bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-cell autonomous OTX2 homeoprotein regulates visual cortex plasticity through Gadd45b/g
Authors: Apulei Jessica , Kim Namsuk , Testa Damien , Ribot Jérôme , Morizet David , Bernard Clémence , Jourdren Laurent , Blugeon Corinne , Di Nardo Ariel A. , Prochiantz Alain
Published: July 2017

The non-cell autonomous transfer of OTX2 homeoprotein transcription factor into juvenile mouse cerebral cortex regulates parvalbumin interneuron maturation and critical period timing. By analyzing gene expression in primary visual cortex of wild-type andOtx2+/GFPmice at plastic and non-plastic ages, we identified several putative genes implicated in Otx2-dependent visual cortex plasticity for ocular dominance. Cortical OTX2 infusion in juvenile mice inducedGadd45b/gexpression through direct regulation of transcription. Intriguingly, a reverse effect was found in the adult, where reducing cortical OTX2 resulted inGadd45b/gup-regulation. Viral expression ofGadd45bin adult visual cortex directly induced ocular dominance plasticity with concomitant changes in MeCP2 foci within parvalbumin interneurons and in methylation states of several plasticity gene promoters, suggesting epigenetic regulation. This interaction provides a molecular mechanism for OTX2 to trigger critical period plasticity yet suppress adult plasticity.
Picky – a simple online method designer for targeted proteomics
Authors: Zauber Henrik , Kirchner Marieluise , Selbach Matthias
Published: July 2017

Targeted proteomic approaches like selected reaction monitoring (SRM) and parallel reaction monitoring (PRM) are increasingly popular because they enable sensitive and rapid analysis of a preselected set of proteins1-3. However, developing targeted assays is tedious and requires the selection, synthesis and mass spectrometric analysis of candidate peptides before the actual samples can be analyzed. The SRMatlas and ProteomeTools projects recently published fragmentation spectra of synthetic peptides covering the entire human proteome4,5. These datasets provide very valuable resources. However, extracting the relevant data for selected proteins of interest is not straightforward. For example, developing scheduled acquisition methods (i.e. analyzing specific peptides in defined elution time windows) is complicated and requires adjustments to specific chromatographic conditions employed. Moreover, the number of peptide candidates to be targeted in parallel often exceeds the analytical abilities of the mass spectrometer. In this case, the key question is which peptides can be omitted without losing too much information. Ideally, a method design tool would automatically select the most informative peptides in each retention time window. Until now, none of the available tools automatically generates such optimized scheduled SRM and PRM methods (Figure S1).
Duplex Proximity Sequencing (Pro-Seq): A method to improve DNA sequencing accuracy without the cost of molecular barcoding redundancy
Authors: Pel Joel , Choi Wendy W. Y. , Leung Amy O. , Shibahara Gosuke , Gelinas Laura , Despotovic Milenko , Ung W. Lloyd , Marziali Andre
Published: July 2017

A challenge in the clinical adoption of cell-free DNA (cfDNA) liquid biopsies for cancer care is their high cost compared to potential reimbursement. The most common approach used in liquid biopsies to achieve high specificity detection of circulating tumor DNA (ctDNA) among a large background of normal cfDNA is to attach molecular barcodes to each DNA template, amplify it, and then sequence it many times to reach a low-error consensus. In applications where the highest possible specificity is required, error rate can be lowered further by independently detecting the sequences of both strands of the starting cfDNA. While effective in error reduction, the additional sequencing redundancy required by such barcoding methods can increase the cost of sequencing up to 100-fold over standard next-generation sequencing (NGS) of equivalent depth.

We present a novel library construction and analysis method for NGS that achieves comparable performance to the best barcoding methods, but without the increase in sequencing and subsequent sequencing cost. Named Proximity-Sequencing (Pro-Seq), the method merges multiple copies of each template into a single sequencing read by physically linking the molecular copies so they seed a single sequencing cluster. Since multiple DNA copies of the same template are compared for consensus within the same cluster, sequencing accuracy is improved without the use of redundant reads. Additionally, it is possible to represent both senses of the starting duplex in a single cluster. The resulting workflow is simple, and can be completed by a single technician in a work day with minimal hands on time.

Using both cfDNA and cell line DNA, we report the average per-mutation detection threshold and per-base analytical specificity to be 0.003% and >99.9997% respectively, demonstrating that Pro-Seq is among the highest performing liquid biopsy technologies in terms of both sensitivity and specificity, but with greatly reduced sequencing costs compared to existing methods of comparable accuracy.
HAM-TBS: High accuracy methylation measurements via targeted bisulfite sequencing
Authors: Röh Simone , Wiechmann Tobias , Sauer Susann , Ködel Maik , Binder Elisabeth B. , Provençal Nadine
Published: July 2017

Background

The ability to accurately and efficiently measure DNA methylation is vital to advance the understanding of this mechanism and its contribution to common diseases. Here, we present a highly accurate method to measure methylation using bisulfite sequencing (termed HAM-TBS). This novel method is able to assess DNA methylation in multiple samples with high accuracy in a cost-effective manner. We developed this assay for theFKBP5locus, an important gene in the regulation of the stress system and previously linked to stress-related disorders, but the method is applicable to any locus of interest.

