bluuebunny/crossref_metadata_2025 huggingface dataset:
Innate and adaptive immune responses against human Puumala virus infection: immunopathogenesis and suggestions for novel treatment strategies for severe hantavirus‐associated syndromes
Authors: Klingström J. , Smed‐Sörensen A. , Maleki K. T. , Solà‐Riera C. , Ahlm C. , Björkström N. K. , Ljunggren H. G.
Published: January 2019

Two related hyperinflammatory syndromes are distinguished following infection of humans with hantaviruses: haemorrhagic fever with renal syndrome (HFRS) seen in Eurasia and hantavirus pulmonary syndrome (HPS) seen in the Americas. Fatality rates are high, up to 10% for HFRS and around 35%–40% for HPS. Puumala virus (PUUV) is the most common HFRS‐causing hantavirus in Europe. Here, we describe recent insights into the generation of innate and adaptive cell‐mediated immune responses following clinical infection with PUUV. First described are studies demonstrating a marked redistribution of peripheral blood mononuclear phagocytes (MNP) to the airways, a process that may underlie local immune activation at the site of primary infection. We then describe observations of an excessive natural killer (NK) cell activation and the persistence of highly elevated numbers of NK cells in peripheral blood following PUUV infection. A similar vigorous CD8 Tcell response is also described, though Tcell responses decline with viraemia. Like MNPs, many NK cells and CD8 T cells also localize to the lung upon acute PUUV infection. Following this, findings demonstrating the ability of hantaviruses, including PUUV, to cause apoptosis resistance in infected target cells, are described. These observations, and associated inflammatory cytokine responses, may provide new insights into HFRS and HPS disease pathogenesis. Based on similarities between inflammatory responses in severe hantavirus infections and other hyperinflammatory disease syndromes, we speculate whether some therapeutic interventions that have been successful in the latter conditions may also be applicable in severe hantavirus infections.
The Role of CT Perfusion in Defining the Clinically Relevant Core Infarction to Guide Thrombectomy Selection in Patients with Acute Stroke
Authors: Shaker Hussam , Khan Muhib , Mulderink Todd , Koehler Tracy J. , Scurek Raymond , Tubergen Tricia , Packard Laurel , Singer Justin , Mazaris Paul , Min Jiangyong , Wees Nabil , Khan Nadeem , Abdelhak Tamer
Published: January 2019

BACKGROUND AND PURPOSE

Infarct core assessment on presentation is important to evaluate salvageable tissue to select patients for thrombectomy. Our study aims to evaluate the correlation between infarct core volume measured by computed tomography (CT) perfusion (CTP) and magnetic resonance diffusion‐weighted imaging (MR‐DWI) in patients with acute large‐vessel occlusion.

METHODS

We studied patients who underwent CTP on presentation to the emergency department for stroke symptoms. National Institute of Health Stroke Scale (NIHSS), collateral status, symptomatic vessels, and modified Rankin scale (mRS) at 90 days were collected. Admission infarct core volume was measured on initial relative cerebral blood volume and final infarct core volume on follow‐up DWI. The correlation between two measures was assessed using Pearson's correlation coefficient.

RESULTS

Seventy‐four patients were studied of which 41.9% were female. Median NIHSS was 13 (2‐30). Middle cerebral artery occlusion was present in 53 (71.6%) patients and 54 (72.9%) had good collaterals. Good functional outcome of mRS 0‐2 was achieved by 60.8% at 90 days. There was a strong correlation between CTP and MR‐DWI (r = .94). There was no significant difference between volume (in milliliters) on CTP (54.1 ± 69.8) and volume on DWI (50.3 ± 59.7; P = .18) using the paired t‐test.

CONCLUSION

CTP provides a good estimation of the core infarct volume. It performs well within the clinically relevant thresholds for patient selection for thrombectomy.
A Full‐Digital Technique to Mount a Maxillary Arch Scan on a Virtual Articulator
Authors: Lepidi Luca , Chen Zhaozhao , Ravida Andrea , Lan Tingting , Wang Hom‐Lay , Li Junying
Published: January 2019

Mounting casts accurately on an articulator is a prerequisite for the treatment planning/execution of complex dental cases that require occlusal rehabilitation. A full digital approach to transfer the position of maxillary dentition to a virtual articulator, by using intraoral scans and cone beam computed tomography (CBCT) files is presented. This technique offers reduced chairside time and the flexibility of choosing the orientation plane. It can be used in orthognathic surgeries, complex interdisciplinary treatments requiring a CBCT scan with a large field of view, or treatments that already have the head CT or CBCT scans from previous diagnosis/treatment.
Identifying and critically examining government legislation relevant to children's dental caries in Calgary, Alberta, Canada: a health inequities lens
Authors: Weijs Cynthia , Gobrail Sara , Lucas Jack , Zwicker Jennifer , McLaren Lindsay
Published: January 2019

Objectives

Children's dental caries is an important and urgent public health concern that is largely preventable. Using a social equity framework, our objectives were to identify and critically examine government legislation relevant to the issue of children's dental health in Calgary, Alberta, Canada.

Methods

We conducted a systematic, gray literature search of federal, provincial (Alberta), and municipal (Calgary) statutes and bylaws related to children's dental caries, through the relevant law databases. Eligibility criteria were applied for document screening and selection. Data extraction and synthesis pertained to objectives of the legislation (policy task), relevant agent or actor (level of government), and upstream or downstream focus, in terms of potential impact on social inequities in health.

