
Authors: Goodier David , Calder Peter
Published: August 2020

In this chapter, we examine the antegrade technique of insertion of magnetically controlled intramedullary lengthening implants. We discuss the indications, preoperative planning, surgical technique, and postoperative management, as well as tips and tricks for success.
Gut-lymph-lung pathway mediates sepsis-induced acute lung injury
Authors: Jin Can , Chen Jie , Gu Juan , Zhang Wei
Published: August 2020

This review attempts to unveil the possible mechanisms underlying how gut lymph affects lung and further gives rise to acute respiratory distress syndrome, as well as potential interventional targets under the condition of ischemia-reperfusion injury. We searched electronic databases including PubMed, MEDLINE, Cochrane Central Register of Controlled Trials, Google Scholar, Web of Science, and Embase to identify relevant literatures published up to December 2019. We enrolled the literatures including the Mesh Terms of “gut lymph or intestinal lymph and acute lung injury or acute respiratory distress syndrome.” Gut is considered to be the origin of systemic inflammation and the engine of multiple organ distress syndrome in the field of critical care medicine, whereas gut lymph plays a pivotal role in initiation of ischemia-reperfusion injury-induced acute respiratory distress syndrome. In fact, in the having been established pathologic model of sepsis leading to multiple organ dysfunction named by Gut Lymph theory, a variety of literatures showed the position and role of changes in gut lymph components in the initiation of systemic inflammatory response, which allows us to screen out potential intervention targets to pave the way for future clinic and basic research.
Blood-retinal barrier as a converging pivot in understanding the initiation and development of retinal diseases
Authors: Yang Xue , Yu Xiao-Wei , Zhang Dan-Dan , Fan Zhi-Gang
Published: August 2020

Clinical ophthalmologists consider each retinal disease as a completely unique entity. However, various retinal diseases, such as uveitis, age-related macular degeneration, diabetic retinopathy, and primary open-angle glaucoma, share a number of common pathogenetic pathways. Whether a retinal disease initiates from direct injury to the blood-retinal barrier (BRB) or a defect/injury to retinal neurons or glia that impairs the BRB secondarily, the BRB is a pivotal point in determining the prognosis as self-limiting and recovering, or developing and progressing to a clinical phenotype. The present review summarizes our current knowledge on the physiology and cellular and molecular pathology of the BRB, which underlies its pivotal role in the initiation and development of common retinal diseases.
Expression profile of circular RNAs in epicardial adipose tissue in heart failure
Authors: Zheng Mei-Li , Du Xiang-Peng , Zhao Lei , Yang Xin-Chun
Published: August 2020

Background

Recent studies have reported circular RNA (circRNA) expression profiles in various tissue types; however, circRNA expression profile in human epicardial adipose tissue (EAT) remains undefined. This work aimed to compare circRNA expression patterns in EAT between the heart failure (HF) and non-HF groups.

Methods

RNA-sequencing was carried out to compare circRNA expression patterns in EAT specimens from coronary artery disease cases between the HF and non-HF groups. Quantitative real-time polymerase chain reaction was performed for validation. Comparisons of patient characteristics between the two groups were using t test, Mann-Whitney U test, and Chi-squared test.

Results

A total of 141 circRNAs substantially different between the HF and non-HF groups (P < 0.05; fold change >2) were detected, including 56 up-regulated and 85 down-regulated. Among them, hsa_circ_0005565 stood out, for it had the highest fold change and was significantly increased in HF patients in quantitative real-time polymerase chain reaction validation. The top highly expressed EAT circRNAs corresponded to genes involved in cell proliferation and inflammatory response, including GSE1, RHOBTB3, HIPK3, UBXN7, PCMTD1, N4BP2L2, CFLAR, EPB41L2, FCHO2, FNDC3B, and SPECC1. The top enriched Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes pathway were positive regulation of metabolic processes and insulin resistance, respectively.

