bluuebunny/crossref_metadata_2025 huggingface dataset:
The inducible response of the nematodeCaenorhabditis elegansto members of its natural microbiome across development and adult life
Authors: Yang W , Petersen C , Pees B , Zimmermann J , Waschina S , Dirksen P , Rosenstiel P , Tholey A , Leippe M , Dierking K , Kaleta C , Schulenburg H
Published: February 2019

The biology of all organisms is influenced by the associated community of microorganisms. In spite of its importance, it is usually not well understood how exactly this microbiome affects host functions and what are the underlying molecular processes. To rectify this knowledge gap, we took advantage of the nematodeC. elegansas a tractable, experimental model system and assessed the inducible transcriptome response after colonization with members of its native microbiome. For this study, we focused on two isolates of the genusOchrobactrum. These bacteria are known to be abundant in the nematode’s microbiome and are capable of colonizing and persisting in the nematode gut, even under stressful conditions. The transcriptome response was assessed across development and three time points of adult life, using general andC. elegans-specific enrichment analyses to identify affected functions. Our assessment revealed an influence of the microbiome members on the nematode’s dietary response, development, fertility, immunity, and energy metabolism. This response is mainly regulated by a GATA transcription factor, most likely ELT-2, as indicated by the enrichment of (i) the GATA motif in the promoter regions of inducible genes and (ii) of ELT-2 targets among the differentially expressed genes. We compared our transcriptome results with a corresponding previously characterized proteome data set, highlighting a significant overlap in the differentially expressed genes and the affected functions. Our analysis further identified a core set of 86 genes that consistently responded to the microbiome members across development and adult life, including several C-type lectin-like genes and genes known to be involved in energy metabolism or fertility. We additionally assessed the consequences of induced gene expression with the help of metabolic network model analysis, using a previously established metabolic network forC. elegans. This analysis complemented the enrichment analyses by revealing an influence of theOchrobactrumisolates onC. elegansenergy metabolism and furthermore metabolism of specific amino acids, fatty acids, and also folate biosynthesis. Our findings highlight the multifaceted impact of naturally colonizing microbiome isolates onC. eleganslife history and thereby provide a framework for further analysis of microbiome-mediated host functions.
Biologically indeterminate yet ordered promiscuous gene expression in single medullary thymic epithelial cells
Authors: Dhalla F. , Baran-Gale J. , Maio S. , Chappell L. , Holländer G. , Ponting C.P.
Published: February 2019

During thymic negative selection, medullary thymic epithelial cells (mTEC) collectively express most protein coding genes, a process termed promiscuous gene expression (PGE). Although PGE is crucial for inducing central T-cell tolerance, this process has not been established definitively as being either stochastic or coordinated. To resolve this question, we sequenced the transcriptomes of 6,894 single mTEC, including 1,795 rare cells expressing either of two tissue-restricted antigens, TSPAN8 or GP2. Transcriptional heterogeneity allowed partitioning of mTEC into 15 robustly-defined subpopulations representing distinct maturational stages and subtypes. Although 50 gene co-expression groups were robustly identified, few could be explained by chromosomal location, biological pathway, or tissue specificity. Further, GP2+ mTEC were randomly dispersed spatially within medullary islands. Thus although PGE exhibits ordered co-expression, biologically it is indeterminate. This likely enhances the presentation of diverse antigens to passing thymocytes during their medullary residency, while simultaneously maintaining mTEC identity throughout PGE.
The oncoprotein DEK affects the outcome of PARP1/2 inhibition during replication stress
Authors: Ganz Magdalena , Vogel Christopher , Czada Christina , Jörke Vera , Kleiner Rebecca , Pierzynska-Mach Agnieszka , Zanacchi Francesca Cella , Diaspro Alberto , Kappes Ferdinand , Bürkle Alexander , Ferrando-May Elisa
Published: February 2019

DNA replication stress is a major source of genomic instability and is closely linked to tumor formation and progression. Poly(ADP-ribose)polymerases1/2 (PARP1/2) enzymes are activated in response to replication stress resulting in poly(ADP-ribose) (PAR) synthesis. PARylation plays an important role in the remodelling and repair of impaired replication forks, providing a rationale for targeting highly replicative cancer cells with PARP1/2 inhibitors. The human oncoprotein DEK is a unique, non-histone chromatin architectural protein whose deregulated expression is associated with the development of a wide variety of human cancers. Recently, we showed that DEK is a high-affinity target of PARylation and that it promotes the progression of impaired replication forks. Here, we investigated a potential functional link between PAR and DEK in the context of replication stress. Under conditions of mild replication stress induced either by topoisomerase1 inhibition with camptothecin or nucleotide depletion by hydroxyurea, we found that the effect of acute PARP1/2 inhibition on replication fork progression is dependent on DEK expression. Reducing DEK protein levels also overcomes the restart impairment of stalled forks provoked by blocking PARylation. Non-covalent DEK-PAR interaction via the central PAR-binding domain of DEK is crucial for counteracting PARP1/2 inhibition as shown for the formation of RPA positive foci in hydroxyurea treated cells. Finally, we show by iPOND and super resolved microscopy that DEK is not directly associated with the replisome since it binds to DNA at the stage of chromatin formation. Our report sheds new light on the still enigmatic molecular functions of DEK and suggests that DEK expression levels may influence the sensitivity of cancer cells to PARP1/2 inhibitors.
Prey abundance drives habitat occupancy by jaguars in Amazonian floodplain river islands
Authors: Rabelo Rafael M. , Aragón Susan , Bicca-Marques Júlio César
Published: February 2019

