bluuebunny/crossref_metadata_2025 huggingface dataset:
Disulfide reduction allosterically destabilizes the β-ladder sub-domain assembly within the NS1 dimer of ZIKV
Authors: Roy P , Roy S , Sengupta N
Published: May 2020

The Zika virus (ZIKV) was responsible for a recent debilitating epidemic that till date has no cure. A potential way to reduce ZIKV virulence is to limit the action of the non-structural proteins involved in its viral replication. One such protein, NS1, encoded as a monomer by the viral genome, plays a major roleviasymmetric oligomerization. We examine the homodimeric structure of the dominant β-ladder segment of NS1 with extensive all atom molecular dynamics. We find it stably bounded by two spatially separated interaction clusters (C1 and C2) with significant differences in the nature of their interactions. Four pairs of distal, intra-monomeric disulfide bonds are found to be coupled to the stability, local structure, and wettability of the interfacial region. Symmetric reduction of the intra-monomeric disulfides triggers marked dynamical heterogeneity, interfacial wettability and asymmetric salt bridging propensity. Harnessing the model-free Lipari-Szabo based formalism for estimation of conformational entropy (Sconf), we find clear signatures of heterogeneity in the monomeric conformational entropies. The observed asymmetry, very small in the unperturbed state, expands significantly in the reduced states. This allosteric effect is most noticeable in the electrostatically bound C2 cluster that underlies the greatest stability in the unperturbed state. Allosteric induction of conformational and thermodynamic asymmetry is expected to affect the pathways leading to symmetric higher ordered oligomerization, and thereby affect crucial replication pathways.

Statement of significance

Controlling viral pathogenesis remains a challenge in the face of modern-day epidemics. Though cumbersome and fraught with misleads, most therapeutic endeavors lean towards the design of drug molecules targeting specific proteins involved in viral pathogenesis. This work demonstrates an alternative approach, namely the usage of allosteric intervention to disrupt the binding integrity of the primary domain of the non-structural NS1 protein dimer crucially important in ZIKV virulence. The intervention, triggered by symmetric reduction of the internal monomeric disulfide bonds, results in weakening and distortion of the distal binding interfaces. It further introduces marked structural and entropic asymmetry within the homooligomeric unit, precluding the formation of higher ordered oligomers of high symmetry. The results have important ramifications for consolidated efforts at limiting ZIKV virulence.
Metapangenomics of the oral microbiome provides insights into habitat adaptation and cultivar diversity
Authors: Utter Daniel R. , Borisy Gary G. , Eren A. Murat , Cavanaugh Colleen M. , Welch Jessica L. Mark
Published: May 2020

Background

The increasing availability of microbial genomes and environmental shotgun metagenomes provides unprecedented access to the genomic differences within related bacteria. The human oral microbiome with its diverse habitats and abundant, relatively well-characterized microbial inhabitants presents an opportunity to investigate bacterial population structures at an ecosystem scale.

Results

Here, we employ a metapangenomic approach that combines public genomes with Human Microbiome Project (HMP) metagenomes to study the diversity of microbial residents of three oral habitats: tongue dorsum, buccal mucosa, and supragingival plaque. For two exemplar taxa,Haemophilus parainfluenzaeand the genusRothia, metapangenomes revealed distinct genomic groups based on shared genome content.H. parainfluenzaegenomes separated into three distinct subgroups with differential abundance between oral habitats. Functional enrichment analyses identified an operon encoding oxaloacetate decarboxylase as diagnostic for the tongue-abundant subgroup. For the genusRothia, grouping by shared genome content recapitulated species-level taxonomy and habitat preferences. However, while mostR. mucilaginosawere restricted to the tongue as expected, two genomes represented a cryptic population ofR. mucilaginosain many buccal mucosa samples. For bothH. parainfluenzaeand the genusRothia, we identified not only limitations in the ability of cultivated organisms to represent populations in their native environment, but also specifically which cultivar gene sequences were absent or ubiquitous.

Conclusions

Our findings provide insights into population structure and biogeography in the mouth and form specific hypotheses about habitat adaptation. These results illustrate the power of combining metagenomes and pangenomes to investigate the ecology and evolution of bacteria across analytical scales.
Shifting trust in construction supply chains through blockchain technology
Authors: Qian Xiaoning (Alice) , Papadonikolaki Eleni
Published: May 2020

Purpose

Blockchain technology is booming in many industries. Its application in supply chain management is also gradually increasing. Supply chain management (SCM) has long been committed to reducing costs and increasing efficiency and is trying to optimise resources and reduce the sector's fragmentation. Trust has always been an important factor in managing supply chain relationships, and it also affects the efficiency of supply chain operations. To this end, this study aims to examine how trust is affected by the introduction of blockchain technology in construction supply chain management.

Design/methodology/approach

This study is based on semi-structured interviews and publicly available information from experts in blockchain and construction supply chain management. Through content analysis, the data are analysed thematically to explore how various types of trust, such as system-based, cognition-based and relation-based, are affected by blockchain technology.

Findings

Blockchain technology provides solutions for data tracking, contracting and transferring resources in supply chain management. These applications help enhance the various sources of trust in SCM and provide supply chain partners with protection mechanisms to avoid the risks and costs of opportunistic behaviour in collaboration, shifting trust from relational to system-based and cognition-based.

