bluuebunny/crossref_metadata_2025 huggingface dataset:
Idea paper: Predicting culturability of microbes from population dynamics under field conditions
Authors: Ushio Masayuki
Published: March 2020

Isolation and cultivation of microbes from environmental samples have been fundamental and important for species identification and investigating functions and ecology of target microbes. Although cultivation and isolation of microbes are not easy, the natural environment can “culture” any endemic microbes, and thus key information for culturing and isolating microbes may be encoded in the natural population dynamics of microbes. In this article, I present the idea that culturability of microbes may be inferred by quantifying the dynamic properties of microbes using nonlinear time series analysis and empirical dynamic modeling (EDM). To briefly demonstrate the idea, I analyzed high‐frequency, quantitative microbial time series obtained for experimental rice plots. I selected bacterial phyla that included sufficient numbers of microbial taxa and analyzed 398 microbial taxa using EDM. The nine phyla analyzed generally followed a similar pattern: many microbial taxa fell into the “Simple” dynamics category, and a small proportion of taxa were categorized in “Simple but nonlinear” or “Nearly random” dynamics categories. The present analysis suggested that many microbes in the study system might be cultivated by modifying a relatively small number of conditions. However, the present idea as well as the result is preliminary, and more precise taxonomic information (i.e., species‐level identification) and a culturability data set will help to validate the idea. If the present idea was found to be valid, a priori evaluation of the culturability of microbes would become possible, which would avoid unnecessary costs (labor, time and money) of attempts to cultivate microbes.
Evaluating a method for eliciting children's voice about educational support with children with speech, language and communication needs
Authors: Bloom Ashley , Critten Sarah , Johnson Helen , Wood Clare
Published: March 2020

This article reports the development and evaluation of a toolkit‐based approach to eliciting children's experiences of educational support, where the children in question experience speech and communication needs. The ‘Your Voice Your Choice’ approach was evaluated using a cross‐case analysis methodology, which represents a novel approach to critical examination of the effectiveness of such resources. We explored seven case studies within a critical realist framework. We found that the toolkit was effective at supporting most (although not all) of the children with speech and communication needs to explore their school learning and support experiences through a scaffolded emotion‐based ‘dialogue’, which was corroborated by observations and other data sources. The toolkit facilitated access to children's voice as they revealed how they felt across a number of relational, learning and support areas, which could be used by services to focus provision and consider how to better support children's social and emotional needs.
Lessons from International Multi‐Option Referendum Experiences
Authors: Wagenaar Charlotte C. L.
Published: March 2020

Referendums are regularly criticised for reducing complex policy decisions to two maximally opposed options. This reduces opportunities for voter expression and can polarise debates. Alternative referendum designs which present more than two ballot options can offer innovative opportunities, but also raise new challenges. We can benefit by learning from previous experiences with multi‐option referendum voting. Discussions of such experiences are rare and have often focussed on a limited number of cases. This article provides an overview of over 100 multi‐option referendum experiences around the world. It discusses the topics on which they were held and the ballot options that were offered. It then analyses the variety in ballot design in terms of questions posed and voting methods applied. Drawing on the experiences of multi‐option referendums, the article concludes with lessons that can be learned in relation to initiating and designing these referendums.
The optics of noncommunicable diseases: from lifestyle to environmental toxicity
Authors: Herrick Clare
Published: March 2020

Until recently, the noncommunicable disease (NCD) category was composed of four chronic diseases (cancer, cardiovascular disease, diabetes and chronic respiratory disease) and four shared, ‘modifiable’ behavioural risk factors (smoking, diet, physical activity and alcohol). In late 2018, the NCD category was expanded to include mental health as an additional disease outcome and air pollution as an explicit environmental risk factor. The newly‐expanded NCD category connects behavioural and environmental readings of risk and shifts attention from individual acts of consumption to unequal and inescapable conditions of environmental exposure. It thus renders the increasing ‘toxicity’ of everyday life amid ubiquitous environmental contamination a new conceptual and empirical concern for NCD research. It also, as this paper explores, signals a new ‘optics’ of a much‐maligned disease category. This is particularly significant as chronic disease research has long been siloed between public and environmental health, with each discipline operationalising the notion of the ‘environment’ as a source of disease causation in contrasting ways. Given this, this paper is positioned as a significant contribution to both research on NCDs and environmental risk, bringing these interdisciplinary domains into a new critical conversation around the concept of toxicity.
Multiple pregnancy and assisted conception treatment
Authors: Chien Patrick
Published: March 2020

Deputy Editor‐in‐Chief, Dr Patrick Chien, discusses the latest thinking in women’s health and highlights articles from this issue in an audio podcast available at: https://soundcloud.com/bjog/april-editorial-2020
Appealing broadly while appearing unified: Resolving an electoral dilemma
Authors: TROMBORG MATHIAS WESSEL
Published: March 2020

Political parties have an electoral incentive to appear ideologically unified, but also to appeal broadly to different groups of voters with diverse preferences. This paper suggests that parties respond to both incentives through the distribution of candidate issue positions. Members of Parliament (MPs) are responsible for their party's national reputation and thus rarely take positions that diverge from those of their party. Non‐incumbent candidates, on the other hand, are mostly visible within their electoral district and thus more likely to diverge from party positions that are unpopular among their constituents. These possibilities are tested with candidate position taking data from nine voting advice applications in Denmark, Finland, Ireland and Switzerland. The results are consistent with the theoretical expectations and have important implications for the way representation works in parliamentary democracies as well as for the broader literature on the topic.
Jurisdiction size and local government effectiveness: Assessing the effects of municipal amalgamations on performance
Authors: BLOM‐HANSEN JENS , HOULBERG KURT , SERRITZLEW SØREN
Published: March 2020