Conclusion

These data indicate EAT circRNAs may contribute to the pathogenesis of metabolic disorders causing HF.
Current biomarkers for the detection of endometriosis
Authors: Tian Zhao , Chang Xiao-Hong , Zhao Yan , Zhu Hong-Lan
Published: August 2020

A clinically reliable non-invasive test for endometriosis is expected to reduce the diagnostic delay. Although varieties of biomarkers have been investigated for decades, and cancer antigen-125, cancer antigen-199, interleukin-6, and urocortin were the most studied ones among hundreds of biomarkers, no clinically reliable biomarkers have been confirmed so far. Some emerging technologies including “omics” technologies, molecular imaging techniques, and microRNAs are promising in solving these challenges, but their utility to detect endometriosis has yet to be verified. New combinations of researched indicators or other non-invasive methods and further exploration of the emerging technologies may be new targets and future research hotspots for non-invasive diagnosis of endometriosis. In conclusion, researches of biomarkers for the detection of endometriosis are still ongoing and may benefit from novel molecular biology, bioinformatics methods and a combination of more diverse monitoring methods. Though it will be a daunting task, the identification of a specific set of diagnostic biomarkers will undoubtedly improve the status of endometriosis.
Including Patients With Stroke in Cardiac Rehabilitation
Authors: Marzolini Susan
Published: August 2020

More than 13 million cases of stroke are occurring annually worldwide. Approximately a quarter of these strokes are recurrent strokes, and there is compelling evidence of the benefit of supervised exercise and risk factor modification programming in the secondary prevention of these strokes. However, there is insufficient time in inpatient and outpatient stroke rehabilitation for focused exercise interventions. General lifestyle interventions on their own, without guidance and supervision, are insufficient for improving physical activity levels. Cardiac rehabilitation (CR) is a setting where cardiac patients, and increasingly stroke patients, receive comprehensive secondary prevention programming, including structured exercise. Unfortunately, not all CR programs accept referrals for people following a stroke and for those that do, only a few patients participate. Therefore, the purpose of this review is to report the barriers and facilitators to improving linkage between health services, with a focus on increasing access to CR. In the next two decades, it is projected that there will be a marked increase in stroke prevalence globally. Therefore, there is an urgent need to create cross-program collaborations between hospitals, outpatient stroke rehabilitation, CR, and community programs. Improving access and removing disparities in access to evidence-based exercise treatments would positively affect the lives of millions of people recovering from stroke.
Kangsaoukella pontilimi gen. nov., sp. nov., a new member of the family Rhodobacteraceae isolated from a tidal mudflat
Authors: Lee Soon Dong , Choe Hanna , Kim Ji-Sun , Kim In Seop
Published: August 2020

A strictly aerobic, Gram-stain-negative, non-motile, ovoid- and rod-shaped bacterium, designated strain GH1-50T, was isolated from a tidal mudflat sample collected from Dongmak seashore on Gangwha Island, Republic of Korea. The organism showed growth at 20–40 °C (optimum, 30 °C), pH 7–8 (optimum, pH 7) and 2–6  % (w/v) NaCl (optimum, 5 %). The pufLM genes were present but bacteriochlorophyll a was not detected. The major isoprenoid quinone was Q-10. The polar lipids were phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, an unidentified aminolipid and five unidentified lipids. The predominant cellular fatty acids were C18 : 1
 ω7c, C18 : 1
 ω7c 11-methyl and C18 : 0. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that the isolate belonged to the family

Rhodobacteraceae

and was loosely associated with members of the recognized genera. The closest relative was the type strain of

Pseudoruegeria marinistellae

(96.8 % similarity) followed by

Boseongicola aestuarii

(96.4 %). Other members of the family shared 16S rRNA gene similarity values below 96.0 % to the novel isolate. The DNA G+C content calculated from the draft genome sequence was 64.0 %. The average amino acid identity, average nucleotide identity and digital DNA–DNA hybridization values between genome sequences of strain GH1-50T and all the type strains of the recognized taxa compared were <70.0, <84.1 and <20.5 %, respectively. Based on data obtained by a polyphasic approach, strain GH1-50T (=KCTC 72224T=NBRC 113929T) represents a novel species of a new genus in the family

Rhodobacteraceae

, for which the name Kangsaoukella pontilimi gen. nov., sp. nov. is proposed.
Mortality from COVID in Colombia and Peru: Analyses of Mortality Data and Statistical Forecasts
Authors: Brown Patrick E , Greenwald Zoë R , Salinas Luis Ernesto , Martens Gabriel Aguirre , Newcombe Leslie , Rodriguez Peter S , Gelband Hellen , Veillard Jeremy , Jha Prabhat
Published: August 2020

