bluuebunny/crossref_metadata_2025 huggingface dataset:
You are here! Negotiating liminality in place in the context of the National Disability Insurance Scheme
Authors: Ramcharan Paul , David Christina , Marx Katie
Published: May 2020

The dynamics of inclusion and exclusion for people with disabilities and the places in which they live are being challenged in Australia with the transition to the National Disability Insurance Scheme. This paper reports on the experiences of a place-based and participatory action research project in regional Tasmania which sought to co-create citizenship opportunities with co-researchers living with disability. We report on our experience of negotiating this ambitious and emergent project through the uncertain and shifting terrain of the contemporary neoliberal policy and service context. We highlight the rich gains as well as the significant relational, contextual and procedural challenges of operationalising and staying true to bottom up and strengths-based community development principles. Key learnings relate to risks of creating liminal spaces for community action, about power and authority, and about the skills, resources and labour needed to unearth and mobilise individual and community strengths. We argue that there remains a significant tension between the aspirations of collective action and contemporary services and policy structures that reproduce liminality, silent positioning and place denial. This research challenges traditional disability centric notions of inclusion and place and has implications for the NDIS, for policies at risk of reproducing disabling dynamics, for service innovation and collaboration and for all social workers and others working to develop more inclusive communities.
Technology and sustainability for/in early childhood education and care
Authors: Crisostomo Anita Tvedt , Reinertsen Anne B
Published: May 2020

Inspired by a posthuman philosophy, this paper explores sustainable natureculture kindergarten praxis as a pragmatic transcorporeal collective engagement with the present and sustainable future events to come. The point of departure is the economic argument for implementing science, technology, engineering and mathematics education within early childhood education and care as a preparation for the challenges a science- and technology-driven society brings at the forefront. By exploring and experimenting with dataphilosophy as our theory-method and the concept of non-position, we embrace and critique technology and technological solutions in connection with kindergarten praxis and steer them towards new forms of solidarity and socially just pedagogies. Through the article, we ask (in)directly what kind of subject position digitalization as part of a sustainable future requires, and the inevitable questions this subject position regarding professionalism within early childhood education and care brings.
Analysis of Radon Awareness and Disclosure Policy in Kentucky: Applying Kingdon’s Multiple Streams Framework
Authors: R. Stanifer Stacy , Hahn Ellen J.
Published: May 2020

The purpose of this article is to analyze radon awareness and disclosure policy proposed during the 2018 Kentucky General Assembly using Kingdon’s Multiple Stream Framework. Radon gas is the second leading cause of lung cancer. Exposure to radon occurs largely in the home. The proportion of homeowners who have completed radon testing remains low, and home radon testing is voluntary in most states. The Environmental Law Institute recommends states enact policies to promote radon awareness and testing. The most common radon awareness policy mandates radon disclosure during a real estate transaction. A bill to mandate radon disclosure during a real estate transaction was proposed during the 2018 Kentucky General Assembly but was met with opposition and was not filed. As a policy alternative, an administrative regulation to amend the Form for Seller’s Disclosure of Conditions was proposed to the Kentucky Real Estate Commission. Administrative regulations set forth by government regulatory agencies are equally enforceable and may be a more politically feasible alternative to enacting public policy. Nurses are positioned to promote the health of patients and populations. Nurses advocating for radon control legislation and/or administrative regulations may push radon control policy higher on the governmental decision agenda leading to policy change to decrease the development of lung cancer.
Costs and consequences of the Portuguese needle-exchange program in community pharmacies
Authors: Borges Margarida , Gouveia Miguel , Fiorentino Francesca , Jesus Gonçalo , Cary Maria , Guerreiro José Pedro , Costa Suzete , Carneiro António Vaz
Published: May 2020

Background:

Needle-exchange programs (NEPs) reduce infections in people who inject drugs. This study assesses the impact community pharmacies have had in the Needle-Exchange Program in Portugal since 2015.

Methods:

Health gains were measured by the number of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections averted, which were estimated, in each scenario, based on a standard model in the literature, calibrated to national data. The costs per infection were taken from national literature; costs of manufacturing, logistics and incineration of injection materials were also considered. The results were presented as net costs (i.e., incremental costs of the program with community pharmacies less the costs of additional infections avoided).

Results:

Considering a 5-year horizon, the Needle Exchange Program with community pharmacies would account for a 6.8% ( n = 25) and a 6.5% reduction ( n = 22) of HCV and HIV infections, respectively. The present value of net savings generated by the participation of community pharmacies in the program was estimated at €2,073,347. The average discounted net benefit per syringe exchanged is €3.01, already taking into account a payment to community pharmacies per needle exchanged.

Interpretation:

We estimate that the participation of community pharmacies in the Needle Exchange Program will lead to a reduction of HIV and HCV infections and will generate over €2 million in savings for the health system.

Conclusions:

The intervention is estimated to generate better health outcomes at lower costs, contributing to improving the efficiency of the public health system in Portugal.
Cytoplasmic levels of high mobility group A2 determine survival prognoses in breast cancer patients
Authors: Heilmann Thorsten , Vondung Florian , Borzikowsky Christoph , Krüger Sandra , Elessawy Mohamed , Alkatout Ibrahim , Wenners Antonia , Bauer Maret , Klapper Wolfram , Röcken Christoph , Maass Nicolai , Schem Christian , Trauzold Anna
Published: May 2020

Background:

High mobility group A proteins are involved in chromatin remodeling, thereby influencing multiple fundamental biological processes. HMGA2 has been linked to oncogenic traits among a variety of malignancies.