The optimal jurisdiction size has been debated since Plato and Aristotle. A large literature has studied economic and democratic scale effects, but we have almost no knowledge of the effects of jurisdiction size on the effectiveness of local services. This is due to two methodological problems. First, selection bias and reverse causality often render change in jurisdiction size an endogenous variable. Second, there is a lack of empirical indicators of effectiveness, and most studies therefore focus on spending measures. Extant research thus studies economies of scale, leaving effectiveness of scale unexamined. We address both problems in a quasi‐experimental study of public schools. Our findings from the school area indicate that jurisdiction size does not have systematic effects on effectiveness. Our analysis therefore supports recent studies of economic and democratic scale effects that indicate that the search for the optimal jurisdiction size is futile.
RNA interference targeting ecdysone receptor blocks the larval–pupal transition in Henosepilachna vigintioctopunctata
Authors: Wu Jian‐Jian , Mu Li‐Li , Kang Wei‐Nan , Ze Long‐Ji , Shen Chen‐Hui , Jin Lin , Anjum Ahmad Ali , Li Guo‐Qing
Published: March 2020

Henosepilachna vigintioctopunctata is a serious insect pest which attacks a large number of nightshades and cucurbits in Asian countries, Brazil and Australia. Prolonged application of traditional pesticides has caused environmental pollution and exerted deleterious effects on human health. Finding new approaches with high target specificity and low environmental contamination has become an urgent task. RNA interference (RNAi) induced by double‐stranded RNA (dsRNA) is expected to be applicable to managing this pest. Here we evaluated the effects of Escherichia coli‐expressed dsRNAs targeting ecdysone receptor (EcR) gene via dietary delivery in laboratory and foliar spraying in a greenhouse. The target transcript was successfully knocked down when the 4th‐instar larvae had fed on potato foliage dipped with dsEcR in a laboratory bioassay. Around 85% of the HvEcR RNAi larvae remained as prepupae or became abnormal pupae, and failed to emerge into adults. Ingestion of dsEcR‐immersed foliage by the 3rd‐instar larvae effectuated a comparable RNAi response and brought about more severe defects: all the resultant larvae arrested development, remained as prepupae and finally died. For assay in the greenhouse, a dsEcR‐contained E. coli suspension was directly sprayed to the foliage of greenhouse‐growing potato plants and the 3rd‐ and 4th‐instar larvae were transferred to the leaves. High RNAi efficacy was obtained and identical RNAi phenotypes were observed in treated larvae. In addition, spraying dsEcR reduced leaf damage. Our results indicate a possibility of practical application of dsEcR as an environmentally friendly RNA pesticide to control H. vigintioctopunctata larvae.
Does sociality drive diversity and composition of airway microbiota in cetaceans?
Authors: Vendl Catharina , Slavich Eve , Nelson Tiffanie , Acevedo‐Whitehouse Karina , Montgomery Kate , Ferrari Belinda , Thomas Torsten , Rogers Tracey
Published: March 2020

The number of social contacts of mammals is positively correlated with the diversity of their gut microbes. There is some evidence that sociality also affects microbes in the respiratory tract. We tested whether the airway microbiota of cetacean species differ depending on the whales' level of sociality. We sampled the blow of blue (Balaenoptera musculus), grey (Eschrichtius robustus), humpback (Megaptera novaeangliae) and long‐finned pilot whales (PWs) (Globicephala melas) and analysed the blow microbiota by barcode tag sequencing targeting the V4 region of the bacterial 16S rRNA gene. Humpback whales (HWs) show higher levels of sociality than blue (BW) and grey (GW), while PWs are the most gregarious among the four species. The blow samples of the HWs showed the highest richness and diversity. HWs were also the only species with a species‐specific clustering of their microbial community composition and a relatively large number of core taxa. Therefore, we conclude that it cannot be sociality alone shaping the diversity and composition of airway microbiota. We suggest the whale species' lung volume and size of the plume of exhaled air as an additional factor impacting the transmission potential of blow microbiota from one individual whale to another.
Molecular mechanism of acquired drug resistance in the EGFR‐TKI resistant cell line HCC827‐TR
Authors: Yu Tao , Xia Qian , Gong Ting , Wang Jing , Zhong DianSheng
Published: March 2020

Background

The first‐line standard treatment of non‐small cell lung cancer (NSCLC) with EGFR mutation is EGFR‐tyrosine kinase inhibitors (TKIs). However, most patients will develop acquired resistance after 9–13 months. This study investigated novel molecular mechanisms of acquired resistance to EGFR‐TKIs to identify a potential new treatment for EGFR‐TKI resistant NSCLC patients.

Methods

We established an EGFR‐TKI resistant cell line (HCC827‐TR) by culturing the HCC827‐P cell line through continuous erlotinib culture. We used Sanger sequencing, RT‐PCR, and western blot to rule out known resistance mechanisms in HCC827‐TR cells, including EGFR‐T790M and MET, PTEN, or EGFR expression changes. Next‐generation sequencing was performed and identified differentially expressed genes between two cell lines and examined the genes with GO and KEGG pathway database analyses. We also examined the molecular alterations in COSMIC and GDSC databases and performed hazard predictions using SIFT, PolyPhen‐2, Mutation Taster, and CADD.