Results

HAM-TBS enables multiplexing of up to 96 samples spanning a region of ~10 kb using the llumina MiSeq. It incorporates a triplicate bisulfite conversion step, pooled target enrichment via PCR, PCR-free library preparation and a minimum coverage of 1,000x. Furthermore, we designed and validated a targeted panel to specifically assess regulatory regions within theFKBP5locus including the transcription start site, topologically associated domain boundaries, intergenic and proximal enhancers as well as glucocorticoid receptor and CTCF binding sites that are not covered in commercially available DNA methylation arrays.

Conclusions

HAM-TBS represents a highly accurate, medium-throughput sequencing approach for robust detection of DNA methylation changes in specific target regions.
Specification of the germline by Nanos-dependent down-regulation of the somatic synMuvB transcription factor LIN-15B
Authors: Lee Chih-Yung S. , Lu Tu , Seydoux Geraldine
Published: July 2017

The Nanos RNA-binding protein has been implicated in the specification of primordial germ cells (PGCs) in metazoans, but the underlying mechanisms remain poorly understood. We have profiled the transcriptome of PGCs lacking thenanoshomologuesnos-1andnos-2iC. elegans.nos-1nos-2PGCs fail to silence hundreds of genes normally expressed in oocytes and somatic cells, a phenotype reminiscent of PGCs lacking the repressive PRC2 complex. Thenos-1nos-2phenotype depends on LIN-15B, a broadly expressed synMuvB class transcription factor known to antagonize PRC2 activity in somatic cells. LIN-15B is maternally-inherited by all embryonic cells and is down-regulated specifically in PGCs in anos-1nos-2-dependent manner. Consistent with LIN-15B being a critical target of Nanos regulation, inactivation of maternal LIN-15B restores fertility tonos-1nos-2mutants. These studies demonstrate a central role for Nanos in reprogramming the transcriptome of PGCs away from an oocyte/somatic fate by down-regulating an antagonist of PRC2 activity.
Customer experience design: a case study in the cultural sector
Authors: Ponsignon Frederic , Durrieu Francois , Bouzdine-Chameeva Tatiana
Published: July 2017

Purpose

The purpose of this paper is to explore the experience design phenomenon in the cultural sector. Specifically, it purports to articulate a set of design characteristics that support the alignment between an organisation’s design intention (i.e. intended experience) and the actual experience of customers (i.e. realised experience).

Design/methodology/approach

A single case study approach is adopted to explore the phenomenon from both the provider and customer perspectives simultaneously. A range of qualitative data, including 42 interviews with managers and customers as well as voluminous documentary evidence, are collected. Provider and customer data are analysed independently using a rigorous inductive analytical process to generate experience design themes and to assess possible gaps between intended and realised experience.

Findings

The findings reveal the design characteristics of touchpoints and the overall customer journey, which constitute the core experience, as well as the design characteristics of the physical and social environment, which support the realisation of the core experience, in a cultural context.

Research limitations/implications

Limitations include difficulties in generalising the findings from a single case and in claiming that the set of design characteristics identified is exhaustive.

Practical implications

The paper makes several recommendations that are useful and relevant for customer experience practitioners in the cultural sector.

Originality/value

The paper’s contribution is to provide novel empirical insights into the four experience design areas of touchpoints, journey, physical elements and social elements in an experience-centric cultural context. On that basis, a conceptual framework for experience design in the cultural context is proposed.
Investigating the fire performance of LSF wall systems using finite element analyses
Authors: Rusthi Mohamed , Keerthan Poologanathan , Mahendran Mahen , Ariyanayagam Anthony
Published: July 2017

Purpose

This research was aimed at investigating the fire performance of LSF wall systems by using 3-D heat transfer FE models of existing LSF wall system configurations.

Design/methodology/approach

This research was focused on investigating the fire performance of LSF wall systems by using 3-D heat transfer finite element models of existing LSF wall system configurations. The analysis results were validated by using the available fire test results of five different LSF wall configurations.

Findings

The validated finite element models were used to conduct a parametric study on a range of non-load bearing and load bearing LSF wall configurations to predict their fire resistance levels (FRLs) for varying load ratios.

Originality/value

Fire performance of LSF wall systems with different configurations can be understood by performing full-scale fire tests. However, these full-scale fire tests are time consuming, labour intensive and expensive. On the other hand, finite element analysis (FEA) provides a simple method of investigating the fire performance of LSF wall systems to understand their thermal-mechanical behaviour. Recent numerical research studies have focused on investigating the fire performances of LSF wall systems by using finite element (FE) models. Most of these FE models were developed based on 2-D FE platform capable of performing either heat transfer or structural analysis separately. Therefore, this paper presents the details of a 3-D FEA methodology to develop the capabilities to perform fully-coupled thermal-mechanical analyses of LSF walls exposed to fire in future.
Antecedents of transition patterns of depressive symptom trajectories from adolescence to young adulthood
Authors: Lee Tae Kyoung , Wickrama Kandauda A. S. , Kwon Josephine A. , Lorenz Frederick O. , Oshri Assaf
Published: July 2017

This study examined (a) transition patterns from adolescent‐specific depressive symptom trajectory classes to young adult‐specific trajectory classes (N = 537; 15–26 years) and (b) identified risk factors associated with these transition patterns. The latent classes and transition analyses identified three transitional patterns of depressive symptom trajectories, including a deteriorating pattern (8.2%), a recovering pattern (22.5%), and a consistently low pattern (69.3%). Additionally, the results showed that contextual risk factors (i.e., negative economic events, negative romantic relationships, and low college enrolment rates) in the transition period to young adulthood were more positively associated with deteriorated or recovered transition patterns of depressive symptom trajectories than with the consistently low transition patterns even after taking into account the effects of adolescent risk factors. The identification of dynamic transition patterns in depressive symptom trajectories from adolescence to young adulthood and risk factors provide useful tools for preventive and intervention efforts.

