bluuebunny/crossref_metadata_2025 huggingface dataset:
The impact of contextual factors on nursing outcomes and the role of placebo/nocebo effects: a discussion paper
Authors: Palese Alvisa , Rossettini Giacomo , Colloca Luana , Testa Marco
Published: June 2019

Introduction:

Placebo and nocebo effects represent one of the most fascinating topics in the health care field.

Objectives:

the aims of this discussion paper were (1) to briefly introduce the placebo and nocebo effects, (2) to elucidate the contextual factors able to trigger placebo and nocebo effects in the nursing field, and (3) to debate the impact of contextual factors on nursing education, practice, organisation, and research.

Methods:

a narrative review was conducted based on the available evidence.

Results:

Placebo responses (from Latin “I shall please”) are a beneficial outcome(s) triggered by a positive context. The opposite are the nocebo effects (from Latin “I shall harm”), which indicates an undesirable outcome(s) caused by a negative context. Both are complex and distinct psychoneurobiological phenomena in which behavioural and neurophysiological changes arise subsequent to an interaction between the patient and the health care context.

Conclusion:

Placebo and nocebo concepts have been recently introduced in the nursing discipline, generating a wide debate on ethical issues; however, the impact on nursing education, clinical practice, nursing administration, and research regarding contextual factors triggering nocebo and placebo effects has not been debated to date.
Placebo analgesia effects across central nervous system diseases: what do we know and where do we need to go?
Authors: Matthiesen Susan Tomczak , Lunde Sigrid Juhl , Wohlert Kjær Sophie , Carlino Elisa , Vase Lene
Published: June 2019

Placebo effects are well established in healthy participants experiencing experimental or acute pain. Yet, little is known about the mechanisms of placebo analgesia effects in patients with chronic pain and even less is known in patients suffering from central nervous system (CNS) diseases where pain is prevalent, difficult to manage, and often undertreated. This article briefly reviews the current knowledge of placebo analgesia effects in healthy participants with the aim of discussing how the mechanisms in placebo analgesia differ between healthy participants and patients. The focus will be on placebo analgesia effects in chronic pain conditions as well as in 2 CNS diseases: Alzheimer disease and Parkinson disease. Finally, strengths and weaknesses of the current knowledge will be discussed and it will be demonstrated how insights from the placebo literature may point to new ways of improving treatments among patients experiencing pain in relation to CNS diseases.
The contribution of patients' presurgery perceptions of surgeon attributes to the experience of trust and pain during third molar surgery
Authors: Ashton-James Claire E. , Forouzanfar Tymour , Costa Daniel
Published: June 2019

Background:

Patients' feeling of trust in their surgeon may modulate the experience of pain during surgery. However, factors that contribute to patients' experience of trust during surgery remain underexamined. The current study examined the contribution of patients' impressions of surgeons' warmth and competence to their experience of trust and pain during wisdom tooth extractions.

Methods:

Patients (N = 135, 47% female) scheduled for a wisdom tooth extraction reported their current distress and impressions of their surgeon's warmth and competence after a brief introduction to their surgeon immediately before surgery. Immediately after their surgery, patients reported their experience of trust (feeling safe and in good hands) and pain during surgery. Path analyses modeled perceptions of surgeon warmth, competence, and their interaction as predictors of patients' experiences of trust and pain during surgery.

Results:

Higher perceived surgeon competence, but not warmth, predicted the experience of higher trust and lower pain during surgery. Perceived competence interacted with perceived warmth such that the competence–trust relationship was only significant at moderate to high levels of perceived surgeon warmth and failed to reach significance at lower levels of perceived surgeon warmth.

Conclusion:

These results indicate that patients feel greater trust in surgeons who are perceived as higher in competence and warmth, underscoring the importance of impression management in surgical care.
Sexual Partner Types and Incident HIV Infection Among Rural South African Adolescent Girls and Young Women Enrolled in HPTN 068: A Latent Class Analysis
Authors: Nguyen Nadia , Powers Kimberly A. , Miller William C. , Howard Annie Green , Halpern Carolyn T. , Hughes James P. , Wang Jing , Twine Rhian , Gomez-Olive F. Xavier , MacPhail Catherine , Kahn Kathleen , Pettifor Audrey E.
Published: June 2019

Background:

Sexual partners are the primary source of incident HIV infection among adolescent girls and young women (AGYW) in sub-Saharan Africa. Identifying partner types at greatest risk of HIV transmission could guide the design of tailored HIV prevention interventions.

Methods:

We conducted a secondary analysis of data from AGYW (aged 13–23 years) enrolled in a randomized controlled trial of cash transfers for HIV prevention in South Africa. Annually, AGYW reported behavioral and demographic characteristics of their 3 most recent sexual partners, categorized each partner using prespecified labels, and received HIV testing. We used latent class analysis (LCA) to identify partner types from reported characteristics, and generalized estimating equations to estimate the relationship between both LCA-identified and prespecified partner types and incident HIV infection.