Results

Our results identified FGF2 as a differentially expressed gene with a G101T point mutation in HCC827‐TR cells that showed high mutation frequency and hazard score. HCC827‐TR cells showed elevated FGF2 compared to parental cells. It is noteworthy that treatment with the FGFR inhibitor AZD4547 could restore the sensitivity of HCC872‐TR cells to erlotinib.

Conclusions

An erlotinib‐resistant cell line HCC827‐TR was successfully constructed and we identified the EGFR‐TKI resistance mechanism involving the FGF2 gene mutation. Targeted inhibition of the FGF2/FGFR signaling pathway may effectively restore the sensitivity of the resistant cells to erlotinib. These results suggest a novel treatment strategy for EGFR‐TKI resistant NSCLC patients.

Key points

Significant findings of the study: Identifies a novel molecular mechanism for EGFR‐TKI acquired resistance.

What this study adds: A potential novel strategy for the treatment of EGFR‐TKI resistant NSCLC patients.
Retrospective analysis of the effectiveness and tolerability of nab‐paclitaxel in Chinese elderly patients with advanced non‐small‐cell lung carcinoma
Authors: Wang Shuhang , Liang Qiuping , Chi Yujia , Zhuo Minglei , An Tongtong , Duan Jianchun , Wang Zhijie , Wang Yuyan , Zhong Jia , Yang Xue , Chen Hanxiao , Wang Jie , Zhao Jun
Published: March 2020

Background

Previous trials have suggested that elderly patients with non‐small‐cell lung cancer (NSCLC) could benefit from nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel). Real‐world data on the elderly Chinese population are lacking. This study aimed to analyze the effectiveness and tolerability of nab‐paclitaxel in Chinese elderly patients (≥65 years) with advanced NSCLC.

Methods

This study included 76 patients with a primary diagnosis of IIIB‐IV NSCLC from January 2010 to December 2017 at Peking University Cancer Hospital, who received nab‐paclitaxel (125 or 130 mg/m2 i.v.) every three weeks. The overall survival (OS), progression‐free survival (PFS), objective response rate (ORR), disease control rate (DCR), and adverse events (AEs) were analyzed.

Results

There were 12 patients who received nab‐paclitaxel as the first‐line treatment (seven also received carboplatin), and 64 received nab‐paclitaxel as the latter‐line treatment. The overall ORR, DCR, median PFS, and median OS were 14.5%, 69.7%, 5.2 months, and 12.2 months, respectively. The Eastern Cooperative Oncology Group performance status of one and the age of 70–74 years were independently associated with longer OS, while early treatment line of nab‐paclitaxel and age of 70–74 years were independently associated with longer PFS. The most common AEs were anemia, leukopenia, gastrointestinal reaction, fatigue, and peripheral neuropathy, which were all manageable. Dose adjustment or treatment discontinuation was encountered in 10 patients because of AEs. The incidence of AEs was not different among age subgroups.

Conclusions

Nab‐paclitaxel has a good clinical response profile in Chinese elderly patients with stage IIIB–IV NSCLC. Prospective clinical trials are needed to confirm these results.

Key points

Significant findings of the study

Nanoparticle albumin‐bound paclitaxel (nab‐paclitaxel) has a good clinical response profile in Chinese elderly (≥65 years) patients with stage IIIB‐IV non‐small‐cell lung cancer (NSCLC), with acceptable and manageable adverse events.

What this study adds

Preliminary evidence shows a good clinical response from treatment with nab‐paclitaxel in Chinese elderly patients with advanced NSCLC.
A quick, easy and non‐invasive method to quantify coral growth rates using photogrammetry and 3D model comparisons
Authors: Lange Ines D. , Perry Chris T.
Published: March 2020

Coral growth rates vary significantly with environmental conditions and are thus important indicators of coral health and reef carbonate production. Despite the importance of this metric, data are sparse for most coral genera and species globally, including for many key reef‐building species. Traditional methods to obtain growth rates, such as coral coring or staining with Alizarin are destructive and only work for a limited number of species and morphological growth forms.

Emerging approaches, using underwater photogrammetry to create digital models of coral colonies, are providing novel and non‐invasive ways to explore colony‐scale growth patterns and to address existing knowledge gaps. We developed an easy‐to‐follow workflow to construct three‐dimensional (3D) models from overlapping photographs and to measure linear, radial and vertical extension rates of branching, massive and encrusting corals after aligning colony models from subsequent years.

The method presented here was applied to measure extension rates for 46 colonies of nine coral species in the remote Chagos Archipelago, Indian Ocean. Proposed image acquisition and software settings produced 3D models of consistently high resolution and detail (precision ≤ 0.2 mm) and variability in growth measurements was small despite manual alignment, clipping and ruler placement (SD ≤ 0.9 mm). Measured extension rates for the Chagos Archipelago are similar to published rates in the Indo‐Pacific where comparable data are available, and provide the first published rates for several species. For encrusting corals, the results emphasize the importance of differentiating between radial and vertical growth.