Results

Legislation (n = 114) was retrieved and grouped into eight policy tasks. Most legislation fit under the policy tasks: protection of public safety and health promotion (n = 40) and benefits and compensation (n = 27). Federal and provincial governments have greater involvement in children's dental caries than municipal (Calgary) government. The majority of legislation was classified as upstream in orientation (e.g., improving living and working conditions; macro‐level policies).

Conclusions

Analysis of legislation relevant to children's dental caries reveals policies that are more often upstream in nature, and unsurprisingly are multijurisdictional. Despite this, there remains a high prevalence and inequitable distribution of children's dental caries in Canada. This suggests that the nature of upstream involvement and fragmented government involvement is ineffective in tackling this pervasive and urgent public health issue. Implications for children's dental health are discussed.
Variation in juvenile Chinook salmon (Oncorhynchus tshawytscha) transcription profiles among and within eight population crosses from British Columbia, Canada
Authors: Toews Shelby D. , Wellband Kyle W. , Dixon Brian , Heath Daniel D.
Published: January 2019

Phenotypic differences among populations within a species have been reported for a variety of traits, ranging from life history to physiology to gene transcription. Population‐level phenotypic variation has been attributed to genetic differences resulting from genetic drift and/or local adaptation as well as environmental differences resulting from plasticity. We studied population‐ and family‐level variation in gene transcription for 22 fitness‐related genes, comprising immune, growth, metabolic, and stress processes in Chinook salmon (Oncorhynchus tshawytscha). We created hybrid Chinook salmon families from eight populations and treated them with an immune stimulus, a handling stress challenge, and held some as a no‐treatment control group. Population effects, sire effects, and narrow‐sense heritability (h2) were calculated for each candidate gene within each treatment group. We expected population to have a significant effect on gene transcription for many of our genes; however, we found a population effect for transcription at only one immune gene at rest. The limited number of significant population effects on gene transcription, combined with significant additive genetic variance within each population does not support the expectation of past strong selection pressures acting on heritable transcription profiles among populations. Instead, our results indicate that Chinook salmon likely adapt to their local environment through transcriptional plasticity rather than fixed differences. The expectation for fixed population‐level differences in gene transcription at fitness‐related genes, reflecting accepted models of local adaptation is high; however, comparisons among multiple populations using half‐sibling breeding designs are rare. Our work fills an important gap in our growing understanding of the process of among and within‐population divergence.
Postcolonial Bifurcation: On John Sharpley'sEmptiness
Authors: LEE GAVIN S. K.
Published: January 2019

One of the lesser‐known terms used by Gilles Deleuze to articulate his conception of difference – or, more accurately, of differentiation – as the condition of existence is ‘bifurcation’, the continuous process of splitting into ever‐more new pathways. Bifurcation is reflected in the life and music of the Texas‐born composer John Sharpley (b. 1955), who moved to Singapore in 1986. In hisEmptiness(2002) for Chinese and Western string quartets, chorus and percussion, which sets excerpts from Buddhist and Taoist texts, musical bifurcation is observed in the continuous splitting of modality from chromaticism at multiple structural levels. Musical bifurcation is paralleled in bifurcation in Sharpley's life, as reflected in his transcontinental migration and multiple mystical experiences. As a concept, bifurcation represents the diametric opposite of syncretism (combining), which dominates composers’ discourse and theorists’ analyses. By attending to the dynamics of bifurcation as musical and biographical processes, we might come to appreciate in its full ambiguity and complexity music that crosses cultures. In doing so, we gain further insights into musical orientalism.
In vitro susceptibility of dematiaceous fungi to nine antifungal agents determined by two different methods
Authors: Zheng Hailin , He Yun , Kan Siyue , Li Dongmei , Lv Guixia , Shen Yongnian , Mei Huan , Li Xiaofang , Liu Weida
Published: January 2019

Background

The infection rate for dematiaceous fungi has increased rapidly over the most recent decades. However, the treatment for such infections has been lacking in empirical support with oral antifungal agents.

Objectives

To provide a better regimen for dematiaceous infections in future, the Sensititre YeastOne® colorimetric antifungal panels were used and compared with Laboratory Standards Institute (CLSI) M38‐A2 reference broth microdilution method.

Methods

Two methods were used for nine antifungals against 67 dematiaceous fungi.

Results

Via two methods, we found that the MICs of itraconazole, voriconazole, posaconazole and amphotericin B were lower than fluconazole. The values obtained with CLSI method for four triazoles, 5‐flucytosine and amphotericin B were in high essential agreements with those observed by YeastOne® method. The results of echinocandins across the two methods showed some divergence, which might be attributed to the methodology itself, particularly when sensitivity was determined in the lowest concentration of the drug. In YeastOne® method, the results were defined as MICs, but as MECs in CLSI method.