The jaguar (Panthera onca) is widely distributed across a broad range of habitat types, where its feeding habits and habitat use patterns vary significantly. The jaguar and its main arboreal prey – the brown-throated sloth (Bradypus variegatus) and the red howler monkey (Alouatta juara) – are widespread in the Amazonian floodplain forests of the Mamirauá Reserve. These forest-dwelling species are the most common mammal species both in the continuous forest and the forest patches surrounded by a river matrix – the fluvial islands – of the Solimões and Japurá rivers. We used sign surveys along line-transects to assess the pattern of habitat occupancy by jaguars in Amazonian floodplain forests. Specifically, we (i) tested whether habitat occupancy by jaguars differs between river islands and continuous forest; and (ii) evaluated whether and how the local abundance of sloths and howler monkeys influence the probability of site occupancy by jaguars. We built an occupancy model and used Bayesian inference to reach these goals. The proportion of sites estimated to be used by jaguars wasψ= 0.75 (HPD95: 0.36–1.00), and it did not differ between islands and continuous forest. The abundance of both prey species had a direct influence on jaguar’s habitat use, whereas the aquatic matrix seems to have a negligible effect on the use of islands by jaguars. We conclude that the isolation of the river islands within the aquatic matrix does not hamper jaguars to use them. We also conclude that prey search modulates jaguars’ habitat occupancy patterns with both prey species having a similar effect. This finding is compatible with the previously reported importance of sloths to the diet of jaguars in the study region despite its lower abundance than howlers. Finally, we suggest that sign surveys are an alternative method to assess the pattern of jaguar habitat occupancy in floodplain forests.
Immunohistochemical and ultrastructural analysis of the maturing larval zebrafish enteric nervous system reveals the formation of a neuropil pattern
Authors: Baker Phillip A. , Meyer Matthew D. , Tsang Ashley , Uribe Rosa A.
Published: February 2019

The gastrointestinal tract is constructed with an intrinsic series of interconnected ganglia that span its entire length, called the enteric nervous system (ENS). The ENS exerts critical local reflex control over many essential gut functions; including peristalsis, water balance, hormone secretions and intestinal barrier homeostasis. ENS ganglia exist as a collection of neurons and glia that are arranged in a series of plexuses throughout the gut: the myenteric plexus and submucosal plexus. While it is known that enteric ganglia are derived from a stem cell population called the neural crest, mechanisms that dictate final neuropil plexus organization remain obscure. Recently, the vertebrate animal, zebrafish, has emerged as a useful model to understand ENS development, however knowledge of its developing myenteric plexus architecture was unknown. Here, we examine myenteric plexus of the maturing zebrafish larval fish histologically over time and find that it consists of a series of tight axon layers and long glial cell processes that wrap the circumference of the gut tube to completely encapsulate it, along all levels of the gut. By late larval stages, complexity of the myenteric plexus increases such that a layer of axons is juxtaposed to concentric layers of glial cells. Ultrastructurally, glial cells contain glial filaments and make intimate contacts with one another in long, thread-like projections. Conserved indicators of vesicular axon profiles are readily abundant throughout the larval plexus neuropil. Together, these data extend our understanding of myenteric plexus architecture in maturing zebrafish, thereby enabling functional studies of its formation in the future.
Biological Process Activity Transformation of Single Cell Gene Expression for Cross-Species Alignment
Authors: Ding Hongxu , Blair Andrew , Yang Ying , Stuart Joshua M.
Published: February 2019

The maintenance and transition of cellular states are controlled by biological processes. Here we present a gene set-based transformation of single cell RNA-Seq data into biological process activities that provides a robust description of cellular states. Moreover, as these activities represent species-independent descriptors, they facilitate the alignment of single cell states across different organisms.
Strategies for sample delivery for femtosecond crystallography
Authors: Martiel Isabelle , Müller-Werkmeister Henrike M. , Cohen Aina E.
Published: February 2019

Highly efficient data-collection methods are required for successful macromolecular crystallography (MX) experiments at X-ray free-electron lasers (XFELs). XFEL beamtime is scarce, and the high peak brightness of each XFEL pulse destroys the exposed crystal volume. It is therefore necessary to combine diffraction images from a large number of crystals (hundreds to hundreds of thousands) to obtain a final data set, bringing about sample-refreshment challenges that have previously been unknown to the MX synchrotron community. In view of this experimental complexity, a number of sample delivery methods have emerged, each with specific requirements, drawbacks and advantages. To provide useful selection criteria for future experiments, this review summarizes the currently available sample delivery methods, emphasising the basic principles and the specific sample requirements. Two main approaches to sample delivery are first covered: (i) injector methods with liquid or viscous media and (ii) fixed-target methods using large crystals or using microcrystals inside multi-crystal holders or chips. Additionally, hybrid methods such as acoustic droplet ejection and crystal extraction are covered, which combine the advantages of both fixed-target and injector approaches.
Dyadic alignment in capital goods companies
Authors: Moori Roberto Giro , Nafal Kalid A. , Kimura Herbert , Sobreiro Vinicius Amorim
Published: February 2019

Purpose

The purpose of this paper is to identify the main factors of the dyadic alignment in the supply chain of capital goods companies.