Photogrammetry and 3D model comparisons provide a fast, easy, inexpensive and non‐invasive method to quantify coral growth rates for a range of species and morphological growth forms. The simplicity of the presented workflow encourages its repeatability and permits non‐specialists to learn photogrammetry with the goal of obtaining linear coral growth rates. Coral growth rates are essential metrics to quantify functional consequences of ongoing community changes on coral reefs and expanded datasets for key coral taxa will aid predictions of geographic variations in coral reef response to increasing global stressors.
Biology, ecology and management of Diuraphis noxia (Hemiptera: Aphididae) in Australia
Authors: Ward Samantha , van Helden Maarten , Heddle Thomas , Ridland Peter M , Pirtle Elia , Umina Paul A
Published: March 2020

The Russian wheat aphid, Diuraphis noxia (Mordvilko ex Kurdjumov), is one of the world's most economically important pests of grain crops and has been recorded from at least 140 grass species within Poaceae. It has rapidly dispersed from its native origin of Central Asia into most major grain‐producing regions of the world including Africa, Asia, Europe, the Middle East, North America and South America. Diuraphis noxia was first found in Australia in a wheat crop in the mid‐north of South Australia in May 2016. Since then, D. noxia has been recorded throughout grain‐growing regions of South Australia, Victoria, New South Wales and Tasmania. The distribution will continue to expand, with climatic suitability modelling suggesting D. noxia can persist in all key grain regions, including large parts of Western Australia and Queensland. Australian populations of D. noxia appear to be anholocyclic, with no sexual stages being observed. The aphids can reproduce year round as long as host plants are available. Australian farmers have generally adopted prophylactic insecticide seed treatments and/or foliar sprays to manage D. noxia. Research is required to fully understand yield impacts, host preferences and host plant resistance associated with D. noxia. Cultural control through managing alternate host plants over summer, agronomic crop management, biological control and developments in host plant resistance should provide considerable future benefits.
Clinical and molecular aspects of PTEN mutations in 10 pediatric patients
Authors: Isik Esra , Simsir Ozguc Semih , Solmaz Asli Ece , Onay Huseyin , Atik Tahir , Aykut Ayca , Durmaz Asude , Cogulu Ozgur , Ozkinay Ferda
Published: March 2020

Introduction

PTEN gene mutations are responsible for the PTEN hamartoma tumor syndrome (PHTS). In this study, clinical and molecular findings of patients carrying PTEN mutations are presented. Our aim is to contribute to genotype–phenotype correlation and define the most common findings of the syndrome in pediatric patients.

Methods and Materials

Ten molecularly confirmed PHTS patients from seven families were included in the study. All patients were examined by a clinical geneticist. Laboratory test results were obtained from hospital records. Sequencing of PTEN gene was performed. Variant interpretation was done in accordance with 2015 recommendations from the American College of Medical Genetics.

Results

Macrocephaly was the most common clinical finding, involving all patients. This was followed by skin lesions, neurodevelopmental delay, and pathologic cranial magnetic resonance imaging findings. Seven different heterozygous PTEN gene variants were found in seven families. Four of these were located in exon 5, which has been described as a hot spot area for the PTEN gene. Four mutations were novel. A wide range of phenotypic and genotypic spectra was found in our study group.

Conclusion

Screening of PTEN mutations in patients with macrocephaly is recommended due to an increased risk of cancer. Further cases are needed to make a phenotype–genotype correlation in PHTS.
Three patients with 46,X,inv(Y)(p11.2q11.2)pat/45,X and their pedigree analysis
Authors: Chen Yunchun , Xu Yuni , Cao Xiaoqiang , Zheng Chunqiao , Lin Liying , Zhu Zhongyuan , Hu Jiandong
Published: March 2020

The present study aimed to perform chromosome examination and pedigree analysis on three patients with semen abnormality who had undergone in vitro fertilization–embryo transfer (IVF‐ET). Peripheral blood cell culture and chromosome karyotyping were performed on 4,200 individuals who had undergone chromosome examination. Among them, 155 pregnant women who had successfully conceived were subjected to amniotic cell culture and chromosome karyotyping and those with abnormal chromosome karyotype were further subjected to C‐banding and whole‐genome sequencing. Mosaicism for a 46,X,inv(Y)(p11.2q11.2)pat/45,X karyotype was identified in the probands and immediate adult male relatives. The incidence of this mosaicism in the study population was only 0.07% (3/4,200), which is reported for the first time. For the proband of pedigree A, the results of whole‐genome sequencing and other tests were normal, and the chromosome karyotype of IVF fetuses was 46,X,inv(Y)(p11.2q11.2)pat. All the male members of three pedigrees have normal phenotypes, with no features of Turner's syndrome (45,X) or hermaphroditism (45,X/46,XY), suggesting that the inverted Y chromosome is extremely unstable and particularly susceptible to loss in somatic cells. So we speculate this karyotype may be a unique type of inverted Y chromosome in somatic cells.
Regional nodal metastasis and 5‐year survival in patients with thin melanoma in Queensland: a population‐based study
Authors: Theile Harrison , Moore Julie , Dunn Nathan , Cossio Danica , Forristal Catherine E. , Green Adele C. , Smithers B. Mark
Published: March 2020

Background

Optimal management of regional lymph nodes for thin cutaneous melanoma is uncertain. We evaluated regional lymph node involvement and 5‐year melanoma‐specific survival (MSS) in patients with thin (≤1 mm) primary melanoma.