Research limitations/implications

This study focuses only on inter-organisational rather than interpersonal trust and empirical data from experts whose knowledge and cognition could be subjective.

Practical implications

Leveraging the potential of digitalisation to manage trust requires that leaders and managers actively try to improve contractual arrangements, information sharing and being open to new innovative technologies like blockchain.

Social implications

From a relational view of supply chain management, the extent to which blockchain technology can develop and spread depends on the readiness of the social capital to accept decentralised governance structures.

Originality/value

This study builds upon an original data set and discusses features and applications of blockchain technology, explores the sources and dimensions of trust in supply chain management and explains the impact of blockchain technology on trust.
Explicating innovation-based human resource management's influence on employee satisfaction and performance
Authors: Lasisi Taiwo Temitope , Ozturen Ali , Eluwole Kayode Kolawole , Avci Turgay
Published: May 2020

Purpose

This study aims to build and test an empirical model that investigates the mechanism with which innovation-based human resource management (HRM) impacts employee satisfaction and performance in Nigerian international airports.

Design/methodology/approach

A time-lagged approach that involved three-waves was used to collect data from passenger-contact employees and their immediate managers for three-month period starting from January to March 2019. A total of 247 dyads of passenger-contact employees and managers were used for the data analysis.

Findings

Results from data analysis showed that coworker support and absorptive capacity mediate the impact of innovation-based HRM on employee satisfaction and performance. Innovation-based human resource effort is best applied when coworker support is evident in the workplace.

Originality/value

The development and application of innovation-driven human resources in the Nigerian aviation context encourage satisfaction with assigned task roles, leading to employee performance. Theory-based implications for managing passenger-contact employees were also given. A significant strength of this study is that it is among the forerunners of scholars that investigated innovation-based HRM as a continuum rather than different aspects of broader management issues.
Simulated home: an effective cross-cultural adjustment model for Chinese expatriates
Authors: Huang Hao , Liu Hong , Huang Xin , Ding Yusen
Published: May 2020

Purpose

The purpose of this study is to explore the adjustment model of expatriates in overseas projects by studying two overseas projects of a Chinese state-owned enterprise.

Design/methodology/approach

Based on the grounded theory, qualitative analysis was performed based on data compiled from 116 pieces of project briefings, 105 questionnaires answered by expatriate workers and 21 interviews conducted to those workers based on briefings and questionnaires.

Findings

The study found that the simulated home is a standard cross-cultural adjustment model for expatriates in Chinese engineering projects, which are project-oriented and often inattentive to employees' individual rights. The simulated home creates a unique work-place and social environment similar to that of expatriates' home country in the cultural setting of the host country, but it also establishes a cultural barrier, limiting the communication between expatriates and the local people, which is not conducive to the cultural exchange between the two sides, causing cultural clashes and consequently hindering the progress of projects.

Originality/value

This research puts forward the model of “simulated home.” And this study bears significance to the cross-cultural adjustment of expatriate workers in Chinese overseas projects.
Harsh environmental regimes increase the functional significance of intraspecific variation in plant communities
Authors: Niu Kechang , Zhang Shiting , Lechowicz Martin J.
Published: May 2020

The relative importance of intraspecific trait variation (rITV) for functional diversity (FD) in plant communities is increasingly apparent, but the influence of abiotic factors on the balance between intraspecific and interspecific effects in contrasting environments is uncertain. Drawing on a novel conceptual and analytic framework, we quantified rITV as the ratio of FD associated with between‐population ITV (Intra_FD) and the interspecific variation (Inter_FD) due to species turnover across sites.

We predicted that rITV would increase with environmental harshness as a result of decreasing interspecific variation and concomitant increases in between‐population ITV. We empirically tested this prediction in a comparison of rITV for five traits (mature plant height, SLA, leaf dry matter content and the foliar concentrations of nitrogen and phosphorus (P)) characterizing species in Tibetan alpine meadow communities from contrasting environmental regimes.

We found that across sites: (a) rITV for all five traits increased with environmental harshness not only through decreasing Inter_FD but also through increasing Intra_FD; (b) increases in rITV were mostly attributable to declines in soil resources, especially soil P, with lower soil P significantly associated with lower Inter_FD but higher Intra_FD for most traits; and (c) although neither Intra_FD nor Inter_FD was significantly impacted by species richness for any traits, a higher rITV for SLA was significantly associated with low species richness.

Taken together, these results support our hypothesis that the functional significance of ITV in plant communities increases with environmental harshness. Moreover, in the Tibetan alpine meadows we studied, the opposing intraspecific and interspecific responses along a gradient of P availability appear to act as a buffering mechanism stabilizing the functional structure of communities on P deficient soils. Our novel conceptual and analytical framework provides a template for evaluating the generality of this favourable mismatch between intraspecific and interspecific responses in FD along environmental gradients.

A free Plain Language Summary can be found within the Supporting Information of this article.
Cause of intrauterine and neonatal death in twin pregnancies (CoDiT): development of a novel classification system
Authors: Gulati N , Mackie FL , Cox P , Marton T , Heazell AEP , Morris RK , Kilby MD
Published: May 2020

Objective

Twin pregnancies have a significantly higher perinatal mortality than singleton pregnancies. Current classification systems for perinatal death lack twin‐specific categories, potentially leading to loss of important information regarding cause of death. We introduce and test a classification system designed to assign a cause of death in twin pregnancies (CoDiT).