Conclusions

The YeastOne® method appeared to be both easier and more efficient for dematiaceous fungi when compared with the CLSI method, and the agreement between the two methods was good for most common antifungals.
Contesting the nation: negotiating national narratives and the Jewish settlements
Authors: Aron Hadas
Published: January 2019

Why and how does national identity reopen for contestation? Existing theories argue that institutional design, social ties or elite manipulation alter the saliency and nature of national identity. These theories view the ethno‐nation as homogenous and shaped vis‐à‐vis other groups. However, I argue that we should examine the re‐emergence of nationalism as an intra‐national struggle between groups with different saliency and understandings of national identity: new issues can raise the importance of national identity for some members of the group but not others. Moreover, members develop diverging understandings of fundamentals of national identity such as citizenship, borders and the role of religion. To support the theory, the paper utilises original not yet studied archival materials to show that struggle over Jewish settlements in the Occupied Territories led to contestation of the saliency and meaning of Jewish Israeli national identity. Specifically, I analyse letters individuals sent to leading government officials in the early days of the settlements and show that settlement supporters tied the issue to Zionist ethos, injecting new content into Zionist identity. Meanwhile, national identity did not rise in importance or alter in meaning for settlement opposition. The method reveals individual understandings of national identity and points at broader societal divisions.
Identifying patient‐important outcomes in polycystic kidney disease: An international nominal group technique study
Authors: Cho Yeoungjee , Sautenet Benedicte , Gutman Talia , Rangan Gopala , Craig Jonathan C , Ong Albert C , Chapman Arlene , Ahn Curie , Coolican Helen , Kao Juliana T‐W , Gansevoort Ron , Perrone Ronald D , Harris Tess , Torres Vicente , Pei York , Kerr Peter G , Ryan Jessica , Johnson David W , Viecelli Andrea K , Geneste Claire , Kim Hyunsuk , Kim Yaerim , Oh Yun Kyu , Teixeira‐Pinto Armando , Logeman Charlotte , Howell Martin , Ju Angela , Manera Karine E , Tong Allison
Published: January 2019

Aim

Patients with autosomal dominant polycystic kidney disease (ADPKD) are at increased risk of premature mortality, morbidities and complications, which severely impair quality of life. However, patient‐centered outcomes are not consistently reported in trials in ADPKD, which can limit shared decision‐making. We aimed to identify outcomes important to patients and caregivers and the reasons for their priorities.

Methods

Nominal group technique was adopted involving patients with ADPKD and caregivers who were purposively selected from eight centres across Australia, France and the Republic of Korea. Participants identified, ranked and discussed outcomes for trials in ADPKD. We calculated an importance score (0–1) for each outcome and conducted thematic analyses.

Results

Across 17 groups, 154 participants (121 patients, 33 caregivers) aged 19 to 78 (mean 54.5 years) identified 55 outcomes. The 10 highest ranked outcomes were: kidney function (importance score 0.36), end‐stage kidney disease (0.32), survival (0.21), cyst size/growth (0.20), cyst pain/bleeding (0.18), blood pressure (0.17), ability to work (0.16), cerebral aneurysm/stroke (0.14), mobility/physical function (0.12), and fatigue (0.12). Three themes were identified: threatening semblance of normality, inability to control and making sense of diverse risks.

Conclusion

For patients with ADPKD and their caregivers, kidney function, delayed progression to end‐stage kidney disease and survival were the highest priorities, and were focused on achieving normality, and maintaining control over health and lifestyle. Implementing these patient‐important outcomes may improve the meaning and relevance of trials to inform clinical care in ADPKD.
Chronic kidney disease, Queensland: Profile of patients with chronic kidney disease from regional Queensland, Australia: A registry report
Authors: Venuthurupalli Sree K , Healy Helen , Fassett Robert , Cameron Anne , Wang Zaimin , Hoy Wendy E
Published: January 2019

Background

Chronic kidney disease, Queensland (CKD.QLD) is a multidisciplinary, collaborative research platform for CKD in Queensland. Most public renal services contribute towards the CKD Registry, including Toowoomba Hospital, which is a referral hospital for Darling Downs Health serving a largely regional population in Queensland. We aim to present the profile of the CKD cohort recruited to the CKD.QLD Registry from Toowoomba Hospital, the first comprehensive report on a pre‐dialysis population from regional Australia.

Methods

Study subjects were patients in the Darling Downs Health Service who consented to be included in the CKD.QLD registry from June 2011 to December 2016. Those who were on renal replacement therapy (RRT) were excluded. Patients were followed until date of RRT, death, discharge or loss to follow up or a censor date of 30th June 2017.

Results

Overall 1051 subjects, representing 13% of all CKD.QLD Registry patients gave consent of whom, 42.7% were ≥70 years of age. The mean age was 63.8 ± 15.1 years (median age 67 years) with male predominance (55.4%). The majority were born in Australia (86.4%). Aboriginal and Torre Strait Islanders (A&TSI) constituted 9.6% of the cohort. The predominant CKD stages were 3b (28.9%) and 4 (27.7%). Hypertension and diabetes were noted in 91% and 44% of subjects, respectively. Diabetic nephropathy was the leading cause of CKD (26.7%) followed by renovascular disease (17.3%) and glomerulonephritis (14.8%). In 12%, the diagnosis was uncertain. Major co‐morbidities included coronary artery disease (24.7%) chronic lung disease (14.8%), cerebrovascular disease (11.6%) and peripheral vascular disease (8.9%). Non‐vascular co‐morbidities included arthritis (24.6%), gout (23.6%) and gastro‐oesophageal reflux disease (19%). The multi‐morbidity profile was differed by gender, diabetic status and age. Over a follow‐up period upto 72 months, 93 (8.8%) started RRT and 175 (16.6%) died. Of those 82% died without RRT and 18% died after RRT.