Objective:

To determine the prognostic implications of subcellular distribution patterns of HMGA2 in breast cancer.

Methods:

Nuclear and cytoplasmic HMGA2 was evaluated in 342 breast cancer specimens and matched with clinico-pathological parameters.

Results:

Overall and cytoplasmic, but not nuclear, levels of HMGA2 correlated with better survival prognoses in our collective (hazard ratio (HR) 0.34, P = 0.001 and HR 0.34, P < 0.001, respectively). The protective effect of cytoplasmic HMGA2 persisted in the Luminal A and triple negative breast cancer subgroups. Evaluating Luminal A and B subgroups jointly, only cytoplasmic, but not overall or nuclear HMGA2 levels were associated with better survival (HR 0.42, 95% confidence interval 0.21, 0.86, P = 0.017), irrespective of tumor size and node status. The addition of HMGA2 overall and cytoplasmic scores strengthened the prognostic selectivity in a model of conventional breast cancer risk factors. No predictive significance with regard to endocrine or chemoendocrine therapies was observed.

Conclusion:

Unexpectedly, we found a favorable survival probability upon overall levels of HMGA2 in our breast cancer collective, which was predominantly determined by the presence of HMGA2 in the cytoplasm.
Pregnancy and medications in inflammatory bowel disease
Authors: Cao Rena H , Grimm Michael C
Published: May 2020

Inflammatory bowel disease (IBD) affects patients at a significant time in their lives, often coinciding with family planning or pregnancy. While advances in IBD therapies have afforded women greater opportunities for successful conception and pregnancy outcomes, there still remains considerable maternal fear surrounding continuation of treatment in pregnancy. With the exception of methotrexate, most IBD drugs are safe and well tolerated during pregnancy and are not associated with significant risk of adverse fetal or pregnancy outcomes. Furthermore, the current evidence overwhelmingly suggests that good control of disease activity and clinical remission at time of conception are the greatest prognostic factors for an uncomplicated pregnancy and maintenance of quiescent disease. Management of pregnant women with IBD should involve discussions with the mother and family about fears or concerns surrounding the impact of IBD on pregnancy. Mothers should be supported and counselled carefully on the safety and importance of adherence to therapy in maintaining remission. Optimal management of these women requires an inter-disciplinary team effort, involving the general practitioner, in close consultation with both gastroenterologists and obstetricians.
HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells
Authors: Yang Jing-Hua , Wu Ming-Zhe , Wang Xu-Bo , Wang Shiyu , Qiu Xue-Shan , Wang En-Hua , Wu Guang-Ping
Published: May 2020

Background:

There is an immediate need for research on the mechanism underlying telomerase activation and overexpression.

Materials & Methods:

A total of 174 patients with lung cancer ( n = 106) and benign lung disease ( n = 68) were recruited for the current study. The mRNA expression levels of E6, E7, LKB1, Sp1, and hTERC in brushing cells were detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and hTERC amplification was also detected by fluorescence in situ hybridization (FISH). To investigate the potential mechanism, bidirectional genetic manipulation was performed in well-established lung cancer cell lines.

Results:

Our results indicated that the mRNA expression levels of E6, E7, Sp1, and hTERC and the amplification level of hTERC were significantly increased in the malignant group compared with those of the benign group ( p < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group ( p < 0.01). The correlation between E6, E7, Sp1, and hTERC expression was positive but was negative with LKB1 ( p < 0.01). Our results also showed that HPV16 E6/E7 downregulated the expression of LKB1 at both the protein and mRNA levels. The loss of LKB1 upregulated Sp1 expression, and also promoted Sp1 activity. Sp1 further upregulated hTERC at the mRNA and gene amplification levels. Thus, we proposed a HPV–LKB1–Sp1–hTERC axis of E6/E7 upregulation of hTERC expression.

Conclusion:

We demonstrated for the first time that E6 and E7 promoted hTERC mRNA expression and the amplification of hTERC by relieving the effect of LKB1 on the phosphorylation of Sp1. Sp1 further activated hTERC by directly binding to the promoter regions of hTERC.
Synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome: review and update
Authors: Liu Shuang , Tang Mingwei , Cao Yihan , Li Chen
Published: May 2020

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a spectrum of heterogeneous diseases characterized by osteoarticular and dermatological manifestations. Osteitis and hyperostosis are core clinical manifestations in SAPHO syndrome, typically affecting multiple areas and possibly progressing to irreversible osteoarticular damage. Most patients with SAPHO have cutaneous involvement, mainly manifested as palmoplantar pustulosis and severe acne. Systemic manifestations are uncommon but occasionally reported. Epidemiological studies suggest the annual prevalence of SAPHO syndrome varies from 0.00144 in 100,000 in Japanese individuals to fewer than 1 in 10,000 in White individuals. The precise etiopathogenesis of SAPHO remains unclear, but it is generally considered an autoinflammatory syndrome that may be related to various etiologies, such as immune dysfunction, infection and genetic predisposition. Owing to the relapsing–remitting disease course, the goal of management is to improve clinical symptoms and prevent disease progression. Various treatments, including nonsteroidal anti-inflammatory drugs, conventional disease-modifying antirheumatic drugs, bisphosphonates, biologics, and antibiotics, are promising options for alleviating the disease.
Piceid Nanoparticles Stabilized by Anionic Phospholipids for Transdermal Delivery
Authors: Uchida Noriyuki , Yanagi Masayoshi , Hamada Hiroki
Published: May 2020