Design

Retrospective cross‐sectional study.

Setting

Tertiary maternity unit in England with a perinatal pathology service.

Population

Twin pregnancies in the West Midlands affected by fetal or neonatal demise of one or both twins between 1 January 2005 and 31 December 2016 in which postmortem examination was undertaken.

Methods

A multidisciplinary panel designed CoDiT by adapting the most appropriate elements of singleton classification systems. The system was tested by assigning cause of death in 265 fetal and neonatal deaths from 144 twin pregnancies. Cause of death was validated by another obstetrician blinded to the original classification.

Main outcome measures

Inter‐rater, intra‐rater, inter‐disciplinary agreement and cause of death.

Results

Cohen’s Kappa demonstrated ‘strong’ (>0.8) inter‐rater, intra‐rater and inter‐disciplinary agreement (95% CI 0.70–0.91). The commonest cause of death irrespective of chorionicity was the placenta; twin‐to‐twin transfusion syndrome (TTTS) was the commonest placental cause in monochorionic twins and acute chorioamnionitis in dichorionic twins.

Conclusions

This novel classification system records causes of death in twin pregnancies from postmortem reports with high inter‐user agreement. We highlight differences in aetiology of death between monochorionic and dichorionic twins.

Tweetable abstract

New classification system for #twin cause of death ‘CoDiT’ shows high rater agreement.
Associations Between Self‐Reported and Biological Measures of Nicotine Consumption Among Young Adult Nondaily Cigarette Smokers
Authors: Doran Neal , Correa John B. , Myers Mark G. , Tully Lyric
Published: May 2020

Background and Objectives

Intermittent, dual use of cigarettes and e‐cigarettes is a common pattern among youth and young adults. However, little is known about the validity of self‐report measures of nicotine consumption in these populations. The goal of the present study was to examine associations between self‐reported frequency of cigarette and e‐cigarette use and nicotine levels in hair samples at two assessments 1 year apart.

Methods

Participants (n = 90; 65% female) were 19‐ to 25‐year‐old intermittent cigarette smokers recruited from the community for a longitudinal study of tobacco use. They submitted hair samples via mail, 1 and 2 years after enrollment in the parent study.

Results

Findings indicated that days of use of both cigarettes and e‐cigarettes in the past 30 days independently predicted hair nicotine in the full sample, and when examining only timepoints at which any cigarette use was reported. Timepoints when any e‐cigarette use was reported, hair nicotine was positively associated with e‐cigarette but not cigarette frequency.

Discussion and Conclusions

Data suggest that self‐report measures are valid methods of assessing intermittent use of both cigarettes and e‐cigarettes. Findings also suggest that dual users may tend to consume more nicotine and thus be at greater risk for dependence than single product users.

Scientific Significance

These results are among the first to indicate that hair analysis can be used to detect intermittent nicotine exposure via both cigarettes and e‐cigarettes. (Am J Addict 2020;29:471–475)
Molecular profiling of a primary cutaneous signet‐ring cell/histiocytoid carcinoma of the eyelid
Authors: Raghavan Shyam S. , Clark Melissa , Louie Christine Y. , Jensen Kristin C. , Dietrich Brian , Beadle Beth Michelle , El‐Sawy Tarek , Baik Fred , Kunder Christian A. , Brown Ryanne A.
Published: May 2020

Primary cutaneous signet‐ring cell/histiocytoid carcinoma of the eyelid is a rare and aggressive neoplasm. Fewer than 50 cases have been reported in the literature, and the genetic driving mutations are unknown. Herein, we present a case of this rare disease along with the results of molecular profiling via targeted next‐generation sequencing. The patient is an 85‐year‐old man who presented with left eyelid swelling initially thought to be a chalazion. After no response to incision and drainage and antibiotics, an incisional biopsy was performed. Histopathologic sections revealed a proliferation of cells with signet‐ring and histiocytoid morphology arranged singly and in cords infiltrating the dermis, subcutaneous tissue, and muscle. The lesional cells strongly expressed cytoplasmic cytokeratin 7 and nuclear androgen receptor. Next‐generation sequencing revealed aCDH1mutation, which is known to confer signet‐ring morphology in other carcinomas. Pathogenic mutations inNTRK3,CDKN1B, andPIK3CAwere also detected. To our knowledge, this is the first documented genetic analysis of this rare disease with findings that offer insights into disease pathogenesis and potential therapeutic targets.
Alcohol use in times of the COVID 19: Implications for monitoring and policy
Authors: Rehm Jürgen , Kilian Carolin , Ferreira‐Borges Carina , Jernigan David , Monteiro Maristela , Parry Charles D. H. , Sanchez Zila M. , Manthey Jakob
Published: May 2020

