bluuebunny/crossref_metadata_2025 huggingface dataset:
Whose story is it? Mental health consumer and carer views on carer participation in research
Authors: Morse Alyssa R. , Forbes Owen , Jones Bethany A. , Gulliver Amelia , Banfield Michelle
Published: August 2019

Background

Mental health carers contribute a unique set of perspectives and lived experiences to research; however, national research ethics guidelines do not specifically address the issues that affect informal carers as participants.

Objective

This study sought to explore Australian mental health consumer and carer views on the ethical conduct of research involving mental health carers.

Design

A public forum (n = 14; consumer = 5, carer = 9) and a subsequent series of interviews (n = 10; consumer = 5, carer = 4, both = 1) were conducted to investigate consumer and carer views on mental health research ethics. Data collection and analysis drew strongly on methodological features of grounded theory.

Results

Conducting research involving carers and consumer‐carer relationships raises potential concerns related to story ownership. Lived experience stories have shared and separate elements; thus, it is important to consider potential risks to the privacy of non‐participants and of social harm to participants' relationships when conducting research in this space. These risks could be minimized and managed through communication between researchers and participants, and within relationships.

Conclusions

When conducting research involving carers and consumer‐carer relationships, researchers may need to facilitate the negotiation of information‐sharing boundaries within relationships and the safe and confidential telling of shared stories.
Cosmetic benefits of a novel biomimetic lamellar formulation containing niacinamide in healthy females with oily, blemish‐prone skin in a randomized proof‐of‐concept study
Authors: Santos-Caetano J.-P. , Gfeller C. F. , Mahalingam H. , Thompson M. , Moore D. J. , Vila R. , Doi R. , Cargill M. R.
Published: August 2019

Objective

A randomized study was designed to evaluate the potential cosmetic benefit of a biomimetic, niacinamide‐containing moisturizing cream in oily, blemish‐prone skin.

Methods

Healthy adult women with oily, blemish‐prone skin were randomized to one of three treatment groups: test, control, or positive control. In the test group, subjects used the test product (containing 4% niacinamide), plus the standard cleanser (Simple® Kind to Skin Moisturizing Facial Wash). In the control group, subjects received no moisturizer but used the standard cleanser. In the positive control group, subjects used Vivatinell Acnecinamide® Gel Cream (containing 4% niacinamide) as a moisturizer and Neutrogena Visibly Clear® Spot Clearing Facial Wash (containing 2% salicylic acid) as a cleanser. The positive control regimen was included to provide a comparison for estimates of effect size. The primary objective was to evaluate skin moisturization as a change from baseline in corneometer values at 8 h for the test regimen vs. the control regimen. Analysis of covariance was applied for the primary efficacy analysis.

Results

A total of 132 subjects were randomized with 44 included in each treatment group. A significant difference was observed in the primary endpoint for the test regimen compared with the control regimen (least‐squares mean difference [95% CI]: 3.12 [0.68, 5.56], P = 0.0128). A trend was observed in favour of the positive control regimen compared with the control regimen. Secondary measurements of moisturization supported the primary efficacy outcome. Assessment of blemishes showed a significant difference between the test regimen vs. the control regimen for change from baseline in mean total blemish count at Week 8 (least‐squares mean difference [95% CI]: −1.80 [−3.41, −0.19], P = 0.0290). No statistical comparisons between the positive control group and the test group were performed.

Conclusion

This study provides proof‐of‐concept evidence that a novel lamellar lipid moisturizer containing niacinamide, in combination with a standard cleanser, can help moisturize the skin and provide an overall improvement in the complexion appearance of people with blemish‐prone skin. Study registration: NCT03093181.
Nomenclature proposal for the sonographic description and reporting of soft tissue fillers
Authors: Schelke Leonie W. , Cassuto Daniel , Velthuis Peter , Wortsman Ximena
Published: August 2019

Background

There is a steady increase in publications about the use of ultrasound and filler treatments, written by physicians from different specialties. The terminology used to describe the ultrasound images of fillers is not uniform, making the different articles difficult to compare. Standardization of the descriptions based on their basic sonographic parameters is recommendable.

Aims

The purpose of this study is to propose a nomenclature for the sonographic description and reporting of cosmetic fillers.

Methods

An assessment of articles indexed for MEDLINE/PubMed and Embed electronic database was conducted; in total of 39 articles could be included.

Results

All articles were investigated for their sonographic descriptions of soft tissue fillers. Ten parameters used for describing and monitoring soft tissue fillers were distinguished.

Conclusion

The proposed sonographic descriptions for cosmetic fillers may contribute to a better standardization and understanding fillers ultrasound images in the reports or literature.
F127 poloxamer effect on cytotoxicity induction of tumour cell cultures treated with doxorubicin
Authors: Gentile Emiliano Alberto , Castronuovo Cynthia Cecilia , Cuestas María Luján , Gómez Natalia , Davio Carlos , Oubiña José Raúl , Mathet Verónica Lidia
Published: August 2019

Introduction

Hepatocellular carcinoma is the most common liver malignancy and the third leading cause of cancer death worldwide. One crucial limitation in the pharmacotherapy for this tumour is its chemotherapy-resistant nature produced by the overexpression of several members of the ATP-binding cassette protein family that efflux drugs out of cells, as observed with the breast cancer resistant protein (BCRP).

Objectives

This study aimed to assess the ability of Pluronic® F127 to reverse the multidrug resistance phenotype in two human hepatocellular cell lines.

