bluuebunny/crossref_metadata_2025 huggingface dataset:
Epilepsy, antiepileptic drugs and dementia
Authors: Beghi Ettore , Beghi Massimiliano
Published: February 2020

Purpose of review

To illustrate the frequency and trends of the comorbidity of epilepsy and dementia and the effects of antiepileptic drugs (AEDs) on cognitive functions.

Recent findings

Although the mortality and incidence of epilepsy are decreasing overall, they are increasing in the elderly as a result of population growth and increased life expectancy. Alzheimer's disease and other dementias are among the commonest causes of seizures and epilepsy. Epilepsy can be also complicated by cognitive impairment, suggesting a bidirectional association. Although epilepsy with onset in the elderly can be the manifestation of a CNS disease/injury, the cause of cognitive impairment is multifactorial and includes static (genetic background, age at seizure onset, developmental and acquired cerebral lesions) and dynamic factors [recurrent seizures, epileptiform discharges, type and number of AEDs and psychiatric comorbidities]. Most AEDs, with special reference to first-generation drugs, have negative effects on cognitive functions; however, none was found to increase the risk of dementia.

A net increase in the burden of epilepsy, dementia and epilepsy-dementia comorbidity is expected. The growing use of second-generation AEDs might help reducing adverse cognitive effects. However, the fairly high cost of these drugs might delay their widespread use in resource-poor countries.

Video abstract

http://links.lww.com/CONR/A49.
‘High vault-age’: non-coding RNA control of autophagy
Authors: Büscher Magdalena , Horos Rastislav , Hentze Matthias W.
Published: February 2020

RNA-binding proteins typically change the fate of RNA, such as stability, translation or processing. Conversely, we recently uncovered that the small non-coding vault RNA 1-1 (vtRNA1-1) directly binds to the autophagic receptor p62/SQSTM1 and changes the protein's function. We refer to this process as ‘riboregulation'. Here, we discuss this newly uncovered vault RNA function against the background of three decades of vault RNA research. We highlight the vtRNA1-1-p62 interaction as an example of riboregulation of a key cellular process.
Sleep disruption after brain injury is associated with worse motor outcomes and slower functional recovery
Authors: Fleming Melanie K , Smejka Tom , Slater David Henderson , van Gils Veerle , Garratt Emma , Kara Ece Yilmaz , Johansen-Berg Heidi
Published: February 2020

Background and Aims

Sleep is important for consolidation of motor learning, but brain injury may affect sleep continuity and therefore rehabilitation outcomes. This study aims to assess the relationship between sleep quality and motor recovery in brain injury patients receiving inpatient rehabilitation.

Methods

59 patients with brain injury were recruited from two specialist inpatient rehabilitation units. Sleep quality was assessed (up to 3 times) objectively using actigraphy (7 nights) and subjectively using the Sleep Condition Indicator. Motor outcome assessments included: Action Research Arm test (upper limb function), Fugl Meyer assessment (motor impairment) and the Rivermead Mobility Index. The functional independence measure (FIM) was assessed at admission and discharge by the clinical team. 55 age and gender matched healthy controls completed one assessment.

Results

Inpatients demonstrated lower self-reported sleep quality (p<0.001) and more fragmented sleep (p<0.001) than controls. For inpatients, sleep fragmentation explained significant additional variance in motor outcomes, over and above that explained by admission FIM score (p<0.017), such that more disrupted sleep was associated with poorer motor outcomes. Using stepwise linear regression, sleep fragmentation was the only variable found to explain variance in rate of change in FIM (R2adj= 0.12, p = 0.03), whereby more disrupted sleep was associated with slower recovery.

Conclusions

Inpatients with brain injury demonstrate impaired sleep quality, and this is associated with poorer motor outcomes and slower functional recovery. Further investigation is needed to determine how sleep quality can be improved and whether this affects outcome.
When will the battle against novel coronavirus end in Wuhan: a SEIR modeling analysis
Authors: Wan Kangkang , Chen Jing , Lu Changming , Dong Lanlan , Wu Zhicheng , Zhang Lianglu
Published: February 2020

Recent outbreak of 2019-nCoV in Wuhan raised serious public health concerns. By February 15, 2020 in Wuhan, the total number of confirmed infection cases has reached 37,914, and the number of deaths has reached 1123, accounting for 56.9% of the total confirmed cases and 73.7% of the total deaths in China. People are eager to know when the epidemic will be completely controlled and when people’s work and life will be on the right track. In this study we analyzed the epidemic dynamics and trend of 2019-nCoV in Wuhan by using the data after the closure of Wuhan city till February 12, 2020 based on the SEIR modeling method. The optimal parameters were estimated as R0=1.44 (interquartile range: 1.40-1.47),TI=14 (interquartile range: 14-14) and TE=3.0 (interquartile range: 2.8-3.1). Based on these parameters, the number of infected individuals in Wuhan city may reach the peak around February 19 at about 45,000 people. Once entering March, the epidemic would gradually decline, and end around the late March. It is worth noting that the above prediction is based on the assumption that the number of susceptible population N = 200,000 will not increase. If the epidemic situation is not properly controlled, the peak of infected number can be further increased and the peak time will be a little postponed. It was expected that the epidemic would subside in early March, and disappear gradually towards the late March.
Rapid learning of the 5-choice serial reaction time task in an automated rodent training system
Authors: Birtalan Eszter , Bánhidi Anita , Sanders Joshua I. , Balázsfi Diána , Hangya Balázs
Published: February 2020