Based on a literature search undertaken to determine the impacts of past public health crises, and a systematic review of the effects of past economic crises on alcohol consumption, two main scenarios—with opposite predictions regarding the impact of the current COVID‐19 pandemic on the level and patterns of alcohol consumption—are introduced. The first scenario predicts an increase in consumption for some populations, particularly men, due to distress experienced as a result of the pandemic. A second scenario predicts the opposite outcome, a lowered level of consumption, based on the decreased physical and financial availability of alcohol. With the current restrictions on alcohol availability, it is postulated that, for the immediate future, the predominant scenario will likely be the second, while the distress experienced in the first may become more relevant in the medium‐ and longer‐term future. Monitoring consumption levels both during and after the COVID‐19 pandemic will be necessary to better understand the effects of COVID‐19 on different groups, as well as to distinguish them from those arising from existing alcohol control policies.
Evidence for early arousal‐based differentiation of emotions in children’s musical production
Authors: Kragness Haley E. , Eitel Matthew J. , Baksh Ammaarah M. , Trainor Laurel J.
Published: May 2020

Accurate perception and production of emotional states is important for successful social interactions across the lifespan. Previous research has shown that when identifying emotion in faces, preschool children are more likely to confuse emotions that share valence, but differ in arousal (e.g. sadness and anger) than emotions that share arousal, but differ on valence (e.g. anger and joy). Here, we examined the influence of valence and arousal on children's production of emotion in music. Three‐, 5‐ and 7‐year‐old children recruited from the greater Hamilton area (N = 74) ‘performed’ music to produce emotions using a self‐pacing paradigm, in which participants controlled the onset and offset of each chord in a musical sequence by repeatedly pressing and lifting the same key on a MIDI piano. Key press velocity controlled the loudness of each chord. Results showed that (a) differentiation of emotions by 5‐year‐old children was mainly driven by arousal of the target emotion, with differentiation based on both valence and arousal at 7 years and (b) tempo and loudness were used to differentiate emotions earlier in development than articulation. The results indicate that the developmental trajectory of emotion understanding in music may differ from the developmental trajectory in other domains.
Whose reading matters? Rereading Exodus 1 in the context of African (South African) women
Authors: Masenya (Ngwan'a Mphahlele) Madipoane
Published: May 2020

The narrative of the interaction of African (South African) women and the Bible is first situated within the framework of the folktale of the Lion and the Rabbit. The theme of the multiplication of (male) babies as featured in Exodus 1 is then re‐read through the hermeneutical lenses of African (South African) women's experiences. If Exodus 1 is read in family‐oriented cultures like that of ancient Israel and Africa, what insights may be gleaned? Which reading(s) may emerge? Will the resultant readings matter especially to African (South) African women? The preceding questions, will be engaged with in this essay.
Churches in transforming mission: A story of Lutheran communion in Africa
Authors: Mungure Elieshi Ayo
Published: May 2020

The argument of this paper is that the legacy of “ecclesia semper reformanda” (churches in a continued reformation and renewal) in Africa should not only transform the theological perspective of the Lutheran communion, but also take stock of the diaconal, social, economic and political realities of its members. In other words, a theology done in Africa needs tools and methodologies that are more comprehensive.
Companion planting to attract pollinators increases the yield and quality of strawberry fruit in gardens and allotments
Authors: Griffiths‐Lee Janine , Nicholls Elizabeth , Goulson Dave
Published: May 2020

1. Global pollinator declines have led to concern that crop yields might fall as a result of a pollination deficit. Companion planting is a traditional practice thought to increase yield of insect pollinated crops by planting a co‐flowering species next to the crop.

2. Using a combination of conventional researcher‐led experiments and observational citizen scientist data, we tested the effectiveness of bee‐friendly borage (Borago officinalis) as a companion plant to strawberry (Fragaria x ananassa). Insect visitors to the ‘Test’ (strawberry + borage) versus ‘Control’ (strawberry only) plants were observed, and strawberry fruit collected. Strawberries collected during the researcher‐led experiment were also subject to fruit measurements and assessments of market quality.

3. Companion plants were found to significantly increase both yield and market quality of strawberries, suggesting an increase in insect pollination per plant. Test strawberries companion planted with borage produced an average of 35% more fruits, and 32% increased yield by weight. Test strawberry plants produced significantly more fruit of higher aesthetic quality when assessed by Marketing Standards for Strawberries.

4. Although there was no significant difference in the overall insect visits, when broken down by broad insect group there were significantly more flies visiting the test strawberries than controls.

5. These results could have implications for both gardeners and commercial growers. As consumers prefer a cosmetically perfect fruit, the production of fruit with increased aesthetics aids food waste reduction.
Survival of native seedlings planted by volunteers: The Lower Cotter, ACT case study
Authors: Hnatiuk Sarah , Rayner Ian , Brookhouse Matthew , Freudenberger David
Published: May 2020

Volunteer labour is often used for planting native seedlings for revegetation projects. The survival of such plantings is seldom monitored and reported. The overall survival of seedlings at three years of age was assessed for eight years of plantings established by nearly 15,000 volunteers in the Lower Cotter River catchment in the Australian Capital Territory. Mean survival was 66.8% across all years. We conclude that volunteers can be effectively integrated into large‐scale revegetation projects if they are well trained and organised.
Letter to the Editor regarding ‘What is the best treatment for mares with post‐partum haemorrhage?’ by P. Wilkins
Authors: Scoggin C. F.
Published: May 2020

See the critically appraised topic by Wilkins and correspondence by Wilkins.
Erenumab Efficacy on Comorbid Cluster Headache in Patients With Migraine: A Real‐World Case Series
Authors: Silvestro Marcello , Tessitore Alessandro , Scotto di Clemente Fabrizio , Tedeschi Gioacchino , Russo Antonio
Published: May 2020

Background

Monoclonal antibodies (mABs) against calcitonin gene‐related peptide (CGRP) or its receptor have emerged as effective and well‐tolerated preventive medications for migraine. The key role played by CGRP has been recently demonstrated also in the pathophysiology of cluster headache (CH), paving the way for studies aimed to investigate the effectiveness of mABs targeting CGRP also in CH. However, no trials have been conducted so far to test the efficacy and tolerability of erenumab as CH preventive treatment.