Methods

PLC/PRF/5 and SKHep1 cells were exposed to Pluronic® F127 at several concentrations. The effect of F127 on BCRP expression (mRNA and protein), mitochondrial transmembrane potential and cell hypodiploidy was assessed. Finally, the effect of this copolymer on cytotoxicity of doxorubicin in both hepatoma cell lines was investigated, as expressed by its reverse resistance index.

Key findings

It was demonstrated that F127 in both cell lines contributes to chemosensitization, as shown by BCRP down-regulation, an altered mitochondrial transmembrane potential and hypodiploidy and reverse resistance index values. A remarkable dependence of these effects significantly correlated with the copolymer concentration.

Conclusions

These findings further uncover the potential usefulness of this copolymer as multidrug resistance reversal agent, increasing the efficacy of cancer therapies.
The effect of induction with propofol or ketamine and diazepam on quality of anaesthetic recovery in dogs
Authors: Reed R. A. , Quandt J. E. , Brainard B. M. , Copeland J. E. , Hofmeister E. H.
Published: August 2019

Objective

To evaluate the quality of recovery in dogs undergoing elective orthopaedic surgery induced with either propofol or a combination of ketamine and diazepam.

Materials and Methods

Sixty client‐owned dogs undergoing single‐limb elective orthopaedic procedures were enrolled. Dogs were randomly assigned to receive induction with propofol (4 mg/kg) (group P) or ketamine (5 mg/kg) with diazepam (0.25 mg/kg) (group KD) to which all scorers were blinded. The recovery monitoring period lasted for 1 hour following extubation. The recovery period was video‐recorded for blinded scoring at a later time. Scoring for quality of recovery was carried out using three different systems (lower numbers=better quality): a simple descriptive scale (1 to 5), a visual analogue scale (0 to 10 cm) and a numeric rating scale (0 to 10). Videos were reviewed by three ACVAA board‐certified anaesthesiologist raters.

Results

Five dogs were deemed to be ineligible. The mean (±SD) duration of anaesthesia was 260.4 ±57.84 minutes in group KD and 261.1 ±51.83 minutes in group P. There was no difference between groups for time to extubation, head lift or sternal recumbency. The number of dogs having a recovery that was scored overall as bad (mean simple descriptive scale > 4, mean visual analogue scale or numeric rating scale > 5) was not different between groups. Dogs in group KD had significantly lower scores than group P dogs (simple descriptive scale P=0.01, numeric rating scale P=0.03, visual analogue scale P=0.03).

Clinical Significance

Induction with ketamine and diazepam resulted in a smoother recovery from anaesthesia than induction with propofol.
Surface markers: An identity card of endothelial cells
Authors: Ribatti Domenico , Tamma Roberto , Ruggieri Simona , Annese Tiziana , Crivellato Enrico
Published: August 2019

All endothelial cells have the common characteristic that they line the vessels of the blood circulatory system. However, endothelial cells display a large degree of heterogeneity in the function of their location in the vascular tree. In this article, we have summarized the expression patterns of a number of well‐accepted endothelial surface markers present in normal microvascular endothelial cells, arterial and venous endothelial cells, lymphatic endothelial cells, tumor endothelial cells, and endothelial precursor cells.
Disruption of the OLE ribonucleoprotein complex causes magnesium toxicity in Bacillus halodurans
Authors: Harris Kimberly A. , Odzer Nicole B. , Breaker Ronald R.
Published: August 2019

OLE RNAs represent an unusual class of bacterial noncoding RNAs common in Gram‐positive anaerobes. The OLE RNA of the alkaliphile Bacillus halodurans is highly expressed and naturally interacts with at least two RNA‐binding proteins called OapA and OapB. The phenotypes of the corresponding knockouts include growth inhibition when exposed to ethanol or other short‐chain alcohols or when incubated at modestly reduced temperatures (e.g. 20°C). Intriguingly, the OapA ‘PM1’ mutant, which carries two amino acid changes to a highly conserved region, yields a dominant‐negative phenotype that causes more severe growth defects under these same stress conditions. Herein, we report that the PM1 strain also exhibits extreme sensitivity to elevated Mg2+ concentrations, beginning as low as 2 mM. Suppressor mutants predominantly map to genes for aconitate hydratase and isocitrate dehydrogenase, which are expected to alter cellular citrate concentrations. Citrate reduces the severity of the Mg2+ toxicity phenotype, but neither the genomic mutations nor the addition of citrate to the medium overcomes ethanol toxicity or temperature sensitivity. These findings reveal that OLE RNA and its protein partners are involved in biochemical responses under several stress conditions, wherein the unusual sensitivity to Mg2+ can be independently suppressed by specific genomic mutations.
Factors influencing employees' eating behaviours in the office‐based workplace: A systematic review
Authors: Clohessy Sophie , Walasek Lukasz , Meyer Caroline
Published: August 2019