Experiments aiming to understand sensory-motor systems, cognition and behavior often require animals trained to perform complex tasks. Traditional training protocols require lab personnel to move the animals between home cages and training chambers, to start and end training sessions, and in some cases, to hand-control each training trial. Human labor not only limits the amount of training per day, but also introduces several sources of variability and may increase animal stress. Here we present an automated training system for the 5-choice serial reaction time task (5CSRTT), a classic rodent task often used to test sensory detection, sustained attention and impulsivity. We found that fully automated training without human intervention greatly increased the speed and efficiency of learning, and decreased stress as measured by corticosterone levels. Introducing training breaks did not cancel these beneficial effects of automated training, and mice readily generalized across training systems when transferred from automated to manual protocols. Additionally, we validated our automated training system with mice implanted with wireless optogenetic stimulators, expanding the breadth of experimental needs our system may fulfill. Our automated 5CSRTT system can serve as a prototype for fully automated behavioral training, with methods and principles transferrable to a range of rodent tasks.
Epidemic Situation of Novel Coronavirus Pneumonia in China mainland
Authors: Liu Youbin , Gong Liming , Li Baohong
Published: February 2020

Objective

Analyze the occurrence of novel coronavirus pneumonia(NCP) in China mainland, explore the epidemiological rules, and evaluate the effect of prevention and control.

Methods

From December 1, 2019 to March 4, 2020, Analysis of 80,409 confirmed cases of NCP in China mainland.

Results

From December 1, 2019 to March 4, 2020, a total of 80,409 cases of NCP were confirmed in China mainland, a total of 67,466 cases were confirmed in Hubei Province, a total of 49,671 cases were confirmed in Wuhan city. From December 1, 2019 to March 4, 2020, a total of 3,012 cases of NCP deaths in China mainland, the mortality was 3.75% (3012/80,409); A total of 52045 cases of cured in China mainland; The turning point of the epidemic have been reached since February 18.2020 in China mainland; The spread index of NCP gradually declined since January 27. 2020, and the extinction index of NCP rose little by little since January 29, 2020.

Conclusion

From December 1, 2019 to March 4, 2020, NCP is under control, and the trend of the epidemic will eventually disappear; The turning point of an epidemic that I’ve created is a great indicator that can calculate the turning date of an outbreak and provide a basis for scientific prevention.
Microbial Stimulation Reverses the Age-Related Decline in M Cells in Aged Mice
Authors: Donaldson David S. , Pollock Jolinda , Vohra Prerna , Stevens Mark P. , Mabbott Neil A.
Published: February 2020

Ageing has a profound effect on the immune system, termed immunosenescence, resulting in increased incidence and severity of infections and decreased efficacy of vaccinations. We previously showed that immunosurveillance in the intestine, achieved primarily through antigen sampling M cells in the follicle associated epithelium (FAE) of Peyer’s patches, was compromised during ageing due to a decline in M cell functional maturation. The intestinal microbiota also changes significantly with age, but whether this affects M cell maturation was not known. We show that housing of aged mice on used bedding from young mice, or treatment with bacterial flagellin, were each sufficient to enhance the functional maturation of M cells in Peyer’s patches. An understanding of the mechanisms underlying the influence of the intestinal microbiota on M cells has the potential to lead to new methods to enhance the efficacy of oral vaccination in aged individuals.
Generation and application of river network analogues for use in ecology and evolution
Authors: Carraro Luca , Bertuzzo Enrico , Fronhofer Emanuel A. , Furrer Reinhard , Gounand Isabelle , Rinaldo Andrea , Altermatt Florian
Published: February 2020

Several key processes in freshwater ecology and evolution are governed by the connectivity inherent to dendritic river networks. These networks have extensively been analyzed from a geomorphological and hydrological viewpoint, yet network structures classically used in modelling have only been partially representative of the structure of real river basins, and have often failed to capture well known scaling features of real river networks. Pioneering work has identified optimal channel networks (OCNs) as spanning trees that reproduce all scaling features characteristic of real, natural stream networks worldwide. While these networks have been used to generate landscapes for studies on metapopulations, biodiversity and epidemiology, their generation has not been generally accessible.

Given the increasing interest in dendritic riverine networks by ecologists and evolutionary biologists, we here present a method to generate OCNs and, to facilitate its application, we also provide the R-package OCNet. Owing to the random search process that generates OCNs, multiple network replicas spanning the same surface can be built, allowing one to perform computational experiments whose results do not depend on the particular shape of a single river network. The OCN construct also enables the generation of elevational gradients derived from the optimal network configuration, which can constitute three-dimensional landscapes for spatial studies in both terrestrial and freshwater realms. Moreover, the OCNet package provides functions that aggregate the OCN into an arbitrary number of nodes, calculate several metrics and descriptors of river networks, and draw relevant features of the network.

We describe the main functionalities of the package and present how it can be integrated into other R-packages commonly used in spatial ecology. Moreover, we exemplify the generation of OCNs and discuss an application to a metapopulation model for an invasive riverine species.