Conclusion

This CKD Registry cohort from regional Queensland consisted mainly of older Caucasians with male predominance. A&TSI patients were overrepresented compared to the overall population. A significant proportion had cardio‐vascular disease and multiple co‐morbidities which differed by gender, diabetic status and age. This report provides valuable data for health services planning and delivery in regional Queensland.
QX‐314 inhibits acid‐induced activation of esophageal nociceptive C fiber neurons
Authors: Hu Youtian , Yu Xiaoyun , Yu Shaoyong
Published: January 2019

Introduction

Acid reflux in the esophagus can induce painful sensations such as heartburn and non‐cardiac chest pain. These nociceptive symptoms are initiated by activation of TRPV1‐positive afferent C fibers in the esophagus. The present study aimed to explore a novel C fiber inhibition approach. We hypothesized that activation of TRPV1 by acid enabled QX‐314, a membrane impermeable sodium channel blocker, to inhibit acid‐induced activation of esophageal nociceptive C fiber neurons.

Method

We determined the inhibitory effect of QX‐314 in the presence of acid in guinea pig esophageal nociceptive vagal jugular C fiber neurons by both patch clamp recording in neuron soma and by extra‐cellular recording at nerve terminals.

Key Results

Our data demonstrated QX‐314 alone did not inhibit sodium currents. However, when applied along with capsaicin to activate TRPV1, QX‐314 was able to block sodium currents in esophageal‐specific jugular C fiber neurons. We then showed that in the presence of acid, QX‐314 significantly blocked acid‐evoked activation of jugular C fiber neurons. This effect was attenuated by TRPV1 antagonist AMG9810, suggesting acid‐mediated inhibitory effect of QX‐314 was TRPV1‐dependent. Finally, we provided evidence at nerve endings that acid‐evoked action potential discharges in esophageal jugular C fibers were inhibited by QX‐314 when applied in the presence of acid.

Conclusion and Inferences

Our data demonstrated that activation of TRPV1 by acid enabled membrane impermeable sodium channel blocker QX‐314 to inhibit acid‐induced activation in esophageal nociceptive C fibers. This supports a localized application of QX‐314 in the esophagus to block esophageal nociception in acid reflux disorders.
Familial chronic megacolon presenting in childhood or adulthood: Seeking the presumed gene association
Authors: Camilleri Michael , Wieben Eric , Eckert Deborah , Carlson Paula , Hurley O’Dwyer Ralph , Gibbons Denys , Acosta Andres , Klee Eric W.
Published: January 2019

Objective

We identified a pedigree over five generations with 49 members, some of whom had chronic megacolon presenting in adolescence or adulthood. We aimed to assess the genetic cause of chronic megacolon through clinical and DNA studies.

Design

After ethical approval and informed consent, family members provided answers to standard bowel disease questionnaires, radiological or surgical records, and DNA (buccal mucosal scraping). Exome DNA sequencing of colon tissue or blood DNA from seven family members with colon or duodenal dilatation, or no megacolon (n = 1) was carried out. Sanger sequencing was performed in 22 additional family members to further evaluate candidate variants. The study focused on genes of potential relevance to enteric nerve (ENS) maturation and Hirschsprung's disease or megacolon, based on the literature (GFRA1, NKX2‐1, KIF26A, TPM3, ACTG2, SCN10A, and C17orf107 [CHRNE]) and other genetic variants that co‐segregated with megacolon in the six affected family members.

Results

Information was available in all except five members alive at time of study; among 30 members who provided DNA, six had definite megacolon, one megaduodenum, seven significant constipation without bowel dilatation, and 16 normal bowel function by questionnaire. Among genes studied, SEMA3F (g.3:50225360A>G; c1873A>G) was found in 6/6 family members with megacolon. The SEMA3F gene variant was assessed as potentially pathogenic, based on M‐CAP in silico prediction. SEMA3F function is associated with genes (KIT and PDGFRB) that impact intestinal pacemaker function.

Conclusion

Familial chronic megacolon appears to be associated with SEMA3F, which is associated with genes impacting enteric nerve or pacemaker function.
Nodule‐specific PLAT domain proteins are expanded in the Medicago lineage and required for nodulation
Authors: Trujillo Diana I. , Silverstein Kevin A. T. , Young Nevin D.
Published: January 2019

Symbiotic nitrogen fixation in legumes is mediated by an interplay of signaling processes between plant hosts and rhizobial symbionts. In legumes, several secreted protein families have undergone expansions and play key roles in nodulation. Thus, identifying lineage‐specific expansions (LSEs) of nodulation‐associated genes can be a strategy to discover candidate gene families.

Using bioinformatic tools, we identified 13 LSEs of nodulation‐related secreted protein families, each unique to either Glycine, Arachis or Medicago lineages. In the Medicago lineage, nodule‐specific Polycystin‐1, Lipoxygenase, Alpha Toxin (PLAT) domain proteins (NPDs) expanded to five members. We examined NPD function using CRISPR/Cas9 multiplex genome editing to create Medicago truncatula NPD knockout lines, targeting one to five NPD genes.

Mutant lines with differing combinations of NPD gene inactivations had progressively smaller nodules, earlier onset of nodule senescence, or ineffective nodules compared to the wild‐type control. Double‐ and triple‐knockout lines showed dissimilar nodulation phenotypes but coincided in upregulation of a DHHC‐type zinc finger and an aspartyl protease gene, possible candidates for the observed disturbance of proper nodule function.