Piceid, stilbenoid glucoside, is a representative resveratrol derivative. Because of a high tyrosinase inhibitory activity of piceid through resveratrol derivatives, transdermal delivery of piceid has been desired for taking advantage of the activity. Here we successfully prepared composite nanoparticles composed of anionic phospholipid of 1,2-dipalmitoyl- sn-glycero-3-phosphorylglycerol (DPPG) and piceid by mixing them in water and a subsequent heating/cooling process. When small-sized fluorescently labeled DPPG-piceid (DPPG-FLpiceid) nanoparticles were added to rat skin tissue, FLpiceid molecules were localized in stratum corneum.
Bioaugmentation in the surgical treatment of anterior cruciate ligament injuries: A review of current concepts and emerging techniques
Authors: Looney Austin MacFarland , Leider Joseph Daniel , Horn Andrew Ryan , Bodendorfer Blake Michael
Published: May 2020

Injuries involving the anterior cruciate ligament are among the most common athletic injuries, and are the most common involving the knee. The anterior cruciate ligament is a key translational and rotational stabilizer of the knee joint during pivoting and cutting activities. Traditionally, surgical intervention in the form of anterior cruciate ligament reconstruction has been recommended for those who sustain an anterior cruciate ligament rupture and wish to remain active and return to sport. The intra-articular environment of the anterior cruciate ligament makes achieving successful healing following repair challenging. Historically, results following repair were poor, and anterior cruciate ligament reconstruction emerged as the gold-standard for treatment. While earlier literature reported high rates of return to play, the results of more recent studies with longer follow-up have suggested that anterior cruciate ligament reconstruction may not be as successful as once thought: fewer athletes are able to return to sport at their preinjury level, and many still go on to develop osteoarthritis of the knee at a relatively younger age. The four principles of tissue engineering (cells, growth factors, scaffolds, and mechanical stimuli) combined in various methods of bioaugmentation have been increasingly explored in an effort to improve outcomes following surgical treatment of anterior cruciate ligament injuries. Newer technologies have also led to the re-emergence of anterior cruciate ligament repair as an option for select patients. The different biological challenges associated with anterior cruciate ligament repair and reconstruction each present unique opportunities for targeted bioaugmentation strategies that may eventually lead to better outcomes with better return-to-play rates and fewer revisions.
Endoscopic ultrasound-guided drainage of difficult-to-access liver abscesses
Authors: Chin Yung Ka , Asokkumar Ravishankar
Published: May 2020

Objectives:

Antibiotic therapy and percutaneous drainage have been the first-line treatments for liver abscesses. However, percutaneous drainage of abscesses may be challenging in difficult-to-access locations such as the caudate lobe. The aim of this review was to determine the indications, technical feasibility and efficacy of endoscopic ultrasound-guided drainage of difficult-to-access liver abscesses.

Methods:

A literature review of original articles, abstracts, case series and case reports describing endoscopic ultrasound-guided liver abscess drainage was performed. The indications, techniques and complications associated with endoscopic ultrasound-guided drainage were reviewed.

Results:

A total of 15 studies were identified. The main indications were failed antibiotic therapy and difficulty in gaining percutaneous access. The technique involved identification and puncturing of an abscess under endoscopic ultrasound guidance followed by placement of a prosthesis via a guide wire. The technique was 97.5% successful with no major complications reported.

Conclusion:

Endoscopic ultrasound-guided drainage was feasible and safe and allowed complete drainage of liver abscesses not accessible by percutaneous drainage.
Growth Limits: A Conceptual Analysis for Sustainable Development in Nigeria
Authors: Adejumo Oluwabunmi O.
Published: May 2020

In the school of development thought, growth has been identified as a viable alternative to the challenge of poverty and economic backwardness. However, the ecologists have continuously challenged the growth position in relation to environmental degradation and depletion. It is against this background; this study examined the limits to growth in Nigeria beyond which there will be inimical consequences for the environment. The study employed time series data that spanned between 1970 and 2014. These data sets were sourced from the World Development Indicators. Based on the assimilation model, threshold estimates were used to identify optimal growth regions, whereas regression estimates were used to measure growth effects. It was discovered that below the identified growth limit, there are currently significant negative impacts on the quality of the environment in Nigeria via economic growth. This study is a single-country case, that is, Nigeria; hence, the study can be expanded to include other sub-Saharan African countries. The study adds to knowledge by establishing the prospects for sustainability in the quality of the environment in the long run; therefore, policies designed in this areas have higher likelihood of attaining sustainability.
Morphometric analysis of medial and lateral tibia plateau and adaptability with Oxford partial knee replacement in a Japanese population
Authors: Kamenaga Tomoyuki , Hiranaka Takafumi , Hida Yuichi , Fujishiro Takaaki , Okamoto Koji
Published: May 2020

Aims:

In unicompartmental knee arthroplasty (UKA), tibial components must be correctly sized and positioned so that tibial cut surfaces are well covered without marked under- or overhang with impingement of the surrounding soft tissue. We used morphometric data of both medial and lateral tibial plateaus separately to plan UKA and evaluated the compatibility of the measurement data to the dimensions of six currently available tibial prostheses in a Japanese population.