Employees spend a large proportion of their time at work and typically consume a third of their total calories during the working day. Research suggests that the workplace environment can affect employees' eating behaviours, leading to various related health consequences. This systematic review aimed to identify and synthesize the evidence surrounding factors influencing eating behaviours within an office‐based workforce. The literature search was restricted to studies published in English between January 2008 and April 2018. A total of 5,017 articles were screened and assessed for eligibility, of which 22 articles (n=23 studies) were included in the review. All included studies were subjected to quality assessment and were summarized into groups (themes) of “factors” affecting any aspect of eating behaviour at work. The findings revealed a number of factors influencing eating behaviours at work relating to the job role, workplace food environment, and social aspects of the office‐based workplace. Most of the existing research implies the office‐based workplace has a negative influence on eating behaviours. The findings of this review provide an evidence based, comprehensive summary of the possible determinants of eating behaviours in the workplace, which may help researchers to identify factors that are potential targets for intervention.
‘Pissed Off and Confused’/‘Grateful and (Re)Moved’: Affect, Privilege and National Commemoration in Aotearoa New Zealand
Authors: McConville Alex , Wetherell Margaret , McCreanor Tim , Borell Belinda , Moewaka Barnes Helen
Published: August 2019

This article explores affect, colonial privilege, and the cultural politics of national commemoration in Aotearoa New Zealand. Based on focus‐group interviews around two major national days, we examine means through which feelings and emotions are deployed in ways that enable the reproduction of social advantage. Situating affect within patterns of relationship, four interrelated affective‐discursive practices are explored. In relation to Waitangi Day, agents tend to work under the rubric of anger and confusion. For Anzac Day, being grateful and moved shapes the interaction, although participants often indicate preferences towards “having a day off.” Given the colonial context in which these practices circulate, analysis observes the associated freedom and ease by which affective‐discursive privilege is (re)produced. Often incongruent and rarely challenged, privilege allows associated actors to do what they want, when they want, however they want. This affective climate authorizes the ongoing reproduction of, and justification for, membership to a higher‐status ethnic group of which unearned opportunities and entitlements remain its everyday, expected currency.
Current approaches to increase blood donations in resource‐limited countries
Authors: Allain J.‐P.
Published: August 2019

Background

Low‐ and middle‐income countries (LMIC) suffer from chronic or seasonal blood shortage. The first review was published in 2007.

Methods

The review of literature since 2005 presented here uncovered a fairly large number of articles justifying the grouping of blood donation issues into five geographical areas sharing common background. These are Sub‐Saharan Africa (SSA), Muslim countries, India, China/South East Asia and Latin America/Caribbean islands (LA&C).

Results

SSA countries start collecting at 16–18 years of age in schools where female donors can be reached better than in other settings. Community‐oriented culture favours family donors who need, similar to volunteer non‐remunerated donors (VNRD), to be actively induced to repeat donation. Muslim countries share the contradiction of religion encouraging blood donation but restrain women from donating. The active involvement of religious leaders and the progressive easing of female participation are the keys to increasing blood donation. In India, ‘social duty’ is a major inducement to blood donation but also benefits and rewards. Ways of involving female donors by reducing the donation age to 16 years and providing donor education in schools need to be considered. In China and East Asia, the option of small‐volume donation impairs blood collection without being justified by scientific evidence but is a concession to culture. Reducing the donation age would also help the supply. In LA&C, the concept of ‘social capital’ was developed as a complement or alternative to the theory of planned behaviour.

Conclusions

Strategies to improve blood donation and repeat donation should be innovative and adapted to local or regional culture and environment.
First-Line Antibiotic Selection in Outpatient Settings
Authors: Palms Danielle L. , Hicks Lauri A. , Bartoces Monina , Hersh Adam L. , Zetts Rachel , Hyun David Y. , Fleming-Dutra Katherine E.
Published: August 2019

Using the 2014 IBM MarketScan commercial database, we compared antibiotic selection for pharyngitis, sinusitis, and acute otitis media in retail clinics, emergency departments, urgent care centers, and offices. Only 50% of visits for these conditions received recommended first-line antibiotics. Improving antibiotic selection for common outpatient conditions is an important stewardship target.
Modulating Pathogenesis with Mobile-CRISPRi
Authors: Qu Jiuxin , Prasad Neha K. , Yu Michelle A. , Chen Shuyan , Lyden Amy , Herrera Nadia , Silvis Melanie R. , Crawford Emily , Looney Mark R. , Peters Jason M. , Rosenberg Oren S.
Published: August 2019

Antibiotic resistance is a growing threat to global health. To optimize the use of our existing antibiotics and identify new targets for future inhibitors, understanding the fundamental drivers of bacterial growth in the context of the host immune response is paramount. Historically, these genetic drivers have been difficult to manipulate precisely, as they are requisite for pathogen survival. Here, we provide the first application of Mobile-CRISPRi to study conditionally essential virulence genes in mouse models of lung infection through partial gene perturbation. We envision the use of Mobile-CRISPRi in future pathogenesis models and antibiotic target discovery efforts.
Draft Genome Sequences of Three Clinical Isolates of the Pathogenic Yeast Candida glabrata
Authors: Pais Pedro , Galocha Mónica , Miranda Isabel M. , Rodrigues Acácio G. , Teixeira Miguel C.
Published: August 2019

Here, we report the draft genome sequences of three
Candida glabrata
clinical isolates, 040, 044, and OL152. The isolates were recovered from patients admitted to Centro Hospitalar de S. João (CHSJ) in Porto, Portugal. Isolates 040 and 044 were taken from blood samples, while isolate OL152 was collected from urine.
Using intermittent pulse oximetry to guide neonatal oxygen therapy in a low-resource context
Authors: Walker Patrick James Berkeley , Bakare Ayobami Adebayo , Ayede Adejumoke Idowu , Oluwafemi Rosena Olubanke , Olubosede Omolayo Adebukola , Olafimihan Iyabo Victoria , Tan Kenneth , Duke Trevor , Falade Adegoke Gbadegesin , Graham Hamish
Published: August 2019

Objective

To evaluate the effectiveness of intermittent pulse oximetry in guiding oxygen therapy in neonates in a low-resource setting.