By postulating that gene family expansions can be used to detect candidate genes, we identified a family of nodule‐specific PLAT domain proteins and confirmed that they play a role in successful nodule formation.
Decreased regional brain activity in response to sleep‐related sounds after cognitive behavioral therapy for psychophysiological insomnia
Authors: Kim Nambeom , Kang Seung‐Gul , Lee Yu Jin , Kim Seog Ju , Kim Soohyun , Choi Jae‐Won , Oh Seong Min , Park Juhyun , Gwak Ah Reum , Kim Hang‐Keun , Jeong Do‐Un
Published: January 2019

Aim

Patients with psychophysiological insomnia (PI) experience hyperarousal, especially as a reaction to sound stimuli. In the current study, we explored brain activity changes in response to sleep‐related sounds (SS) in patients with insomnia after cognitive behavioral therapy for insomnia (CBT‐I).

Methods

In 14 drug‐free PI patients, regional brain activity in response to SS, and to white noise sound (NS) as neutral stimuli, was investigated before and after individual CBT‐I using functional magnetic resonance imaging. Blood oxygen level‐dependent (BOLD) signals to SS and NS were compared before and after CBT‐I. In addition, the association between clinical improvement after CBT‐I and changes in brain activity in response to SS and NS was analyzed.

Results

Compared with baseline, regional brain activity in response to SS after CBT‐I decreased in the left middle temporal and left middle occipital gyrus. In regression analysis, a reduction in the Dysfunctional Beliefs and Attitudes about Sleep (DBAS) Scale score after CBT‐I was associated with decrease in brain activity in response to SS in both thalami. However, brain activity in response to NS showed no BOLD signal changes and no association with DBAS change.

Conclusion

Cortical hyperactivity, which may cause hyperarousal in PI, was found to decrease after CBT‐I. CBT‐I targeting changes in beliefs and attitudes about sleep may induce its therapeutic effects by reducing thalamic brain activity in response to sleep‐related stimuli.
Scrap or Sell: The Decision on Production Yield Loss
Authors: Li Rong , Xia Yu , Yue Xiaohang
Published: January 2019

Many production processes not only produce desired quality products (high‐end products), but also generate yield loss or Not‐Quite‐Perfect Products (NQPPs) that do not fully meet the quality standards. In practice, a manufacturer may choose to (1) scrap all NQPPs at a cost and carry the high‐end products only, or (2) sell some or all NQPPs to a value‐conscious low‐end market and carry both high‐end products and low‐end products (NQPPs). This research studies the optimal decision on production yield loss (scrap or sell) and the corresponding pricing and operational strategies under different practical situations. Building upon a standard marketing model for two separated markets, that is, the high‐end and the low‐end markets, we model the manufacturer’s profit maximization problem as a nonlinear programming problem. We characterize the optimal yield–loss decision and the corresponding optimal pricing for each market and production quantity. We also consider the situation that the NQPPs may face competition in the low‐end market with products designed and produced specifically for that market. In contrast to the common belief that selling NQPPs to a low‐end market can recover some of the cost and hence lead to a higher profit, we show that when the yield rate is small or large enough, selling NQPPs may hurt the manufacturer due to the loss of full control over both markets. This is especially true when competition exists in the low‐end market. This research provides practitioners with detailed guidelines on when and how a specific yield loss (product line or marketing) strategy should be adopted. Managerial insights are generated for the optimal yield loss strategies; numerical tests further demonstrate our results.
An isolate of Wheat streak mosaic virus from foxtail overcomes Wsm2 resistance in wheat
Authors: Kumssa T. T. , Rupp J. S. , Fellers M. C. , Fellers J. P. , Zhang G.
Published: January 2019

Wheat streak mosaic virus (WSMV) is an economically important pathogen of wheat (Triticum aestivum) causing major yield losses in regions where severe infection occurs. To detect the presence of any new virus or new WSMV isolates, green foxtail (Setaria viridis) plants exhibiting virus‐like symptoms were sampled in a summer‐fallowed wheat field at the Agricultural Research Center‐Hays, Kansas State University, Hays, Kansas. These plants were tested serologically for four wheat viruses: WSMV, Triticum mosaic virus (TriMV), High Plains wheat mosaic virus (HPWMoV) and Foxtail mosaic virus (FoMV). Among 38 plant samples exhibiting virus‐like symptoms, 29 contained WSMV as indicated by ELISA. Four isolates from samples with relatively strong reactions were transferred to healthy wheat seedlings by mechanical inoculation in a growth chamber for pathogenicity testing. Three isolates were avirulent to a wheat variety RonL, which contains Wsm2, a gene providing temperature‐sensitive resistance to currently prevalent isolates of WSMV. However, one isolate, KSH294, was able to infect RonL and showed more virulence on two other varieties/lines containing Wsm2. Further sequence and phylogenetic analysis of KSH294 confirmed that this isolate displays a sequence homology with WSMV, but has sequence differences making it distinct from previously identified WSMV isolates included in the phylogenetic analysis.
Response of proteome and morphological structure to short‐term drought and subsequent recovery in Cucumis sativus leaves
Authors: Du Changxia , Chai Li'ang , Wang Zhe , Fan Huaifu
Published: January 2019