Materials and Methods:

Using computed tomography, we preoperatively examined 60 patients (30 medial and 30 lateral osteoarthritis (OA)) scheduled for primary UKA at our hospital between 2013 and 2017. Each tibial cutting surface was measured in the transverse plane at 2 mm below the respective joint line. We used anteroposterior and mediolateral length to calculate the mediolateral length/anteroposterior ratio of both medial and lateral compartments. We then compared measurements across six current UKA systems: Oxford fixed tibia and fixed lateral tibia, Triathlon, TRIBRID, JOURNEY UNI, and HLS Uni Evolution.

Results:

We found no significant differences in morphometric data between the medial and the lateral OA. The cutting surface of lateral plateau, however, had smaller anteroposterior dimensions, greater mediolateral length, and higher mediolateral length/anteroposterior ratio than those of medial plateau. Therefore, in this Japanese population-based study, Oxford lateral tibia had good compatibility with the measurement data of lateral compartments.

Conclusions:

Lateral compartments had lower anteroposterior length, greater mediolateral length, and higher mediolateral length/anteroposterior ratio than those of medial compartments. We, therefore, strongly recommend using Oxford fixed lateral tibia for lateral OA over other current tibial prostheses because of superior coverage.
Subverting Surveillance or Accessing the Dark Web? Interest in the Tor Anonymity Network in U.S. States, 2006–2015
Authors: Lindner Andrew M. , Xiao Tongtian
Published: May 2020

The U.S. government engaged in unprecedented forms of mass surveillance in the twenty-first century. Users of the The Onion Router (Tor), an anonymity-granting technology, mask themselves from state surveillance and can gain access to illicit content on the Dark Web. Drawing on theory regarding “exposure” to surveillance, this study examines how two issue-attention cycles (related to the Edward Snowden state surveillance revelations and the Dark Web respectively) are associated with public interest in the Tor browser in the United States. Using data at the state-year level from 2006 to 2015, this study estimates fixed effects models, controlling for sociodemographics, the presence of journalism, tech, and political jobs, as well as multiple measures of state political ideology. The results indicate that state-years with greater popularity of Google searches related to the Snowden story had significantly higher popularity of searches for Tor. By contrast, there was no association between Dark Web search popularity and Tor search popularity. These findings are consistent with the notion that the Snowden incident increased Americans’ sense of exposure, leading to interest in anonymity-granting technology.
Direct oral anticoagulants for cancer-associated venous thromboembolism: a systematic review and meta-analysis
Authors: Mulder Frits I. , Bosch Floris T. M. , Young Annie M. , Marshall Andrea , McBane Robert D. , Zemla Tyler J. , Carrier Marc , Kamphuisen Pieter Willem , Bossuyt Patrick M. M. , Büller Harry R. , Weitz Jeffrey I. , Middeldorp Saskia , van Es Nick
Published: May 2020

Direct oral anticoagulants (DOACs) are an emerging treatment option for patients with cancer and acute venous thromboembolism (VTE), but studies have reported inconsistent results. This systematic review and meta-analysis compared the efficacy and safety of DOACs and low-molecular-weight heparins (LMWHs) in these patients. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and conference proceedings were searched to identify relevant randomized controlled trials. Additional data were obtained from the original authors to homogenize definitions for all study outcomes. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Other outcomes included the composite of recurrent VTE and major bleeding, clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Summary relative risks (RRs) were calculated in a random effects meta-analysis. In the primary analysis comprising 2607 patients, the risk of recurrent VTE was nonsignificantly lower with DOACs than with LMWHs (RR, 0.68; 95% CI, 0.39-1.17). Conversely, the risks of major bleeding (RR, 1.36; 95% CI, 0.55-3.35) and CRNMB (RR, 1.63; 95% CI, 0.73-3.64) were nonsignificantly higher. The risk of the composite of recurrent VTE or major bleeding was nonsignificantly lower with DOACs than with LMWHs (RR, 0.86; 95% CI, 0.60-1.23). Mortality was comparable in both groups (RR, 0.96; 95% CI, 0.68-1.36). Findings were consistent during the on-treatment period and in those with incidental VTE. In conclusion, DOACs are an effective treatment option for patients with cancer and acute VTE, although caution is needed in patients at high risk of bleeding.
Mechanical circulatory support in refractory cardiogenic shock due to influenza virus-related myocarditis
Authors: Sieweke Jan-Thorben , Akin Muharrem , Stetskamp Sebastian , Riehle Christian , Jonigk Danny , Flierl Ulrike , Pfeffer Tobias J. , Hirsch Valentin , Dutzmann Jochen , Hoeper Marius M. , Kühn Christian , Bauersachs Johann , Schäfer Andreas
Published: May 2020

Background

There is scarce evidence for mechanical circulatory support (MCS) in patients with influenza-related myocarditis complicated by refractory cardiogenic shock (rCS). We sought to investigate the impact of MCS using combined veno-arterial extracorporeal membrane oxygenation (VA-ECMO) and micro-axial flow pumps (the ECMELLA concept) in influenza-related myocarditis complicated by rCS.