Design/methodology/approach

A survey was conducted among 159 respondents (53 supplier companies, 53 manufacturers and 53 clients).

Findings

Using structural equation modelling, no evidence of alignment between suppliers and manufacturers was identified. However, for the manufacturers, there is a partial mediation effect of the operational capabilities in the relationship between supply chain management and business performance.

Originality/value

This research investigates whether there is a dyadic alignment among supplier–manufacturer, manufacturer–customer and supplier–customer from the capital goods manufacturers’ perspective.
Impacts of Lean Six Sigma on improving a higher education system: a case study
Authors: Haerizadeh Milad , Sunder M. Vijaya
Published: February 2019

Purpose

The purpose of this paper is to demonstrate the applicability and impact of Lean Six Sigma (LSS), a contemporary quality excellence methodology, for improving education system in a reputed University in Iran.

Design/methodology/approach

The paper follows a case study approach illustrating how theory has been put into practice, explaining how to implement the LSS define-measure-analyze-improve-control framework in a field-setting in a higher education institution (HEI), and to highlight the subsequent challenges occurred and lessons learned during the implementation.

Findings

The key finding from the study is the confirmation of LSS applicability in education systems. The goals of the LSS team were to baseline student satisfaction levels and improve the overall rating by 10 percent; to decrease student advising wait times by 15 percent; and increase enrollment by 5 percent. The application of the LSS methodology has delivered promising results to improve the education system of the University by achieving the set goals. Further, the implementation of LSS has demonstrated student-facing benefits of improved quality on the education system.

Research limitations/implications

LSS implementation in HEIs is relatively a new topic for research. Hence, this case study adds to the body of knowledge with directions to progress future research in this area.

Practical implications

The outputs of the case study have provided greater stimulus within the facilities for wider full-blown deployment of LSS as a strategic resource for problem solving. Additionally, this case study sets the foundation for many other future projects, and to trigger interest among the HEIs in their journeys for quality excellence.

Social implications

Higher education sector being a socially responsible field of service, LSS offers continuous improvement benefits, highlighted as part of this paper.

Originality/value

The applicability of LSS in HEIs is relatively an upcoming research area with immense potential and value. This paper would serve as a valuable means for both researchers and practitioners working in HEIs, in terms of understanding the systematic application of the LSS methodology, and implications in a real-world situation.
Viewpoint: CPS guidance on prosecuting rape and sexual assault cases
Authors: Foley Marian , Cummins Ian
Published: February 2019

Purpose

The purpose of this paper is to highlight concerns about recent CPS guidance on the prosecution of rape and sexual assault cases.

Design/methodology/approach

The paper places the CPS guidance in the wider policy context of concerns about sexual violence on mental health wards.

Findings

The paper concludes that the reported CPS guidance appears to run counter to other policy directives particularly the recent report from the CQC.

Originality/value

The paper is a first response to these issues.
Antecedents of supplier selection decisions in the public sector in Nigeria
Authors: Essien Eyo , Lodorfos George , Kostopoulos Ioannis
Published: February 2019

Purpose

This paper aims to develop and test a conceptual model of supplier selection decisions in the public sector. The study seeks to determine the relative importance of a broad range of non-economic variables in explaining supplier selection decisions during strategic organizational purchases.

Design/methodology/approach

Data were collected from a national sample of 341 senior staff and top management team (TMT) members in 40 public sector organizations in Nigeria by using structured questionnaires.

Findings

Results of structural equation modeling (SEM) analysis shows that government policy requirements, social ties of organizational actors, party politics, decision-makers’ experience and the perception of instrumental ethical work climates are the most important determinants of strategic supplier selection decisions, followed in a descending order of importance by the perception of rules ethical work climates, self-enhancement personal values, CEOs’ structural position, self-transcendent personal values and the perception of time pressure. Findings also indicate that the choice of a supplier per se is not an important determinant of organizational performance.

Originality/value

No prior study has brought together, in a single model, the broad range of variables employed in this study with a view to exploring their relative importance in explaining public sector supplier selection decisions in a non-western country context. The findings of this study have implications for Marketing Managers looking to do business with public sector firms in emerging markets.
An empirical framework for soft CSFs of TQM in Chinese manufacturing companies
Authors: Yan Jianwen , Zhang Kexin , Zhu Weiwei , Fan Yu
Published: February 2019

Purpose

The purpose of this paper is to frame an empirical model with the priority of implementing soft critical successful factors (CSFs) of total quality management (TQM) in Chinese manufacturing companies.

Design/methodology/approach

In total, 23 hypotheses regarding the relationships among TQM factors and business results have been developed through literature review and are tested using the structural equation modelling (SEM). The data used in this study are collected from 228 manufacturing companies in the central area of China.