Results:

Across 2140 AGYW visits, 1034 AGYW made 2968 partner reports and 63 AGYW acquired HIV infection. We identified 5 LCA partner types, which we named monogamous HIV-negative peer partner; one-time protected in-school peer partner; out-of-school older partner; anonymous out-of-school peer partner; and cohabiting with children in-school peer partner. Compared to AGYW with only monogamous HIV-negative peer partners, AGYW with out-of-school older partners had 2.56 times the annual risk of HIV infection (95% confidence interval: 1.23 to 5.33), whereas AGYW with anonymous out-of-school peer partners had 1.72 times the risk (95% confidence interval: 0.82 to 3.59). Prespecified partner types were not associated with incident HIV.

Conclusion:

By identifying meaningful combinations of partner characteristics and predicting the corresponding risk of HIV acquisition among AGYW, LCA-identified partner types may provide new insights for the design of tailored HIV prevention interventions.
Low Disclosure of PrEP Nonadherence and HIV-Risk Behaviors Associated With Poor HIV PrEP Adherence in the HPTN 067/ADAPT Study
Authors: Ojeda Victoria D. , Amico K. Rivet , Hughes James P. , Wilson Ethan , Li Maoji , Holtz Timothy H. , Chitwarakorn Anupong , Grant Robert M. , Dye Bonnie J. , Bekker Linda-Gail , Mannheimer Sharon , Marzinke Mark , Hendrix Craig W.
Published: June 2019

Objective:

We evaluated the relationship between 2 types of social relationships, ie, (1) external support for use of HIV pre-exposure prophylaxis (PrEP) and related study supplies and (2) participants' disclosure of PrEP use and condom use and HIV PrEP adherence among daily-dosing regimen participants in HIV Prevention Trials Network (HPTN) 067, an open-label trial of oral tenofovir (TFV) disoproxil fumarate (TDF) 300 mg/emtricitabine (FTC) 200 mg.

Methods:

Using HPTN 067 survey data, we developed scales examining (1) Low Perceived External Support for PrEP: low perceived support by others for PrEP use or perceived negative reactions to the pill case (scoring ranges from 0 to 2) and (2) Participant–Staff Disclosure Challenges Scale, which identifies challenges to sharing nonuse of PrEP or condoms to study staff (scoring ranges from 0 to 4); these scales are the primary independent variables. Adherence, the dependent variable, was determined using log-transformed plasma TFV concentrations. generalized estimating equation (GEE) linear regression was used to assess the association between both scales and adherence.

Results:

Participants (n = 161) included HIV-uninfected women in South Africa, and men who have sex with men and transgender women, in Thailand and the United States. In multivariable analyses, higher scores in the Participant–Staff Disclosure Challenges Scale were significantly associated with lower PrEP adherence [exp(β) = 0.62, 95% CI: (0.46 to 0.84); P = 0.002] as were increased days since the last PrEP dose [exp(β) = 0.73, 95% CI: (0.65 to 0.83); P ≤ 0.001].

Conclusions:

Given the association with adherence, study staff–participant interactions and participants' disclosure of PrEP challenges may be worthwhile intervention targets for improving PrEP adherence in confirmatory studies.
Risk of invasive fungal infections during hospital construction: how to minimize its impact in immunocompromised patients
Authors: Alvarez-Moreno Carlos Arturo , Combariza Juan Felipe
Published: June 2019

Purpose of review

Fungal outbreaks have been reported in healthcare settings, showing that construction activities are a serious threat to immunocompromised hosts. Preventive measures to control fungal outbreaks (especially Aspergillus spp.) are considered essential during hospital construction. In this article, we update the main advances in each of preventive strategies.

Recent findings

Anticipation and multidisciplinary teamwork are the keystone for fungal outbreaks prevention. Strategies focused on environmental control measures of airborne dissemination of fungal spores have proven to be successful. It is important to recommend azole-resistant Aspergillus fumigatus active surveillance from both air (outdoors and indoors) and clinical samples during hospital construction works. Apart from genotyping, studies should be further encouraged to understand the environmental dynamics. Risk assessment and implement preventive measures (environment control strategies, air surveillance, inpatients immunocompromised patients in high-efficiency particulate air filters rooms, patient education, antifungal prophylaxis in high-risk patient groups, etc.) have shown that these accomplish to reduce the incidence of invasive fungal infection (IFI).

In general, it is not only a strategy that should be implemented to reduce the risk of IFI but is a bundle of preventive measures, which have proven to be successful in control infection and prevention of airborne transmission of fungi.
SliceIt: A genome-wide resource and visualization tool to design CRISPR/Cas9 screens for editing protein-RNA interaction sites in the human genome
Authors: Vemuri Sasank , Srivastava Rajneesh , Mir Quoseena , Hashemikhabir Seyedsasan , Dong X. Charlie , Janga Sarath Chandra
Published: June 2019