Methods

This is a prospective, observational analysis from the single centre HAnnover Cardiac Unloading REgistry (HACURE) from two recent epidemic influenza seasons. We analysed patients with verified influenza-associated myocarditis complicated by rCS who were admitted to our intensive care unit (ICU) on MCS. Subsequently, we performed a propensity score (PS) matched analysis to patients with acute myocardial infarction (AMI) complicated by rCS and non-ischaemic cardiomyopathy (DCM) related rCS.

Results

We describe a series of seven patients with rCS-complicated influenza-related myocarditis (mean age 56±10 years, 58% male, influenza A (n=2)/influenza B (n=5)). No patient had been vaccinated prior to the influenza season. MCS was provided using combined VA-ECMO and Impella micro-axial flow pump. In two patients with out-of-hospital cardiac arrest, VA-ECMO had been implanted for extracorporeal cardiopulmonary resuscitation. All patients died within 18 days of hospital admission. By PS-based comparison to patients with AMI- or DCM-related rCS and combined MCS, 30-day mortality was significantly higher in influenza-related rCS.

Conclusion

Despite initial stabilisation with combined MCS in patients with rCS-complicated influenza-related myocarditis, the detrimental course of shock could not be stopped and all patients died. Influenza virus infection potentially critically affects other organs besides the heart, leading to irreversible end-organ damage that MCS cannot compensate for and, therefore, results in a devastating outcome.
Studying the Pyroelectric Effects of LiNbO3 Modified Composites
Authors: Zhang Fan , Kang Hua , Lin Yixuan , Guan Li , Aslan Hüsnü , Zhang Meining , Niu Lin , Dong Mingdong
Published: May 2020

LiNbO3 (LN) crystal has been widely used as a pyroelectric material due to its spontaneous electric polarization, which could be recharged easily and can directly convert heat energy into electricity. LN crystal’s heat-resistant, low-cost, and low dielectric loss properties make it possible for its applications in room-temperature pyroelectric devices and thermal sensors. However, LN crystal suffers from fragility, inflexibility, and other mechanical properties, which limit its suitability for many applications in various fields. In this study, the LN modified flexible pyroelectric films, composed of LN micro-particles, polypropylene (PP) matrix, and multiwalled carbon nanotubes (MWCNTs), are successfully fabricated. The pyroelectric effects of LN crystal and LN/PP/MWCNT composite films are characterized by monitoring the patterned self-assembly of nanoparticles and the output pyroelectric currents. The excellent pyroelectric properties of the composites have potential applications in energy harvesters or sensors.
Linkage mapping and genome-wide association study reveals conservative QTL and candidate genes for Fusarium rot resistance in maize
Authors: Wu Yabin , Zhou Zijian , Dong Chaopei , Chen Jiafa , Ding Junqiang , Zhang Xuecai , Mu Cong , Chen Yuna , Li Xiaopeng , Li Huimin , Han Yanan , Wang Ruixia , Sun Xiaodong , Li Jingjing , Dai Xiaodong , Song Weibin , Chen Wei , Wu Jianyu
Published: May 2020

Background

Fusariumear rot (FER) caused byFusarium verticillioidesis a major disease of maize that reduces grain yield and quality globally. However, there have been few reports of major loci for FER were verified and cloned.

Result

To gain a comprehensive understanding of the genetic basis of natural variation in FER resistance, a recombinant inbred lines (RIL) population and one panel of inbred lines were used to map quantitative trait loci (QTL) for resistance. As a result, a total of 10 QTL were identified by linkage mapping under four environments, which were located on six chromosomes and explained 1.0–7.1% of the phenotypic variation. Epistatic mapping detected four pairs of QTL that showed significant epistasis effects, explaining 2.1–3.0% of the phenotypic variation. Additionally, 18 single nucleotide polymorphisms (SNPs) were identified across the whole genome by genome-wide association study (GWAS) under five environments. Compared linkage and association mapping revealed five common intervals located on chromosomes 3, 4, and 5 associated with FER resistance, four of which were verified in different near-isogenic lines (NILs) populations. GWAS identified three candidate genes in these consistent intervals, which belonged to the Glutaredoxin protein family, actin-depolymerizing factors (ADFs), and AMP-binding proteins. In addition, two verified FER QTL regions were found consistent withFusariumcob rot (FCR) andFusariumseed rot (FSR).

Conclusions

These results revealed that multi pathways were involved in FER resistance, which was a complex trait that was controlled by multiple genes with minor effects, and provided important QTL and genes, which could be used in molecular breeding for resistance.
Involvement of ABC-transporters and acyltransferase 1 in intracellular cholesterol-mediated autophagy in bovine alveolar macrophages in response to the Bacillus Calmette-Guerin (BCG) infection
Authors: Xu Jinrui , Zhou Yanbing , Yang Yi , Lv Cuiping , Liu Xiaoming , Wang Yujiong
Published: May 2020

Background

Understanding pathogenic mechanisms is imperative for developing novel treatment to the tuberculosis, an important public health burden worldwide. Recent studies demonstrated that host cholesterol levels have implications in the establishment of Mycobacterium tuberculosis (M. tuberculosis, Mtb) infection in host cells, in which the intracellular cholesterol-mediated ATP-binding cassette transporters (ABC-transporters) and cholesterol acyltransferase1 (ACAT1) exhibited abilities to regulate macrophage autophagy induced by Mycobacterium bovis bacillus Calmette–Guérin (BCG).