Statement of contribution

What is already known on this subject?

Heterogeneous trajectories of depressive symptoms across adolescence and young adulthood have been reported.

Psychosocial characteristics differentiate trajectories of depressive symptoms from adolescence to young adulthood.

What does this study add?

Dynamic transition patterns of depressive symptom trajectories are found between adolescence and young adulthood.

Life experiences in the transition period are uniquely associated with the transition patterns of depressive symptom trajectories even after adjusting the effects of adolescent characteristics.
Sleep disorders in patients with erectile dysfunction
Authors: Kalejaiye Odunayo , Raheem Amr Abdel , Moubasher Amr , Capece Marco , McNeillis Sara , Muneer Asif , Christopher Andrew N. , Garaffa Giulio , Ralph David J.
Published: July 2017

Objective

To assess the prevalence of obstructive sleep apnoea (OSA) in men presenting with erectile dysfunction (ED) at a single centre.

Patients and Methods

All men attending a specialised andrology outpatient department with a new diagnosis of ED were included in this prospective study. All patients completed three questionnaires: the International Index of Erectile Function (IIEF) and two sleep questionnaires [the Obstructive Sleep Apnoea Screening questionnaire and the Insomnia Severity Index (ISI)]. Their ED management was subsequently undertaken in accordance with local and European guidelines. An OSA diagnosis was made based on a score of ≥3 on the Obstructive Sleep Apnoea Screening questionnaire and those patients were referred for specialist management.

Results

Between February and September 2016, 129 patients with ED completed the study questionnaires. In all, 71 patients (55%) had a score of ≥3 on the Obstructive Sleep Apnoea Screening questionnaire, indicating a need for specialist sleep referral. Men who scored ≥3 on the Obstructive Sleep Apnoea Screening questionnaire were significantly older (61.4 vs 46.5 years; P < 0.001) and had a significantly higher body mass index (29.4 vs 26.7 kg/m2; P < 0.001) when compared to the control group (OSA score of <3). The sleep apnoea group (OSA score of ≥3) had significantly worse IIEF‐ED scores (6.2 vs 9.1; P = 0.018) and ISI scores (7.9 vs 5.5; P = 0.061).

Conclusion

Men presenting to the andrology clinic with ED are at significant risk of having undiagnosed sleep disorders. This has serious adverse health consequences, as well as being associated with potential dangers at work and travel. The patient compliance was high with 78% completing all three questionnaires. It is feasible to screen this population for sleep disturbance and this should be part of the ED assessment.
ATR‐101 inhibits cholesterol efflux and cortisol secretion by ATP‐binding cassette transporters, causing cytotoxic cholesterol accumulation in adrenocortical carcinoma cells
Authors: Burns Veronica Elizabeth , Kerppola Tom Klaus
Published: July 2017

Background and Purpose

To further the development of new agents for the treatment of adrenocortical carcinoma (ACC), we characterized the molecular and cellular mechanisms of cytotoxicity by the adrenalytic compound ATR‐101 (PD132301‐02).

Experimental Approach

We compared the effects of ATR‐101, PD129337, and ABC transporter inhibitors on cholesterol accumulation and efflux, on cortisol secretion, on ATP levels, and on caspase activation in ACC‐derived cell lines. We examined the effects of these compounds in combination with methyl‐β‐cyclodextrin or exogenous cholesterol to determine the roles of altered cholesterol levels in the effects of these compounds.

Key Results

ATR‐101 caused cholesterol accumulation, ATP depletion, and caspase activation within 30 minutes after addition to ACC‐derived cells, whereas PD129337 did not. Suppression of cholesterol accumulation by methyl‐β‐cyclodextrin or exogenous cholesterol, prevented ATP depletion and caspase activation by ATR‐101. ATR‐101 blocked cholesterol efflux and cortisol secretion, suggesting that it inhibited ABCA1, ABCG1, and MDR1 transporters. Combinations of ABCA1, ABCG1, and MDR1 inhibitors were also cytotoxic. Combinations of ATR‐101 with inhibitors of ABCG1, MDR1, or mitochondrial functions had increased cytotoxicity. Inhibitors of steroidogenesis reduced ATP depletion by ATR‐101, whereas U18666A enhanced cholesterol accumulation and ATP depletion together with ATR‐101. ATR‐101 repressed ABCA1, ABCG1, and IDOL transcription by mechanisms that were distinct from the mechanisms that caused cholesterol accumulation.