Findings

Of the 23 hypotheses, 11 were statistically significant, and according to the empirical results a conceptual framework complying to Chinese condition is constructed and discussed in the finding parts to group soft CSFs of TQM into different levels of importance.

Research limitations/implications

Researchers can use the framework to further study soft CSFs of TQM in detail, and extend it to explore their impact mechanism for a clearer and deeper understanding of the TQM.

Practical implications

The empirical framework for soft CSFs of TQM provides a new perspective for managers to implement the soft CSFs and optimise the quality management system of their manufacturing companies.

Originality/value

This research uses multiple, distinct indicators for each soft factor to test an elaborate SEM model of the relationships among them, according to the empirical results constructs a holistic framework classifying the importance level of soft CSFs of TQM, which is novel and subjected with Chinese condition and manufacturing characteristics.
Issues and challenges in implementing the Skill India movement
Authors: De Debpriya
Published: February 2019

Purpose

The purpose of this paper is to discuss the issues and challenges that become a hurdle towards implementation of the “Skill India Movement” at the ground level. It is critical to identify the challenges that are faced or experienced by training partners with the National Skill Development Corporation (NSDC), skills councils and other bodies if an effort to resolve the same is to be made.

Design/methodology/approach

A round-table discussion was organised to seek feedback from all the stakeholders who are directly or indirectly involved in strategising, decision-making and implementing the government’s skills initiative. The primary data were collected through discussions and questionnaires, and the official sites of NSDC and Pradhan Mantri Kaushal Vikas Yojna, along with ministry reports, were referred to as well.

Findings

The research is likely to identify gaps in administration of the initiative at various levels and will hopefully provide guidance on removing bottlenecks to achieve effective implementation. It is imperative that the challenges be understood and solutions found, with focus on a long-term sustainable approach, rather than short-term gains for political propaganda purposes alone.

Practical implications

This paper will try to bring value to the stakeholders by exploring the various measures that can be taken to take this mission in a more meaningful direction and work towards giving more employability to the youth and supporting the respective industry segments with much needed trained manpower.

Originality/value

This study discusses the issues and challenges that are impeding effective implementation of the Skill India initiative at the local level and identifies the gaps in administration. Also, it outlines how bottlenecks could be addressed to ensure that the mission is back on track and that the employability of youth is enhanced.
Semi‐automatic fault/fracture interpretation based on seismic geometry analysis
Authors: Di Haibin , AlRegib Ghassan
Published: February 2019

Fault and fracture interpretation is a fundamental but essential tool for subsurface structure mapping and modelling from 3D seismic data. The existing methods for semi‐automatic/automatic fault picking are primarily based on seismic discontinuity analysis that evaluates the lateral changes in seismic waveform and/or amplitude, which is limited by its low resolution on subtle faults and fractures without apparent vertical displacements in seismic images. This study presents an innovative workflow for computer‐aided fault/fracture interpretation based on seismic geometry analysis. First, the seismic curvature and flexure attributes are estimated for highlighting both the major faults and the subtle fractures in a seismic volume. Then, fault probability is estimated from the curvature and flexure volumes for differentiation between the potential faults and non‐faulting features in the geometric attributes. Finally, the seeded fault picking is implemented for interpreting the target faults and fractures guided by the knowledge of interpreters to avoid misinterpretation and artefacts in the presence of faulting complexities as well as coherent seismic noises. Applications to two 3D seismic volumes from the Netherlands North Sea and the offshore New Zealand demonstrate the added values of the proposed method in imaging and picking the subtle faults and fractures that are often overlooked in the conventional seismic discontinuity analysis and the following fault‐interpretation procedures.
Humour in clinical–educational interactions between graduate student clinicians and people with aphasia
Authors: Archer Brent , Azios Jamie H. , Moody Samantha
Published: February 2019

Background

During clinical interactions, clinicians and people with aphasia (PWA) use humour and laughter for a range of purposes, most of which contribute to friendly interactions in which the participants appear to develop a positive regard for one another. Moreover, humour is a vital component of facework, or the processes interactants engage in to protect their own and one another's well‐respected, public personas.

Aims

To examine the ways in which speech–language pathology graduate student clinicians enlist humour during one‐on‐one therapy sessions for PWA.

Methods & Procedures

Three dyads composed of one graduate student clinician and one person with aphasia acted as participants. We recorded six routine individual aphasia therapy sessions that were each about 60 min in length. All sessions were orthographically transcribed by a trained research assistant. Transcriptions included verbal and non‐speech communication (e.g., facial expressions, gestures, writing). For analysis, we employed an ethnographic microanalysis framework. First, by focusing on laughter produced by the interactants, we identified segments in the data that involved clinician‐led humour. Next, we sought to understand patterns that represented potential functions of humour. We consciously sought out instances that did not appear consistent with our developing understanding of the functions of humour. Such negative cases were used to refine our description of how graduate student clinicians use humour. Other verification procedures included member checking and peer debriefing.