National predictions of the course of COVID mortality can be used to plan for effective healthcare responses as well as to support COVID policymaking. We developed the Global COVID Assessment of Mortality (GCAM), a statistical model with continually improving precision that combines actual mortality counts with Bayesian inference, to predict COVID trends, currently until December 1, 2020. In Colombia, the GCAM analysis found the peak of COVID mortality around August 12 and an expected total of COVID deaths of 24,000-31,000, or 48%-92% over the total through August 21. In Peru, a first mortality peak occurred around May 24, and given the current trajectory, a second peak is predicted around September 6. Peru can expect 29,000-43,000 COVID deaths, representing an increase of 7%-55% over COVID deaths through August 21. GCAM projections are also used to estimate medical surge capacity needs. To gauge the reliability of COVID mortality forecasts, we compared all-cause mortality from January through June 2020 with average all-cause mortality in previous years in Colombia and Peru, and found that the excesses were consistent with GCAM forecast, most notably a doubling of overall mortality from May 25-June 7th of weeks in Peru. The GCAM results predict that as a percentage of all adult deaths in previous years, Colombia can expect about 13% excess from COVID deaths, whereas Peru can expect 34% excess. Comparisons of GCAM analyses of several other countries with Colombia and Peru demonstrate the extreme variability that characterizes COVID mortality around the world, emphasizing the need for country-specific analyses and ongoing monitoring as more mortality data become available.
Orthosteric-allosteric dual inhibitors of PfHT1 as selective anti-malarial agents
Authors: Huang Jian , Yuan Yafei , Zhao Na , Pu Debing , Tang Qingxuan , Zhang Shuo , Luo Shuchen , Yang Xikang , Wang Nan , Xiao Yu , Zhang Tuan , Liu Zhuoyi , Sakata-Kato Tomoyo , Jiang Xin , Kato Nobutaka , Yan Nieng , Yin Hang
Published: August 2020

Artemisinin-resistant malaria parasites have emerged and been spreading, posing a significant public health challenge. Anti-malarial drugs with novel mechanisms of action are therefore urgently needed. In this report, we exploit a “selective starvation” strategy by selectively inhibitingPlasmodium falciparumhexose transporter 1 (PfHT1), the sole hexose transporter inPlasmodium falciparum, over human glucose transporter 1 (hGLUT1), providing an alternative approach to fight against multidrug-resistant malaria parasites. Comparison of the crystal structures of human GLUT3 and PfHT1 bound to C3361, a PfHT1-specific moderate inhibitor, revealed an inhibitor binding-induced pocket that presented a promising druggable site. We thereby designed small-molecules to simultaneously block the orthosteric and allosteric pockets of PfHT1. Through extensive structure-activity relationship (SAR) studies, the TH-PF series was identified to selectively inhibit PfHT1 over GLUT1 and potent against multiple strains of the blood-stageP. falciparum. Our findings shed light on the next-generation chemotherapeutics with a paradigm-shifting structure-based design strategy to simultaneously targeting the orthosteric and allosteric sites of a transporter.

Significance statement

Blocking sugar uptake inP. falciparumby selectively inhibiting the hexose transporter PfHT1 kills the blood-stage parasites without affecting the host cells, indicating PfHT1 as a promising therapeutic target. Here, we report the development of novel small-molecule inhibitors that are selectively potent to the malaria parasites over human cell lines by simultaneously targeting the orthosteric and the allosteric binding sites of PfHT1. Our findings established the basis for the rational design of next-generation anti-malarial drugs.
MiMIC analysis reveals an isoform specific role forDrosophilaMusashi in follicle stem cell maintenance and escort cell function
Authors: Siddall Nicole A. , Casagranda Franca , Johanson Timothy M. , Dominado Nicole , Heaney James , Sutherland Jessie M. , McLaughlin Eileen A. , Hime Gary R.
Published: August 2020