Conclusions and Implications

Inhibition of multiple ABC transporters and the consequent accumulation of cholesterol mediated the cytotoxicity of ATR‐101. Compounds that replicate these effects in tumours are likely to be useful in the treatment of ACC.
Food allergy phenotypes: The key to personalized therapy
Authors: Deschildre A. , Lejeune S. , Cap M. , Flammarion S. , Jouannic L. , Amat F. , Just J.
Published: July 2017

Food allergies (FAs) are of increasing public health concern and are characterized by a large spectrum of diseases. Their diversity is well known for immunologic pathways (IgE, non‐IgE‐mediated FAs) and natural history. Many other factors and patient characteristics are involved including type of food, exposure route, allergic comorbidities, gender, racial and ethnic backgrounds, cofactors and health conditions. Food allergen components and sensitization profiles are also involved in FA phenotypes. A new approach to chronic disorders based on the identification of phenotypes through extensive knowledge of all the complex components is also applicable to FAs and could lead towards integrative care management. Diagnostic biomarkers for FAs are emerging which also contribute to better care modalities. The aim of this article was to highlight current knowledge regarding the phenotypic diversity of FA. This review will focus on IgE‐mediated FAs and how identifying phenotypes may help to better understand the pathophysiological complexity, improve diagnosis and lead to personalized treatment strategies.
6-Mercaptopurine modifies cerebrospinal fluid T cell abnormalities in paediatric opsoclonus–myoclonus as steroid sparer
Authors: Pranzatelli M R , Tate E D , Allison T J
Published: July 2017

The purpose of this study was to evaluate the capacity of 6-mercaptopurine (6-MP), a known immunosuppressant, to normalize cerebrospinal fluid (CSF) lymphocyte frequencies in opsoclonus–myoclonus syndrome (OMS) and function as a steroid sparer. CSF and blood lymphocytes were immunophenotyped in 11 children with OMS (without CSF B cell expansion) using a comprehensive panel of cell surface adhesion, activation and maturation markers by flow cytometry, and referenced to 18 paediatric controls. Drug metabolites, lymphocyte counts and liver function tests were used clinically to monitoring therapeutic range and toxicity. In CSF, adjunctive oral 6-MP was associated with a 21% increase in the low percentage of CD4+ T cells in OMS, restoring the CD4/CD8 ratio. The percentage of CD4+ T cells that were interferon (IFN)-γ+ was reduced by 66%, shifting the cytokine balance away from T helper type 1 (Th1) (proinflammatory) predominance. The percentage of natural killer (NK) cells decreased significantly in CSF (–32%) and blood (–67 to −82%). Low blood absolute lymphocyte count was more predictive of improvement in CSF lymphocyte proportions (correlated with % CD4+ T cells) than the 6-thioguanine level (no correlation). 6-MP was difficult to titrate: 50% achieved the target absolute lymphocyte count (< 1·5 K/mm); 20%, the ‘therapeutic’ 6-thioguanine level; and 40% the non-toxic 6-methylmercaptopurine level. Side effects and transaminase elevation were mild and reversible. Clinical steroid-sparing properties and lowered relapse frequency were demonstrated. 6-MP displayed unique pharmacodynamic properties that may be useful in OMS and other autoimmune disorders. Its steroid sparer capacity is limited to children in whom the therapeutic window can be reached without limiting pharmacokinetic factors or side effects.
Clinical features and mutation spectrum in Chinese patients with CADASIL: A multicenter retrospective study
Authors: Chen Sheng , Ni Wang , Yin Xin‐Zhen , Liu Han‐Qiu , Lu Cong , Zheng Qiao‐Juan , Zhao Gui‐Xian , Xu Yong‐Feng , Wu Lei , Zhang Liang , Wang Ning , Li Hong‐Fu , Wu Zhi‐Ying
Published: July 2017

Aim

To characterize clinical features and mutation spectrum in Chinese patients with CADASIL.

Methods

We collected 261 clinically suspected Chinese CADASIL patients from three hospitals located in different regions of China. Sanger sequencing is performed to screen the exons 2 to 24 of NOTCH3 gene. Clinical and genetic data were retrospectively studied. Haplotype analyses were performed in patients carrying p.Arg544Cys and p.Arg607Cys, respectively.

Results

A total of 214 patients were finally genetically diagnosed as CADASIL, with 45 known NOTCH3 mutations and a novel c.1817G>T mutation. We found that patients carrying p.Arg607Cys or p.Arg544Cys mutation located in exon 11 occupied nearly 35% in our mutation spectrum. In retrospectively study of clinical data, we found a higher number of patients having cognitive impairment and a lower number of patients having migraine with aura. Furthermore, we identified that patients carrying mutations in exon 11 seemed to experience a later disease onset (p=6.8×10−5). Additionally, a common haplotype was found in patients from eastern China carrying p.Arg607Cys, and the patients from Fujian carrying p.Arg544Cys shared the same haplotype with patients from Taiwan carrying p.Arg544Cys.

Conclusions

These findings broaden the mutational and clinical spectrum of CADASIL and provide additional evidences for the existence of founder effect in CADASIL patients.
Association between thyroid dysfunction and dysglycaemia: a prospective cohort study
Authors: Chang C.‐H. , Yeh Y.‐C. , Shih S.‐R. , Lin J.‐W. , Chuang L.‐M. , Caffrey J. L. , Tu Y.‐K.
Published: July 2017

Aims

To compare the incidence of hyperglycaemia among participants with low, elevated and normal serum thyroid‐stimulating hormone concentration, as well as the incidence of abnormal thyroid function test results among participants with normal blood glucose and those with hyperglycaemia.

Methods

In a prospective study, a cohort of 72 003 participants with normal, low and elevated serum thyroid‐stimulating hormone concentration were followed from the study beginning to the first report of diabetes and prediabetes. A proportional hazards regression model was used to calculate the hazard ratios and 95% CIs for each outcome, adjusting for age, sex, education level, smoking, alcohol consumption and obesity. Analyses for the association between dysglycaemia and incident abnormal thyroid function test were also conducted.