Case Series

We describe the cases of 5 patients with both migraines and CH with previous failures of preventive treatments. All patients were treated with monthly erenumab (70 or 140 mg) showing good results not only on migraine but also on CH attacks frequency and intensity. Improvements of both intensity and frequency of CH attacks occurred only after at least 3 months of treatment, with monthly erenumab 140 mg, suggesting that longer treatment and higher doses are needed in CH in comparison to migraine.

Discussion and Conclusion

Our findings support the efficacy and tolerability of monthly erenumab 140 mg as a preventive treatment in patients suffering from both migraines without aura and CH. We speculate that erenumab could represent a low‐risk alternative for CH patients (with or without comorbid migraine) who did not tolerate common CH preventatives therapies or for whom the therapies were not successful. Certainly, randomized trials are needed to confirm these observations and we hope that our data, showing a delayed therapeutic effect only with the highest dose of erenumab (140 mg/month), can be taken into account in designing future trials.
Morphologically high‐grade microcystic adnexal carcinoma: a report of two cases
Authors: Brenn Thomas , Wiedemeyer Katharina , Calonje Eduardo
Published: May 2020

Aims

Microcystic adnexal carcinoma is a distinctive sweat duct carcinoma of low‐grade malignant potential with a risk for locally destructive growth and local recurrence. Distant metastases and disease‐related mortality are exceptional. The histological hallmarks of these tumours are the diffusely infiltrative growth within the dermis, the frequent invasion of subcutaneous structures, the presence of perineurial invasion, and the bland cytological features. The tumours are organised in cords and strands, and show keratocyst formation and duct differentiation in varying proportions. Marked cytological atypia, nuclear pleomorphism, brisk and atypical mitotic activity and necrosis are not typically seen in these tumours.

Methods and results

We report two patients presenting with large, slowly growing tumours on the face showing areas of morphologically high‐grade carcinoma arising on a background of unequivocal microcystic adnexal carcinoma. Both patients are alive with follow‐up of up to 6 years, with no evidence of disease.

Conclusions

Morphologically high‐grade transformation in microcytic adnexal carcinoma is a rare phenomenon that does not appear to confer a risk for aggressive behaviour. Recognition depends on sampling of the areas of conventional microcystic adnexal carcinoma.
Grading of prostate cancer: the impact of including intraductal carcinoma on the overall Grade Group assigned in diagnostic biopsies
Authors: Chen‐Maxwell Daphne , Prendeville Susan
Published: May 2020

Aims

The Gleason score/Grade Group (GrG) is a key parameter for clinical decision‐making in prostate cancer. The World Health Organization currently recommends that intraductal carcinoma of the prostate (IDCP) should not be factored into the GrG; however, grading of IDCP is controversial, with variability among genitourinary pathologists. The aim of this study was to evaluate the impact of grading of the IDCP component on the final GrG in prostate biopsies.

Methods and results

The study included 123 prostate biopsies (12 cores +/− additional MRI‐targeted cores) with GrG1–GrG4 invasive carcinoma and IDCP. All cases were graded by a genitourinary pathologist using two different methods: (i) grading of invasive carcinoma only; and (ii) grading of both invasive carcinoma and IDCP. The overall GrG, excluding the IDCP component, was GrG1 in 3% (n = 4) of cases, GrG2 in 37% (n = 45), GrG3 in 52% (n = 64), and GrG4 in 8% (n = 10). When the IDCP component was included in grading, the overall GrG changed in 28 cases (23%). The GrG increased by one grade in 15 of 28 cases (54%), and by two or more grades in 13 of 28 cases (46%). Upgrading was due to comedonecrosis (39%, 11/28), solid growth (4%, 1/28), or an increased proportion of Gleason grade 4 (57%, 16/28).

Conclusions

Although the GrG was unchanged in the majority of cases, grading of IDCP altered the final GrG in a significant minority of biopsies in this series, and often by more than one grade, which may have important implications for risk categorisation of individual patients. These findings highlight the need for consensus on grading of IDCP in routine practice, and the optimal method of incorporating IDCP into clinical risk models for patient management.
Identification of acquiredPIGAmutations and additional variants by next‐generation sequencing in paroxysmal nocturnal hemoglobinuria
Authors: Li Jing , Lin Yani , Chen Long , Qin Li , Tan Hao , Zou Junyan , Zhang Donglei , Nie Yanbo , Wang Guangjuan , Zhang Hong , Liu Enbin , Chen Xuejing , Ru Kun
Published: May 2020

Introduction

Paroxysmal Nocturnal Hemoglobinuria (PNH) is an acquired clonal disease of hematopoietic stem cells. It is caused by somatic mutation of the X‐linkedPIGAgene, resulting in a deficient expression of glycosylphosphatidylinositol‐anchored proteins (GPI‐APs). In this study, we aimed to explore the diagnostic value of next‐generation sequencing (NGS) and potential molecular basis in PNH patients.