In conclusion, OCNet provides a powerful tool to generate and use realistic river network analogues for various applications. It thereby allows the design of spatially realistic studies in increasingly impacted ecosystems, and enhances our knowledge on spatial processes in freshwater ecology in general.
Building a high-quality reference genome assembly for the the eastern Mediterranean Sea invasive sprinterLagocephalus sceleratus(Tetraodontiformes, Tetraodontidae)
Authors: Danis Theodoros , Tsakogiannis Alexandros , Kristoffersen Jon B. , Golani Daniel , Tsaparis Dimitris , Kasapidis Panagiotis , Kotoulas Georgios , Magoulas Antonios , Tsigenopoulos Costas S. , Manousaki Tereza
Published: February 2020

The Tetraodontidae family encompasses several species which attract scientific interest in terms of their ecology and evolution. However, the genomic resources and especially reference assemblies are sparse for the members of the family. In this study, we focus on the silver-cheeked toadfish (Lagocephalus sceleratus) a well-known ‘invasive sprinter’ that has invaded and spread throughout the Eastern and part of the Western Mediterranean Sea from the Red Sea through the Suez Canal within a decade. We sequenced the genome ofL. sceleratususing a single MinION flow cell for the main assembly, and Illumina reads for polishing the assembly. The resulted assembly consisted of 241 contigs (N50 = 11,3 Mb) with a total size of 360 Mb and yielded 98% BUSCO completeness. The high-quality genome assembly built here is expected to set the ground for future studies on this focal species’ invasive biology.
Altered patterning of trisomy 21 interneuron progenitors
Authors: Giffin-Rao Yathindar , Sheng Jie , Strand Bennett , Xu Ke , Huang Leslie , Medo Margaret , Risgaard Kirstin A. , Dantinne Samuel , Mohan Sruti , Keshan Aratrika , Daley Roger A. , Levesque Bradley , Amundson Lindsey , Reese Rebecca , Sousa André M.M. , Tao Yunlong , Wang Daifeng , Zhang Su-Chun , Bhattacharyya Anita
Published: February 2020

Individuals with Down syndrome (DS, Ts21), the most common genetic cause of intellectual disability, have smaller brains that reflect fewer neurons at pre- and post-natal stages, implicating impaired neurogenesis during development. Our stereological analysis of adult DS cortex indicates a reduction of calretinin expressing interneurons. Using Ts21 human induced pluripotent stem cells (iPSCs) and isogenic controls, we find Ts21 progenitors generate fewer COUP-TFII+ progenitors with reduced proliferation. Single cell RNA-sequencing of Ts21 progenitors confirms the altered specification of progenitor subpopulations and identifies reduced WNT signaling. Activation of WNT signaling partially restores the COUP-TFII+ progenitor population in Ts21, suggesting that altered WNT signaling contributes to the defective development of cortical interneurons in DS.
Estimating voluntary and involuntary attention in bistable visual perception: A MEG study
Authors: Chholak Parth , Maksimenko Vladimir A. , Hramov Alexander E. , Pisarchik Alexander N.
Published: February 2020

We introduce a method for measuring human attention when performing a visual task consisting in different interpretations of a bistable image. The Necker cube with flickering faces was presented to nine conditionally healthy volunteers. The pixels intensity in the front and rear cube faces were modulated by a sinusoidal signal with 6.67-Hz (60/9) and 8.57-Hz (60/7) frequencies, respectively. The tags of these frequencies and their second harmonics were clearly identified in the average Fourier spectra of the magnetoencephalographic (MEG) data recorded from the occipital cortex. In the first part of the experiment, the subjects were asked to voluntary control their attention by interpreting the cube orientation as either left- or right-orientated. Accordingly, we observed the dominance of the corresponding spectral component and voluntary attention performance was measured. In the second part of the experiment, the subjects were just asked to observe the cube image without any effort in its interpretation. The alternation of the dominant spectral energies at the second harmonic tag frequencies was treated as changes in the cube orientation. Based on the results of the first experimental stage and using wavelet analysis, we developed a novel method which allowed us to identify currently perceived cube orientations. Finally, we characterized involuntary attention using the dominance time distribution and related it to voluntary attention performance and brain noise. In particular, we have shown that higher attention performance is associated with stronger brain noise.
Genetic diversity of the spinach downy mildew pathogen based on hierarchical sampling
Authors: Feng Chunda , Lamour Kurt , Dhillon Braham Deep Singh , Villarroel-Zeballos Maria Isabel , Castroagudin Vanina Lilian , Bluhm Burt H. , Shi Ainong , Rojas Alejandro , Correll James C.
Published: February 2020