Results

During a median 2.6 year follow‐up, the incident rates for dysglycaemia, particularly prediabetes, were substantially higher in participants with elevated thyroid‐stimulating hormone concentrations at baseline, while the rates for participants with normal and low thyroid‐stimulating hormone were similar. After controlling for risk factors, participants with elevated thyroid‐stimulating hormone retained a 15% increase in risk of prediabetes (adjusted hazard ratio 1.15, 95% CI 1.04–1.26), but were not at greater risk of diabetes (adjusted hazard ratio 0.96, 95% CI 0.64–1.44). By contrast, participants with normal and low thyroid‐stimulating hormone concentrations had similar dysglycaemia risks. Participants with diabetes and prediabetes were not at greater risks of developing abnormal thyroid function test results when compared with participants with euglycaemia.

Conclusions

People with elevated serum thyroid‐stimulating hormone concentration are at greater risk of developing prediabetes. Whether this includes a greater risk of developing frank diabetes may require an extended period of follow‐up to clarify.
Fracture of the medial intercondylar eminence of the tibia in horses treated by arthroscopic fragment removal (21 horses)
Authors: Rubio‐Martínez L. M. , Redding W. R. , Bladon B. , Wilderjans H. , Payne R. J. , Tessier C. , Geffroy O. , Parker R. , Bell C. , Collingwood F. A.
Published: July 2017

Background

Fractures of the medial intercondylar eminence of the tibia (MICET) are scarcely reported in horses.

Objectives

To report the clinical and diagnostic findings, surgical treatment and outcome in a series of horses presented withMICETfracture and treated with arthroscopic fragment removal.

Study design

Multicentre retrospective case series.

Methods

Case records of horses diagnosed withMICETfractures that had undergone surgical treatment were reviewed. Follow‐up information was obtained from re‐examination visits and/or owners.

Results

Twenty‐one cases were identified at 9 equine hospitals between 2004 and 2016. A history of trauma and acute onset of lameness was reported in 12 horses. All cases underwent fracture removal via arthroscopy of the medial femorotibial joint. The cranial cruciate ligament was intact in 6 horses and damaged in 15 horses (damage was ≤25% [n = 9], 25–50% [n = 4] or ≥50% [n = 2] of the cross‐sectional area). The cranial ligament of the medial meniscus was damaged in 11 horses (≤25% [n = 8], 25–50% [n = 3]). The medial meniscus was damaged in 5 horses and articular cartilage damage was identified in 14 horses (mild [n = 8], moderate [n = 6]). Follow‐up information (median 14 months; 4 months–6 years) was available for 20 cases; 2 horses were sound but convalescing; 13 horses were sound and returned to their previous or expected use. Of the 4 horses with the most severe changes to the articular soft tissue structures, 2 remained lame and 2 were subjected to euthanasia because of persistent lameness.

Main limitations

The retrospective, multicentre nature of this study and the limited number of horses are the main limitations.

Conclusions

Fractures of theMICETare commonly associated with a traumatic event. Prompt diagnosis and early arthroscopic removal of the fracture are recommended.
Associations between antibody to hepatitis B core antigen positivity and outcomes in hepatocellular carcinoma patients undergoing hepatic resection
Authors: Itoh Shinji , Yoshizumi Tomoharu , Tomino Takahiro , Nagatsu Akihisa , Motomura Takashi , Harada Noboru , Harimoto Norifumi , Ikegami Toru , Soejima Yuji , Maehara Yoshihiko
Published: July 2017

Aim

We aimed to evaluate the effect of antibody to hepatitis B core antigen (HBcAb) positivity on clinical outcomes after hepatic resection in hepatocellular carcinoma (HCC) patients with negative hepatitis B surface antigen (HBsAg) and hepatitis C virus antibody (HCVAb), termed non‐B, non‐C HCC (NBNC‐HCC), or with HCV‐related HCC.

Methods

Two hundred and sixty‐three patients who underwent hepatic resection for HCC and measurements of HBsAg, HCVAb, and HBcAb were enrolled in this study.

Results

The percentages of HBcAb positivity were 52.3% (n = 57) and 56.9% (n = 66) in patients with NBNC‐ and HCV‐related HCC, respectively. The proportion of multiple NBNC‐HCCs was significantly greater in patients with HBcAb positivity compared to HBcAb negativity (P = 0.028). There were no significant differences in the recurrence‐free and overall survival rates between NBNC‐HCC patients with HBcAb positivity versus negativity (P = 0.461 and P = 0.190, respectively). Furthermore, for HCV‐related HCC patients, there were no significant differences in the baseline factors between patients with positive versus negative HBcAb. The proportion of patients with HBcAb‐positive HCV‐related HCC who underwent anatomical resection of the liver was significantly greater than that of HBcAb‐negative patients, whereas the recurrence‐free and overall survival rates were not significantly different (P = 0.158 and P = 0.191, respectively).

Conclusion

In our study, the presence of HBcAb had no impact on surgical outcomes after hepatic resection in patients with NBNB‐ and HCV‐related HCC. Occult HBV infection might be associated with hepatocarcinogenesis in patients with NBNC‐related HCC.
Prognostic significance of a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis in primary myelofibrosis patients
Authors: Gianelli Umberto , Fiori Stefano , Cattaneo Daniele , Bossi Anna , Cortinovis Ivan , Bonometti Arturo , Ercoli Giulia , Bucelli Cristina , Orofino Nicola , Bulfamante Gaetano , Iurlo Alessandra
Published: July 2017

Aims

To evaluate whether a comprehensive histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis in bone marrow trephine biopsies (BMBs) of primary myelofibrosis (PMF) patients may have prognostic implications.