Outcomes & Results

The findings illustrate that graduate student clinicians use laughter and humour for a range of interactional purposes when interacting with clients with aphasia. Humour was used as a means of (1) softening exposure to client's errors, (2) equalizing interactional power, (3) mitigating errors made by graduate student clinicians, (4) supporting own narrative production and (5) demonstrating affiliation.

Conclusions & Implications

The current study demonstrates that graduate student clinicians we observed, like the clinicians studied in previous investigations of humour in therapeutic encounters, possess the humour and laughter‐related skills that help to foster positive interactions with PWA. Future investigations of the source of these skills should determine if students are adept because of natural abilities or if students can be taught to be better interactants via instruction. Findings emanating from these studies can be used to inform curriculum design, which will in turn help our field better meet the needs of clients.
STRIDER NZAus: a multicentre randomised controlled trial of sildenafil therapy in early‐onset fetal growth restriction
Authors: Groom KM , McCowan LM , Mackay LK , Lee AC , Gardener G , Unterscheider J , Sekar R , Dickinson JE , Muller P , Reid RA , Watson D , Welsh A , Marlow J , Walker SP , Hyett J , Morris J , Stone PR , Baker PN
Published: February 2019

Objective

To assess the effect of maternal sildenafil therapy on fetal growth in pregnancies with early‐onset fetal growth restriction.

Design

A randomised placebo‐controlled trial.

Setting

Thirteen maternal–fetal medicine units across New Zealand and Australia.

Population

Women with singleton pregnancies affected by fetal growth restriction at 22+0 to 29+6 weeks.

Methods

Women were randomised to oral administration of 25 mg sildenafil citrate or visually matching placebo three times daily until 32+0 weeks, birth or fetal death (whichever occurred first).

Main Outcome Measures

The primary outcome was the proportion of pregnancies with an increase in fetal growth velocity. Secondary outcomes included live birth, survival to hospital discharge free of major neonatal morbidity and pre‐eclampsia.

Results

Sildenafil did not affect the proportion of pregnancies with an increase in fetal growth velocity; 32/61 (52.5%) sildenafil‐treated, 39/57 (68.4%) placebo‐treated [adjusted odds ratio (OR) 0.49, 95% CI 0.23–1.05] and had no effect on abdominal circumference Z‐scores (P = 0.61). Sildenafil use was associated with a lower mean uterine artery pulsatility index after 48 hours of treatment (1.56 versus 1.81; P = 0.02). The live birth rate was 56/63 (88.9%) for sildenafil‐treated and 47/59 (79.7%) for placebo‐treated (adjusted OR 2.50, 95% CI 0.80–7.79); survival to hospital discharge free of major neonatal morbidity was 42/63 (66.7%) for sildenafil‐treated and 33/59 (55.9%) for placebo‐treated (adjusted OR 1.93, 95% CI 0.84–4.45); and new‐onset pre‐eclampsia was 9/51 (17.7%) for sildenafil‐treated and 14/55 (25.5%) for placebo‐treated (OR 0.67, 95% CI 0.26–1.75).

Conclusions

Maternal sildenafil use had no effect on fetal growth velocity. Prospectively planned meta‐analyses will determine whether sildenafil exerts other effects on maternal and fetal/neonatal wellbeing.

Tweetable abstract

Maternal sildenafil use has no beneficial effect on growth in early‐onset FGR, but also no evidence of harm.
Meeting Report: Key Outcomes from a Collaborative Summit on Agricultural Water Standards for Fresh Produce
Authors: Wall Gretchen L. , Clements Donna P. , Fisk Connie L. , Stoeckel Donald M. , Woods Kristin L. , Bihn Elizabeth A.
Published: February 2019

On February 27 to 28, 2018, the Produce Safety Alliance convened a national water summit in Covington, KY to discuss the requirements of the United States Food and Drug Administration's (FDA) Food Safety Modernization Act Standards for the Growing, Harvesting, Packing, and Holding of Produce for Human Consumption (Produce Safety Rule [PSR]). The goals of the meeting were to better understand the challenges growers face in implementing the requirements in Subpart E–Agricultural Water and work collaboratively to develop practical solutions to meet fruit and vegetable production needs while protecting public health. To meet these goals, the summit engaged a diverse group of stakeholders including growers, researchers, extension educators, produce industry members, and regulatory personnel. Key outcomes included defining implementation barriers due to diversity in water sources, distribution systems, commodity types, climates, farm size, and production activities. There was an articulated need for science‐based solutions, such as the use of agricultural water system assessments and sharing of federal, state, and regional water quality data, to ensure qualitative and quantitative standards reduce microbial risks. These identified challenges and needs resulted in significant debate about whether reopening the PSR–Subpart E for modification or attempting to address concerns through guidance would provide the best mechanism for alleviating concerns. In addition, training, outreach, and technical assistance were identified as vital priorities once the concerns are formally addressed by FDA. The water summit highlighted the critical need for transparency of FDA's progress on reevaluating the Subpart E requirements to help guide growers’ decisions regarding the use of agricultural water.
Criminal network security: An agent‐based approach to evaluating network resilience*
Authors: Duxbury Scott W. , Haynie Dana L.
Published: February 2019