TheDrosophilaovary is regenerated from germline and somatic stem cell populations that have provided fundamental conceptual understanding on how adult stem cells are regulated within their niches. Recent ovarian transcriptomic studies have failed to identify mRNAs that are specific to follicle stem cells (FSCs), suggesting that their fate may be regulated post-transcriptionally. We have identified that the RNA-binding protein, Musashi (Msi) is required for maintaining the stem cell state of FSCs. Loss ofmsifunction results in stem cell loss, not due to cell death, but mutant FSCs upregulate Lamin C, indicating a change in differentiation state. Inmsimutant ovaries, Lamin C upregulation was also observed in posterior escort cells and mutant somatic cells within regions 2/3 were dysfunctional, as evidenced by the presence of germline cyst collisions and fused egg chambers. Themsilocus produces two classes of mRNAs (long and short). We show that FSC maintenance and escort cell function specifically requires the long transcripts, thus providing the first evidence of isoform-specific regulation in a population ofDrosophilaepithelial cells. We further demonstrate that although male germline stem cells have previously been shown to require Msi function to prevent differentiation this is not the case for female germline stem cells, indicating that these similar stem cell types have different requirements for Msi, in addition to the differential use of Msi isoforms between soma and germline.
Integrative genomics of the mammalian alveolar macrophage response to intracellular mycobacteria
Authors: Hall Thomas J. , Mullen Michael P. , McHugo Gillian P. , Killick Kate E. , Ring Siobhán C. , Berry Donagh P. , Correia Carolina N. , Browne John A. , Gordon Stephen V. , MacHugh David E.
Published: August 2020

Bovine tuberculosis (bTB), caused by infection withMycobacterium bovis, is a major disease affecting cattle globally as well as being a zoonotic risk to human health. The key innate immune cell that first encountersM. bovisis the alveolar macrophage, previously shown to be substantially reprogrammed during intracellular infection by the pathogen. Here we use multi-omics and network biology approaches to analyse the macrophage transcriptional response toM. bovisinfection and identify core infection response pathways and gene modules. These outputs were integrated with results from genome-wide associations ofM. bovisinfection to enhance the detection of putative genomic variants for disease resistance. Our results show that network-based integration of relevant transcriptomics data can extract additional information from large genome-wide associations and that this approach could also be used to integrate relevant functional genomics outputs with results from genomic association studies for human tuberculosis caused by the relatedMycobacterium tuberculosis.
Evaluation of the 7 & 7 Synch and 7-day CO-Synch + CIDR®protocols for estrus synchronization of beef cows prior to fixed-time artificial insemination with conventional or sex-sorted semen
Authors: Andersen C.M. , Bonacker R.C. , Smith E.G. , Spinka C.M. , Poock S.E. , Thomas J.M.
Published: August 2020

An experiment was designed to compare the recently developed 7 & 7 Synch and the 7-day CO-Synch + CIDR protocols for synchronization of estrus among beef cows prior to fixed-time artificial insemination (FTAI) with conventional or sex-sorted semen.Bos tauruscows (n = 1538) were blocked based on age and days postpartum (DPP) and randomly assigned to protocol and semen type. Cows treated with the 7-day CO-Synch + CIDR protocol (n = 769) received administration of gonadotropin-releasing hormone (GnRH; 100 μg gonadorelin) and insertion of a 1.38 g intravaginal progesterone releasing insert (CIDR) on Day -10, and administration of prostaglandin F2α(PG; 500 μg cloprostenol) coincident with CIDR removal on Day -3. Cows treated with 7 & 7 Synch (n = 769) received PG and insertion of CIDR on Day -17, GnRH on Day -10, and PG coincident with CIDR removal on Day -3. Estrus detection aids (Estrotect™) were applied to all cows on Day -3, and activation status was recorded at FTAI. Cows received FTAI 66 h after CIDR removal with either conventional (20 × 106cells per unit) or sex-sorted (4 × 106cells per unit; SexedULTRA 4M™) semen. A greater proportion of cows expressed estrus (P= 0.01) prior to FTAI following 7 & 7 Synch (82%; 629/769) compared with the 7-day CO-Synch + CIDR (64%; 492/769). Estrus expression was also affected by protocol × DPP (P= 0.0004), with 7 & 7 Synch resulting in a greater increase in the proportion of cows expressing estrus prior to FTAI among cows with greater DPP. Across protocols, body condition score (BCS) affected (P= 0.05) estrus expression, with greater proportion of cows expressing estrus prior to FTAI at greater BCS. Sex-sorted semen resulted in reduced (P< 0.0001) pregnancy rates to FTAI. Irrespective of semen type, greater (P= 0.001) pregnancy rates to FTAI were obtained among cows treated with 7 & 7 Synch (conventional semen: 72% [280/389]; sex-sorted semen: 52% [199/380]) compared with the 7-day CO-Synch + CIDR (conventional semen: 60% [231/383]; sex-sorted semen: 44% [171/386]). In summary, 7 & 7 Synch resulted in an increased proportion of cows expressing estrus prior to FTAI and an increased pregnancy rate to FTAI with conventional and sexed semen. With these results and ease of application, 7 & 7 Synch offers potential as a platform to improve success with fixed-time AI in beef cows.
DNA methylation landscapes of matched primary and recurrent high grade serous ovarian cancers are preserved throughout disease progression and chemoresistance
Authors: Gull Nicole , Jones Michelle R. , Peng Pei-Chen , Coetzee Simon G. , Silva Tiago C. , Plummer Jasmine T. , Reyes Alberto Luiz P. , Davis Brian D. , Chen Stephanie , Lawrenson Kate , Lester Jenny , Walsh Christine , Rimel Bobbie J. , Li Andrew J. , Cass Ilana , Berg Yonatan , Govindavari John-Paul B. , Rutgers Joanna K.L. , Karlan Beth Y. , Berman Benjamin P. , Gayther Simon A.
Published: August 2020