Methods and results

Reticulin fibrosis, collagen deposition and osteosclerosis were graded from 0 to 3 in a series of 122 baseline BMBs. Then, we assigned to each case a comprehensive score [reticulin, collagen, osteosclerosis (RCO) score, ranging from 0 to 9] that allowed us to distinguish two groups of patients, with low‐grade (RCO score 0–4) and high‐grade (RCO score 5–9) stromal changes. Of 122 patients, 88 displayed a low‐grade and 34 a high‐grade RCO score. The latter was associated more frequently with anaemia, thrombocytopenia, peripheral blood blasts and increased lactate dehydrogenase levels. The RCO score was correlated strictly with overall mortality (P = 0.013) and International Prognostic Scoring System (IPSS) risk categories, and was able to discriminate the overall survival of both low‐ and high‐grade patients (log‐rank test: P < 0.001). Moreover, it proved to be more accurate than the European Consensus on Grading of Bone Marrow Fibrosis (ECGMF grade) in identifying high‐risk patients with poor prognosis. Finally, a combined analysis of RCO scores and IPSS risk categories in an integrated clinical–pathological evaluation was able to increase the positive predictive value (PPV) for mortality in high‐risk patients.

Conclusion

The comprehensive RCO score, obtained by histological evaluation of reticulin fibrosis, collagen deposition and osteosclerosis was prognostically significant and more accurate than ECGMF grade in identifying high‐risk patients and improved PPV when applied in addition to IPSS.
Silver‐doped 58S bioactive glass as an anti‐Leishmania agent
Authors: Pires Emanuene Galdino , Bonan Roberta Ferreti , Rocha Ítalo Martins , Gonçalves Ingrid Morgana Fernandes , de Souza Joelma Rodrigues , Gonzales Laura Helena Vega , Silva Júnior José Valter Joaquim , Perez Danyel Elias da Cruz , Tavares Paula Cristina Brígido , Silva Sydnei Magno da , Alves‐Balvedi Renata Pereira , Goulart Luiz Ricardo , de Medeiros Eliton Souto , Castellano Lucio Roberto , Bonan Paulo Rogério Ferreti
Published: July 2017

Bioactive glasses (BG) incorporating antimicrobial agents can be effectively used against microorganisms. In this work, the in vitro effectiveness of silver‐doped 58S BG (BGAg) against Leishmania species was studied. BG, BGAg1, and BGAg2 belonging to the system 58SiO2∙(36‐x) CaO·6P2O5·xAg2O, where x=0, 1, and 2 mol.% Ag, were synthesized via sol‐gel, and characterized by scanning electron (SEM) and atomic force (AFM) microscopy, thermogravimetric analyses (TGA), X‐ray diffraction (XRD), Fourier‐transform infrared (FTIR), and surface‐enhanced Raman (Raman‐SERS) spectroscopy. Cytotoxicity was assessed in A549 lung adenocarcinoma cells. Leishmania amazonensis and Leishmania braziliensis cultures were exposed to all groups, and C57BL/6 macrophages were infected by over metacyclic form L. amazonensis under the exposure of BGAg particles. SEM and AFM images showed an irregular and network arranged surface. TGA, XRD, FTIR, and RAMAN‐SERS analyses confirmed silver inclusion within BG. None of the BG and BGAg presented toxicity. BGAg2 was effective in controlling promastigote forms under 150 and 300 μg/mL concentrations of both evaluated species. On macrophage invasion assay, BGAg2 presented reduction in metacyclic forms. For 72 hours, BGAg1 (150 μg/mL), BGAg1 (300 μg/mL), and BGAg2 in all concentrations were effective against intracellular infection. BGAg could be used as an alternative or complimentary agent to current chemotherapy.
Defect‐driven evolution of piezoelectric and ferroelectric properties in CuSb2O6‐doped K0.5Na0.5NbO3 lead‐free ceramics
Authors: Wang Tao , He Lihua , Deng Yunlong , Zheng Qiaoji , Xie Fengyu , Xu Chenggang , Lin Dunmin
Published: July 2017

Defect greatly affects the microscopic structure and electrical properties of perovskite piezoelectric ceramics, but the microscopic mechanism of defect‐driven macroscopic properties in the materials is not still completely comprehended. In this work, K0.5Na0.5NbO3+x mol CuSb2O6 lead‐free piezoelectric ceramics were fabricated by a solid‐state reaction method and the defect‐driven evolution of piezoelectric and ferroelectric properties was studied. The addition of CuSb2O6 induces the formation of dimeric (DC1) and trimeric (DC2) defect dipoles. At low doping concentration of CuSb2O6 (0.5‐1.0 mol%), DC1 and DC2 coexist in the ceramics and harden the ceramics, inducing a constricted double P‐E loop and high Qm of 895 at x=0.01. However, DC2 becomes more dominant in the ceramics with high concentration of CuSb2O6 (≥1.5 mol%) and thus leads to softening behavior of piezoelectricity and ferroelectricity as compared to the ceramic with x=0.01, giving a single slanted P‐E loop and relatively low Qm of 206 at x=0.025. All ceramics exhibit relatively high d33 of 106‐126 pC/N. Our study shows that the piezoelectricity and ferroelectricity of K0.5Na0.5NbO3 ceramics can be tailored by controlling defect structure of the materials.
Quality attributes of bread fortified with staghorn sumac extract
Authors: Wang Sunan , Zhu Fan
Published: July 2017