Criminal networks are frequently at risk of disruption through arrest and interorganizational violence. Difficulties in designing empirical studies of criminal network recovery, however, have problematized research into network responses to disruption. In this study, we evaluate criminal network resilience by examining network recovery from disruption in an array of different criminal networks and across different disruption strategies. We use an agent‐based model to evaluate how criminal networks recover from disruption. Our results reveal the vulnerabilities and time to recovery of numerous criminal organizations, and through them, we identify which disruption strategies are most effective at damaging various criminal networks.
Role of voice in the legal process*
Authors: Pennington Liana , Farrell Amy
Published: February 2019

As communities face unrest and protest because of perceived racial bias and decreased trust and confidence in the criminal justice system, it is critical to explore mechanisms that foster institutional legitimacy. Voice is a central element in the procedural justice framework because it is anticipated to promote process control as well as a shared understanding between institutions and communities. As a concept, however, voice is undertheorized. Measures of voice used in legitimacy research may result in oversimplification of the concept, not fully capturing the struggles disadvantaged people face in trying to exercise influence in the court system. Through the use of rich data from qualitative interviews with youth and families involved in the juvenile justice system and in‐depth observations of juvenile court events, we explore what voice is, the mechanisms through which people try to assert voice, and how voice matters in the legal process. Respondents sought voice for many reasons, including to validate their experiences, to affirm their membership in a community, and to assert concerns about perceived police misconduct. Contrary to traditional conceptualizations of voice as a static event (e.g., having voice or not having voice), voice was a process of negotiating dialogue between court officials and court participants throughout the legal process.
Metabarcoding a diverse arthropod mock community
Authors: Braukmann Thomas W. A. , Ivanova Natalia V. , Prosser Sean W. J. , Elbrecht Vasco , Steinke Dirk , Ratnasingham Sujeevan , de Waard Jeremy R. , Sones Jayme E. , Zakharov Evgeny V. , Hebert Paul D. N.
Published: February 2019

Although DNA metabarcoding is an attractive approach for monitoring biodiversity, it is often difficult to detect all the species present in a bulk sample. In particular, sequence recovery for a given species depends on its biomass and mitome copy number as well as the primer set employed for PCR. To examine these variables, we constructed a mock community of terrestrial arthropods comprised of 374 species. We used this community to examine how species recovery was impacted when amplicon pools were constructed in four ways. The first two protocols involved the construction of bulk DNA extracts from different body segments (Bulk Abdomen, Bulk Leg). The other protocols involved the production of DNA extracts from single legs which were then merged prior to PCR (Composite Leg) or PCR‐amplified separately (Single Leg) and then pooled. The amplicons generated by these four treatments were then sequenced on three platforms (Illumina MiSeq, Ion Torrent PGM and Ion Torrent S5). The choice of sequencing platform did not substantially influence species recovery, although the Miseq delivered the highest sequence quality. As expected, species recovery was most efficient from the Single Leg treatment because amplicon abundance varied little among taxa. Among the three treatments where PCR occurred after pooling, the Bulk Abdomen treatment produced a more uniform read abundance than the Bulk Leg or Composite Leg treatment. Primer choice also influenced species recovery and evenness. Our results reveal how variation in protocols can have substantial impacts on perceived diversity unless sequencing coverage is sufficient to reach an asymptote.
Adjudin synergizes with paclitaxel and inhibits cell growth and metastasis by regulating the sirtuin 3–Forkhead box O3a axis in human small‐cell lung cancer
Authors: Wang Xue , Zeng Qingyu , Li Ziming , Yang Xiao , Xia Weiliang , Chen Zhiwei
Published: February 2019

Background

Small‐cell lung cancer (SCLC), a malignant tumor, is usually widely metastatic when diagnosed. The lack of important therapeutic clinical advances makes it difficult to treat. Previous studies showed that Adjudin had anticancer effects in many other human cancers, and it was synergetic with cisplatin in non‐small cell lung cancer. However, the mechanism on SCLC was unclear.

Methods

We investigated the potential mechanism and effect of Adjudin on SCLC both in vitro and in vivo.

Results

An SCLC xenograft model showed that Adjudin inhibited tumor growth and was significantly synergetic with paclitaxel (in vitro as well). Cell Counting Kit‐8 assays, flow cytometric analysis and western blotting showed that Adjudin effectively suppressed SCLC cell proliferation by inducing S phase arrest and caspase‐dependent apoptosis. Moreover, Transwell and scratch assays showed that Adjudin also effectively inhibited migration and invasion. Furthermore, Adjudin activated the sirtuin 3 (SIRT3)–Forkhead box O3a (FOXO3a) pathway. Downregulating SIRT3 or FOXO3a significantly attenuated Adjudin‐induced anticancer effects. Furthermore, higher expression of SIRT3 and FOXO3a were positively correlated, and both were associated with longer survival in lung cancer patients.