Design and setting

Prospective validation study at three hospitals in southwest Nigeria. We performed concealed continuous pulse oximetry on participants to evaluate intermittent SpO2 monitoring.

Patients

We recruited all preterm or low birthweight neonates, and all term neonates who required oxygen therapy, who were admitted to the neonatal ward(s) of the study hospitals during the study period.

Main outcome measures

Proportion of time preterm/low birthweight neonates on oxygen spent within, above and below the target SpO2 range of 90%–95%; and the proportion of time term neonates and neonates not on oxygen spent within and below the target range of 90%–100%.

Results

Preterm/low birthweight neonates receiving oxygen therapy (group A) spent 15.7% (95% CI 13.3 to 18.9) of time in the target SpO2 range of 90%–95%. They spent 75.0% (63.6–81.1) of time above 95%, and 2.7% (1.7–5.6) of time below 85%. Term neonates and all neonates not receiving oxygen (group B) spent 97.3% (95% CI 96.4 to 98.6) of time within the target range of 90%–100%, and 0.9% (0.3–1.4) of time below 85%. Guidelines recommended SpO2 monitoring 3 times per day for all patients, however neonates in groups A and B were monitored an average of 4.7 and 5.3 times per day, respectively.

Conclusions

To better maintain SpO2 within the target range, preterm/low birthweight neonates on oxygen should have their SpO2 monitored more frequently than the current 4.7 times per day. In all other neonates, however, monitoring SpO2 5.3 times per day appears suitable.
Frequency of urinary tract infection in children with antenatal diagnosis of urinary tract dilatation
Authors: Pennesi Marco , Amoroso Stefano , Bassanese Giulia , Pintaldi Stefano , Giacomini Giulia , Barbi Egidio
Published: August 2019

Background

Neonates with congenital urinary tract dilatation (UTD) may have an increased risk of urinary tract infections (UTI). At present, the management of these patients is controversial and the utility of continuous antibiotic prophylaxis (CAP) remains uncertain as the literature presents contradicting evidence. The aim of this observational study was to assess UTI occurrence in children with prenatal diagnosis of urinary collecting system dilatation without antibiotic prophylaxis.

Methods

Between June 2012 and August 2016, we evaluated the incidence of UTI and the clinical and ultrasonography evolution in 407 children with a prenatally diagnosed UTD. All subjects underwent two prenatal ultrasounds scans (USs) at 20 weeks and 30 weeks of gestation and within 1 month of birth. Patients with a confirmed diagnosis of UTD underwent US follow-up at 6, 12 and 24 months of life. According to the UTD classification system stratify risk, after birth UTD were classified into three groups: UTD-P1 (low risk group), UTD-P2 (intermediate risk group), and UTD-P3 (high risk group). Voiding cystourethrogram was performed in all patients who presented a UTI and in those with UTD-P3. No patient underwent CAP.

Results

Postnatal US confirmed UTD in 278 out of 428 patients with the following rates: UTD-P1 (126), UTD-P2 (95) and UTD-P3 (57). During postnatal follow-up, 6.83% patients presented a UTI (19 out of 278). Eleven out of 19 had vesicoureteral reflux (VUR), and other four were diagnosed with obstructive uropathy and underwent surgical correction. Five patients presented a UTI reinfection.

Conclusion

The occurrence of UTI in patients with urinary collecting system dilatation was low. The recent literature reports an increased selection of multirestistant germs in patients with VUR exposed to CAP. This study constitutes a strong hint that routine continuous antibiotic prophylaxis could be avoided in patients with UTD.
Oxygen saturation thresholds in bronchiolitis: examining admissions
Authors: van Hasselt Tim J , Singham Bhavna , Bassett Eve , Wacogne Ian D ,   Paediatric Research Across the Midlands (PRAM) Network
Published: August 2019

Objective

Examine admissions for bronchiolitis, comparing centres with oxygen saturation thresholds for admission of 90% versus 92%.

Design

Prospective multi-centre service evaluation, all admissions for bronchiolitis during 4-week period, November 2018.

Setting

Paediatric departments across 12 hospitals in the West Midlands, UK.

Patients

320 patients aged 6 weeks–1 year, diagnosis of bronchiolitis, exclusions: chronic illness or high dependency/intensive care admission.

Main outcome measures

Reason for admission, admission saturations and length of stay.

Results

Inadequate feeding was the the most common reason for admission (80%). Only 20 patients were admitted solely because of low saturations. Median peripheral oxygen saturation in this group was 88%. Median length of stay in 90% centres was 41 hours, against 59 hours for 92% centres (p=0.0074).

Conclusions

Few patients were admitted solely due to low oxygen saturations, only one had a potentially avoidable admission if thresholds were 90%. Length of stay was significantly reduced in the 90% threshold centres.
Prevalence and causes of vision loss in East Asia in 2015: magnitude, temporal trends and projections
Authors: Cheng Ching-Yu , Wang Ningli , Wong Tien Y , Congdon Nathan , He Mingguang , Wang Ya Xing , Braithwaite Tasanee , Casson Robert J , Cicinelli Maria Vittoria , Das Aditi , Flaxman Seth R , Jonas Jost B , Keeffe Jill Elizabeth , Kempen John H , Leasher Janet , Limburg Hans , Naidoo Kovin , Pesudovs Konrad , Resnikoff Serge , Silvester Alexander J , Tahhan Nina , Taylor Hugh R , Bourne Rupert R A
Published: August 2019

Background

To determine the prevalence and causes of blindness and vision impairment (VI) in East Asia in 2015 and to forecast the trend to 2020.