Little is known about the role of global DNA methylation in recurrence and chemoresistance of high grade serous ovarian cancer (HGSOC). We performed whole genome bisulfite sequencing (WGBS) and whole transcriptome sequencing (RNA-seq) to establish methylation and gene expression signatures in 62 primary and recurrent tumors from 28 patients diagnosed with stage III/IV HGSOC. Eleven of these patients carried pathogenic germlineBRCA1/BRCA2mutations. Genome-wide methylation and transcriptomic features identified in primary tumors were largely preserved in matched recurrent tumors from the same patient (P-value = 7.16 × 10−7and 1.41 × 10−3inBRCA1/2and non-BRCA1/2cases respectively). Tumors fromBRCA1/2carriers displayed high levels of heterogeneity, with significantly more shared methylation changes identified between primary and recurrent tumors from non-BRCA1/2patients, which may be related to the poorer survival we observe in HGSOCs from non-BRCA1/2carriers (P-value = 0.0056). Partially methylated domains (PMDs) dominated the epigenetic variation across all tumors, and were more hypomethylated inBRCA1/2than non-BRCA1/2cases. Differential gene expression analysis identified upregulation of genes from immune pathways including antigen processing and presentation in tumors fromBRCA1/2carriers, implicating increased immune response in the improved survival observed in these patients. In summary, this study shows a previously unreported conservation of methylation and gene expression in recurrent HGSOCs. These data have implications for the possible effectiveness of epigenetic based therapies to treat both primary and recurrent ovarian cancers.
A unique view of SARS-CoV-2 through the lens of ORF8 protein
Authors: Hassan Sk. Sarif , Ghosh Shinjini , Attrish Diksha , Choudhury Pabitra Pal , Seyran Murat , Pizzol Damiano , Adadi Parise , El-Aziz Tarek Mohamed Abd , Soares Antonio , Kandimalla Ramesh , Lundstrom Kenneth , Tambuwala Murtaza , Aljabali Alaa A. A. , Lal Amos , Azad Gajendra Kumar , Uversky Vladimir N. , Sherchan Samendra P. , Baetas-da-Cruz Wagner , Uhal Bruce D. , Rezaei Nima , Brufsky Adam M.
Published: August 2020

Immune evasion is one of the unique characteristics of COVID-19 attributed to the ORF8 protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This protein is involved in modulating the host adaptive immunity through downregulating MHC (Major Histocompatibility Complex) molecules and innate immune responses by surpassing the interferon mediated antiviral response of the host. To understand the immune perspective of the host with respect to the ORF8 protein, a comprehensive study of the ORF8 protein as well as mutations possessed by it, is performed. Chemical and structural properties of ORF8 proteins from different hosts, that is human, bat and pangolin, suggests that the ORF8 of SARS-CoV-2 and Bat RaTG13-CoV are very much closer related than that of Pangolin-CoV. Eighty-seven mutations across unique variants of ORF8 (SARS-CoV-2) are grouped into four classes based on their predicted effects. Based on geolocations and timescale of collection, a possible flow of mutations was built. Furthermore, conclusive flows of amalgamation of mutations were endorsed upon sequence similarity and amino acid conservation phylogenies. Therefore, this study seeks to highlight the uniqueness of rapid evolving SARS-CoV-2 through the ORF8.
Integrated Collection of Stem Cell Bank data, a data portal for standardized stem cell information
Authors: Chen Ying , Sakurai Kunie , Maeda Sumihiro , Masui Tohru , Okano Hideyuki , Dewender Johannes , Seltmann Stefanie , Kurtz Andreas , Masuya Hiroshi , Nakamura Yukio , Sheldon Michael , Schneider Juliane , Stacey Glyn N. , Panina Yulia , Fujibuchi Wataru
Published: August 2020