Results

The results showed that a down-regulated expression of the ABC-transporters and ACAT1 in primary bovine alveolar macrophages (AMs) and murine RAW264.7 cells in response to a BCG infection. The inhibited expression of ABC-transporters and ACAT1 was associated with the reduction of intracellular free cholesterol, which in turn induced autophagy in macrophages upon to the Mycobacterial infection. These results strongly suggest an involvement of ABC-transporters and ACAT1 in intracellular cholesterol-mediated autophagy in AMs in response to BCG infection.

Conclusion

This study thus provides an insight into into a mechanism by which the cholesterol metabolism regulated the autophagy in macrophages in response to mycobacterial infections.
Optimizing 16S rRNA gene profile analysis from low biomass nasopharyngeal and induced sputum specimens
Authors: Claassen-Weitz Shantelle , Gardner-Lubbe Sugnet , Mwaikono Kilaza S. , du Toit Elloise , Zar Heather J. , Nicol Mark P.
Published: May 2020

Background

Careful consideration of experimental artefacts is required in order to successfully apply high-throughput 16S ribosomal ribonucleic acid (rRNA) gene sequencing technology. Here we introduce experimental design, quality control and “denoising” approaches for sequencing low biomass specimens.

Results

We found that bacterial biomass is a key driver of 16S rRNA gene sequencing profiles generated from bacterial mock communities and that the use of different deoxyribonucleic acid (DNA) extraction methods [DSP Virus/Pathogen Mini Kit® (Kit-QS) and ZymoBIOMICS DNA Miniprep Kit (Kit-ZB)] and storage buffers [PrimeStore® Molecular Transport medium (Primestore) and Skim-milk, Tryptone, Glucose and Glycerol (STGG)] further influence these profiles. Kit-QS better represented hard-to-lyse bacteria from bacterial mock communities compared to Kit-ZB. Primestore storage buffer yielded lower levels of background operational taxonomic units (OTUs) from low biomass bacterial mock community controls compared to STGG. In addition to bacterial mock community controls, we used technical repeats (nasopharyngeal and induced sputum processed in duplicate, triplicate or quadruplicate) to further evaluate the effect of specimen biomass and participant age at specimen collection on resultant sequencing profiles. We observed a positive correlation (r = 0.16) between specimen biomass and participant age at specimen collection: low biomass technical repeats (represented by< 500 16S rRNA gene copies/μl) were primarily collected at< 14 days of age. We found that low biomass technical repeats also produced higher alpha diversities (r = − 0.28); 16S rRNA gene profiles similar to no template controls (Primestore); and reduced sequencing reproducibility. Finally, we show that the use of statistical tools for in silico contaminant identification, as implemented through thedecontampackage in R, provides better representations of indigenous bacteria following decontamination.

Conclusions

We provide insight into experimental design, quality control steps and “denoising” approaches for 16S rRNA gene high-throughput sequencing of low biomass specimens. We highlight the need for careful assessment of DNA extraction methods and storage buffers; sequence quality and reproducibility; and in silico identification of contaminant profiles in order to avoid spurious results.
Genetic diversity in developmental responses to light spectral quality in barley (Hordeum vulgare L.)
Authors: Monteagudo Arantxa , Kiss Tibor , Mayer Marianna , Casas Ana M. , Igartua Ernesto , Karsai Ildikó
Published: May 2020

Background

Plants use light wavelength, intensity, direction and duration to predict imminent seasonal changes and to determine when to initiate physiological and developmental processes. Among them, crop responses to light are not fully understood. Here, we study how light quality affects barley development, using two broad-spectrum light sources, metal halide (M) and fluorescent (F) lamps. Eleven varieties with known allelic variants for the major flowering time genes were evaluated under controlled conditions (long days, same light intensity). Two experiments were carried out with fully-vernalized plants: 1) control treatments (M, F); 2) shifting chambers 10 days after the start of the experiment (MF, FM).

Results

In general, varieties developed faster under longer exposure to M conditions. The greatest differences were due to a delay promoted by F light bulbs, especially in the time to first node appearance and until the onset of stem elongation. Yield related-traits as the number of seeds were also affected by the conditions experienced. However, not each variety responded equally, and they could be classified in insensitive and sensitive to light quality. Expression levels of flowering time genes HvVRN1, HvFT1 and PPD-H1 were high in M, while HvFT3 and HvVRN2 were higher under F conditions. The expression under shift treatments revealed also a high correlation between HvVRN1 and PPD-H1 transcript levels.

Conclusions

The characterization of light quality effects has highlighted the important influence of the spectrum on early developmental stages, affecting the moment of onset of stem elongation, and further consequences on the morphology of the plant and yield components. We suggest that light spectra control the vernalization and photoperiod genes probably through the regulation of upstream elements of signalling pathways. The players behind the different responses to light spectra found deserve further research, which could help to optimize breeding strategies.
Specialist LINK and primary care network clinical pathways - a new approach to patient referral: a cross-sectional survey of awareness, utilization and usability among family physicians in Calgary
Authors: Arain Mubashir , Rostami Mahnoush , Zaami Mariama , Kiss Valerie , Ward Richard
Published: May 2020

Background

Specialist LINK is a real-time, non-urgent telephone collaboration line designed to link family doctors and specialists. The purpose was to reduce wait times, improve efficiency and enhance the coordination of patient care through enhanced communication between primary and specialty care. The aim of this study was to determine the awareness and utilization of Specialist LINK and Primary Care Network (PCN) Clinical Pathways among family physicians.