Several protein-RNA cross linking protocols have been established in recent years to delineate the molecular interaction of an RNA Binding Protein (RBP) and its target RNAs. However, functional dissection of the role of the RBP binding sites in modulating the post-transcriptional fate of the target RNA remains challenging. CRISPR/Cas9 genome editing system is being commonly employed to perturb both coding and noncoding regions in the genome. With the advancements in genome-scale CRISPR/Cas9 screens, it is now possible to not only perturb specific binding sites but also probe the global impact of protein-RNA interaction sites across cell types. Here, we present SliceIt (http://sliceit.soic.iupui.edu/), a database of in silico sgRNA (single guide RNA) library to facilitate conducting such high throughput screens. SliceIt comprises of ~4.8 million unique sgRNAs with an estimated range of 2–8 sgRNAs designed per RBP binding site, for eCLIP experiments of >100 RBPs in HepG2 and K562 cell lines from the ENCODE project. SliceIt provides a user friendly environment, developed using advanced search engine framework, Elasticsearch. It is available in both table and genome browser views facilitating the easy navigation of RBP binding sites, designed sgRNAs, exon expression levels across 53 human tissues along with prevalence of SNPs and GWAS hits on binding sites. Exon expression profiles enable examination of locus specific changes proximal to the binding sites. Users can also upload custom tracks of various file formats directly onto genome browser, to navigate additional genomic features in the genome and compare with other types of omics profiles. All the binding site-centric information is dynamically accessible via “search by gene”, “search by coordinates” and “search by RBP” options and readily available to download. Validation of the sgRNA library in SliceIt was performed by selecting RBP binding sites in Lipt1 gene and designing sgRNAs. Effect of CRISPR/Cas9 perturbations on the selected binding sites in HepG2 cell line, was confirmed based on altered proximal exon expression levels using qPCR, further supporting the utility of the resource to design experiments for perturbing protein-RNA interaction networks. Thus, SliceIt provides a one-stop repertoire of guide RNA library to perturb RBP binding sites, along with several layers of functional information to design both low and high throughput CRISPR/Cas9 screens, for studying the phenotypes and diseases associated with RBP binding sites.
EpCAM Aptamer siRNA chimeras: Therapeutic efficacy in epithelial cancer cells
Authors: Balasubramanyam Jayashree , Badrinarayanan Lakshmi , Dhaka Bharti , Gowda Harsha , Pandey Akhilesh , Subramanian Krishnakumar , Subadhra Lakshmi B. , Elchuri Sailaja V.
Published: June 2019

In the era of personalized medicine as well as precision medicine, targeted therapy has become an integral part of cancer treatment in conjunction with conventional chemo- and radiotherapy. We designed aptamer-siRNA chimeras that can specifically target cancers expressing EpCAM, a stem cell marker and deliver the specific siRNA required for therapy response. The siRNAs were chosen against PLK1, BCL2 and STAT3 as these oncogenes play prominent role in tumour progression of several cancers. Targeted delivery of EpCAM-siRNA chimeras resulted in cell death in several cancer cell lines such as cancers of the breast, lung, head and neck, liver and retinoblastoma. In vivo analysis of EpCAM-siRNA chimera mediated silencing on RB xenografts tumour model showed increased tumor reduction in all the three EpCAM-siRNA treated conditions. However, regulation of PLK1 exhibited higher efficacy in tumour reduction. Therefore. We studied signaling mechanism using global phosphoproteomics analysis. An increased P53 mediated downstream signalling pathway might have enabled increased apoptosis in the cancer cells. In conclusion, this study demonstrated the efficacy of EpCAM aptamer chimeras coupled to siRNA gene silencing for targeted anti-cancer therapy.

Graphical abstract

Illustration showing how EpCAM aptamer-mediated silencing of PLK1 could control the cell cycle progression at multiple number of check points and induce apoptosis involving hyper and hypophosphorylation of variety of signalling molecules
Making thebrain-activity-to-informationleap using a novel framework: Stimulus Information Representation (SIR)
Authors: Schyns Philippe G. , Ince Robin A.A.
Published: June 2019

A fundamental challenge in neuroscience is to understand how the brain processes information. Neuroscientists have approached this question partly by measuring brain activity in space, time and at different levels of granularity. However, our aim is not to discover brain activityper se, but to understand the processing of information that this activity reflects. To make thisbrain-activity-to-informationleap, we believe that we should reconsider brain imaging from the methodological foundations of psychology. With this goal in mind, we have developed a new data-driven framework, called Stimulus Information Representation (SIR), that enables us to better understand how the brain processes information from measures of brain activity and behavioral responses. In this article, we explain this approach, its strengths and limitations, and how it can be applied to understand how the brain processes information to perform behavior in a task.

“It is no good poking around in the brain without some idea of what one is looking for. That would be like trying to find a needle in a haystack without having any idea what needles look like. The theorist is the [person] who might reasonably be asked for [their] opinion about the appearance of needles.” HC Longuet-Higgins, 1969.
Distinguishing Different Levels of Consciousness using a Novel Network Causal Activity Measure
Authors: Agarwal Nikita , Kathpalia Aditi , Nagaraj Nithin
Published: June 2019

Characterizing consciousness, the inner subjective feeling that is present in every experience, is a hard problem in neuroscience, but has important clinical implications. A leading neuro-scientific approach to understanding consciousness is to measure the complex causal neural interactions in the brain. Elucidating the complex causal interplay between cortical neural interactions and the subsequent network computations is very challenging. In this study, we propose a novel quantitative measure of consciousness - Network Causal Activity - using a recently proposed Compression-Complexity Causality measure to analyze electrocorticographic signals from the lateral cortex of four monkeys during two states of consciousness (awake and anaesthesia). Our results suggest that Network Causal Activity is consistently higher in the awake state as compared with anaesthesia state for all the monkeys.
On the Effectiveness of UAS for Anti-Poaching in the African Arid Savanna
Authors: van Vuuren Marlice , van Vuuren Rudie , Lutz Graham D. , Silverberg Larry M.
Published: June 2019