The last decade has witnessed an extremely rapid increase in the number of newly established stem cell lines. However, due to the lack of a standardized format, data exchange among stem cell line resources has been challenging, and no system can search all stem cell lines across resources worldwide. To solve this problem, we have developed Integrated Collection of Stem Cell Bank data (ICSCB) (http://icscb.stemcellinformatics.org/), the largest database search portal for stem cell line information, based on the standardized data items and terms of the MIACARM framework. Currently, ICSCB can retrieve >16,000 cell lines from four major data resources in Europe, Japan, and the United States. ICSCB is automatically updated to provide the latest cell line information, and its integrative search helps users collect cell line information for over 1,000 diseases including many rare diseases worldwide, which has been a formidable task, thereby distinguishing itself from other database search portals.
Potential For Applying Continuous Directed Evolution To Plant Enzymes
Authors: García-García Jorge D. , Joshi Jaya , Patterson Jenelle A. , Trujillo-Rodriguez Lidimarie , Reisch Christopher R. , Javanpour Alex A. , Liu Chang C. , Hanson Andrew D.
Published: August 2020

Plant evolution has produced enzymes that may not be optimal for maximizing yield and quality in today’s agricultural environments and plant biotechnology applications. By improving enzyme performance, it should be possible to alleviate constraints on yield and quality currently imposed by kinetic properties or enzyme instability. Enzymes can be optimized faster than naturally possible by applying directed evolution, which entails mutating a target genein vitroand screening or selecting the mutated gene products for the desired characteristics. Continuous directed evolution is a more efficient and scalable version that accomplishes the mutagenesis and selection steps simultaneouslyin vivovia error-prone replication of the target gene and coupling of the host cell’s growth rate to the target gene’s function. However, published continuous systems require custom plasmid assembly, and convenient multipurpose platforms are not available. We discuss two systems suitable for continuous directed evolution of enzymes, OrthoRep inSaccharomyces cerevisiaeand EvolvR inEscherichia coli, and our pilot efforts to adapt each system for high-throughput plant enzyme engineering. To test our modified systems, we used the thiamin synthesis enzyme THI4, previously identified as a prime candidate for improvement. Our adapted OrthoRep system shows promise for efficient plant enzyme engineering.
Neural tracking of the fundamental frequency of the voice: the effect of voice characteristics
Authors: Van Canneyt Jana , Wouters Jan , Francart Tom
Published: August 2020

Traditional electrophysiological methods to study temporal auditory processing of the fundamental frequency of the voice (f0) often use unnaturally repetitive stimuli. In this study, we investigated f0 processing of meaningful continuous speech. EEG responses evoked by stories in quiet were analysed with a novel method based on linear modelling that characterizes the neural tracking of the f0. We studied both the strength and the spatio-temporal properties of the f0-tracking response. Moreover, different samples of continuous speech (six stories by four speakers: two male and two female) were used to investigate the effect of voice characteristics on the f0 response.

The results indicated that response strength is inversely related to f0 frequency and rate of f0 change throughout the story. As a result, the male-narrated stories in this study (low and steady f0) evoked stronger f0-tracking compared to female-narrated stories (high and variable f0), for which many responses were not significant. The spatio-temporal analysis revealed that f0-tracking response generators were not fixed in the brainstem but were voice-dependent as well. Voices with high and variable f0 evoked subcortically-dominated responses with a latency between 7 and 12 ms. Voices with low and steady f0 evoked responses that are both subcortically (latency of 13-15 ms) and cortically (latency of 23-26 ms) generated, with the right primary auditory cortex as a likely cortical source. Finally, additional experiments revealed that response strength greatly improves for voices with strong higher harmonics, which is particularly useful to boost the small responses evoked by voices with high f0.
EEG Alpha Power Predicts the Temporal Sensitivity of Multisensory Integration
Authors: London Raquel E. , Benwell Christopher S. Y. , Cecere Roberto , Quak Michel , Thut Gregor , Talsma Durk
Published: August 2020