Drought is the primary limitation to plant growth and yield in agricultural systems. Cucumber (Cucumis sativus) is one of the most important vegetables worldwide and has little tolerance for water deficit. To understand the drought stress response strategy of this plant, the responses of cucumber to short‐term drought and rewatering were determined in this study by morphological structure and proteomic analyses. The leaf relative water content was significantly decreased under drought, and the cell structure was altered, while rewatering obviously alleviated the symptoms of water shortage and cell damage. A total of 320 and 246 proteins exhibiting significant abundance changes in response to drought and recovery, respectively, were identified. Our proteome analysis showed that 63 co‐regulated proteins were shared between drought and rewatering, whereas most of the responsive proteins were unique. The proteome is adjusted through a sequence of regulatory processes including the biosynthesis of secondary metabolites and the glutathione metabolism pathway, which showed a high correlation between protein abundance profile and corresponding enzyme activity. Drought and recovery regulated different types of proteins, allowing plants to adapt to environmental stress or restore growth, respectively, which suggests that short‐term drought and recovery are almost fully uncoupled processes. As an important component of the antioxidant system in plants, glutathione metabolism may be one of the main strategies for regulating antioxidant capacity during drought recovery. Our results provide useful information for further analyses of drought adaptability in cucumber plants.
Topology of TROL protein in thylakoid membranes of Arabidopsis thaliana
Authors: Vojta Lea , Fulgosi Hrvoje
Published: January 2019

Thylakoid rhodanase‐like protein (TROL) is a nuclear‐encoded protein of thylakoid membranes required for tethering of ferredoxin:nicotinamide adenine dinucleotide phosphate (NADPH) oxydoreductase (FNR). It has been proposed that the dynamic interaction of TROL with flavoenzyme FNR, influenced by environmental light conditions, regulates the fate of photosynthetic electrons, directing them either to NADPH synthesis or to other acceptors, including reactive oxygen species detoxification pathways. Inside the chloroplasts, TROL has a dual localization: an inner membrane precursor form and a thylakoid membrane mature form, which has been confirmed by several large‐scale chloroplast proteomics studies, as well as protein import experiments. Unlike the localization, the topology of TROL in the membranes, which is a prerequisite for further studies of its properties and function, has not been experimentally confirmed yet. Thermolysin was proven to be a valuable protease to probe the surface of chloroplasts and membranes in general. By treating the total chloroplast membranes using increasing protease concentration, sequential degradation of TROL was observed, indicating protected polypeptides of TROL and possible domain orientation. To further substantiate the obtained results, TROL‐overexpressing Arabidopsis line (OX) and line in which the central rhodanase‐like domain (RHO) has been partially deleted (ΔRHO), were used as well. While OX line showed the same degradation pattern of TROL as the wild‐type, surprisingly, TROL from ΔRHO membranes was not detectable even at the lowest protease concentration applied, indicating the importance of this domain to the integrity of TROL. In conclusion, TROL is a polytopic protein with a stroma‐exposed C‐terminal FNR‐binding region, and the thylakoid lumen‐located RHO domain.
Attention to a threat‐related feature does not interfere with concurrent attentive feature selection
Authors: Boylan Maeve R. , Kelly Mia N. , Thigpen Nina N. , Keil Andreas
Published: January 2019

Visual features associated with a task and those that predict noxious events both prompt selectively heightened visuocortical responses. Conflicting views exist regarding how the competition between a task‐related and a threat‐related feature is resolved when they co‐occur in time and space. Utilizing aversive classical Pavlovian conditioning, we investigated the visuocortical representation of two simultaneously presented, fully overlapping visual stimuli. Isoluminant red and green random dot kinematogram (RDK) stimuli were flickered at distinct tagging frequencies (8.57 Hz, 12 Hz) to elicit distinguishable steady‐state visual evoked potentials (ssVEPs). Occasional coherent motion events prompted a motor response (task) or predicted a noxious noise (threat). These events occurred either in the green (task cue), the red (threat cue), or in both RDKs simultaneously. In the initial habituation phase, participants responded to coherent motion of the green RDK with a key press, but no loud noise was presented at any time. Here, selective amplification was seen for the task‐relevant (green) RDK, and interference was observed when both RDKs simultaneously showed coherent motion. Upon pairing the threat cue with the noxious noise in the subsequent acquisition phase, the threat cue‐evoked ssVEP (red RDK) was also amplified, but this amplification did not interact with amplification of the task cue or alter the behavioral or visuocortical interference effect observed during simultaneous coherent motion. Although competing feature conjunctions resulted in interference in the visual cortex, the acquisition of a bias toward an individual threat‐related feature did not result in additional cost effects.
Interoception and respiratory sinus arrhythmia in gambling disorder
Authors: Kennedy Dawn , Goshko Caylee‐Britt , Murch W. Spencer , Limbrick‐Oldfield Eve H. , Dunn Barnaby D. , Clark Luke
Published: January 2019