Staghorn sumac (Rhus typhina) is rich in polyphenols and may be used as an innovative ingredient in maintaining and enhancing food quality. In this report, aqueous extracts of sumac fruit powder were added up to 10% in wheat bread formulation. The extract concentration‐dependently delayed the mold growth (up to 5 log reduction in 7‐day storage) and the staling of bread. Adding sumac extracts dose‐dependently increased the total phenolic and anthocyanin contents of the breads. Minimal changes were observed in loaf volume, water activity, moisture content, texture (cohesiveness, springiness, and adhesive), and aroma of breads containing extracts of less than 4%. Overall, sumac addition altered several quality attributes of bread, including hardness, color, and sensory acceptance in appearance, flavor, and texture. Sumac holds potential as a natural preservative and an antistaling agent in bread formulation.

Practical applications

The rising healthy food market demands bakery products fortified with novel functional ingredients. Staghorn sumac is an emerging healthy food ingredient that has attracted much research attention recently. This study provides a scientific basis to develop bread fortified with sumac‐derived functional ingredients. The results pointed out the feasibility of making sumac‐fortified breads with enhanced phenolic content, increased shelf life, and acceptable sensory profile.
Can quantitative hepatitis B surface antigen levels predict the severity of liver disease in genotype E Patients?
Authors: Chakrabarty Gayatri , Bruce Matthew , Horner Mary , Wang Bo , Agarwal Kosh , Carey Ivana
Published: July 2017

The utility of quantitative Hepatitis B surface antigen (qHBsAg) level as a marker of chronic hepatitis B (CHB)‐related liver damage is not fully delineated, but is becoming increasingly relevant. Quantitative HBsAg levels are linked with progression of liver disease in HBeAg‐negative genotype B and C patients, but it is not clear whether this is consistent across all HBV genotypes. In this single‐centre, cross‐sectional observational study, we evaluated whether qHBsAg levels can predict the severity of liver disease in genotype E patients. Demographic characteristics, viral, biochemical markers and qHBsAg levels were assessed at time of liver biopsy [all HBV DNA>2000 IU/mL and/or abnormal alanine transaminase (ALT)]. Patients were divided into three groups according to the severity of fibrosis on biopsy: mild (F0‐1), moderate (F2‐4), severe (F5‐6) liver disease and into two groups according to the NI grading, low (NI 0‐3) and high inflammation (NI ≥4). A total of 259 HBeAg‐negative CHB treatment‐naive genotype E patients were studied. The median age of this cohort was 38 years, and 61% were males. Advanced (severe) fibrosis patients had higher ALT, HBV DNA, and lower HBsAg level and qHBsAg/DNA ratio. Patients with NI ≥4 had higher ALT, HBV DNA, but lower qHBsAg/DNA ratio. There was no correlation between HBsAg and HBV DNA levels. Quantitative HBsAg levels were lower in more advanced liver fibrosis. There was no correlation between qHBsAg and HBV DNA levels. This may reflect discordance between viral replication and transcriptional activity or differential HBsAg expression in HBeAg‐negative genotype E patients with advanced liver disease.
An Arabidopsis kinase cascade influences auxin‐responsive cell expansion
Authors: Enders Tara A. , Frick Elizabeth M. , Strader Lucia C.
Published: July 2017

Mitogen‐activated protein kinase (MPK) cascades are conserved mechanisms of signal transduction across eukaryotes. Despite the importance of MPK proteins in signaling events, specific roles for many Arabidopsis MPK proteins remain unknown. Multiple studies have suggested roles for MPK signaling in a variety of auxin‐related processes. To identify MPK proteins with roles in auxin response, we screened mpk insertional alleles and identified mpk1‐1 as a mutant that displays hypersensitivity in auxin‐responsive cell expansion assays. Further, mutants defective in the upstream MAP kinase kinase MKK3 also display hypersensitivity in auxin‐responsive cell expansion assays, suggesting that this MPK cascade affects auxin‐influenced cell expansion. We found that MPK1 interacts with and phosphorylates ROP BINDING PROTEIN KINASE 1 (RBK1), a protein kinase that interacts with members of the Rho‐like GTPases from Plants (ROP) small GTPase family. Similar to mpk1‐1 and mkk3‐1 mutants, rbk1 insertional mutants display auxin hypersensitivity, consistent with a possible role for RBK1 downstream of MPK1 in influencing auxin‐responsive cell expansion. We found that RBK1 directly phosphorylates ROP4 and ROP6, supporting the possibility that RBK1 effects on auxin‐responsive cell expansion are mediated through phosphorylation‐dependent modulation of ROP activity. Our data suggest a MKK3 • MPK1 • RBK1 phosphorylation cascade that may provide a dynamic module for altering cell expansion.
Giant convecting mud balls of the early solar system
Authors: Bland Philip A. , Travis Bryan J.
Published: July 2017

Primitive meteorites may have come from objects that were once an unconsolidated mixture of mud and clasts.
Physiological Evidence for Isopotential Tunneling in the Electron Transport Chain of Methane-Producing Archaea
Authors: Duszenko Nikolas , Buan Nicole R.
Published: July 2017