Downy mildew, caused by the obligate oomycete pathogenPeronospora effusa, is the most economically important disease of spinach. In the past 30 years, 14 new races and 13 strains with novel virulence have been identified. However, the mechanism(s) driving the rapid evolution of virulence remains unknown. To understand reproductive strategies potentially driving the emergence of new races inP. effusa, 67 composite isolates (a collection of symptomatic leaves from a single cultivar grown in a defined area) ofP. effusaobtained from 13 states between 2010 and 2018 were used to analyze the population genetic diversity hierarchically. Genotypes at 33 SNP loci of 719 lesions from these 67 isolates were determined by targeted sequencing. Diversity was then evaluated among individual lesions within the composite isolates, between isolates, host cultivars, geographic locations, and years of isolates collected. A total of 380 genotypes were identified from 719 individual lesions. Of the 380 genotypes, 350 (92%) were unique while the most common genotype was identified in 110 lesions of 16 isolates collected from 13 cultivars from CA and AZ in 2016. Variation within composite isolates ranged from none (a single genotype among lesions from a composite isolate) to 38 unique genotypes recovered from 39 lesions of a composite isolate. An index of association analysis suggested asexual (clonal) and sexual reproduction play important roles in population structure. Based on discriminant analysis of principal components, four distinct subpopulations were identified. Host cultivar, origin, and time of collection had an effect on population differentiation, and genotypes specific to a certain location or collection period were identified. Some subpopulations were unique to certain areas, and were only detected after 2014-2016. The co-existence of sexual and asexual reproduction strategies may partially explain the rapid emergence and spread of new races and novel strains ofP. effusa.
Impact of gestational low-protein intake on embryonic kidney microRNA expression and in the nephron progenitor cells of the male offspring fetus
Authors: de Barros Sene Letícia , Lopes-Cendes Íscia , Scarano Wellerson Rodrigo , Zapparoli Adriana , Gontijo José Antônio Rocha , Boer Patrícia Aline
Published: February 2020

Authors have demonstrated that gestational low-protein (LP) intake offspring showed a lower birth weight, reduced nephrons numbers and renal salt excretion, chronic renal failure, and arterial hypertension development when compared to normal (NP) protein intake group in adult life. The current study was aimed to evaluate the miRNAs and predicted gene expression patterns in the fetal kidney at 17 days of gestational (17-DG) protein-restricted male offspring (LP) in an attempt to elucidate the possible molecular pathways and disorders involved in renal cell proliferation and differentiation during kidney development. By NGS and RT-qPCR were identified, 44 differentially expressed miRNAs, which 19 miRNA were up- and 25 downregulated in LP compared to NP offspring metanephros. Among the top 10 deregulated miRNAs, the study selected 7 miRNAs which its biological targets were related to proliferation, differentiation, and cellular apoptosis processes. As could be seen below, both miRNA-Seq and TaqMan data analysis have shown a consistent change of miRNA expression in LP animals relative to control NP age-matched animals. By immunofluorescence, the LP fetus showed a significant 28% reduction of Six-2 labeled cells when compared to NP offspring associated with a reduced percentage of cell number and c-Myc metanephogenic cap and ureter bud immunostained cells in LP relative to NP offspring.

Additionally, the Ki-67 labeled area in CM was 48% lesser in LP compared to NP age-matched fetus. On the other hand, in LP, the CM and UB β-catenin marked area were 154 and 85% raised, respectively. Mtor immunoreactivity was also significantly higher in LP CM (139%) and UB (104%) compared to the NP fetus. In the LP offspring, the TGFβ-1 in UBs cells staining increased (about 30%). In contrast, Zeb1 metanephros-stained, located in the CM nuclei cells, enhanced 30% in LP and Zeb2 immunofluorescence, although present in whole metanephros structures, was similar in both experimental groups. In conclusion, the present study demonstrates that the miRNAs, mRNAs, and proteins are modified in LP animals with 17 DGs leading to the reduction of the reciprocal induction between CM and UB, and hence the number of nephrons. These findings will facilitate new functional approaches and further studies to elucidate the regulatory mechanisms involved in the processes of proliferation, differentiation, and apoptosis that occurs during renal development.
A Legionella effector kinase is activated by host inositol hexakisphosphate
Authors: Sreelatha Anju , Nolan Christine , Park Brenden C. , Pawłowski Krzysztof , Tomchick Diana R. , Tagliabracci Vincent S.
Published: February 2020

The transfer of a phosphate from ATP to a protein substrate, a modification known as phosphorylation, is catalyzed by protein kinases. Protein kinases play a crucial role in virtually every cellular activity. Recent studies of atypical protein kinases have highlighted the structural similarity of the kinase superfamily despite notable differences in primary amino acid sequence. We searched for putative protein kinases in the intracellular bacterial pathogen,Legionella pneumophilaand identified the Type-4 secretion system (T4SS) effector, Lpg2603 as a remote member of the protein kinase superfamily. We show that Lpg2603 is an active protein kinase with several atypical structural features. Importantly, we find that the eukaryotic-specific host signaling molecule, inositol hexakisphosphate (IP6) is required for Lpg2603 kinase activity. Crystal structures of Lpg2603 in the apo-form and bound to IP6 reveal active site rearrangement that allows for ATP binding and catalysis. Our results on the structure and activity of Lpg2603 reveal a unique mode of regulation of protein kinases and will aid future work into the function of this effector duringLegionellapathogenesis.
An investigation of research gaps in reported skills required for Industry 4.0 readiness of Brazilian undergraduate students
Authors: Rampasso Izabela Simon , Mello Sidney L.M. , Walker Rubens , Simão Victor G. , Araújo Robson , Chagas Juliana , Quelhas Osvaldo Luiz Gonçalves , Anholon Rosley
Published: February 2020

Purpose

The objective of this study is to identify research gaps related to skills required for Industry 4.0, considering research in the context of Brazilian undergraduate courses. In this sense, the question of this study was established: What are the educational gaps related to skills required in Industry 4.0 context, considering considering research in the previously mentioned?

Design/methodology/approach

To answer this question, the ten top work-related skills required for professionals in Industry 4.0 published by the World Economic Forum were used to perform a systematic literature review. From this review, 100 articles were found in the searched databases. From them, 18 were within the research scope.