Gambling has longstanding links with excitement and physiological arousal, but prior research has not considered (a) gamblers’ ability to detect internal physiological signals, or (b) markers of parasympathetic functioning. The present study measured interoception in individuals with gambling disorder, using self‐report measures and a heartbeat counting task administered at rest. Resting state respiratory sinus arrhythmia (RSA), an index of heart rate variability, was measured as a proxy for parasympathetic control and emotional regulation capacity. In a case‐control design, 50 individuals with gambling disorder were compared against 35 controls without gambling problems. Participants completed two self‐report measures of bodily awareness and a behavioral test of heartbeat counting. A resting state electrocardiogram (5 min) was used to calculate RSA. There were no significant differences on the self‐report or behavioral interoception probes. The group with gambling disorder displayed significantly reduced RSA, which at face value is consistent with reduced parasympathetic control. However, the group difference in RSA did not survive controlling for age and smoking status, as established predictors of heart rate variability. Our findings do not support any changes in interoceptive processing in people with gambling disorder, at least under resting conditions. Our observation that group differences in RSA are partly explained by smoking behavior highlights the importance of controlling for nicotine use in future research characterizing physiological functioning and emotional regulation in disordered gambling.
Rapid versus gradual lung function decline in bronchiolitis obliterans syndrome after haematopoietic stem cell transplantation is associated with survival outcome
Authors: Kwok Wang‐Chun , Liang Bin‐Miao , Lui Macy M.S. , Tam Terence C.C. , Sim Joycelyn P.Y. , Tse Eric W.C. , Leung Anskar Y.H. , Kwong Yok L. , Lie Albert K.W. , Ip Mary S.M. , Lam David C.L.
Published: January 2019

Background and objective

Bronchiolitis obliterans syndrome (BOS) after haematopoietic stem cell transplantation (HSCT) presents with lung function decline. The pattern of lung function decline after BOS diagnosis could impact prognostication of BOS as a complication after HSCT. The aim of this study was to assess the impact of lung function decline on overall survival (OS) in BOS subjects.

Methods

Subjects with BOS were compared to those without BOS and matched for age, gender, primary diagnoses, conditioning regimes and chronic graft versus host disease. Lung function tests at baseline, at BOS diagnosis and every 3 months after HSCT were evaluated.

Results

Of the 1461 subjects undergoing allogeneic HSCT (allo‐HSCT) between 1998 and 2015, 95 (6.5%) were diagnosed with BOS. A total of 159 matched HSCT recipients without BOS were identified. A 25% decline in FEV1 within the first 3 months after BOS diagnosis would separate BOS subjects into a subgroup with initial rapid decline and another subgroup with initial gradual decline in lung function. The rapid decline group showed lower subsequent lung function parameters and significantly worse OS compared to the gradual decline group (P = 0.013).

Conclusion

Post‐HSCT BOS subjects with initial rapid lung function decline within 3 months after BOS diagnosis will have significantly poorer lung function and worse OS compared to those with initial gradual decline in lung function after BOS diagnosis. HSCT BOS patients with rapid initial decline in lung function warrant closer monitoring for the development of other post‐HSCT complications that could affect their survival.
Immunomodulatory role of chitosan‐based nanoparticles and oligosaccharides in cyclophosphamide‐treated mice
Authors: Mudgal Jayesh , Mudgal Piya Paul , Kinra Manas , Raval Ritu
Published: January 2019

Chitosan, the deacetylated form of chitin, a natural polysaccharide, is known for its various biomedical applications. The present study aimed at exploring the immunomodulatory properties of chitosan (CSNP) and gallic acid‐grafted chitosan (cGANP) nanoparticles in mice model of cyclophosphamide (CPA)‐induced immunosuppression. In addition, chitooligosaccharides, the hydrolysed form of chitin and chitosan, were also evaluated for its potential against immunosuppression in mice. CPA (80 mg/kg/ip) induced significant immunosuppression, which was reversed with cGANP treatment as indicated by a significant increase in the thymus and spleen indices compared to the CPA‐treated group. The CSNP and chitooligosaccharides (chitin and chitosan) failed to reverse CPA‐induced changes. ELISA revealed an elevation in the levels of IL‐6 and a reduction in IFN‐γ levels with CPA treatment. All the test compounds reduced the IL‐6 levels, whereas only the nanoparticle formulations (CSNP and cGANP) exhibited a significant augmentation in the IFN‐γ levels. Both the cytokines, IL‐6 and IFN‐γ, are secreted separately by two different types of T helper cells (Th cells), which mediate cellular and humoral immune responses in a coordinated manner. Th‐1 cells release IFN‐γ, facilitating cell‐mediated immunity, whereas IL‐6 is released by Th‐2 cells, expediting humoral immune response. The nanoparticles (CSNP and cGANP) seemed to be better immune enhancers than the chitooligosaccharides owing to their ability to reverse the cytokine changes induced by CPA. Overall, it was evident that the nanoparticles, most likely, boosted the cell‐mediated immunity through the induction of the Th‐1 branch of the immune response.
Effectiveness of a physical activity intervention in preschoolers: A cluster‐randomized controlled trial
Authors: Hacke Claudia , Ketelhut Sascha , Wendt Ulrike , Müller Götz , Schlesner Claudia , Ketelhut Kerstin
Published: January 2019