Methods

Through a systematic literature review and meta-analysis, we estimated prevalence of blindness (presenting visual acuity <3/60 in the better eye), moderate-to-severe vision impairment (MSVI; 3/60≤presenting visual acuity <6/18), mild vision impairment (mild VI: 6/18≤presenting visual acuity <6/12) and uncorrected presbyopia for 1990, 2010, 2015 and 2020. A total of 44 population-based studies were included.

Results

In 2015, age-standardised prevalence of blindness, MSVI, mild VI and uncorrected presbyopia was 0.37% (80% uncertainty interval (UI) 0.12%–0.68%), 3.06% (80% UI 1.35%–5.16%) and 2.65% (80% UI 0.92%–4.91%), 32.91% (80% UI 18.72%–48.47%), respectively, in East Asia. Cataract was the leading cause of blindness (43.6%), followed by uncorrected refractive error (12.9%), glaucoma, age-related macular degeneration, corneal diseases, trachoma and diabetic retinopathy (DR). The leading cause for MSVI was uncorrected refractive error, followed by cataract, age-related macular degeneration, glaucoma, corneal disease, trachoma and DR. The burden of VI due to uncorrected refractive error, cataracts, glaucoma and DR has continued to rise over the decades reported.

Conclusions

Addressing the public healthcare barriers for cataract and uncorrected refractive error can help eliminate almost 57% of all blindness cases in this region. Therefore, public healthcare efforts should be focused on effective screening and effective patient education, with access to high-quality healthcare.
Hospital physicians’ views on discharge and readmission processes: a qualitative study from Norway
Authors: Knutsen Glette Malin , Kringeland Tone , Røise Olav , Wiig Siri
Published: August 2019

Objectives

To explore hospital physicians’ views on readmission and discharge processes in the interface between hospitals and municipalities.

Design

Qualitative case study.

Setting

The Norwegian healthcare system.

Participants

Fifteen hospital physicians (residents and consultants) from one hospital, involved in the treatment and discharge of patients.

Results

The results of this study showed that patients were being discharged earlier, with more complex medical conditions, than they had been previously, and that discharges sometimes were perceived as premature. Insufficient capacity at the hospital resulted in pressure to discharge patients, but the primary healthcare service of the area was not always able to assume care of these patients. Communication between levels of the healthcare service was limited. The hospital stay summary was the most important, and sometimes only, form of communication between levels. The discharge process was described as complicated and was affected by healthcare personnel, by patients themselves and by aspects of the primary healthcare service. Early hospital discharges, poor communication between healthcare services and inadequacies in the discharge process were perceived to affect hospital readmissions.

Conclusion

The results of this study provide a better understanding of hospital physicians’ views on the discharge and hospital readmission processes in the interface between the hospital and the primary healthcare service. The study also identifies discrepancies in governmental requirements, reform regulations and current practices in municipalities and hospitals.
Whole-genome sequencing reveals distinct genetic bases for insulinomas and non-functional pancreatic neuroendocrine tumours: leading to a new classification system
Authors: Hong Xiafei , Qiao Sitan , Li Fuqiang , Wang Wenze , Jiang Rui , Wu Huanwen , Chen Hao , Liu Lulu , Peng Junya , Wang Jing , Jia Congwei , Liang Xiaolong , Dai Hongmei , Jiang Jialin , Zhang Taiping , Liao Quan , Dai Menghua , Cong Lin , Han Xianlin , Guo Dan , Liang Zhiyong , Li Dongjing , Zheng Zetian , Ye Chen , Li Siliang , Zhao Yupei , Wu Kui , Wu Wenming
Published: August 2019

Objective

Insulinomas and non-functional pancreatic neuroendocrine tumours (NF-PanNETs) have distinctive clinical presentations but share similar pathological features. Their genetic bases have not been comprehensively compared. Herein, we used whole-genome/whole-exome sequencing (WGS/WES) to identify genetic differences between insulinomas and NF-PanNETs.

Design

The mutational profiles and copy-number variation (CNV) patterns of 211 PanNETs, including 84 insulinomas and 127 NF-PanNETs, were obtained from WGS/WES data provided by Peking Union Medical College Hospital and the International Cancer Genome Consortium. Insulinoma RNA sequencing and immunohistochemistry data were assayed.

Results

PanNETs were categorised based on CNV patterns: amplification, copy neutral and deletion. Insulinomas had CNV amplifications and copy neutral and lacked CNV deletions. CNV-neutral insulinomas exhibited an elevated rate ofYY1mutations. In contrast, NF-PanNETs had all three CNV patterns, and NF-PanNETs with CNV deletions had a high rate of loss-of-function mutations of tumour suppressor genes. NF-PanNETs with CNV alterations (amplification and deletion) had an elevated risk of relapse, and additionalDAXX/ATRXmutations could predict an increased relapse risk in the first 2-year period.