Many, but not all, organisms use quinones to conserve energy in their electron transport chains. Fermentative bacteria and methane-producing archaea (methanogens) do not produce quinones but have devised other ways to generate ATP. Methanophenazine (MPh) is a unique membrane electron carrier found inMethanosarcinaspecies that plays the same role as quinones in the electron transport chain. To extend the analogy between quinones and MPh, we compared the MPh pool sizes between two well-studiedMethanosarcinaspecies,Methanosarcina acetivoransC2A andMethanosarcina barkeriFusaro, to the quinone pool size in the bacteriumEscherichia coli. We found the quantity of MPh per cell increases as cultures transition from exponential growth to stationary phase, and absolute quantities of MPh were 3-fold higher inM. acetivoransthan inM. barkeri. The concentration of MPh suggests the cell membrane ofM. acetivorans, but not ofM. barkeri, is electrically quantized as if it were a single conductive metal sheet and near optimal for rate of electron transport. Similarly, stationary (but not exponentially growing)E. colicells also have electrically quantized membranes on the basis of quinone content. Consistent with our hypothesis, we demonstrated that the exogenous addition of phenazine increases the growth rate ofM. barkerithree times that ofM. acetivorans. Our work suggests electron flux through MPh is naturally higher inM. acetivoransthan inM. barkeriand that hydrogen cycling is less efficient at conserving energy than scalar proton translocation using MPh.

IMPORTANCECan we grow more from less? The ability to optimize and manipulate metabolic efficiency in cells is the difference between commercially viable and nonviable renewable technologies. Much can be learned from methane-producing archaea (methanogens) which evolved a successful metabolic lifestyle under extreme thermodynamic constraints. Methanogens use highly efficient electron transport systems and supramolecular complexes to optimize electron and carbon flow to control biomass synthesis and the production of methane. Worldwide, methanogens are used to generate renewable methane for heat, electricity, and transportation. Our observations suggestMethanosarcina acetivorans, but notMethanosarcina barkeri, has electrically quantized membranes.Escherichia coli, a model facultative anaerobe, has optimal electron transport at the stationary phase but not during exponential growth. This study also suggests the metabolic efficiency of bacteria and archaea can be improved using exogenously supplied lipophilic electron carriers. The enhancement of methanogen electron transport through methanophenazine has the potential to increase renewable methane production at an industrial scale.
Novel Alphacoronaviruses and Paramyxoviruses Cocirculate with Type 1 and Severe Acute Respiratory System (SARS)-Related Betacoronaviruses in Synanthropic Bats of Luxembourg
Authors: Pauly Maude , Pir Jacques B. , Loesch Catherine , Sausy Aurélie , Snoeck Chantal J. , Hübschen Judith M. , Muller Claude P.
Published: July 2017

Several infectious disease outbreaks with high mortality in humans have been attributed to viruses that are thought to have evolved from bat viruses. In this study from Luxembourg, the genetic diversity and epidemiology of paramyxoviruses and coronaviruses shed by the bat species
Rhinolophus ferrumequinum
and
Myotis emarginatus
were evaluated. Feces collection (
n
= 624) was performed longitudinally in a mixed-species colony in 2015 and 2016. In addition, feces (
n
= 254) were collected cross-sectionally from six
Myotis emarginatus
colonies in 2016. By use of degenerate primers in a nested format, overall prevalences of 1.1% (10/878) and 4.9% (43/878) were determined for paramyxoviruses and coronaviruses. Sequences of the partial RNA-dependent RNA polymerase and spike glycoprotein genes of coronaviruses, as well as sequences of the partial L gene of paramyxoviruses, were obtained. Novel paramyxovirus and
Alphacoronavirus
strains were identified in different
Myotis emarginatus
colonies, and severe acute respiratory syndrome (SARS)-related
Betacoronavirus
strains were shed by
Rhinolophus ferrumequinum
. Logistic regression revealed that the level of
Alphacoronavirus
shedding was highest in July (odds ratio, 2.8;
P
< 0.01), probably due to periparturient stress. Phylogenetic analyses point to close virus-host coevolution, and the high genetic similarity of the study strains suggests that the
Myotis emarginatus
colonies in Luxembourg are socially connected. Most interestingly, we show that bats also host
Betacoronavirus
1
strains. The high similarity of the spike gene sequences of these viruses with mammalian
Betacoronavirus 1
strains may be of concern. Both the SARS-related and
Betacoronavirus 1
strains detected in bats in Luxembourg may cross the species barrier after a host adaptation process.

IMPORTANCE
Bats are a natural reservoir of a number of zoonotic pathogens. Several severe outbreaks in humans (e.g., a Nipah virus outbreak in Malaysia in 1998, and the almost global spread of severe acute respiratory syndrome in 2003) have been caused by bat-borne viruses that were transmitted to humans mostly after virus adaptation (e.g., in intermediate animal hosts). Despite the indigenousness of bat species that host viruses with suspected zoonotic potential and despite the zoonotic transmission of European bat 1 lyssavirus in Luxembourg, knowledge about the diversity and epidemiology of bat viruses remains limited in this country. Moreover, in contrast to other European countries, bat viruses are currently not included in the national surveillance activities of this land-locked country. We suggest that this gap in disease surveillance should be addressed, since we show here that synanthropic bats host viruses that may be able to cross the species barrier.