Several activity interventions in preschool settings exist, but little attention has been paid to effects on hemodynamic factors. The study aimed to assess the effectiveness of an exercise program on health‐related outcomes including blood pressure (BP) and markers of vascular function in preschoolers, with focus on socioeconomic background. This study is a cluster‐randomized controlled trial, with preschool as unit of randomization and children as unit of analysis. Preschools with 3‐ to 6‐year‐old children, stratified by social area, were randomly allocated to: intervention (three clusters, n = 92) including 2 d·wk−1/45 min (6 months) exercise lessons or control (two clusters, n = 43). In total, 135 children (4.8 ± 0.8 y) had minimum one outcome measurement at baseline and follow‐up. Primary outcome: peripheral BP. Secondary outcomes: central BP, pulse wave velocity (PWV), BMI, waist circumference, physical activity measures, motor skills. Maternal education was used as an indicator of socioeconomic status. Mixed models were applied to evaluate differences in mean change. Group allocation had no effect on primary or secondary outcomes. However, the intervention was effective in reducing increases in peripheral systolic BP (−3.4 mm Hg; 95% CI: −6.6; −0.2; P = 0.037), central systolic BP (−3.8 mm Hg; −6.4; −1.1; P = 0.006), and PWV (−0.1 m/s; −0.2; −0.0; P = 0.045) among children whose mothers had the lowest educational level. We found no evidence for effectiveness of a 6‐months preschool‐based exercise program on hemodynamics, anthropometrics, activity, or motor skills, but lack of process evaluations and poor fidelity preclude interpretation of the causal relation. However, the results indicate that children from lower social backgrounds could benefit from early exercise‐promoting interventions.
High‐sensitivity troponin T in marathon runners, marathon runners with heart disease and collapsed marathon runners
Authors: Leckie Todd , Richardson Alan , Watkins Emily , Fitzpatrick Daniel , Galloway Rob , Grimaldi Rachael , Roberts Andrew , Baker Polly
Published: January 2019

Endurance exercise is an established cause of cardiac troponin (cTn) elevation, of further interest is whether this rise represents clinical significance. This study compared cTnT rise in three cohorts of marathon runners using a high‐sensitivity assay; control runners, those with known heart disease and runners who collapsed at the finish line. Control runners (n = 126) and runners with heart disease (n = 12) were prospectively recruited with cTnT levels measured pre‐race and at race completion. Collapsed runners (n = 15) were retrospectively recruited. A mixed model ANCOVA was used to compare the three groups. Pre‐race median cTnT for the control group and heart disease groups was 3.9 ng/L (IQR 3.1 ng/L) and 4.1 ng/L (IQR 3.4 ng/L). Post‐race values for the three groups were control 45.6 ng/L (IQR 42.5 ng/L), heart disease 41.2 ng/L (IQR 36.1 ng/L), and collapsed 41.9 ng/L (IQR 57.8 ng/L). Post‐race cTnT and cTnT change were significantly correlated with pre‐race cTnT within the control group (r = 0.38 and 0.30, P < 0.01). There was no difference in post‐race cTnT (adjusted for pre‐race cTnT) between the three groups. None of the runners reported symptoms suggestive of acute myocardial infarction on follow‐up. These results demonstrate that marathon running is associated with an asymptomatic cTnT rise for all runners, and this rise is significantly correlated to baseline cTnT levels, in addition, marathon runners with pre‐existing cardiac pathology or who collapse at the finish line do not exhibit an increased cTnT rise compared to healthy runners.
Low prevalence of MDR‐TB in Lao PDR: results from the first national anti‐tuberculosis drug resistance survey
Authors: Iem Vibol , Dean Anna , Zignol Matteo , Vongvichit Phouvang , Inthavong Donekham , Siphanthong Souvimone , Sorsavanh Theppouthone , Kim Sang Jae , Shin Soyoun , Sébert Jacques , Chittamany Phonenaly
Published: January 2019

Objective

To present results of the first national anti‐tuberculosis (TB) drug resistance survey conducted in Lao PDR between May 2016 and August 2017 to determine the prevalence of resistance to first‐line anti‐TB drugs among new and previously treated pulmonary TB cases in the country.

Methods

Patients with sputum smear‐positive pulmonary TB were enrolled from 42 TB laboratories distributed in 40 clusters throughout the country. Survey sites were selected using probability‐proportional‐to‐size sampling among all diagnostic centres in the country. In addition to smear microscopy, all patients underwent Xpert MTB/RIF testing and those found positive to Mycobacterium tuberculosis underwent sputum culture and drug susceptibility testing using the proportion method on solid Löwenstein–Jensen medium.

Results

Among 1006 eligible patients, 946 sputum smear‐positive and Xpert MTB/RIF positive (Mycobacterium tuberculosis detected) patients were included in the survey, comprising 897 new and 49 previously treated TB cases. The prevalence of rifampicin‐resistant TB was 1.2% (95% CI: 0.5–2.0%, n = 11/897) among new cases and 4.1% (95% CI: 0–9.6%, n = 2/49) among previously treated cases. Among the 946 TB cases confirmed by Xpert MTB/RIF, phenotypic drug sensitivity testing was available for 820 (776 new and 44 previously treated). The prevalence of multidrug‐resistant TB (MDR‐TB) was 0.5% (95% CI: 0–1.0%, n = 4/776) among new cases and 2.3% (95% CI: 0–6.7%, n = 1/44) among previously treated cases. No resistance to second‐line injectable agents nor to fluoroquinolones was detected among MDR‐TB patients.

Conclusions

The first national anti‐TB drug resistance survey in Lao PDR demonstrated an encouragingly low prevalence of MDR‐TB. The results appear lower than previous WHO estimates, and in line with the routine surveillance based on Xpert MTB/RIF testing (conducted among 50% of presumptive TB patients in 2017). The country should continue to expand its Xpert MTB/RIF network and strive to achieve universal drug susceptibility testing.