Methods

Patients with a melanoma, American Joint Committee on Cancer Staging 8th Edition pT1a (<0.8 mm) or pT1b (ulceration; and/or 0.8–1.0 mm), diagnosed during 2001–2015 were identified from the Queensland Oncology Repository. We extracted demographic, pathology and clinical details, including sentinel lymph node biopsy (SLNB), regional nodal dissection and nodal recurrence. Poisson regression was used to assess recurrence risk in patients who did not undergo SLNB. The 5‐year MSS was calculated using the Kaplan–Maier method with Cox regression to compare survival outcomes according to SLNB performance.

Results

Of the 27 824 eligible patients, 240 (0.9%) underwent SLNB. One hundred and seventy‐eight patients (0.6%) without SLNB had nodal recurrence. Of the 4848 patients with a pT1b lesion, 166 (3.4%) had SLNB with 12 (7.2%) positive; of the remainder, 99 (2.1%) had clinical recurrence. Risk of recurrence was higher in males, nodular subtype and T1b lesions and lower if patients were aged >60 years. The 5‐year MSS was similar for observed and SLNB cohorts (99.66% versus 98.92%) but worse for T1b lesions (98.90%) and clinical nodal recurrence (66.89%).

Conclusion

Overall prognosis for T1 melanoma is excellent with nodal involvement being rare. However, the American Joint Committee on Cancer 8th Edition T1b melanoma correlates with significantly worse 5‐year MSS and increased regional nodal recurrence (notably for 0.8–1.0 mm lesions with ulceration). Further characterization of high‐risk groups for nodal positivity that impacts patient outcome is needed for the pT1 melanoma cohort.
Perinatal outcomes of twin pregnancies affected by early twin‐twin transfusion syndrome: A systematic review and meta‐analysis
Authors: D’Antonio Francesco , Benlioglu Can , Sileo Filomena G. , Thilaganathan Basky , Papageorghiou Aris , Bhide Amarnath , Khalil Asma
Published: March 2020

Introduction

Twin‐to‐twin transfusion syndrome (TTTS) is associated with a high risk of perinatal mortality and morbidity if not treated. However, the optimal timing and management in case of early (occurring < 18 weeks) TTTS has not been established yet.

Material and methods

This is a systematic review and meta‐analysis aiming at evaluating the outcomes of monochorionic diamniotic twin pregnancies complicated by early (ie before 18 weeks) TTTS according to different management options (expectant, laser therapy, amnioreduction or cord occlusion). The primary outcome was mortality, including single and double intrauterine, neonatal and perinatal death. Secondary outcomes were: composite morbidity, neuromorbidity, respiratory distress syndrome, admission to neonatal intensive care unit, intact survival (defined as survival free from neurological complications) and preterm birth < 32 weeks of gestation. All outcomes were reviewed according to the different management options (expectant, laser therapy, amnioreduction or cord occlusion) and reported FOR the overall population of twins, and for the donor and recipient separately. Subgroup analysis for TTTS occurring before 16 weeks of gestation was performed. Random‐effect meta‐analyses of proportions were used to analyse the data.

Results

Thirteen studies were included. Early TTTS occurred in 14.3% (95% confidence interval [CI] 11.9‐17.0) of cases. The incidence of intrauterine death was 19.0% (95% CI 2.6‐45.5) in twins managed expectantly, 32.4% (95% CI 16.5‐50.7) in those who received laser treatment and 12.5% (95% CI 4.8‐23.0) in those treated with amnioreduction. The incidence of neonatal death was 22.6% (95% CI 4.2‐49.8) in twins managed expectantly, 24.7% (95% CI 0.5‐80.3) in those who received laser and 20.2 (95% CI 5.8‐43.4) in those who had amnioreduction; it was not possible to compute the incidence of these outcomes in twins undergoing cord occlusion because of insufficient sample and lack of reporting of most of the observed outcomes. Overall, the incidence of perinatal death was 43.9% (95% CI 5.9‐87.7) in twins managed expectantly, 47.3% (95% CI 21.4‐70.0) in those treated with laser and 28.5% in those who had amnioreduction.

Conclusions

Twin pregnancies affected by early TTTS are at substantial risk of perinatal mortality and morbidity; however, the data come from very small studies with a high risk of selection bias.
Pseudoexfoliation syndrome and relating factors in a rural Japanese population: the Kumejima Study
Authors: Arakaki Yoshikuni , Sawaguchi Shoichi , Iwase Aiko , Tomidokoro Atsuo , Araie Makoto
Published: March 2020

Purpose

To report the prevalence of pseudoexfoliation (PEX) syndrome and glaucoma associated with PEX (PEX‐G) and their relating factors of them in a south‐western island of Japan.

Methods

A population‐based survey of all residents aged ≥ 40 years was conducted in Kumejima, Okinawa, Japan, and 3762 subjects (participation rate, 81.2%) underwent detailed ophthalmic examinations. Presence of PEX material on the lens capsule, iris surface and/or pupillary margin was determined by slit‐lamp biomicroscopy. Glaucoma was diagnosed according to the criteria of the International Society of Geographical and Epidemiological Ophthalmology.

Results

In subjects aged ≥ 40 years, prevalence rates of PEX syndrome, PEX without glaucoma and PEX‐G in at least one eye were 1.5% (95% confidence interval [CI]: 1.0–1.9%), 1.3% (95% CI: 0.9–1.7%) and 0.1% (95% CI: 0.0–0.2%), respectively, excluding eyes after cataract surgery; and 2.8% (95% CI: 2.3–3.3%), 2.2% (95% CI: 1.8–2.6 %) and 0.4% (95% CI: 0.2–0.6%), respectively, including eyes after cataract surgery. Cataract surgery had been performed in 61% of subjects with PEX in at least one eye; presence of PEX showed no significant effects on the intraocular pressure (IOP). A multivariate analysis showed that PEX was associated with older age (p < 0.0001, odds ratio: 1.10 [95% CI: 1.07–1.13]) and working outdoors (p = 0.0395, odds ratio: 2.18 [95% CI: 0.99–4.82]).