Methods

Genomic DNA of 85 PNH patients was analyzed by a 114‐gene NGS panel.

Results

Mutational analysis ofPIGAidentified 124 mutations in 92% PNH patients, including 101 distinct mutations and 23 recurrent mutations. Among them, 102 mutations were newly reported. Most mutations were located in exon 2 ofPIGAgene, and truncated mutation was the most common one. Other mutations were detected in 26 out of 85 cases, including five cases ofDNMT3Avariants, four cases ofASXL1variants, and four cases ofU2AF1variants. Clonal analysis was performed in one case and outlined a linear evolution pattern in classic PNH. There was a positive correlation between number ofPIGAmutations and fraction of GPI‐APs deficient granulocytes.

Conclusion

The detection ofPIGAmutations and additional variants by targeted NGS not only shed light on the genetic characteristics of PNH, but also provided an important reference value in the diagnosis of PNH at molecular level.
Health status and healthcare trends of individuals accessing Australian aged care programmes over a decade: the Registry of Senior Australians historical cohort
Authors: Inacio Maria C. , Lang Catherine , Bray Sarah C. E. , Visvanathan Renuka , Whitehead Craig , Griffith Elizabeth C. , Evans Keith , Corlis Megan , Wesselingh Steve
Published: May 2020

Background

Understanding the health profile, service and medicine use of Australians in the aged care sector will help inform appropriate service provision for our ageing population.

Aims

To examine the 2006–2015 trends in (i) comorbidities and frailty of individuals accessing aged care, and (ii) health services, medicine use and mortality after entry into long‐term care.

Methods

Cross‐sectional and population‐based trend analyses were conducted using the Registry of Senior Australians.

Results

From 2006 to 2015, 509 944 individuals accessed permanent residential care, 206 394 home care, 283 014 respite and 124 943 transition care. Over this time, the proportion of individuals accessing permanent residential care with high frailty scores (≥0.3) increased (19.7–49.7%), as did the proportion with 5–9 comorbidities (46.4–54.5%), with similar trends observed for those accessing other services. The median number of medicines dispensed in the year after entering permanent residential care increased from 9 (interquartile range (IQR) 6–12) to 10 (IQR 7–14), while remaining stable in home care (2006: 9, IQR 5–12, 2015: 9, IQR 6–13). Short‐term (within 100 days) mortality in those accessing permanent care was higher in 2006 (15.6%, 95% CI 15.2–16.0) than 2015 (14.6%, 95% CI 14.3–14.9). Longer term (101–1095 days, 2006: 44.3%, 95% CI 43.7–45.0, 2015: 46.4%, 95% CI 45.8–46.9) mortality was higher in 2015 compared to 2006. Mortality in individuals accessing home care did not change.

Conclusion

The health of older Australians accessing aged care programmes has declined while frailty increased, with an increasing use of medicine and worse long‐term mortality in some. Funding and care models need to adapt to this changing profile.
Utility of ‘back‐up’ arterio‐venous fistulae in patients on peritoneal dialysis and use of haemodialysis catheters
Authors: Rao Nitesh N. , Borlace Monique , Taylor Rebecca , Matthew Yvonne , Johnson David W. , Jaffrey Lauren , Mudge David W. , Bannister Kym
Published: May 2020

Background

Patients undergoing peritoneal dialysis may require unanticipated transfer to haemodialysis. Back up fistula are often created in selected patients. These may help reduce the infective burden of haemodialysis (HD) catheter.

Aim

To study the utility of back‐up arterio‐venous fistulae (AVF) in patients initiated on peritoneal dialysis (PD) and to determine the rates of HD catheter use in patients requiring conversion to HD.

Methods

Data on HD transfer and HD catheter usage were retrospectively analysed in all patients initiating PD between January 2010 and December 2014 at Royal Adelaide Hospital (RAH; universal back‐up AVF creation at PD commencement) and Princess Alexandra Hospital (PAH; selective back‐up AVF creation in ‘high risk’ patients).

Results

A total of 374 patients initiated PD during the study period: 142 in RAH group and 232 in PAH group. The groups were reasonably comparable, except that RAH patients were more likely to be older, Caucasian and diabetic. Transfer to HD occurred in 33 (23%) patients in RAH group and 99 (43%) in the PAH group with respective median times to HD transfer of 289 and 295 days. HD catheter usage was required at the time of HD transfer in 11 (33%) patients at RAH and 64 (65%) in patients at PAH (P < 0.001). AVF complications occurred in 13 (9%) patients in RAH group (fistuloplasty n = 8, transposition n = 2, ligation due to ischaemia n = 2 and construction of new AVF n = 1).