Methods

A family physician experience cross-sectional survey was conducted from March to May 2018 in Calgary and Area. The survey was designed to assess family physicians’ awareness and utilization of Specialist LINK and PCN Clinical Pathways. We also used a 1–10 scale for respondents to rate the utility of Specialist LINK (1 was least useful and 10 represented highly useful). To obtain a true representative sample, family physicians were selected through a random sampling method. We applied multiple approaches to ensure a high response rate: paper survey, telephone reminders, and an on-site survey for non-responders.

Results

A total of 251 participants completed the survey of the 650 randomly selected family physicians (Response rate≈39%). Eighty-nine percent of the family physicians were aware of Specialist LINK [95% Confidence Interval (84–92%)]. The average rating was 8.1 (on a scale of 1–10) for the usefulness of Specialist LINK. We found that the odds of being aware of Specialist LINK were two times higher in female family physicians compared to male physicians. Also, those with less than 5 years of experience, the odds of being aware of Specialist LINK were around five times higher compared to those with 5 or more years of experience. Fifty-five percent of family physicians were aware of PCN Clinical Pathways (95% CI = 48–60%); of those, 82% were accessing and following PCN Clinical Pathways in their clinical practice. The average rating was 7.9 (on a scale of 1–10) for the usefulness of PCN Clinical Pathways.

Conclusion

Most of the respondents in Calgary and area were aware of Specialist LINK and a large proportion of them were using it to access advice for their patients.
Impact of hepatic steatosis on treatment response in nuclesos(t)ide analogue-treated HBeAg-positive chronic hepatitis B: a retrospective study
Authors: Chen Yi-Cheng , Jeng Wen-Juei , Hsu Chao-Wei , Lin Chun-Yen
Published: May 2020

Background

The impact of hepatic steatosis (HS) on treatment response following nucleos(t)ide analogue (NA) treatment for chronic hepatitis B (CHB) patients has not been clearly elucidated. We aimed to investigate the difference in HBeAg seroclearance between NA-treated HBeAg-positive CHB patients with and without HS.

Methods

We retrospectively recruited HBeAg-positive CHB patients receiving liver biopsy and NA monotherapy. The baseline clinical characteristics and cumulative incidence of HBeAg seroclearance were compared between patients with and without HS and age/gender-matched subgroup analysis was performed.

Results

A total of 196 patients were enrolled from 2003 April to 2016 October. The mean age was 39.6 ± 11.2 years, 142 (72.4%) were males and 94 (48%) had histological evidence of HS. Median treatment duration and follow-up period were 24.3 months and 54.9 months, respectively. HBeAg seroclearance was achieved in 56/102 (54.9%) and 54/94 (57.4%) patients with and without HS, respectively (p = 0.830). The 5-year cumulative incidence of HBeAg seroclearance in patients with and without HS was 62.8 and 67.7% in overall population (p = 0.398) and 62.4 and 66.9% in age/gender-matched subgroups (p = 0.395), respectively. The rate of HBeAg seroclearance was comparable between patients with or without HS in different NA monotherapy (allp > 0.05).

Conclusions

HS had no significant impact on HBeAg seroclearance in HBeAg-positive CHB patients with NA monotherapy during long-term follow-up.
Impact of Enterobius vermicularis infection on biochemical parameters in the blood of children in Erbil Province, Iraq
Authors: Al-Daoody Ahmed Akil Khudhair , Al-Bazzaz Eman Najdy Haydar
Published: May 2020

Background

Enterobius vermicularisis an intestinal helminthic parasite that causes a gastrointestinal infection called enterobiasis. Children are more susceptible to infection than adults. The current study aimed to explore the prevalence ofE. vermicularisinfection among children in Erbil City concerning demographic factors and certain blood parameters.

Methods

A cross-sectional and analytical study was conducted on 505 children (3–10 years). Cellophane tape samples and blood samples were taken from participants. The cellophane tape samples were examined microscopically, whereas blood samples were examined using the auto-analyzer and Cobas.

Results

The overall prevalence ofE. vermicularisinfection was 27.13%, and the infection rate was non-significantly (P = 0.371) higher in females (28.85%) than in males (25.31%). The incidence of enterobiasis was directly proportional to family size. This study demonstrated that the mean serum total protein and iron levels were significantly decreased in infected children, while other trace element levels were not significantly affected.

Conclusions

The prevalence ofE. vermicularisis relatively lower than that in previous studies. Serum total protein and iron levels significantly decreased in the enterobiasis-positive group.
Clinical characteristics and prognostic factors of Hurthle cell carcinoma: a population based study
Authors: Zhou Xingtong , Zheng Zhibo , Chen Chuyan , Zhao Bangbo , Cao Hongtao , Li Tianhao , Liu Xudong , Wang Weibin , Li Yongning
Published: May 2020

Background

Thyroid Hurthle cell carcinoma (HCC) is a rare disease with high risk of invasion and metastasis and poor prognosis. The clinical characteristics, prognosis and treatment of HCC are still controversial, and clinical data are still limited to some case reports. Therefore, understanding the characteristics and survival factors of HCC is clinically necessary.