Conclusions

The prevalence rates of PEX syndrome and PEX‐G in a south‐western island of Japan were reported. PEX showed no significant effect on IOP, and age and working outdoors were significantly related with PEX.
Editorial: a clinical decision tool to identify patients who might benefit most from intensified dosing in the biological era—getting nearer? Authors' reply
Authors: Dulai Parambir S.
Published: March 2020

LINKED CONTENT

This article is linked to Dulai et al and Verstockt and Ferrante papers. To view these articles, visit https://doi.org/10.1111/apt.15609 and https://doi.org/10.1111/apt.15634.
A population pharmacokinetic model for escitalopram and its major metabolite in depressive patients during the perinatal period: Prediction of infant drug exposure through breast milk
Authors: Weisskopf Etienne , Guidi Monia , Fischer Céline J. , Bickle Graz Myriam , Beaufils Etienne , Nguyen Kim An , Morisod Harari Mathilde , Rouiller Sylvie , Rothenburger Sophie , Gaucherand Pascal , Kassai‐Koupai Behrouz , Borradori Tolsa Cristina , Epiney Manuella , Tolsa Jean‐François , Vial Yvan , Hascoët Jean‐Michel , Claris Olivier , Eap Chin B , Panchaud Alice , Csajka Chantal
Published: March 2020

Background and objectives

Escitalopram (SCIT) is frequently prescribed to breastfeeding women. Available information on SCIT excretion into breast milk is based on heterogeneous and incomplete data. A population pharmacokinetic model that aimed to better characterize maternal and infant exposure to SCIT and its metabolite was developed.

Methods

The study population was composed of women treated by SCIT or racemic citalopram and enrolled in the multicenter prospective cohort study SSRI‐Breast Milk study (ClinicalTrial.gov NCT01796132). A joint structural model was first built for SCIT and S‐desmethylcitalopram (SDCIT) in plasma using NONMEM and the milk‐to‐plasma ratio (MPR) was estimated by adding the drug breast milk concentrations. The effect of different influential covariates was tested and the average drug exposure with variability through breastfeeding was predicted under various conditions by simulation.

Results

The study enrolled 33 patients treated with SCIT or racemic citalopram who provided 80 blood and 104 milk samples. Mean MPR for both parent drug and metabolite was 1.9. Increased milk fat content was significantly associated with an increased drug transfer into breast milk (+28% for SCIT and +18% for SDCIT when fat amount doubles from 3.1 to 6.2 g/100 mL). Simulations suggested that an exclusively breastfed infant would ingest daily through breast milk 3.3% of the weight‐adjusted maternal SCIT dose on average.

Conclusion

The moderate between‐subject variability in milk concentration of SCIT and the limited exposure to escitalopram through breast milk observed provide reassurance for treated mothers of breastfed healthy infants.
RAPP‐children: A new tool for assessing quality of life in patients with asthma and rhinitis
Authors: Fasola Salvatore , Montalbano Laura , Ferrante Giuliana , Cilluffo Giovanna , Malizia Velia , Baiardini Ilaria , Braido Fulvio , Viegi Giovanni , La Grutta Stefania
Published: March 2020

Background

RhinAsthma Patient Perspective (RAPP) is a short, validated questionnaire for assessing health‐related quality of life (HRQoL) in adult patients with comorbid asthma and rhinitis, while a paediatric version is still not available.

Objective

The current study aimed to develop and validate the RAPP‐children questionnaire.

Methods

RAPP‐children was derived by combining RhinAsthma‐children subscales into five unique items. At baseline (T0) and after 30 days (T1), 150 children (6‐11 years) with comorbid asthma (predominantly intermittent or mild persistent) and rhinitis were given the following: RAPP‐children, RhinAsthma‐children, Paediatric Asthma Quality of Life Questionnaire (PAQLQ, age >6 years), Paediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ), Childhood Asthma Control Test (CACT), KiddyKindl® (age 6 years) or KidKindl® (age >6 years), and a Visual Analogue Scale for nasal symptoms (VAS). At the final visit, a Global Rating of Change (GRC) scale was administered. The approved study was registered on the central registration system ClinicalTrials.gov (ID: NCT03276416).

Results

RAPP‐children fairly reproduced RhinAsthma‐children scores (concordance correlation coefficients between 0.91 and 0.95). RAPP‐children showed adequate convergent validity (absolute Spearman's rho larger than 0.5 with PAQLQ, PRQLQ, CACT, KiddyKindl/KidKindl, and VAS), internal consistency (Cronbach's alpha > 0.70), repeatability (intra‐cluster correlation coefficient between 0.61 and 0.8) in the presence of clinical stability (GRC = 0), discriminant validity (sensitivity to asthma control status and rhinitis severity), and sensitivity to symptom improvements (GRC > 1). The minimal important difference (MID) was −20. Floor and ceiling effects were minimal. RAPP‐children showed fair usability also in younger children (6‐8 years).