Conclusion

Patients undergoing PD frequently require urgent unanticipated transfer to HD and back‐up AVF can be successfully utilised in this setting in the majority of cases, which in turn can reduce the infective burden of HD catheter exposure.
Highly efficient field emission from aligned ZnO/TiN core‐shell nanorods
Authors: Ma Li An , Lai Wen Zong , Wei Zhao Hui , Chen Yan Bin , Chen Hong Xiang
Published: May 2020

Novel polycrystalline TiN coated ZnO core‐shell heterostructure nanorods have been prepared on carbon paper substrate via a low‐temperature hydrothermal and sputtering process. The core‐shell emitters exhibit a highly efficient field‐emission performance with a low threshold of electric field ∼0.72 V/μm, and a high emission current density ~16.41 mA/cm2, a level that is the highest of ZnO emitters reported to date. The improved field‐emission characteristics may be attributed to the unique materials combination of ZnO core and TiN shell, resulting in the conductivity enhancement, emission sites increase, and the work function reduction. Our results demonstrate that ZnO/TiN core‐shell emitter will be a distinguished candidate for electronic source devices.
Novel yeast extract is superior to colloidal oatmeal in providing rapid itch relief
Authors: Dhurat Rachita , Sharma Aseem , Surve Ravina , McCoy John , Kovacevic Maja , Goren Andy , Tan Yimei , Zou Ying , Goldust Mohamad , Situm Mirna , Stanimirovic Andrija
Published: May 2020

Background

Approximately, 13.5% of the population suffers from chronic itch. Many cosmetic and pharmaceutical treatments for itch are available; however, cosmetic treatments are not reliably effective and most pharmaceutical formulations carry the risk of adverse events with chronic use.

Aims

Previously, we have reported a novel extraction process of Saccharomyces cerevisiae, that is, Baker's yeast. The extract obtained from the novel process demonstrates superior anti‐itch properties compared to other yeast extracts. In our previous study, we demonstrated that, after 30 minutes, the extract significantly reduced itch when compared to a placebo lotion (P = .002).

Methods

In the present study we conducted a head‐to‐head comparison with the leading cosmetic itch product: lotion containing colloidal oatmeal (CO). A randomized double‐blinded study of 60 patients was conducted.

Results

In our study, the novel yeast extract was vastly superior to the CO containing lotion (Aveeno™ Eczema Therapy Moisturizing Cream). We saw statistically significant difference in the reduction of itch (P = .0001) using the novel yeast extract vs the CO lotion. Additionally, the yeast extract was shown to relieve itch in as little as one minute after application.

Conclusion

The novel yeast extract rapidly relieves itch and is superior to the cosmetic market leader, CO lotion.
Chloroplast Dual Divergent Promoter Plasmid for Heterologous Protein Expression in Tetraselmis suecica (Chlorophyceae, Chlorodendrales)
Authors: Gutiérrez Carla L. , Muñoz Carla , San Martín Margarita , Cadoret Jean‐Paul , Henríquez Vitalia
Published: May 2020

The eukaryotic green microalga Tetraselmis suecica is commonly used for aquaculture purposes because of its high stress tolerance and ease of culture in a wide spectrum of environments; they are therefore suitable candidates for biotechnology applications. To date, no data are available regarding chloroplast transformation vectors based on specific endogenous promoters and homologous targeting regions. We report on the identification of Tetraselmis suecica genes encoding the ribulose bisphosphate carboxylase/oxygenase large subunit protein, the photosystem II D1 protein and the ATP synthase CF1‐beta subunit protein together with their untranslated regions (5′UTR, 3′UTR). The full‐length ORFs of the putative genes with their regulatory sequences were obtained. We were also able to identify the downstream 3′ end of the large subunit ribosomal RNA gene (23S) along with the 5S RNA end‐to‐end with the psbA gene on the complementary strand. The intergenic region between these genes appears to be a good target site for the integration of target proteins. Moreover, we identified a back‐to‐back promoter region among the rbcL and atpB genes. To assess the bidirectionality activities of both promoters, a dual reporter vector was constructed for Tetraselmis suecica transformation containing the cat and TurboGFP genes driven by the 5′rbcL/5′atpB divergent promoter. The vector included the 23S‐5S and psbA nucleotide sequences as flanking regions. These flanking regions provided suitable insertion sites within the chloroplast genome for cassette integration via homologous recombination. Simultaneous expression of the chloramphenicol‐resistant conferring gene and the gene coding for TurboGFP driven by 5′rbcL/5′atpB showed a potent natural bidirectional promoter as a reliable genetic tool.
High sustained viral response rate in patients with hepatitis C using generic sofosbuvir and daclatasvir in Phnom Penh, Cambodia
Authors: Zhang Meiwen , O’Keefe Daniel , Iwamoto Momoko , Sann Kimchamroeun , Kien Antharo , Hang Vithurneat , Brucker Cecile , Jolivet Pascal , Ly Sovann , Chhit Dimanche , Balkan Suna , Marquardt Tonia , Le Paih Mickael , Dousset Jean‐Philippe
Published: May 2020