This paper describes a field study that examined the effectiveness of unmanned aerial vehicles (UAV) in anti-poaching enforcement in parks and game reserves. In the field study, a UAV attempted to spot mock poachers while the mock poachers tried to spot the UAV. The field study was conducted at N/a’an ku sê, an operational game reserve in the central region of Namibia. In total, 118 trials were completed, providing 236 UAV-poacher interdiction scenarios. Of these, 198 were during the day, 152 with a quadcopter and 46 with a fixed-wing. Live spotting success during the day varied due to the hiding behavior of the mock poachers, with the highest and lowest success rates of spotting being 86% for poachers in the open and 25% for poachers hiding under canopy cover. The UAVs were demonstrated to be a potentially effective tool for anti-poaching patrol and interdiction, in part, because of their ability to spot poachers. The pursuit of integrating the UAV into current anti-poaching patrol and interdiction efforts in arid savanna landscapes is strongly recommended.
Synthesis of Extended, Self-Assembled Biological Membranes containing Membrane Proteins from Gas Phase
Authors: Wilm Matthias
Published: June 2019

Membrane proteins carry out a wide variety of biological functions. The reproduction of their specific properties in a technically controlled environment is of significant interest. Here, a method is presented that allows the self-assembly of a macroscopically large, freely transportable membrane with Outer membrane porin G from Escherichia Coli. The technique does not use protein specific characteristics and therefore could represent a path to the generation of extended layers of membranes with integrated, arbitrary membrane proteins. The composition of the membrane, its lipid and protein content, is experimentally controlled. Such in-vitro systems are relevant for the study of membrane-protein function and structure and the self-assembly of membrane-based protein complexes. They might become important for the incorporation of lipid-membranes into technical devices.
Environmental influences on acoustic divergence inRhinolophusbats of the Western Ghats-Sri Lanka region
Authors: Deshpande Kadambari , Kelkar Nachiket
Published: June 2019

According to the acoustic adaptation hypothesis, environmental and biogeographic factors such as atmospheric humidity can influence divergence of acoustic signals and speciation in high duty-cycle echolocating bats (e.g.Rhinolophussp.), although this remains disputed. In this study we tested the hypothesis that Resting Frequency (RF) would decrease with increasing humidity along a large latitudinal gradient (6°-21°N), for fourRhinolophusspecies with different evolutionary histories, in the Western Ghats-Sri Lanka (WGSL) region. We conducted acoustic recordings and compiled published information on RFs of stationaryRhinolophus indorouxi, R. rouxi, R. beddomei, andR. lepidusfrom 40 roosts in 18 localities of the WGSL. These data comprised of recordings made with different devices and with different settings. Hence, due to the unknown measurement error involved in the recorded RFs, it was not possible to conduct conventional regression analyses to test our hypotheses. Hence, we qualitatively assessed effects of Relative Humidity (RH) and other environmental variables by interpreting only the sign, but not the magnitude of the RF responses (from the slopes of generalized least squares regression models). We also tested how RF and RH varied across biogeographic zones, and with bat body size. RFs of the Miocene-diverged speciesR. indorouxiandR. rouxiwere higher at lower RH, as expected. In contrast, RF of the Pleistocene-diverged speciesR. beddomeiandR. lepiduswere higher at higher RH. Elevation and rainfall also emerged as important predictors of RF variation in these species. Bat body size differed in dry and humid regions of the WGSL. RF variation was not consistent across biogeographic zones. The cryptic, phonically differentiated sibling speciesR. indorouxiandR. rouxico-occurred only in mid-elevation zones along the Western Ghats escarpment. The variable but significant influences of humidity and correlated factors on RF suggest the importance of environmentally mediated acoustic divergence in differentRhinolophusspecies in the WGSL. We propose some hypotheses on interacting effects of environmental and phylogenetic factors on acoustic divergence inRhinolophusbats of the WGSL. These ideas could be further tested with phylogenetic and acoustic studies, as more consistent and comparable data on these species become available in the future.
Temozolomide-induced guanine mutations create exploitable vulnerabilities of guanine-rich DNA and RNA regions in drug resistant gliomas
Authors: Tiek Deanna M , Erdogdu Beril , Razaghi Roham , Jin Lu , Sadowski Norah , Alamillo-Ferrer Carla , Hogg J Robert , Haddad Bassem R , Drewry David H , Wells Carrow I , Pickett Julie E. , Song Xiao , Goenka Anshika , Hu Bo , Goldlust Samuel L , Zuercher William J , Pertea Mihaela , Timp Winston , Cheng Shi-Yuan , Riggins Rebecca B
Published: June 2019