Conclusion & Clinical Relevance

RAPP‐children is a valid, five‐item questionnaire for assessing HRQoL in children aged 6 to 11 years with concomitant asthma and rhinitis. Although further investigation is required in moderate and severe asthmatics, this tool can be useful in clinical trials and in routine medical practice for improving the management of respiratory allergy in children.
When to think outside the autozygome: Best practices for exome sequencing in “consanguineous” families
Authors: Eaton Alison , Hartley Taila , Kernohan Kristin , Ito Yoko , Lamont Ryan , Parboosingh Jillian , Barrowman Nick ,   The Care4Rare consortium, Innes A. Micheil , Boycott Kym
Published: March 2020

Exome sequencing (ES) is an effective diagnostic tool with a high yield in consanguineous families. However, how diagnostic yield and mode of inheritance relate to family structure has not been well delineated. We reviewed ES results from families enrolled in the Care4Rare Canada research consortium with various degrees of consanguinity. We contrasted the diagnostic yield in families with parents who are second cousins or closer (“close” consanguinity) vs those more distantly related or from isolated populations (“presumed” consanguinity). We further stratified by number of affected individuals (multiple affected [“multiplex”] vs single affected [simplex]). The overall yield in 116 families was 45.7% (n = 53) with no significant difference between subgroups. Homozygous variants accounted for 100% and 75% of diagnoses in close and presumed consanguineous multiplex families, respectively. In simplex presumed consanguineous families, a striking 46.2% of diagnoses were due to de novo variants, vs only 11.8% in simplex closely consanguineous families (88.2% homozygous). Our data underscores the high yield of ES in consanguineous families and highlights that while a singleton approach may frequently be reasonable and a responsible use of resources, trio sequencing should be strongly considered in simplex families in the absence of confirmed consanguinity given the proportion of de novo variants.
Optimisation of process parameters of Alpaca wool printing with Juglans regia natural dye
Authors: Glogar Martinia , Tancik Josipa , Brlek Iva , Sutlovic Ana , Tkalec Marijana
Published: March 2020

The aim of this research study was to optimise the process parameters of Alpaca wool hand‐knitted samples screen‐printing with Juglans regia natural dye and to set the optimal conditions regarding colour yield, colour fastness and colouristic properties of printed samples. An extensive preliminary examination of the Alpaca woollen yarn and hand‐knitted samples characteristics, the characteristics of suitable thickeners and the optimisation of the printing paste composition, was performed. A starch‐based thickener, British Gum, with a dry matter content of 4% was selected due to its rheological properties responding to properties of the Alpaca yarn and knitwear. It was determined that the fluidity increases while the viscosity and the elasticity decrease in acidic pH, so a pH of 4 was set for the thickener preparation. The thickener of lower viscosity and higher fluidity assures easier pressing of printing paste through the screen, giving uniform colour yield on the substrate, contributing to easier absorption of dyes into the fibre. A 45‐minute fixing process at 105°C by steaming delivered the best results of printing quality. Iron sulphate was used as the mordanting agent. The colour fastness to washing, dry and wet rubbing, and to light, was tested for samples with and without mordanting. The highest light and washing fastness were obtained with the iron sulphate mordanting agent printed in acid (pH 4) with paste containing 4% dry matter‐based thickener. The rubbing fastness was satisfactory for samples with iron sulphate printed with paste containing 4% dry matter thickener, fixed for 45 minutes, regardless of the pH.
The roles of mutated SWI/SNF complexes in the initiation and development of hepatocellular carcinoma and its regulatory effect on the immune system: A review
Authors: Hu Bo , Lin Jian‐Zhen , Yang Xiao‐Bo , Sang Xin‐Ting
Published: March 2020

Hepatocellular carcinoma (HCC) is a primary liver malignancy with a high global prevalence and a dismal prognosis. Studies are urgently needed to examine the molecular pathogenesis and biological characteristics of HCC. Chromatin remodelling, an integral component of the DNA damage response, protects against DNA damage‐induced genome instability and tumorigenesis by triggering the signalling events that activate the interconnected DNA repair pathways. The SWI/SNF complexes are one of the most extensively investigated adenosine triphosphate‐dependent chromatin remodelling complexes, and mutations in genes encoding SWI/SNF subunits are frequently observed in various human cancers, including HCC. The mutated SWI/SNF complex subunits exert dual functions by accelerating or inhibiting HCC initiation and progression. Furthermore, the abnormal SWI/SNF complexes influence the transcription of interferon‐stimulated genes, as well as the differentiation, activation and recruitment of several immune cell types. In addition, they exhibit synergistic effects with immune checkpoint inhibitors in the treatment of diverse tumour types. Therefore, understanding the mutations and deficiencies of the SMI/SNF complexes, together with the associated functional mechanisms, may provide a novel strategy to treat HCC through targeting the related genes or modulating the tumour microenvironment.
Anti‐tumour effects of Keratin 6A in lung adenocarcinoma
Authors: Xiao Jian , Kuang Xiao , Dai Longxia , Zhang Lihai , He Bixiu
Published: March 2020

Background

To examine the effects of Keratin 6A (KRT6A) protein on the proliferation, migration and invasion abilities of lung adenocarcinoma cells, and to analyse the relationship between the expression level of KRT6A protein and the survival prognosis of lung adenocarcinoma patients.