Safe and efficacious pan‐genotypic direct‐acting antiviral (DAA) regimens, such as sofosbuvir and daclatasvir (SOF + DCV), facilitate simplified models of care for hepatitis C virus (HCV). However, in Cambodia access to HCV testing and treatment has typically been low. In response, Médecins Sans Frontières (MSF) implemented a HCV testing and treatment pilot project in Phnom Penh, Cambodia in 2016. This project provides the first real‐world evidence of SOF + DCV effectiveness across a large patient cohort using a simplified care model in Cambodia. Patients treated with SOF + DCV from September 2016 to June 2019 were included in the analysis. Medical standard operational procedures (SOPs) were simplified significantly across the study period. Treatment effectiveness was assessed by sustained viral response at 12 weeks post‐treatment (SVR12) according to a modified intention‐to‐treat methodology. Treatment safety was assessed by clinical outcome and occurrence of serious and nonserious adverse events (S/AE). Of 9158 patients, median age was 57 years and 39.6% were male. At baseline assessment, 27.2% of patients had compensated cirrhosis and 2.9% had decompensated cirrhosis. Genotype 6 was predominant (53.0%). Among patients analysed according to modified intention to treat (n = 8525), treatment effectiveness was high, with 97.2% of patients achieving SVR12. Occurrence of SAE was low (0.7%). Treatment effectiveness and safety was not affected by the iterative simplification to treatment modality. In conclusion, in this large treatment cohort in Phnom Penh, Cambodia, the SOF + DCV regimen showed high rates of treatment effectiveness and safety across patient sub‐groups and during progressive simplification.
Feeding intensity and molecular prey identification of the mantis shrimp, Oratosquilla oratoria (De Haan, 1844), in the Tianjin coastal zone of Bohai Bay
Authors: Bo Qi‐Kang , Lu Yun‐Zhao , Mi Hui‐Jing , Yu Yan‐Guang , Gu De‐Xian , You Hong‐Zheng , Hao Shuang
Published: May 2020

Bohai Bay, a representative semi‐enclosed bay of China, has been severely impacted in recent decades by rapid human development. Although the mantis shrimp Oratosquilla oratoria plays an important role in the Bohai Bay ecosystem and fishery, its feeding ecology and the impact of habitat changes on its feeding habits are poorly known. In this study, we sought to identify its feeding strategy through the separation of stomach contents, and to describe its trophic ecology during maturation in the Tianjin coastal zone of Bohai Bay by the DNA barcoding method using a fragment (about 690 bp) of the mitochondrial cytochrome oxidase I (CO I) gene. A total of 594 specimens were collected from March to July 2018, and 347 (58.42%) stomachs were found to have food remains. More than half of the O. oratoria individuals had poor feeding activity, and the degree of feeding of females was higher than that of males, but there was no significant difference in the visual fullness index and the fullness weight index (FWI) between sexes for each month. In addition, the feeding activity of O. oratoria was consistent across the months, suggesting in artificial breeding programs it is not worried too much about the accessional diet supplied to the female bloodstocks except maintaining their normal food. A total of 167 retrieved prey items yielded 187 readable sequences; 86.63% of these sequences could be assigned to the species level. Consequently, 25 different prey taxa covering all readable sequences were identified, showing O. oratoria is a generalist predator. In terms of percent composition by frequency of occurrences (%N), crustaceans and fishes accounted for the same and highest percentage (35.83%) in the mantis shrimp diet, followed by mollusks (24.59%) and the remaining marine organisms (3.73%) including Polychaeta (2.67%), Sagittoidea (0.53%), and Chromadorea (0.53%). The result shows the benthic fish Oxudercidae (family) appears to be an especially important food supply for O. oratoria during maturation. The degree of cannibalism decreased with an increase in diet species and the frequencies of cannibalism in this study was noticeably higher than that in previous studies, suggesting that cannibalism may be a significant feeding strategy in the mantis shrimp O. oratoria in the Tianjin coastal zone of Bohai Bay, and because of the frequently cannibalistic behavior, the high stocking density of broodstocks should be avoided.
How can we optimise antifungal use in a solid organ transplant centre? Local epidemiology and antifungal stewardship implementation: A single‐centre study
Authors: Mularoni Alessandra , Adamoli Lucia , Polidori Piera , Ragonese Barbara , Gioè Santi Mauro , Pietrosi Astrid , Tuzzolino Fabio , Guadagnino Giuliana , Monaco Francesco , Grossi Paolo Antonio , Conaldi Pier Giulio , Luca Angelo , Mikulska Malgorzata
Published: May 2020

Purpose

We aimed to implement and to assess the impact of the antifungal stewardship programme (AFSp) on prescription appropriateness of antifungals, management and outcomes of candidaemia patients, and antifungal consumption and costs at our solid organ transplant (SOT) institute.

Methods

Local epidemiology of invasive fungal infections (IFIs) from 2009 to 2017 was analysed in order to prepare an effective AFSp, implemented in January 2018. It included suspension of empirical antifungal prescriptions after 72 hours (antifungal time‐out), automated alert and infectious disease (ID) consult for empirical prescriptions and for every patient with IFI, and indication for step‐down to oral fluconazole when possible. We used process measures and results measures to assess the effects of the implemented programme.

Results

The ASFp led to significant improvements in selection of the appropriate antifungal (40.5% in pre‐AFS vs 78.6% in post‐AFS), correct dosing (51.2% vs 79.8%), correct length of treatment (55.9% vs 75%) and better management of patients with candidaemia. Analysis of prescribed empirical antifungal revealed that defined daily doses (DDDs) per 100 patient days decreased by 36.7% in 2018 compared to the average of pre‐AFSp period, with important savings in costs.

Conclusion

This AFSp led to a better use of antifungal drugs in terms of appropriateness and consumption, with stable clinical and microbiological outcomes in patients with IFI.