Methods

This study collected data from HCC patients diagnosed pathologically from 2004 to 2015, including basic population characteristics, tumor characteristics, and epidemiological and survival data. The data were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to conduct a population cohort study.

Results

A total of 2101 HCC patients with an average age of 55.42 ± 15.27 years were enrolled in this study. Of them, 1740 (82.82%) patients had local disease, 245 (11.66%) had regional disease, and 89 (4.24%) had distant disease. Total thyroidectomy was performed in 1669 (79.44%) patients, partial thyroidectomy was performed in 382 (18.18%) patients, and radioactive iodine (RAI) was used in 1155 (54.97%) patients. The 5-year and 10-year cancer-specific survival rate was 95.4 and 92.6%, respectively. The distant disease group had significantly more male patients, multifocal tumors, and extensive tumors compared to the local disease group. Multivariate survival analysis showed that age (P < 0.05), SEER stage (P < 0.001), and T-stage (P = 0.001) had significant effects on survival. There was no significant difference in survival between total and partial thyroidectomy (P = 0.078), or between RAI and non-RAI (P = 0.733).

Conclusion

Male gender, multifocal tumors, and extended tumors are associated with increased risk of late stage HCC. Age over 45 years, distant SEER stage, and late T-stage are independent risk factors for mortality in HCC.
Mutational spectrum of acquired resistance to reversible versus irreversible EGFR tyrosine kinase inhibitors
Authors: Wagener-Ryczek Svenja , Heydt Carina , Süptitz Juliane , Michels Sebastian , Falk Markus , Alidousty Christina , Fassunke Jana , Ihle Michaela Angelika , Tiemann Markus , Heukamp Lukas , Wolf Jürgen , Büttner Reinhard , Merkelbach-Bruse Sabine
Published: May 2020

Background

Over the past years, EGFR tyrosine kinase inhibitors (TKI) revolutionized treatment response. 1st-generation (reversible) EGFR TKI and later the 2nd –generation irreversible EGFR TKI Afatinib were aimed to improve treatment response. Nevertheless, diverse resistance mechanisms develop within the first year of therapy. Here, we evaluate the prevalence of acquired resistance mechanisms towards reversible and irreversible EGFR TKI.

Methods

Rebiopsies of patients after progression to EGFR TKI therapy (> 6 months) were targeted to histological and molecular analysis. Multiplexed targeted sequencing (NGS) was conducted to identify acquired resistance mutations (e.g. EGFR p.T790M). Further, Fluorescence in situ hybridisation (FISH) was applied to investigate the status of bypass mechanisms like, MET or HER2 amplification.

Results

One hundred twenty-three rebiopsy samples of patients that underwent first-line EGFR TKI therapy (PFS ≥6 months) were histologically and molecularly profiled upon clinical progression. TheEGFRp.T790M mutation is the major mechanism of acquired resistance in patients treated with reversible as well as irreversible EGFR TKI. Nevertheless a statistically significant difference for the acquisition of T790M mutation has been identified: 45% of afatinib- vs 65% of reversible EGFR TKI treated patients developed a T790M mutation (p-value 0.02). Progression free survival (PFS) was comparable in patients treated with irreversibleEGFRirrespective of the sensitising primary mutation or the acquisition of p.T790M.

Conclusions

TheEGFRp.T790M mutation is the most prominent mechanism of resistance to reversible and irreversible EGFR TKI therapy. Nevertheless there is a statistically significant difference of p.T790M acquisition between the two types of TKI, which might be of importance for clinical therapy decision.
Patterns and correlates of objectively measured physical activity in 3-year-old children
Authors: Bergqvist-Norén Linnea , Johansson Elin , Xiu Lijuan , Hagman Emilia , Marcus Claude , Hagströmer Maria
Published: May 2020

Background

To increase the knowledge about physical activity (PA) patterns and correlates among children under the age of 4, there is a need for study’s using objective measurements. The aim of this study was therefore to investigate if objectively measured PA among 3-year-old children differed between day of week and time of day and whether it correlated to child weight status and sex as well as parental weight status and education.

Methods

Totally 61 children (51% girls) aged 3, participating in Early Stockholm Obesity Prevention Project were included. PA was measured with a tri-axial accelerometer (ActiGraph GT3X+) worn on the non-dominant wrist for one week. The main outcome was average PA expressed as counts per minute from the vector magnitude. PA and demographics/family-related factors were collected at baseline and at age 3. To analyze the results simple linear regression, ANOVA and paired t-tests were performed.

Results

The mean number of valid days was 6.7 per child. The children were more active on weekdays than weekends (p < 0.01) and the hourly pattern differed over the day with children being most active midmorning and midafternoon (p = 0.0001). Children to parents with low education were more active (p = 0.01) than those with highly educated parents. No differences in PA by child weight status, sex nor parental weight status were found.

Conclusions

PA in 3-year-old children was lower during weekends than weekdays and varied over the day. Boys and girls had similar PA patterns, these patterns were independent of child or parental weight status. Children to parents with low education were more active than their counterparts. The fact that PA differed between weekdays and weekends indicates that PA might be affectable in 3-year-old children.