Findings

Through an analysis of their content, it was possible to verify that, from the 10 skills analyzed, only six were identified in the articles. That is, no research was found for: people management, service orientation, negotiation, and cognitive flexibility. Additionally, there are undergraduate courses that are not considered in current researches and should be analyzed.

Originality/value

The gaps pointed out in this study are relevant to guide future analyzes of the Brazilian educational model and may provide insights for research in other countries.
Second law analysis of magneto-natural convection in a nanofluid filled wavy-hexagonal porous enclosure
Authors: Seyyedi Seyyed Masoud , Dogonchi A.S. , Hashemi-Tilehnoee M. , Ganji D.D. , Chamkha Ali J.
Published: February 2020

Purpose

Natural convection heat transfer analysis can be completed using entropy generation analysis. This study aims to accomplish both the natural convection heat transfer and entropy generation analyses for a hexagonal cavity loaded with Cu-H2O nanoliquid subjected to an oriented magnetic field.

Design/methodology/approach

Control volume-based finite element method is applied to solve the non-dimensional forms of governing equations and then, the entropy generation number is computed.

Findings

The results portray that both the average Nusselt and entropy generation numbers boost with increasing aspect ratio for each value of the undulation number, while both of them decrease with increasing the undulation number for each amplitude parameter. There is a maximum value for the entropy generation number at a specified value of Hartmann number. Also, there is a minimum value for the entropy generation number at a specified value of angle of the magnetic field. When the volume fraction of nanoparticles grows, the average Nusselt number increases and the entropy generation number declines. The entropy generation number attains to a maximum value at Ha = 14 for each value of aspect ratio. The average Nusselt number ascends 2.9 per cent and entropy generation number decreases 1.3 per cent for Ha = 0 when ϕ increases from 0 to 4 per cent.

Originality/value

A hexagonal enclosure (complex geometry), which has many industrial applications, is chosen in this study. Not only the characteristics of heat transfer are investigated but also entropy generation analysis is performed in this study. The ecological coefficient of performance for enclosures is calculated, too.
The potential for collaboration between AI and archival science in processing data from the French great national debate
Authors: Chabin Marie-Anne
Published: February 2020

Purpose

The purpose of this paper is to show how archival expertise and diplomatic analysis can enrich the documentary corpuses analyzed by artificial intelligence tools. Here, the demonstration is based on a freely accessible material: the data from the great national debate launched in early 2019 by the French President Macron in response to the large-scale social movement known as the “yellow vests”.

Design/methodology/approach

Step 1 consisted of understanding the methods and conclusions of the providers responsible for processing the data of the great debate (1.5 million contributors). Step 2 was to analyze the formal elements of a random set of online contributions. Then, to compare the results.

Findings

This research shows that the processing of the data is based almost exclusively on texts, to the detriment of data on the source, date and arrangement of contributions, which could nevertheless be exploited as metadata.

Research limitations/implications

The mass of data and the lack of online accessibility of part of the corpus did not make it possible to complete the experiment.

Practical implications

This research lays the foundation for other projects for collaboration between archival science and artificial intelligence tools.

Social implications

There is a social challenge involving researchers in information sciences in public debate and governmental consultations. There is also an issue for a records manager to become more involved in the production of public records by promoting their specific skills in information management.

Originality/value

The originality of this paper is to show how archival science can help to improve the quality of the documentary corpuses used by artificial intelligence tools, and therefore, to improve the performance of these tools.
Exendin‐4 exhibits a tumour suppressor effect in SKOVR‐3 and OVACR‐3 ovarian cancer cells lines by the activation of SIRT1 and inhibition of NF‐κB
Authors: Khaleel Eman F. , Badi Rehab M. , Satti Huda H. , Mostafa Dalia G.
Published: February 2020

This study investigated if EX‐527 has an anti‐tumour effect in SKOV‐3 and OVCAR‐3 ovarian cancer (OC) cell lines and if this effect involves the SIRT1/NF‐κB axis. Cells were cultured in the presence or absence of EX‐527, a selective SIRT‐1 inhibitor. Exendin‐4 significantly induced cell death in both cell lines and inhibited cell migration and invasion. Also, it decreased protein levels of Bcl‐2, MMP‐9, and ICAM‐1 and increased those of Bax, cyclin D1 and cleaved caspase‐3. Mechanistically, Exendin‐4 increased the activity and nuclear accumulation of SIRT1 and decreased nuclear levels of NF‐κB p65; acetylated levels of NF‐κB p65, and cytoplasmic levels of p‐IKKα and p‐IκBα. EX‐527 partially ameliorated the effect of Exendin‐4 on cell death, migration, and invasion, as well as on the expression of Bcl‐2, MMP‐9, Bax, cleaved caspase‐3 and ICAM‐1. In addition, EX‐527 did not affect the levels of nuclear p65 and p‐p65 (Ser536); p‐IκBα (Ser32) and p‐IKKαβ. In conclusion, Exendin‐4 can suppress OC by inhibiting NF‐kB through SIRT1 dependent and independent mechanisms.
The impact of water access on short‐term migration in rural India
Authors: Zaveri Esha D. , Wrenn Douglas H. , Fisher‐Vanden Karen
Published: February 2020