Methods

Western Blot was used to detect the expression of KRT6A protein in lung adenocarcinoma cell lines. CCK‐8 experiment and colony formation assays were performed to detect the proliferation ability. Wound healing assay and transwell migration assay were conducted to detect the migration ability. Transwell invasion assay was conducted to detect the invasion ability. Immunohistochemistry was used to detect the expression of KRT6A protein in lung adenocarcinoma tissues.

Results

We first found that the expression of KRT6A protein in lung adenocarcinoma cell lines was low. After overexpressed KRT6A protein in lung adenocarcinoma cells, we then found that KRT6A protein could not only inhibit the proliferation ability of lung adenocarcinoma cells but also inhibit them migration and invasion abilities. In addition, we also found that there had obvious difference in the expression of KRT6A protein in between patients. And through further analysis, we finally discovered that high expression of KRT6A protein was related to favourable prognosis in lung adenocarcinoma patients.

Conclusions

KRT6A protein inhibits the proliferation, migration and invasion abilities of lung adenocarcinoma cells, and high expression of KRT6A protein is a predictor of good prognosis in patients with lung adenocarcinoma.
Bastard Spice or Champagne of Cinnamon? Conflicting Value Creations along Cinnamon Commodity Chains in Northern Vietnam
Authors: Derks Annuska , Turner Sarah , Thúy Hạnh Ngô
Published: March 2020

In upland northern Vietnam ethnic minority farmers are cultivating what some global retailers refer to as the ‘champagne of cinnamon’. However, a closer examination reveals that this spice is not ‘true cinnamon’ but cassia, with the exact species remaining uncertain. Drawing on commodity chain literature and debates over the creation of value and quality, the aims of this article are twofold. First, it investigates the making of ‘Vietnamese cinnamon’ as it moves from the hills of northern Vietnam to supermarket shelves in the global North, and the actors and livelihoods involved. Second, it explores how different actors define ‘Vietnamese cinnamon’ and infuse it with often‐contradictory values. Based on multi‐sited ethnographic fieldwork over a four‐year period, the study finds that the state and cooperating non‐government organizations tend to ignore ongoing taxonomic confusion while creating a geographical indicator to highlight the uniqueness of this commodity. Yet, concurrently, exporters and retailers in the global North focus on other distinctions as key marketing tools including remoteness, ethnicity, taste and health benefits. The article thus calls for an expanded analytical focus on competing value creation for agro‐food products and on the impacts for commodity producers, in this case ethnic minority farmers in the global South.
Self‐perceived gait quality in young adults with cerebral palsy
Authors: Bonnefoy‐Mazure Alice , De Coulon Geraldo , Armand Stephane
Published: March 2020

Aim

To explore how patients with cerebral palsy (CP) perceive their gait and evaluate associations between subjective gait perception and: objective gait parameters, endurance, pain, and fatigue.

Method

Sixty‐two patients (21 females and 41 males; mean [SD] age 20y [5y 1mo], range 15–29y) performed a clinical gait analysis. Self‐selected walking speed, Gait Profile Score, and Gait Variable Score were calculated. Subjective gait perception was assessed with a visual analogue scale using the question: ‘On a scale from 0 (worst) to 10 (optimal), how would you describe your walking today?’. A 6‐minute walk test (6MWT) measured endurance; the 36‐Item Short Form Health Survey (SF‐36) evaluated quality of life. T‐tests, Pearson correlations, and univariate and multiple linear regression models were used to compare and find associations between the data.

Results

Overall mean (SD) subjective gait perception was 7.5 (1.8) and was significantly higher for patients in Gross Motor Function Classification System (GMFCS) level I (7.9 [1.5]) than for patients in GMFCS levels II and III (5.9 [2.0]). Positive correlations were found between subjective gait perception and gait scores, walking speed, 6MWT distance, and SF‐36 score. Only walking speed was a significant predictor of subjective gait perception.

Interpretation

Subjective gait perception was influenced by GMFCS level and linked partially with the walking speed. The gait quality did not explain subjective gait perception. It is important to combine subjective and objective gait scores to develop personalized therapeutic goals.

What this paper adds

Subjective gait perception is influenced by the physical impairment levels of patients with cerebral palsy.

Subjective gait perception and objective gait scores are associated.

Walking speed is the only predictor of gait perception.
Growth and muscle strength development in children with developmental coordination disorder
Authors: Demers Isabelle , Moffet Hélène , Hébert Luc , Maltais Désirée B
Published: March 2020

Aim

To assess effects of growth on lower limb maximal isometric muscle strength (MIMS) development in children with developmental coordination disorder (DCD).

Method

This observational study used hand‐held dynamometry to evaluate MIMS (hip abductors, flexors, extensors; knee flexors and extensors; ankle dorsiflexors) in children with DCD (n=33, 12 females, 21 males, 6–12y, mean [SD] age 9y [2y]). Regression analysis compared changes in MIMS for similar changes in growth (height or body mass) for children with DCD and typically developing children (pre‐existing database, n=183), controlling for age and sex.

Results

For the same height gain, the gain in muscle strength was 37.3% to 69.2% less in children with DCD compared with typically developing children, with significantly lower slopes (p‐value between <0.001–0.042) in all muscle groups tested except knee extensors and ankle dorsiflexors in females. Strength gains related to body mass gains were not different for children with DCD compared to typically developing children.

Interpretation

Even when growing at a similar rate, children with DCD do not develop muscle strength gains at the same rate as their typically developing peers.

What this paper adds

Strength gains with growth (height) may be reduced in children with developmental coordination disorder.