Conclusion

These WGS/WES data allowed a comprehensive assessment of genetic differences between insulinomas and NF-PanNETs, reclassifying these tumours into novel molecular subtypes. We also proposed a novel relapse risk stratification system using CNV patterns andDAXX/ATRXmutations.
Characterisation of clinical and immune reactivity to barley and rye ingestion in children with coeliac disease
Authors: Hardy Melinda Y , Russell Amy K , Pizzey Catherine , Jones Claerwen M , Watson Katherine A , La Gruta Nicole L , Cameron Donald J , Tye-Din Jason A
Published: August 2019

Objective

Barley and rye are major components of the Western diet, and historic feeding studies indicate that they cause clinical effects in patients with coeliac disease (CD). This toxicity has been attributed to sequence homology with immunogenic wheat sequences, but in adults with CD, these cereals stimulate unique T cells, indicating a critical contribution to gluten immunity independent of wheat. Clinical and immune feeding studies with these grains in children with CD are sparse. We undertook a barley and rye feeding study to characterise the clinical and T-cell responses in children with CD.

Design

42 children with human leucocyte antigen (HLA)-DQ2.5+(aged 3–17 years) consumed barley or rye for 3 days. Blood-derived gluten-specific T cells were tested for reactivity against a panel of barley (hordein) and rye (secalin) peptides. Hordein and secalin-specific T-cell clones were generated and tested for grain cross-reactivity. T-cell receptor sequencing was performed on sorted single cells. T-cell responses were compared with those observed in adults with CD.

Results

90% of the children experienced adverse symptoms, mostly GI, and 61% had detectable gluten-specific T-cell responses targeting peptides homologous to those immunogenic in adults. Deamidation was important for peptide reactivity. Homozygosity for HLA-DQ2.5 predicted a stronger T-cell response. Gluten-specific T cells showed striking similarities in their cross-reactivity between children and adults.

Conclusions

Barley and rye induce a consistent range of clinical and T-cell responses in children with CD. The findings highlight the importance of a series of dominant hordein and secalin peptides pathogenic in children with CD, some independent of wheat, which closely correspond to those seen in adults.
Familial disclosure by genetic healthcare professionals: a useful but sparingly used legal provision in France
Authors: Derbez Benjamin , de Pauw Antoine , Stoppa-Lyonnet Dominique , Galactéros Frédéric , de Montgolfier Sandrine
Published: August 2019

Familial disclosure of genetic information is an important, long-standing ethical issue that still gives rise to much debate. In France, recent legislation has created an innovative and unprecedented procedure that allows healthcare professionals (HCPs), under certain conditions, to disclose relevant information to relatives of a person carrying a deleterious genetic mutation. This article will analyse how HCPs in two medical genetics clinics have reacted to these new legal provisions and show how their reticence to inform the patients’ relatives on their behalf leads them to use this option sparingly.
An efficient graph clustering algorithm in signed graph based on modularity maximization
Authors: Zhuo Kefan , Yang Zhuoxuan , Yan Guan , Yu Kai , Guo Wenqiang
Published: August 2019

The unsigned graphs containing positive links only, have been analyzed fruitfully. However, the physical relations behind complex networks are dissimilar. We often encounter the signed networks that have both positive and negative links as well. It is very important to study the characteristics of complex networks and predict individual attitudes by analyzing the attitudes of individuals and their neighbors, which can divide individuals into different clusters or communities. To detect the clusters in signed networks, first, a modularity function for signed networks is proposed on the basis of the combination of positive and negative part. Then, a new graph clustering algorithm for signed graphs has also been proposed based on CNM algorithm, which has high efficiency. Finally, the algorithm has been applied on both artificial and the real networks. The results show that the proposed method has been able to achieve near-perfect solution, which is suitable for multiple types real networks.
A Computational Technique for Free Vibration Response of a 2-DOF Parametric System
Authors: Huang Dishan , Hong Li , Liu Cheng
Published: August 2019

In this paper, a closed-form solution is presented for the free vibration response of a 2-DOF parametric system by a technique with special trigonometric series. The technique extends the concept of modulation feedback to the problem of multiple degrees of freedom (M-DOF) parametric system using an equivalent dynamic system. The characteristic equation is derived by the harmonic balance in a parametric equation with the principal oscillation frequencies computed. The computation of modes and splitting modes is carried out by operation on a mixed matrix. The arbitrary constants in the general solution are determined by the initial conditions. A real-life example of a coupled inverted-pendulum system is provided to illustrate the applicability of the proposed approach. An approaching error is adopted to assess the computational errors both using the proposed technique and the Runge–Kutta algorithm. Of interest is that the time-periodic coefficient results in the changeability of the mode in the 2-DOF parametric system, while exciting the splitting mode in the harmonic combination resonance. The proposed technique is numerically demonstrated to possess not only high approaching accuracy, but is also capable of revealing some new phenomena in the parametric system, such as characteristics of mode and slitting mode, etc. It proves to be useful for future research and engineering applications of parametric systems.
Systems of polynomials with at least one positive real zero
Authors: Wang Jie
Published: August 2019

In this paper, we prove several theorems on systems of polynomials with at least one positive real zero based on the theory of conceive polynomials. These theorems provide sufficient conditions for systems of multivariate polynomials admitting at least one positive real zero in terms of their Newton polytopes and combinatorial structure. Moreover, a class of polynomials attaining their global minimums in the first quadrant are given, which is useful in polynomial optimization.
Study of thermal stability for different dark energy models
Authors: Mamon Abdulla Al , Bhandari Pritikana , Chakraborty Subenoy
Published: August 2019