Migration is an important risk‐reduction strategy for households in developing countries. In this paper, we examine the impact of rainfall variability and irrigation availability on short‐term migration decisions in India. Our results show that both rainfall shocks and the availability of irrigation impact the decisions of households to dispatch migrants. For irrigation, we find that migration responds to costs and that deep fossil‐water wells, which provide a constant source of water, eliminate any benefit of short‐term migration. This suggests that regions with access to more secure and stable sources of water are less likely to rely on migration as an income‐smoothing mechanism, at least in the short run. Whether this holds in the long run will depend on the continued stability and availability of irrigation water.
Utilisation of an online forum to engage adolescents with autism in direct participation in qualitative research
Authors: Vine Foggo Rebecca S. , Webster Amanda A. , Dixon Roselyn
Published: February 2020

Difficulties with social communication may present challenges in gathering data from individuals with autism in research. To encourage individuals with autism to participate directly in research, methods that allow for autistic symptomology should be considered. An online forum was developed to enable adolescents with autism to share their social experiences. Ten female adolescents with autism, aged 12 to 19, engaged with the forum over 12 weeks. Questions were posted weekly and data were collected on the frequency of participant responses, quality of responses, and participants' engagement with each other. Data indicated that the frequency and quality of participants' responses were high, and participants' engagement with each other facilitated the introduction of new topics. The online forum was an effective tool for adolescents with autism to have direct participation in research. It offers promise in future studies as a practical research tool that accommodates the social communication challenges of individuals with autism.
Response rate of patients with baseline brain metastases from recently diagnosed non‐small cell lung cancer receiving radiotherapy according to EGFR, ALK and KRAS mutation status
Authors: Arrieta Oscar , Ramírez‐Tirado Laura‐Alejandra , Caballé‐Perez Enrique , Mejia‐Perez Alberto , Zatarain‐Barrón Zyanya Lucia , Cardona Andrés F. , Lozano‐Ruíz Francisco , Segura‐González Manuel , Cruz‐Rico Graciela , Maldonado Federico , Rosell Rafael
Published: February 2020

Background

Previous studies have identified that patients with EGFR mutations tend to have better responses to targeted therapy, as well as chemotherapy; however, the effect of genetic alterations in terms of radiotherapy (RT)‐related outcomes has not been fully assessed. We studied the impact of common non‐small cell lung cancer (NSCLC) genetic alterations (EGFR, ALK and KRAS) in relation to objective response rate (ORR) to RT in patients with brain metastases.

Methods

From 2009–2015, 153 patients with an available genotyping status were treated with whole‐brain irradiation (WBI) before receiving systemic therapy. Primary outcome was ORR; secondary outcomes included intracranial progression‐free survival (IPFS) and overall survival (OS).

Results

Overall, ORR was 47.1%. ORR to RT varied significantly according to molecular status: EGFR (64.5%) ALK (54.5%) KRAS (20%) and WT (35.4%) (P = 0.001). EGFR mutation was the only independently associated factor for response to WBI (RR 3.52 [95% CI 1.6–7.7]; P = 0.002). Median IPFS was 10.8 months [95% CI 8.2–13.5] overall; however, IPFS also varied significantly according to molecular status: EGFR (18.2 months), ALK (18.4 months), KRAS (6.0 months) and WT (8.7 months) (P < 0.0001). OS for EGFR, ALK, KRAS and WT patients was 36.6, 32.2, 15.5 and 22.4 months, respectively (P = 0.014). Intracranial‐ORR (HR 0.4 [95% CI 0.2–0.6], P < 0.001) and mutation status (HR 0.7 [95% CI 0.6–0.9], P < 0.042) were independently associated with a higher OS.

Conclusions

RT response varies as per tumor molecular status. The presence of EGFR mutations favors the organ‐specific response to RT, and is associated with longer OS in patients with NSCLC and BM.

Key points

This study addressed for the first time the difference in radiotherapy‐related outcomes in patients with different genotypes of non‐small cell lung cancer (NSCLC) before they received systemic therapy.

Results show that response to radiotherapy varies as per tumor molecular status, particularly EGFR‐mutated tumors, have a favorable response to radiotherapy, contrary to KRAS‐mutated tumors.
LSD1 contributes to programmed oocyte death by regulating the transcription of autophagy adaptor SQSTM1/p62
Authors: He Meina , Zhang Tuo , Zhu Zijian , Qin Shaogang , Wang Huarong , Zhao Lihua , Zhang Xinran , Hu Jiayi , Wen Jia , Cai Han , Xin Qiliang , Guo Qirui , Lin Lin , Zhou Bo , Zhang Hua , Xia Guoliang , Wang Chao
Published: February 2020