Pre-stimulus EEG oscillations, especially in the alpha range (8-13 Hz), can affect the integration of stimulus features into a coherent percept. The effects of alpha power are often explained in terms of alpha’s inhibitory functions, whereas effects of alpha frequency have bolstered theories of discrete perceptual cycles, where the length of a cycle, or window of integration, is determined by alpha frequency. Such studies typically employ visual detection paradigms with near-threshold or even illusory stimuli. It is unclear whether such results generalize to above-threshold stimuli. Here, we recorded electroencephalography, while measuring temporal discrimination sensitivity in a temporal order judgement task using above-threshold auditory and visual stimuli. We tested whether pre-stimulus oscillations predict audio-visual temporal discrimination sensitivity on a trial-by-trial basis. By applying a jackknife procedure to link single-trial pre-stimulus oscillatory power and instantaneous frequency to psychometric measures, we identified two highly overlapping clusters over posterior sites. One where lower alpha power was associated with higher temporal sensitivity of audiovisual discrimination, and another where higher instantaneous alpha-frequency predicted higher temporal discrimination sensitivity. A follow-up analysis revealed that these effects were not independent, and that the effect of instantaneous frequency could be explained by power modulations in the lower alpha band. These results suggest that temporal sensitivity for above-threshold multisensory stimuli changes spontaneously from moment to moment and is likely related to fluctuations in cortical excitability. Moreover, our results caution against interpreting instantaneous frequency effects as independent from power effects if these effects overlap in time and space.
ALS-FUS mutation affects the activities of HuD/ELAVL4 and FMRP leading to axon phenotypes in motoneurons
Authors: Garone Maria Giovanna , Birsa Nicol , Rosito Maria , Salaris Federico , Mochi Michela , de Turris Valeria , Nair Remya R. , Cunningham Thomas J. , Fisher Elizabeth M. C. , Morlando Mariangela , Fratta Pietro , Rosa Alessandro
Published: August 2020

Mutations in the RNA-binding protein (RBPs) FUS have been genetically associated with the motoneuron disease amyotrophic lateral sclerosis (ALS). Using both human induced pluripotent stem cells and mouse models, we found that FUS-ALS causative mutations affect the activity of two relevant RBPs with important roles in neuronal RNA metabolism: HuD/ELAVL4 and FMRP. Mechanistically, mutant FUS leads to upregulation of HuD protein levels through competition with FMRP forHuDmRNA 3’UTR binding. In turn, increased HuD levels overly stabilize the transcript levels of its targets, NRN1 and GAP43. As a consequence, mutant FUS motoneurons show increased axon branching and growth upon injury, which could be rescued by dampening NRN1 levels. Since similar phenotypes have been previously described in SOD1 and TDP-43 mutant models, increased axonal growth and branching might represent broad early events in the pathogenesis of ALS.
Casino development and regulation in Asia: the experience of Macau and Singapore for Japan and other destinations
Authors: Ho Hong Wai
Published: August 2020

Purpose

The purpose of this paper is to examine the casino development and regulation in Macau and Singapore. The paper also seeks to assess the potential for casino development in Asia, with a particular focus on the prospects of Japan's casino resorts.

Design/methodology/approach

The paper reviews the gaming history, gaming/tourism policies and casino regulations of Macau and Singapore. The key aspects concerned with the casino development in Asia are also examined.

Findings

The paper identifies the fundamentals that have contributed to the prosperity of casino resorts in Macau and Singapore, as well as highlights the potential and challenges for the casino developments in Japan and other Asian destinations.

Research limitations/implications

A number of legal and tourism-related factors are identified to be the determinants of casino development. However, more research is needed to examine the political, economic and socio-cultural factors associated with casino gaming.

Practical implications

The paper, discussing the casino development and regulation in Macau and Singapore, provides practical implications for the design of gaming/tourism policy and casino control in Japan and other prospective gaming jurisdictions.

Originality/value

The paper contributes to the growing body of literature on the gaming law and casino development in Asia and provides insights for policymakers contemplating the adoption of casinos as a strategic policy for tourism development and economic growth.
Governance and ownership in Malaysia: their impacts on corporate performance
Authors: Mohd Ghazali Nazli Anum
Published: August 2020

Purpose

The aim of this paper is to examine the relative influence of regulatory enhancements relating to corporate governance and attributes of business traits on performance of Malaysian listed companies.