In this work, we have made an attempt to investigate the dark energy possibility from the thermodynamical point of view. For this purpose, we have studied thermodynamic stability of three popular dark energy models in the framework of an expanding, homogeneous, isotropic and spatially flat FRW Universe filled with dark energy and cold dark matter. The models considered in this work are Chevallier–Polarski–Linder (CPL) model, Generalized Chaplygin Gas (GCG) model and Modified Chaplygin Gas (MCG) model. By considering the cosmic components (dark energy and cold dark matter) as perfect fluid, we have examined the constraints imposed on the total equation of state parameter ([Formula: see text]) of the dark fluid by thermodynamics and found that the phantom nature ([Formula: see text]) is not thermodynamically stable. Our investigation indicates that the dark fluid models (CPL, GCG and MCG) are thermodynamically stable under some restrictions of the parameters of each model.
Complexity factors for static axial system in self-interacting Brans–Dicke gravity
Authors: Sharif M. , Majid Amal
Published: August 2019

This paper explores the physical attributes of a static axial source that induce complexity within the fluid in the background of self-interacting Brans–Dicke theory. Bel’s approach is used to split the Riemann tensor and construct structure scalars that involve physical features of the fluid in the presence of scalar field. Using the evolution equations derived from Bianchi identities as well as structure scalars, five complexity factors are identified which include constraints on the scalar field. Finally, the conditions of vanishing complexity are used to present solutions for an anisotropic inhomogeneous spheroid. It is concluded that scalar field is an additional source of complexity.
Some models with repulsion effect on superinfecting viruses by infected cells
Authors: Li Jun-Feng
Published: August 2019

In this paper, we study some models with repulsion effect on superinfecting viruses by infected cells [Formula: see text] where [Formula: see text], [Formula: see text] and [Formula: see text] are the density of uninfected cells, infected cells and viruses at time [Formula: see text] at location [Formula: see text], respectively. The functions [Formula: see text] and [Formula: see text] are assumed to be positive, continuous and bounded. [Formula: see text] denotes the production rate of uninfected cells. The infection rate is [Formula: see text] and the function [Formula: see text] is the production rate of free viruses. And [Formula: see text] is the rate of transfer from uninfected cells to infected cells. The positive constants [Formula: see text] and [Formula: see text] denote the death rate of uninfected cells, infected cells and viruses, respectively. The stability of the infection-free equilibrium solution and infection equilibrium solution is discussed. It is shown that if the basic reproduction number [Formula: see text] then the chemotaxis has no effect, that is, the infection-free constant solution is stable. For the system with chemotactic sensitivity [Formula: see text], if [Formula: see text], then the infection constant solution will be unstable under some conditions.
A large palaeo-landslide reactivated by high-speed railway construction works (northern Spain)
Authors: Pando L. , Díaz-Díaz L. M. , Arias D. , Castañón C. , López-Fernández C.
Published: August 2019

The presence of large palaeo-landslides can hinder the construction of railway lines if they cause an alteration of the natural balance of the slope, significantly increasing the cost of the project. During the construction works in a section of the Madrid–Asturias high-speed railway line (Spain), a large-scale hillside instability affected 460 m of the section. The ground movement began 10 months after the start of the excavations and remained active throughout the observation period (2008–2010). Data provided by fieldwork, boreholes and instrumental monitoring have allowed the investigation of the geological units involved, together with the geometry and the kinematics of the mass movement. This landslide involves a Paleozoic basement with an estimated volume of 4 400 000 m
3
. It shows low displacement rates (<45 mm a
−1
) and was accommodated on a single surface of rupture, which reaches more than 60 m depth. The kinematics is favoured by structural and lithological conditions, there being a strong rheological contrast in the lower part of the mobilized ground. This movement is linked to a large palaeo-landslide that was partially reactivated when excavations undermined the lower slopes of the hillside. Technical solutions for the stabilization have already caused an additional cost of 17% over the initial budget.
Threat Management in Data-centric IoT-Based Collaborative Systems
Authors: Felemban Muhamad , Felemban Emad , Kobes Jason , Ghafoor Arif
Published: August 2019

In this article, we propose a threat management system (TMS) for Data-centric Internet-of-Things-based Collaborative Systems (DIoTCSs). In particular, we focus on tampering attacks that target shared databases and can affect the execution of the DIoTCS services. The novelty of the proposed system is to isolate the damage caused by tampering attacks into data partitions. We formulate the partitioning problem as a cost-driven optimization problem, prove its NP-hardness, and propose two polynomial-time heuristics. We evaluate a TMS experimentally and demonstrate that intelligent partitioning of the database improves the overall availability of the DIoTCS.
Roles of the noradrenergic nucleus locus coeruleus and dopaminergic nucleus A11 region as supraspinal defecation centers in rats
Authors: Nakamori Hiroyuki , Naitou Kiyotada , Horii Yuuki , Shimaoka Hiroki , Horii Kazuhiro , Sakai Hiroki , Yamada Akihiro , Furue Hidemasa , Shiina Takahiko , Shimizu Yasutake
Published: August 2019