In female mammals, the size of the initially established primordial follicle (PF) pool within the ovaries determines the reproductive lifespan of females. Interestingly, the establishment of the PF pool is accompanied by a remarkable programmed oocyte loss for unclear reasons. Although apoptosis and autophagy are involved in the process of oocyte loss, the underlying mechanisms require substantial study. Here, we identify a new role of lysine‐specific demethylase 1 (LSD1) in controlling the fate of oocytes in perinatal mice through regulating the level of autophagy. Our results show that the relatively higher level of LSD1 in fetal ovaries sharply reduces from 18.5 postcoitus (dpc). Meanwhile, the level of autophagy increases while oocytes are initiating programmed death. Specific disruption of LSD1 resulted in significantly increased autophagy and obviously decreased oocyte number compared with the control. Conversely, the oocyte number is remarkably increased by the overexpression of Lsd1 in ovaries. We further demonstrated that LSD1 exerts its role by regulating the transcription of p62 and affecting autophagy level through its H3K4me2 demethylase activity. Finally, in physiological conditions, a decrease in LSD1 level leads to an increased level of autophagy in the oocyte when a large number of oocytes are being lost. Collectively, LSD1 may be one of indispensible epigenetic molecules who protects oocytes against preterm death through repressing the autophagy level in a time‐specific manner. And epigenetic modulation contributes to programmed oocyte death by regulating autophagy in mice.
Unplanned inter‐hospital transfers following elective paediatric surgery in a private hospital
Authors: Sacks Brett , Toomey Brigid , de Winter Ashleigh , Berkowitz Robert G.
Published: February 2020

Background

A significant number of surgeries in children are being performed in the private setting. Our aim was to determine the rate of unplanned inter‐hospital transfers (IHTs) for paediatric patients undergoing elective surgical procedures in a private hospital without a paediatric intensive care unit to a tertiary hospital, and to investigate the reasons for these transfers.

Methods

A retrospective clinical audit was performed searching hospital coded data of all patients aged 18 years or less at the date of admission, who underwent elective surgery between 1 January 2013 and 31 October 2018 at St Vincent's East Melbourne Private Hospital.

Results

A total of 17 366 patients were identified, of whom 23 required IHT, with an overall transfer rate of 0.13%. Adenotonsillectomy had the highest IHT rate of 0.26%; however, operative specialty had no statistical correlation with IHT (P = 0.24) with a comparable transfer rate across all specialties. Hypoxia was the most frequent reason for IHT and was the cause in 16 out of 23 transfers (69%). Nine cases (39%) were transferred due to hypoxia while awake and seven (30%) due to hypoxia only while asleep. Three patients requiring IHT were identified as having preoperative acute respiratory illness.

Conclusion

Elective paediatric surgery undertaken at St Vincent's East Melbourne Private Hospital is safe and has a low IHT rate, with surgery involving the upper airway having a higher risk. In the paediatric population, hypoxia while awake is the most frequent cause for IHT.
Risk of adverse pregnancy outcomes of late‐ and postterm pregnancies in advanced maternal age: A national cohort study
Authors: Kortekaas Joep C. , Kazemier Brenda M. , Keulen Judit K. J. , Bruinsma Aafke , Mol Ben W. , Vandenbussche Frank , Van Dillen Jeroen , De Miranda Esteriek
Published: February 2020

Introduction

There is an increase in women delivering ≥35 years of age. We analyzed the association between advanced maternal age and pregnancy outcomes in late‐ and postterm pregnancies.

Material and methods

A national cohort study was performed on obstetrical low‐risk women using data from the Netherlands Perinatal Registry from 1999 to 2010. We included women ≥18 years of age with a singleton pregnancy at term. Women with a pregnancy complicated by congenital anomalies, hypertensive disorders or diabetes mellitus were excluded. Composite adverse perinatal outcome was defined as stillbirth, neonatal death, meconium aspiration syndrome, 5‐minute Apgar score <7, neonatal intensive care unit admittance and sepsis. Composite adverse maternal outcome was defined as maternal death, placental abruption and postpartum hemorrhage of >1000 mL.

Results

We stratified the women into three age groups: 18‐34 (n = 1 321 366 [reference]); 35‐39 (n = 286 717) and ≥40 (n = 40 909). Composite adverse perinatal outcome occurred in 1.6% in women aged 18‐34, 1.7% in women aged 35‐39 (relative risk [RR] 1.06, 95% confidence interval [95% CI] 1.03‐1.08) and 2.2% in women aged ≥40 (RR 1.38, 95% CI 1.29‐1.47), with 5‐minute Apgar score <7 as the factor contributing most to the outcome. Composite adverse maternal outcome occurred in 4.6% in women aged 18‐34, 5.0% in women aged 35‐39 (RR 1.08, 95% CI 1.06‐1.10) and 5.2% in women aged ≥40 (RR 1.14, 95% CI 1.09‐1.19), with postpartum hemorrhage >1000 mL as the factor contributing most to the outcome. In all age categories, the risk of adverse pregnancy outcomes was higher for nulliparous than for multiparous women. The risk of adverse outcomes increased in both nulliparous and parous women with advancing gestational age. When adjusted for parity, onset of labor and gestational age, advanced maternal age is associated with an increase in both composite adverse perinatal and maternal outcomes.

Conclusions

The risk of adverse pregnancy outcome increases with advancing maternal age. Women aged ≥40 have an increased risk of adverse perinatal and maternal outcome when pregnancy goes beyond 41 weeks.
Risk of molecular recurrence after tyrosine kinase inhibitor discontinuation in chronic myeloid leukaemia patients: a systematic review of literature with a meta‐analysis of studies over the last ten years
Authors: Dulucq Stéphanie , Astrugue Cyril , Etienne Gabriel , Mahon François‐Xavier , Benard Antoine
Published: February 2020