Conclusion

Overall, the present study is the first to show that Adjudin synergizes with paclitaxel and inhibits cell growth and metastasis by regulating the SIRT3–FOXO3a axis in SCLC; thus, Adjudin has great potential to be an anticancer agent.
Malignant pleural effusion supernatant is an alternative liquid biopsy specimen for comprehensive mutational profiling
Authors: Guo Zhihua , Xie Zhanhong , Shi Huifang , Du Wei , Peng Lijun , Han Wei , Duan Feidie , Zhang Xin , Chen Mingyan , Duan Junli , Lin Jing , Chen Xuewei , Lizaso Analyn Ang , Han‐Zhang Han , He Jianxing , Yin Weiqiang
Published: February 2019

Background

The clinical utility of malignant pleural effusion (MPE) to detect mutation has been well documented; however, routine practice of the use of MPE involves collection of the cell pellet to detect mutation, and limited studies have interrogated the MPE supernatant as an alternative source of tumor‐derived DNA for mutation profiling. In this study, we investigated the potential of MPE supernatant as a liquid biopsy specimen by comparing its mutation profile with that of matched MPE cell pellets, tissue, and plasma samples.

Methods

Sequencing data from 17 patients with matched lung tissue, plasma, and MPE samples were retrospectively analyzed. Capture‐based targeted sequencing was performed on matched plasma and MPE supernatant samples obtained from 154 patients with advanced lung adenocarcinoma.

Results

MPE supernatants had significantly higher median maximum allelic fractions (maxAFs) than their corresponding cell pellets (P = 0.008) and plasma samples (P = 0.036), and a comparable maxAF value to that of tissue samples (P = 0.675). Comparison of MPE supernatant and matched plasma samples from the larger cohort (n = 154) revealed a comparable mutation detection rate; however, MPE supernatant had a significantly higher median maxAF than plasma (20.3% vs. 1.13%; P < 0.001). Furthermore, the concordance rates between MPE supernatant and plasma for single‐nucleotide and copy number variations were 56% and 18%, respectively, suggesting that MPE supernatant reveals a more comprehensive mutation spectrum, particularly for copy number variations.

Conclusion

Overall, our study shows that MPE supernatant is an optimal alternative source of tumor‐derived DNA for comprehensive mutation profiling.
Curative effect assessment of immunotherapy for non‐small cell lung cancer: The “blind area” of Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
Authors: Song Peng , Zhang Jingcheng , Shang Congcong , Zhang Li
Published: February 2019

Background

Immunotherapy has considerably changed the treatment of lung cancer. As immunotherapy has a special mechanism of action, the disease remission that it can induce is unique. Recently, Immune Response Evaluation Criteria in Solid Tumors (iRECIST), which focus on assessing the apparent curative effect of immunotherapy, have become widely accepted. Based on iRECIST criteria, if the response to immunotherapy is determined to be immunity‐confirmed progressive disease or immunity‐unconfirmed progressive disease, and the Eastern Cooperative Oncology Group score is worse than before treatment, immunotherapy should be discontinued. We report two immunity‐confirmed progressive disease cases after pembrolizumab treatment and one immunity‐unconfirmed progressive disease case after nivolumab treatment. All three patients benefited from continued immunotherapy, which indicates that the iRECIST criteria may have limitations in assessing the efficacy of immunotherapy for non‐small cell lung cancer patients.
Predictors of Adverse Alcohol Use Consequences Among Tertiary Students
Authors: Poulton Antoinette , Mata Adrienn , Pan Jason , Bruns Loren Richard , Sinnott Richard O. , Hester Robert
Published: February 2019

Background

The alcohol consumption patterns of young adults are of concern. Critically, tertiary students consume greater quantities of alcohol, are at increased risk of injury/harm, and have higher rates of alcohol use disorders as compared to their nonuniversity enrolled peers. The Brief Young Adult Alcohol Consequences Questionnaire (BYAACQ) is one of several tools utilized to explore adverse alcohol‐related outcomes among tertiary students. Alcohol intake behavior, assessed via retrospective summary measures, has been linked to BYAACQ score. It is unclear, however, how drinking assessed in real time, in conjunction with variables such as age of drinking onset, might predict severity of adverse alcohol consequences as captured by the BYAACQ.

Methods

The psychometric properties of the BYAACQ were explored using a large Australian sample of tertiary students (N = 893). A subsample (n = 504) provided alcohol intake information in real time (21 days; event and notification contingent) via a smartphone app (CNLab‐A) plus details related to age of drinking onset, drug use, parental alcohol/drug use, and anxiety/depression symptomology.

Results

Average BYAACQ score was 7.53 (SD = 5.37). Classical and item response theory analyses revealed inconsistencies related to dimensionality, progressive item severity, and male/female differential item functioning. Current drinking—namely, frequency of intake and quantity per drinking occasion—plus age of drinking onset predicted BYAACQ score after controlling for age, other drug use, and depression symptomology.

Conclusions

The BYAACQ is a sound tool for use with Australian samples. Information related to current drinking, age of drinking onset, and drug use is useful for predicting severity of alcohol use consequences. These markers might enable tertiary institutions to better target students who could benefit from prevention/intervention programs.
Comorbidity of Alcohol Use and Other Psychiatric Disorders and Suicide Mortality: Data from the South Korean National Health Insurance Cohort, 2002 to 2013
Authors: Park Subin , Rim Soo Jung , Jo MinKyung , Lee Min Geu , Kim Chul Eung
Published: February 2019

Background

Previous studies have indicated that alcohol use disorder (AUD) and other psychiatric disorders increase the risk of suicide mortality. However, little research has investigated the concomitant effect of comorbid psychiatric disorders on suicide mortality. This study aimed to investigate the effect of comorbid AUD on suicide mortality of individuals with another psychiatric disorder using a national data sample.