Temozolomide (TMZ) is a chemotherapeutic agent that has been the first-line standard of care for the aggressive brain cancer glioblastoma (GBM) since 2005. Though initially beneficial, TMZ- resistance is universal and second-line interventions are an unmet clinical need. Here we took advantage the mechanism of action of TMZ to target guanines (G) and investigated G-rich g- quadruplex (G4) and splice site changes that occur upon TMZ-resistance. We report TMZ-resistant GBM has guanine mutations that disrupt the G-rich DNA G4s and splice sites that lead to deregulated alternative splicing. These alterations create vulnerabilities, which are selectively targeted by either the G4 stabilizing drug TMPyP4 or a novel splicing kinase inhibitor of cdc2- like kinase. Finally, we show that the G4 and RNA-binding protein EWSR1 aggregates in the cytoplasm in TMZ-resistant GBM cells and patient samples. Together, our findings provide insight into targetable vulnerabilities of TMZ-resistant GBM and present cytoplasmic EWSR1 as a putative biomarker.

Teaser

Targeting temozolomide mutations in drug resistant glioma via g-quadruplex and splicing modulators with a putative biomarker.
Methylation at nucleotide C62 in spliceosomal RNA U6 alters mRNA splicing which is important for embryonic development
Authors: Ogren Allison , Kibiryeva Nataliya , Marshall Jennifer , O’Brien James E. , Bittel Douglas C.
Published: June 2019

Understanding the regulation of development can help elucidate the pathogenesis behind many developmental defects found in humans and other vertebrates. Evidence has shown that alternative splicing of messenger RNA (mRNA) plays a role in developmental regulation, but our knowledge of the underlying mechanisms that regulate alternative splicing are inadequate. Notably, a subset of small noncoding RNAs known as scaRNAs (small cajal body associated RNAs) contribute to spliceosome maturation and function through covalently modifying spliceosomal RNAs by either methylating or pseudouridylating specific nucleotides, but the developmental significance of these modifications is not well understood. Our focus is on one such scaRNA, known as SNORD94 or U94, that methylates one specific cytosine (C62) on spliceosomal RNA U6, thus potentially altering spliceosome function during embryogenesis. We previously showed that mRNA splicing is significantly different in myocardium from infants with congenital heart defects (CHD) compared to controls. Furthermore, we showed that modifying expression of scaRNAs alters mRNA splicing in human cells, and zebrafish embryos. Here we present evidence that SNORD94 levels directly influence levels of methylation at C62 in U6, which we have previously shown is associated with altered splicing and congenital heart defects. The potential importance of scaRNAs as a developmentally important regulatory mechanism controlling alternative splicing of mRNA is unappreciated and needs more research.

Author summary

Splicing of mRNA transcripts by removal of introns and some non-critical exons is a crucial part of mRNA processing, gene expression, and cell function, and regulation of this process is still under investigation. Alternative splicing of mRNA transcripts of genes is tissue and time specific throughout life, although this process occurs everywhere in the body according to local tissue needs and signals. The spliceosome, the large ribonucleoprotein complex that carries out splicing, is biochemically modified by small noncoding RNAs, which is important for its structure and function. Here we show that the amount of 2’-O-ribose methylation at nucleotide C62 in spliceosomal RNA U6 is dependent on the level of the scaRNA SNORD94. We hypothesize that alternative splicing is dependent, at least in part, on biochemical modification to the spliceosomal RNAs. Furthermore, when scaRNA directed modifications are dysregulated, the result causes inappropriate alternative splicing that may contribute to developmental defects such as congenital heart defects. To our knowledge, this is the first demonstration that 2’-O-ribose methylation is indeed dependent on scaRNA levels in human cells and tissues.
Schistosomiasis among pregnant women in the Njombe-Penja health district, Littoral region of Cameroon: A cross sectional study
Authors: Tonga Calvin , Bayoi Charlie Ngo , Tchanga Flore Chanceline , Yengue Jacqueline Félicité , Wepnje Godlove Bunda , Nyabeyeu Hervé Nyabeyeu , Kangam Lafortune , Kouodjip Larissa Nono , Akono Patrick Ntonga , Lehman Léopold Gustave
Published: June 2019

Background

Schistosomiasis is a Neglected Tropical Disease with endemic foci in Cameroon. Epidemiological data on schistosomiasis in pregnancy are scarce in the country. This study is about schistosomiasis among pregnant women in the Njombe-Penja health district, where schistosomiasis was reported since 1969.

Methodology

Overall, 282 pregnant women were enrolled upon informed consent at first antenatal consultation. A questionnaire was administered to document socio-economic and obstetric information. Stool and terminal urine samples were collected and analysed using the Kato-Katz/formol-ether concentration techniques and centrifugation method respectively. Haemoglobin concentration was measured with finger prick blood, using a URIT-12® electronic haemoglobinometer.

Principal findings

The overall prevalence of schistosomiasis was 31.91%. Schistosoma guineensis, S. haematobium and S. mansoni infections were found in 0.35%, 04.96% and 28.01% of participants respectively. Co-infection with 2 species of Schistosoma was found in 04.44% of these women. The prevalence of schistosomiasis was significantly higher in younger women (≤20) and among residents of Njombe. All S. haematobium infected women were anemic and infection was associated with significantly lower haemoglobin levels (p=0.02).