More than 10 years ago, the first pilot observational study of imatinib discontinuation was reported in chronic myeloid leukaemia (CML) patients in deep molecular response (DMR). Several studies have been published since then, in patients treated with frontline imatinib, or second‐generation tyrosine kinase inhibitors (TKI) in first or second line but also on second attempt of TKI discontinuation. Our objective was to estimate, through meta‐analyses of the literature data, the probability of molecular recurrence (MolRec) in the time periods of 0–6, 6–12, 12–18 and 18–24 months after a first and second TKI discontinuation and the probability of re‐acquisition of DMR after MolRec. The Medline and Scopus databases were searched up to April 2019. The studies were selected by three independent reviewers. Random‐effect meta‐analyses were conducted using the MetaXL software. The probability of MolRec in the time periods 0–6, 6–12, 12–18 and 18–24 months after the first attempt was respectively 35%, 8%, 3% and 3%, whereas the probability of MolRec in the time periods 0‐6, 6‐12 and 12‐18 after the second attempt was 48%, 27% and 12% respectively. Re‐acquisition of a DMR was observed in 90% of patients. Most of the MolRec occur during the first six months in case of a first attempt, whereas the second MolRec occurs over a larger window of time.
Satisfaction with life and depressive symptoms in living organ donors and non‐donors: New insights from the National Living Donor Assistance Center
Authors: Mathur Amit K. , Hong Barry A. , Goodrich Nathan P. , Xing Jiawei , Warren Patricia H. , Gifford Kimberly A. , Merion Robert M. , Ojo Akinlolu O.
Published: February 2020

Background

Previous studies indicate there may be psychological consequences of being unable to serve as a living donor, but these have not been explored in a large national cohort of low‐income individuals who initiated living donor evaluation in US transplant centers.

Methods

Using data from 6574 National Living Donor Assistance Center (NLDAC) participants (November 1, 2007‐December 31, 2018), we utilized a cross‐sectional study design to evaluate short‐term depressive symptoms and satisfaction with life in living donors and non‐donors (those who were declined or withdrew from evaluation) using the Satisfaction with Life Scale (SWLS) and the PHQ‐8, with and without risk adjustment using linear regression.

Results

National Living Donor Assistance Center participants originated from 207 US transplant centers. 52% of NLDAC participants responded to the survey (n = 3423; donors = 2848 (58.6% of all donors), non‐donors = 575 (33.5% of all non‐donors); ncenters = 201)). Respondents were significantly older, more likely to be female, white, non‐Hispanic, married, more educated, more full‐time employed, and more likely to be unrelated to the recipient vs non‐respondents (all, P < .001). Among survey respondents, donors were significantly younger, more likely to be non‐Hispanic, employed, and related to the recipient compared to non‐donors (all, P < .05). Higher PHQ‐8 scores were correlated with lower SWL scores (r = −.32, P < .001). Both groups displayed high SWLS (donors vs non‐donors: 27.1 vs 26.3, P = .002). Both groups had low levels of depressive symptoms overall, but donors had more symptoms than non‐donors (3.5 vs 2.4, P < .001). After risk adjustment, non‐donors had significantly less depressive symptoms by PHQ‐8 (28% lower, P < .001), but had lower life satisfaction (1.2 points lower, P < .001).

Conclusions

Donors and non‐donors have high global levels of overall life satisfaction and low levels of depressive symptoms at 8 weeks after donation or denial. While small effect sizes were observed between groups in these outcomes, being a non‐donor was an independent risk factor for lower life satisfaction, which warrants further evaluation.
The ‘Populist’ Right Challenge to Neoliberalism: Social Policy between a Rock and a Hard Place
Authors: Putzel James
Published: February 2020

This article looks at the rise of right populist politics in both developed and developing countries, and its implications for social policy. The author locates the cause for the right populist surge in the legacies of neoliberalism, paying particular attention to the way neoliberal reforms have affected popular attitudes towards politics. The commodification of politics and social services has stoked mass cynicism towards reigning neoliberal elites, creating receptive audiences for populist slogans to ‘drain the swamp’ at the heart of governments. More controversially, the author argues that popular resentments toward neoliberal social policies based on the recognition of the rights of women, minorities, migrants and the poor have made communities susceptible to the racist and misogynist messages of the right populists. Through case studies looking at the United States, Brazil and the Philippines the author argues that the biggest impact of right populists on social policies can be found in their discourses and authoritarian practices of social exclusion.
Cover Image, Volume 22, Issue 3
Authors: Toth Peter P. , Fazio Sergio , Wong Nathan D. , Hull Michael , Nichols Gregory A.
Published: February 2020

The outside front cover image is based on the Review Article Risk of Cardiovascular Events in Patients with Hypertriglyceridemia: A Review of Real‐World Evidence by Peter Paul Toth, NATHAN D. WONG, GREGORY, A. NICHOLS et al., https://doi.org/10.1111/dom.13921.

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Cover Image, Volume 22, Issue 3
Authors: Matza Louis S. , Boye Kristina S. , Stewart Katie D. , Coyne Karin S. , Wullenweber Paula K. , Cutts Katelyn N. , Jordan Jessica B. , Wang Qianqian , Yu Maria , Currie Brooke M. , Malley Karen G. , Ishak K. Jack , Hietpas Ryan T. , García‐Pérez Luis‐Emilio
Published: February 2020

The outside back cover image is based on the Original Article Crossover Clinical Trial Assessing Patient PREFERence between the Dulaglutide Pen and the Semaglutide Pen (PREFER) by Louis S. Matza, Katie Stewart, KARIN S. COYNE et al., https://doi.org/10.1111/dom.13902.

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