Methods

We used the National Health Insurance Service–National Sample Cohort data from 2002 to 2013. We selected individuals with specific psychiatric disorders based on the International Classification of Diseases, 10th revision (F10–F48). Overall, the study included 741,601 participants. We utilized a prioritization process to identify the primary diagnosis for those with multiple diagnoses. All‐cause mortality rates and suicide rates per 100,000 person‐year (days) and the standardized mortality ratio (SMR) were calculated. Then, we compared the suicide‐specific SMR of 3 different groups: (i) specific psychiatric disorder versus general public; (ii) specific psychiatric disorder comorbid with AUD versus general public; and (iii) specific psychiatric disorder comorbid with AUD versus specific psychiatric disorder without comorbid AUD.

Results

Patients with any specific psychiatric disorder showed higher suicide‐specific SMR compared to the general population. Being comorbid with AUD further increased the risk of suicide among psychiatric patients. In particular, patients with bipolar affective disorders, organic mental disorders, or depressive disorders comorbid with AUD had about 2 to 4 times higher suicide‐specific SMR compared to those without AUD (bipolar affective disorder: SMR = 3.01, 95% confidence interval (CI) [1.49, 4.54]; organic mental disorder: SMR = 3.43, 95% CI [1.05, 5.81]; depressive disorder: SMR = 2.06, 95% CI [1.52, 2.61]).

Conclusions

Our data indicate that having a psychiatric disorder increases the risk of committing suicide. More importantly, comorbid AUD further increases this risk of suicidal death for certain psychiatric disorders. This shows the importance of determining whether patients with psychiatric disorders have comorbid AUD to prevent suicide.
Adolescence versus adulthood: Differences in basal mesolimbic and nigrostriatal dopamine transmission and response to drugs of abuse
Authors: Corongiu Silvia , Dessì Christian , Cadoni Cristina
Published: February 2019

Epidemiological studies have shown that people who begin experimenting drugs of abuse during adolescence are more likely to develop substance use disorders, and the earliest is the beginning of their use, the greatest is the likelihood to become dependent. Understanding the neurobiological changes increasing adolescent vulnerability to drug use is becoming imperative. Although all neurotransmitter systems undergo relevant developmental changes, dopamine system is of particular interest, given its role in a variety of functions related to reward, motivation, and decision making. Thus, in the present study, we investigated differences in mesolimbic and nigrostriatal dopamine transmission between adolescent (5, 6, 7 weeks of age) and adult rats (10‐12 weeks of age), in basal conditions and following drug challenge, by using in vivo brain microdialysis. Although no significant difference between adolescents and adults was observed in dopamine basal levels in the nucleus accumbens (NAc)shell and core, reduced DA levels were found in the dorsolateral striatum (DLS) of early and mid‐adolescent rats. Adolescent rats showed greater increase of dopamine in the NAc shell following nicotine (0.4 mg/kg), THC (1.0 mg/kg), and morphine (1.0 mg/kg), in the NAc core following nicotine and morphine, and in the DLS following THC, morphine, and cocaine (10 mg/kg). These results, while adding new insight in the development and functionality of the dopamine system during different stages of adolescence, might provide a neurochemical basis for the greater vulnerability of adolescents to drugs of abuse and for the postulated gateway effect of nicotine and THC toward abuse of other illicit substances.
Amplitude‐integrated electroencephalography shows alterations in children born preterm displaying poor literacy precursor skills
Authors: Burger Christina , Biermayr Marlene , Posod Anna , Neubauer Vera , Pupp Peglow Ulrike , Kuenz Katrin , Kiechl‐Kohlendorfer Ursula , Griesmaier Elke
Published: February 2019

Aim

To assess whether amplitude‐integrated electroencephalography (aEEG) alterations in the newborn period are associated with poor precursor skills of literacy at five years of age in children born preterm.

Methods

Between October 2007 and September 2011 248 preterm infants were eligible for the study at Innsbruck Medical University Hospital. aEEG was analysed for dominating background activity, calculation of the percentage of continuous activity, the Burdjalov scoring system, the minimum, mean and maximum amplitude. At the age of five years, we evaluated preterm born children by the Bielefelder screening (BISC) to assess for early diagnosis of reading problems and weak spelling and classified them as normal performers (n = 64) or poor performers (n = 20). Completion of testing was not possible for one infant.

Results

The minimum amplitude was significantly lower in the poor BISC performance group as compared to the normal BISC performance group at postnatal week two. The percentage of continuous background activity was significantly higher in infants with normal BISC performance than in infants with poor BISC performance at postnatal week three.

Conclusion

Children with poor developed precursor skills of literacy showed alterations in aEEG signals. The aEEG could be useful in further diagnosing preterm infants at risk for developmental complications.