Conclusion

The prevalence of schistosomiasis is high in pregnant women of the Njombe-Penja health district, with possible adverse pregnancy outcomes. Female of childbearing age should be considered for mass drug administration.

Author summary

Pregnant women are known to be more vulnerable to infectious diseases and in their case, at least two lives are at risk. Although schistosomiasis remains a major public health issue in Cameroon, epidemiological data on schistosomiasis in pregnancy are scarce. These data are of high interest for informed decision-making. We examined stools and urines from 282 women of the Njombe-Penja Health district and measured their blood levels. Overall, 31.91% of women were infected, mostly younger ones and those living in the town of Njombe. Three species of Schistosoma parasite were identified. Women having urinary schistosomiasis had lower blood levels. These results show that the prevalence of schistosomiasis is high in pregnant women of Njombe. Also, because of the anemia it induces, the disease can lead to adverse pregnancy outcomes on the woman and her foetus. Treating female of childbearing age would cure the disease and prevent adverse outcomes.
Analysis of meiosis in Pristionchus pacificus reveals plasticity in homolog pairing and synapsis in the nematode lineage
Authors: Rillo-Bohn Regina , Adilardi Renzo S. , Mitros Therese , Avşaroğlu Bariş , Stevens Lewis , Köhler Simone , Bayes Joshua , Wang Clara , Lin Sabrina , Baskevitch K. Alienor , Rokhsar Daniel S. , Dernburg Abby F.
Published: June 2019

Meiosis is conserved across eukaryotes yet varies in the details of its execution. Here we describe a new comparative model system for molecular analysis of meiosis, the nematode Pristionchus pacificus, a distant relative of the widely studied model organism Caenorhabditis elegans. P. pacificus shares many anatomical and other features that facilitate analysis of meiosis in C. elegans. However, while C. elegans has lost the meiosis-specific recombinase Dmc1 and evolved a recombination-independent mechanism to synapse its chromosomes, P. pacificus expresses both DMC-1 and RAD-51. We find that SPO-11 and DMC-1 are required for stable homolog pairing, synapsis, and crossover formation, while RAD-51 is dispensable for these key meiotic processes. RAD-51 and DMC-1 localize sequentially to chromosomes during meiotic prophase and show nonoverlapping functions. We also present a new genetic map for P. pacificus that reveals a crossover landscape very similar to that of C. elegans, despite marked divergence in the regulation of synapsis and crossing-over between these lineages.
BAGSE: a Bayesian hierarchical model approach for gene set enrichment analysis
Authors: Hukku Abhay , Quick Corbin , Luca Francesca , Pique-Regi Roger , Wen Xiaoquan
Published: June 2019

Gene set enrichment analysis has been shown to be effective in identifying relevant biological pathways underlying complex diseases. Existing approaches lack the ability to quantify the enrichment levels accurately, hence preventing the enrichment information to be further utilized in both upstream and downstream analyses. A modernized and rigorous approach for gene set enrichment analysis that emphasizes both hypothesis testing and enrichment estimation is much needed. We propose a novel computational method, Bayesian Analysis of Gene Set Enrichment (BAGSE), for gene set enrichment analysis. BAGSE is built on a Bayesian hierarchical model and fully accounts for the uncertainty embedded in the association evidence of individual genes. We adopt an empirical Bayes inference framework to fit the proposed hierarchical model by implementing an efficient EM algorithm. Through simulation studies, we illustrate that BAGSE yields accurate enrichment quantification while achieving similar power as the state-of-the-art methods. Further simulation studies show that BAGSE can effectively utilize the enrichment information to improve the power in gene discovery. Finally, we demonstrate the application of BAGSE in analyzing real data from a differential expression experiment and a Transcriptome-wide Association Study (TWAS). Our results indicate that the proposed statistical framework is effective in aiding the discovery of potentially causal pathways and gene networks. BAGSE is implemented using the C++ programming language and is freely available from https://github.com/xqwen/bagse/. Simulated and real data used in this paper are also available at the Github repository for reproducibility purposes.
The Role of Parvalbumin-positive Interneurons in Auditory Steady-State Response Deficits in Schizophrenia
Authors: Metzner Christoph , Zurowski Bartosz , Steuber Volker
Published: June 2019

Despite an increasing body of evidence demonstrating subcellular alterations in parvalbumin-positive (PV+) interneurons in schizophrenia, their functional consequences remain elusive. Since PV+ interneurons are involved in the generation of fast cortical rhythms, these changes have been hypothesized to contribute to well-established alterations of beta and gamma range oscillations in patients suffering from schizophrenia. However, the precise role of these alterations and the role of different subtypes of PV+ interneurons is still unclear. Here we used a computational model of auditory steady-state response (ASSR) deficits in schizophrenia. We investigated the differential effects of decelerated synaptic dynamics, caused by subcellular alterations at two subtypes of PV+ interneurons: basket cells and chandelier cells. Our simulations suggest that subcellular alterations at basket cell synapses rather than chandelier cell synapses are the main contributor to these deficits Particularly, basket cells might serve as target for innovative therapeutic interventions aiming at reversing the oscillatory deficits.
Essential roles of Hdac1 and 2 in lineage development and genome-wide DNA methylation during mouse preimplantation development
Authors: Zhao Panpan , Wang Huanan , Wang Han , Dang Yanna , Luo Lei , Li Shuang , Shi Yan , Wang Lefeng , Wang Shaohua , Mager Jesse , Zhang Kun
Published: June 2019