Design/methodology/approach

Regression analysis was performed on all 742 non-financial main board companies listed on Bursa Malaysia using data from 2013 annual reports.

Findings

The results show that the number of board meetings held during the year, role separation and board size have a significant impact on corporate performance. By contrast, independent directors, government ownership and director ownership do not influence corporate performance.

Research limitations/implications

The study investigated non-financial companies for the financial year 2013. Hence, the results may not apply to financial companies and other years. Future research can perhaps include all types of listed companies and carry out a longitudinal study to gain more comprehensive results and understanding on the relationship between corporate governance and corporate performance. Additionally, future research could also consider employing a different methodology to further unveil factors influencing corporate performance.

Practical implications

The above findings provide new evidence of the effectiveness of the Malaysian Code on Corporate Governance in improving company performance. The significance of board meetings, role separation and board size shows the importance of internal governance in shaping company processes and hence performance.

Originality/value

The result suggests that although the Malaysian Code on Corporate Governance follows the corporate governance code of developed countries, the applicability of the recommendations to a developing country is evidenced. Companies in Malaysia are predominantly government-owned or closely held, but it appears that role separation matters even in these types of companies in achieving better performance.
Analysis of issues in sustainable water management of irrigation systems: case of a developing country
Authors: Sirimewan D.C. , Mendis A.P.K.D. , Rajini Damitha , Samaraweera Aparna , Manjula Naiduwa Handi Chathuri
Published: August 2020

Purpose

Sustaining the irrigated agriculture, while conserving the natural eco-system, are the two main objectives of sustainable water management (SWM) in irrigation. Achieving both the objectives simultaneously is a complex task in most developing countries. This requires a holistic approach of understanding the issues in irrigation water management (IWM) from social, economic and environmental perspectives. Therefore, this paper aims to analyse the issues towards the SWM of irrigation systems in Sri Lanka to help maintain a stable relationship between the aforementioned two objectives.

Design/methodology/approach

Qualitative interview survey was selected as the research strategy to achieve the research aim. 16 semi-structured interviews were conducted with experts in IWM sector to collect data in the Sri Lankan context. Data were analysed using code-based content analysis, based on directed approach.

Findings

Findings revealed the issues in SWM in terms of efficiency of irrigation infrastructure; equity of water distribution; environmental integrity and economic acceptability. Most of the issues were related to the inefficiency towards SWM of irrigation systems. Conflicts among water users, especially the people in downstreams aggravated the problem of equity of water sharing. Depletion of groundwater and waterlogging were the major issues towards environmental integrity. Loss of water happened due to the issues in different irrigation infrastructure components hindering economic acceptability.

Originality/value

Theoretical contribution includes an analysis of issues in IWM from a sustainability perspective. Practical implications include an overview of deficiencies in the SWM to generate appropriate strategies to achieve sustainability for decision-makers such as policymakers in the irrigation sector in developing countries similar to Sri Lanka.
Effect of journal misalignment on the static characteristics of an innovative journal bearing with adjustable elements in load-on-pad and load-between-pad configurations
Authors: Girish H. , Pai Raghuvir
Published: August 2020

Purpose

The purpose of this paper is to theoretically analyze an innovative form of variable bearing configuration having four pads with unique adjustability principle operated under journal misaligned conditions. The parameters such as load positions, degrees of misalignment (DM) and pad adjustment configurations influencing the steady-state performance of the four-pad adjustable bearing are detailed in this paper.

Design/methodology/approach

The proposed adjustable pad geometry possesses the ability to undergo radial and tilt motions in both inward and outward directions. Analysis is carried out by considering journal misalignment in vertical and horizontal planes with bearing modelled for load-on-pad and load-between-pad configurations. The film thickness equation derived to incorporate the radial and tilt adjustment parameters is further modified to accommodate the different load orientations and misaligned journal conditions. The pressure field equation is solved by applying finite-difference technique combined with Gauss Siedel iterative method.

Findings

At higher DM, peak pressures generated in the minimum film thickness region near the pad ends highly influences the bearing load carrying capacity. Results indicated that the adjustable four-pad bearing geometry is highly efficient in withstanding the journal misalignment by radially displacing and tilting the four pads in negative directions.

Originality/value

For bearing designers, this research highlights the importance of considering the misalignment factor during the design stages of an adjustable journal bearing. The proposed adjustability concept is proven to be effective enough to improve the bearing performance and, in turn, withstand the journal misalignment.