We previously demonstrated that administration of norepinephrine, dopamine, and serotonin into the lumbosacral defecation center caused propulsive contractions of the colorectum. It is known that the monoamines in the spinal cord are released mainly from descending neurons in the brainstem. In fact, stimulation of the medullary raphe nuclei, the origin of descending serotonergic neurons, enhances colorectal motility via the lumbosacral defecation center. Therefore, the purpose of this study was to examine the roles of the noradrenergic nucleus locus coeruleus (LC) and dopaminergic nucleus A11 region in the defecation reflex. Colorectal motility was measured with a balloon in anesthetized rats. Electrical stimulation of the LC and A11 region increased colorectal pressure only when a GABAA receptor antagonist was injected into the lumbosacral spinal cord. The effects of the LC stimulation and A11 region stimulation on colorectal motility were inhibited by antagonists of α1-adrenoceptors and D2-like dopamine receptors injected into the lumbosacral spinal cord, respectively. Spinal injection of a norepinephrine-dopamine reuptake inhibitor augmented the colokinetic effect of LC stimulation. The effect of stimulation of each nucleus was abolished by surgical severing of the parasympathetic pelvic nerves. Our findings demonstrate that activation of descending noradrenergic neurons from the LC and descending dopaminergic neurons from the A11 region causes enhancement of colorectal motility via the lumbosacral defecation center. The present study provides a novel concept that the brainstem monoaminergic nuclei play a role as supraspinal defecation centers.

NEW & NOTEWORTHY The present study demonstrates that electrical and chemical stimulations of the locus coeruleus or A11 region augment contractions of the colorectum. The effects of locus coeruleus and A11 stimulations on colorectal motility are due to activation of α1-adrenoceptors and D2-like dopamine receptors in the lumbosacral defecation center, respectively. The present study provides a novel concept that the brainstem monoaminergic nuclei play a role as supraspinal defecation centers.
Loss of endothelial sulfatase-1 after experimental sepsis attenuates subsequent pulmonary inflammatory responses
Authors: Oshima Kaori , Han Xiaorui , Ouyang Yilan , El Masri Rana , Yang Yimu , Haeger Sarah M. , McMurtry Sarah A. , Lane Trevor C. , Davizon-Castillo Pavel , Zhang Fuming , Yue Xinping , Vivès Romain R. , Linhardt Robert J. , Schmidt Eric P.
Published: August 2019

Sepsis patients are at increased risk for hospital-acquired pulmonary infections, potentially due to postseptic immunosuppression known as the compensatory anti-inflammatory response syndrome (CARS). CARS has been attributed to leukocyte dysfunction, with an unclear role for endothelial cells. The pulmonary circulation is lined by an endothelial glycocalyx, a heparan sulfate-rich layer essential to pulmonary homeostasis. Heparan sulfate degradation occurs early in sepsis, leading to lung injury. Endothelial synthesis of new heparan sulfates subsequently allows for glycocalyx reconstitution and endothelial recovery. We hypothesized that remodeling of the reconstituted endothelial glycocalyx, mediated by alterations in the endothelial machinery responsible for heparan sulfate synthesis, contributes to CARS. Seventy-two hours after experimental sepsis, coincident with glycocalyx reconstitution, mice demonstrated impaired neutrophil and protein influx in response to intratracheal lipopolysaccharide (LPS). The postseptic reconstituted glycocalyx was structurally remodeled, with enrichment of heparan sulfate disaccharides sulfated at the 6- O position of glucosamine. Increased 6- O-sulfation coincided with loss of endothelial sulfatase-1 (Sulf-1), an enzyme that specifically removes 6- O-sulfates from heparan sulfate. Intravenous administration of Sulf-1 to postseptic mice restored the pulmonary response to LPS, suggesting that loss of Sulf-1 was necessary for postseptic suppression of pulmonary inflammation. Endothelial-specific knockout mice demonstrated that loss of Sulf-1 was not sufficient to induce immunosuppression in non-septic mice. Knockdown of Sulf-1 in human pulmonary microvascular endothelial cells resulted in downregulation of the adhesion molecule ICAM-1. Taken together, our study indicates that loss of endothelial Sulf-1 is necessary for postseptic suppression of pulmonary inflammation, representing a novel endothelial contributor to CARS.
Complement C3 exacerbates renal interstitial fibrosis by facilitating the M1 macrophage phenotype in a mouse model of unilateral ureteral obstruction
Authors: Cui Jiong , Wu Xiaoting , Song Yankun , Chen Yi , Wan Jianxin
Published: August 2019

The impact of the renal microenvironment on macrophage phenotype determination can contribute to the progression or resolution of renal fibrosis. Although the complement proteins affect macrophage polarization, whether complement component 3 (C3) can induce macrophage polarization and regulate renal interstitial fibrosis remains undetermined. In the present study, we investigated the contribution of C3 on macrophage polarization and renal fibrosis in C3-deficient mice with unilateral ureteral obstruction and bone marrow-derived macrophages. C3-deficient mice exhibited attenuated renal fibrosis and ameliorated peritubular capillary rarefaction. Lack of C3 contributed to M2 macrophage polarization, increased IL-10 and VEGF164, and decreased TNF-α and soluble VEGF receptor 1 expression in the obstructed kidneys at the early stages of unilateral ureteral obstruction. C3a facilitated LPS-induced M1 polarization and inflammatory factor production in bone marrow-derived macrophages in vitro, accompanied by increased ERK, NF-κB, and STAT1 phosphorylation. The ERK-specific inhibitor PD98059 inhibited the phosphorylation of ERK, NF-κB, and STAT1 and attenuated M1 polarization-related inflammatory factor production. Furthermore, the culture supernatant from M1 macrophages and C3a-treated M2 macrophages were more detrimental to angiogenesis compared with M2 macrophage supernatants. Thus, complement C3 exacerbates renal interstitial fibrosis by facilitating macrophage M1 polarization, promoting proinflammatory cytokine expression, and deteriorating peritubular capillary rarefaction in the kidney.