Epigenetic modifications, including DNA methylation and histone modifications, are reprogrammed considerably following fertilization during mammalian early embryonic development. Incomplete epigenetic reprogramming is a major factor leading to poor developmental outcome in embryos generated by assisted reproductive technologies, such as somatic cell nuclear transfer. However, the role of histone modifications in preimplantation development is poorly understood. Here, we show that co-knockdown (cKD) of Hdac1 and 2 (but not individually) resulted in developmental failure during the morula to blastocyst transition. This outcome was also confirmed with the use of small-molecule Hdac1/2-specific inhibitor FK228. We observed reduced cell proliferation and increased incidence of apoptosis in cKD embryos, which were likely caused by increased acetylation of Trp53. Importantly, both RNA-seq and immunostaining analysis revealed a failure of lineage specification to generate trophectoderm and pluripotent cells. Among many gene expression changes, a substantial decrease of Cdx2 may be partly accounted for by the aberrant Hippo pathway occurring in cKD embryos. In addition, we observed an increase in global DNA methylation, consistent with increased DNA methyltransferases and Uhrf1. Interestingly, deficiency of Rbbp4 and 7 (both are core components of several Hdac1/2-containing epigenetic complexes) results in similar phenotypes as those of cKD embryos. Overall, Hdac1 and 2 play redundant functions required for lineage specification, cell viability and accurate global DNA methylation, each contributing to critical developmental programs safeguarding a successful preimplantation development.

Significance

Substantial changes to epigenetic modifications occur during preimplantation development and can be detrimental when reprogrammed incompletely. However, little is known about the role of histone modifications in early development. Co-knockdown of Hdac1 and 2, but not individually, resulted in developmental arrest during morula to blastocyst transition, which was accompanied by reduced cell number per embryo and increased incidence of apoptosis. Additionally, we observed a failure of first lineage specification to generate trophectoderm and pluripotent cells, which were associated with reduced expression of key lineage-specific genes and aberrant Hippo pathway. Moreover, an increase in global DNA methylation was found with upregulated Dnmts and Uhrf1. Thus, Hdac1 and 2 play overlapping roles in lineage development, apoptosis, and global methylation during preimplantation development.
Long-term single-cell passaging of human iPSC fully supports pluripotency and high-efficient trilineage differentiation capacity
Authors: Cruvinel Estela , Ogusuku Isabella , Cerioni Rosanna , Gonçalves Jéssica , Góes Maria Elisa , Alvim Juliana Morais , Silva Anderson Carlos , Pereira Alexandre , Dariolli Rafael , Valadares Marcos , Biagi Diogo
Published: June 2019

Objectives

To validate a straightforward single-cell passaging cultivation method that enables high-quality maintenance of hiPSC without the appearance of karyotypic abnormalities or loss of pluripotency.

Methods

Cells were kept in culture for over 50 passages, following a structured chronogram of passage and monitoring cell growth by population doubling time (PDT) calculation and cell confluence. Standard procedures for iPSC monitoring as embryonic body (EB) formation, karyotyping and pluripotency markers expression were evaluated in order to monitor the cellular state in the long-term culture. Cells that underwent these tests were then subjected to differentiation into keratinocytes and cardiomyocytes to evaluate its differentiation capacity.

Results

hiPSC clones maintained its pluripotent capability as well as chromosomal integrity and were able to generate derivatives from the three germ layers at high passages by embryoid body formation and high-efficient direct differentiation into keratinocytes and cardiomyocytes.

Conclusion

Our findings support the routine of hiPSC single-cell passaging as a reliable procedure even after long-term cultivation, providing healthy PSCs to be used in drugs discovery, toxicity and disease modeling as well as for therapeutic approaches.
Hypertriglyceridemia and obesity exacerbate the course of SIRS induced by SAP in Rats
Authors: Hua Kelei , Li RuiXia , Cao LiYing , Lao WanSheng
Published: June 2019

The aim of the present study was to explore the mechanism underlying how HTG (hypertriglyceridaemia) and obesity exacerbate the course of the systemic inflammatory response syndrome (SIRS) induced by severe acute pancreatitis (SAP) in rats. Seventy-two rats were fed a normal or high-fat diet to induce HTG and obesity, and SAP was induced by retrograde injection of 5% sodium taurocholate solution at a volume of 1 ml/kg into the biliopancreatic duct. The injury to the pancreas was assessed by macroscopic observation, pancreatic histological evaluation and serum levels of amylase and lipase. SIRS was estimated by measuring SIRS scores and interleukin-6 (IL-6), tumour necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) expression. The results showed that the SIRS scores and pancreatic histological scores increased significantly and the blood calcium level decreased significantly in the hypertriglyceridaemia SAP (HSAP) group compared with those of the SAP group. In addition, HTG and obesity significantly increased plasma levels of the proinflammatory cytokines IL-6 and TNF-α and significantly downregulated the proinflammatory cytokine IL-10. Our findings showed that HSAP rats exhibited more severe pancreatic injury and more serious SIRS scores than the SAP rats did. The underlying mechanism may be that HTG and obesity intensify early-stage SIRS by regulating the levels of inflammatory and anti-inflammatory cytokines.
Cooperative 2′-O-methylation of the wobble cytidine of human elongator tRNAMet(CAT) by a nucleolar and a Cajal body-specific box C/D RNP
Authors: Vitali Patrice , Kiss Tamás
Published: June 2019

Site-specific 2′-O-ribose methylation of mammalian rRNAs and RNA polymerase II-synthesized spliceosomal small nuclear RNAs (snRNAs) is mediated by small nucleolar and small Cajal body (CB)-specific box C/D ribonucleoprotein particles (RNPs) in the nucleolus and the nucleoplasmic CBs, respectively. Here, we demonstrate that 2′-O-methylation of the C34 wobble cytidine of human elongator tRNAMet(CAT) is achieved by collaboration of a nucleolar and a CB-specific box C/D RNP carrying the SNORD97 and SCARNA97 box C/D 2′-O-methylation guide RNAs. Methylation of C34 prevents site-specific cleavage of tRNAMet(CAT) by the stress-induced endoribonuclease angiogenin, implicating box C/D guide RNPs in controlling stress-responsive production of putative regulatory tRNA fragments.
The local and average structure of Ba(Ti, Ce)O3 perovskite solid solution: effect of cerium concentration and particle size
Authors: Confalonieri Giorgia , Buscaglia Vincenzo , Canu Giovanna , Buscaglia Maria Teresa , Dapiaggi Monica
Published: June 2019

The amazing properties of ferroelectric perovskite BaTiO3 (BT) and its solid solutions make them indispensable for many technological applications (e.g. multilayer capacitors). Unfortunately, the so-called `size effect' limits their use. Indeed, under a certain critical particle size, these materials show a suppression of the spontaneous polarization and thus of the ferroelectric properties. In pure nanometric BaTiO3, this is related to a certain local structural disorder. However, only a few studies have explored BT solid solutions, where the doping effect, coupled to the reduced particle size, can play an important role. Therefore, in this work, the structure of BaCe
x
Ti1–x
O3 (x = 0.02–0.20) was explored by traditional Rietveld method and Pair Distribution Function. Samples present a particle size from 80–160 nm to 400–1000 nm depending on increasing x. The carbox approach was applied, investigating the evolution of the local structure, its modifications and the structural coherent correlation length, as a function of cerium amount. Results demonstrate a cooperative effect of composition and reduced size in the ferroelectricity loss. The two, in fact, contribute to intensify the local structural disorder, decreasing the structural coherent correlation length. The local structural disorder is thus confirmed to be a relevant factor in the ferroelectric properties degradation.
Crystal structure determination ofPseudomonas stutzeriA1501 endoglucanase Cel5A: the search for a molecular basis for glycosynthesis in GH5_5 enzymes
Authors: Dutoit Raphaël , Delsaute Maud , Collet Laetitia , Vander Wauven Corinne , Van Elder Dany , Berlemont Renaud , Richel Aurore , Galleni Moreno , Bauvois Cédric
Published: June 2019

The discovery of new glycoside hydrolases that can be utilized in the chemoenzymatic synthesis of carbohydrates has emerged as a promising approach for various biotechnological processes. In this study, recombinant Ps_Cel5A fromPseudomonas stutzeriA1501, a novel member of the GH5_5 subfamily, was expressed, purified and crystallized. Preliminary experiments confirmed the ability of Ps_Cel5A to catalyze transglycosylation with cellotriose as a substrate. The crystal structure revealed several structural determinants in and around the positive subsites, providing a molecular basis for a better understanding of the mechanisms that promote and favour synthesis rather than hydrolysis. In the positive subsites, two nonconserved positively charged residues (Arg178 and Lys216) were found to interact with cellobiose. This adaptation has also been reported for transglycosylating β-mannanases of the GH5_7 subfamily.
Understanding cross-border crime: the value of international business research
Authors: Enderwick Peter
Published: June 2019

Purpose

Based on a considerable degree of commonality between multinational enterprises (MNEs) and cross-border criminal organisations, the purpose of this paper is to identify ways and areas in which international business (IB) research could be of value in improving understanding of the operations of cross-border criminal organisations and in the development of effective countermeasures to global crime.

Design/methodology/approach

A review of the characteristics of legitimate MNEs and cross-border criminal organisations is undertaken to assess the applicability of IB research approaches in understanding the strategies and structures of organised criminal groups.

Findings

Despite some obvious differences there appears to be sufficient commonality between legitimate and illegitimate international commerce so that the firm-centric focus of IB research could provide valuable insights complementing the policy-oriented approach of criminology. Some adaptation of IB research tools may be required. The exchange is not one-way: studies of cross-border crime also offer lessons for IB scholars.

Research limitations/implications

IB scholarly work on cross-border crime could enrich both the fields of IB and transnational criminology. Better understanding of criminal enterprises could also facilitate the design of more effective interdiction policies.

Originality/value

Despite their commonalities and interactions, the two sectors of international enterprise have developed separately, and this paper identifies and explores possible synergies between the two.